CA2767377A1 - Method for genome editing - Google Patents

Abstract

The present invention encompasses a method for creating an animal or cell with at least one chromosomal edit. In particular, the invention relates to the use of targeted zinc finger nucleases to edit chromosomal sequences. The invention further encompasses an animal or a cell created by a method of the invention.

Description

DEMANDE OU BREVET VOLUMINEUX

LA PRRSENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.

NOTE : Pour les tomes additionels, veuillez contacter le Bureau canadien des brevets JUMBO APPLICATIONS/PATENTS

THIS SECTION OF THE APPLICATION/PATENT CONTAINS MORE THAN ONE
VOLUME

NOTE: For additional volumes, please contact the Canadian Patent Office NOM DU FICHIER / FILE NAME:

NOTE POUR LE TOME / VOLUME NOTE:

METHOD FOR GENOME EDITING

REFERENCE TO SEQUENCE LISTING
[0001] A paper copy of the sequence listing and a computer readable form of the same sequence listing are appended below and herein incorporated by reference. The information recorded in computer readable form is identical to the written sequence listing, according to 37 C.F.R. 1.821 (f).
FIELD OF THE INVENTION

[0002] The invention encompasses a method for creating an animal or cell with at least one chromosomal edit. In particular, the invention relates to the use of targeted zinc finger nucleases to edit chromosomal sequences.
BACKGROUND OF THE INVENTION

[0003] Rational genome engineering has enormous potential across basic research, drug discovery, and cell-based medicines. Existing methods for targeted gene knock-out or site-specific gene insertion rely on homologous recombination. The low rate of spontaneous recombination in certain cell types, however, has been an enormous hurdle to universal genome editing. The scale of screening effort and the time required to isolate the targeted event was prohibitive. Thus, there exists a strong need for a technology that can rapidly achieve genomic editing in most cell types with high speed and efficiency, so as to greatly reduce the overall engineering effort.

SUMMARY OF THE INVENTION

[0004] One aspect of the present invention encompasses a method for editing a chromosomal sequence. The method comprises, in part, (a) introducing into a cell comprising the chromosomal sequence at least one nucleic acid encoding a zinc finger nuclease that recognizes a target sequence in the chromosomal sequence and is able to cleave a cleavage site in the chromosomal sequence, and, optionally, (i) at least one donor polynucleotide comprising a donor sequence for integration, an upstream sequence, and a downstream sequence, wherein the donor sequence is flanked by the upstream sequence and the downstream sequence, and wherein the upstream sequence and the downstream sequence share substantial sequence identity with either side of the cleavage site, or (ii) at least one exchange polynucleotide comprising an exchange sequence that is substantially identical to a portion of the chromosomal sequence at the cleavage site, and further comprising at least one nucleotide change; and (b) culturing the cell to allow expression of the zinc finger nuclease such that the zinc finger nuclease introduces a double-stranded break into the chromosomal sequence at the cleavage site, and wherein the double-stranded break is repaired by (i) a non-homologous end-joining repair process such that a mutation is introduced into the chromosomal sequence, or optionally (ii) a homology-directed repair process such that the donor sequence is integrated into the chromosomal sequence or the exchange sequence is exchanged with the portion of the chromosomal sequence.

[0005] Another aspect of the present invention encompasses a non-human animal. The non-human animal may be created in part, by (a) introducing into a cell comprising the chromosomal sequence at least one nucleic acid encoding a zinc finger nuclease that recognizes a target sequence in the chromosomal sequence and is able to cleave a cleavage site in the chromosomal sequence, and, optionally, (i) at least one donor polynucleotide comprising a donor sequence for integration, an upstream sequence, and a downstream sequence, wherein the donor sequence is flanked by the upstream sequence and the downstream sequence, and wherein the upstream sequence and the downstream sequence share substantial sequence identity with either side of the cleavage site, or (ii) at least one exchange polynucleotide comprising an exchange sequence that is substantially identical to a portion of the chromosomal sequence at the cleavage site, and further comprising at least one nucleotide change; and (b) culturing the cell to allow expression of the zinc finger nuclease such that the zinc finger nuclease introduces a double-stranded break into the chromosomal sequence at the cleavage site, and wherein the double-stranded break is repaired by (i) a non-homologous end-joining repair process such that a mutation is introduced into the chromosomal sequence, or optionally (ii) a homology-directed repair process such that the donor sequence is integrated into the chromosomal sequence or the exchange sequence is exchanged with the portion of the chromosomal sequence.

[0006] Yet another aspect of the present invention encompasses a cell. The cell may be created in part, by in part, by (a) introducing into the cell comprising the chromosomal sequence at least one nucleic acid encoding a zinc finger nuclease that recognizes a target sequence in the chromosomal sequence and is able to cleave a cleavage site in the chromosomal sequence, and, optionally, (i) at least one donor polynucleotide comprising a donor sequence for integration, an upstream sequence, and a downstream sequence, wherein the donor sequence is flanked by the upstream sequence and the downstream sequence, and wherein the upstream sequence and the downstream sequence share substantial sequence identity with either side of the cleavage site, or (ii) at least one exchange polynucleotide comprising an exchange sequence that is substantially identical to a portion of the chromosomal sequence at the cleavage site, and further comprising at least one nucleotide change; and (b) culturing the cell to allow expression of the zinc finger nuclease such that the zinc finger nuclease introduces a double-stranded break into the chromosomal sequence at the cleavage site, and wherein the double-stranded break is repaired by (i) a non-homologous end-joining repair process such that a mutation is introduced into the chromosomal sequence, or optionally (ii) a homology-directed repair process such that the donor sequence is integrated into the chromosomal sequence or the exchange sequence is exchanged with the portion of the chromosomal sequence.

[0007] A further aspect of the present invention encompasses an embryo. Typcially, the embryo comprises at least one nucleic acid encoding a zinc finger nuclease that recognizes a target sequence in the chromosomal sequence and is able to cleave a cleavage site in the chromosomal sequence, and, optionally, (i) at least one donor polynucleotide comprising a donor sequence for integration, an upstream sequence and a downstream sequence, wherein the donor sequence is flanked by the upstream sequence and the downstream sequence and wherein the upstream sequence and the downstream sequence share substantial sequence identity with either side of the cleavage site, or (ii) at least one exchange polynucleotide comprising an exchange sequence that is substantially identical to a portion of the chromosomal sequence at the cleavage site and which further comprises at least one nucleotide change.

[0008] Other aspects and iterations of the invention are described more thoroughly below.

REFERENCE TO COLOR FIGURES

[0009] The application file contains at least one photograph executed in color. Copies of this patent application publication with color photographs will be provided by the Office upon request and payment of the necessary fee.

BRIEF DESCRIPTION OF THE FIGURES

[0010] FIG. 1 is a schematic depicting the repair outcomes after a targeted ZFN-induced double stranded break. Shaded bars represent the donor fragment, whereas white bars depict target site for ZFN double stranded break.

[0011] FIG. 2 is a schematic depicting the construction of RFLP
donor plasmids. Shown, are the plasmid, and left and right PCR-amplified fragments homologous to the integration target site. Restriction enzymes used for cloning are denoted. The left fragment used Kpnl and Notl or Pmel. The right fragment used Notl or Pmel and Sacll.

[0012] FIG. 3 is a schematic depicting the construction of GFP-expressing donor plasmids. The GFP cassette was PCR amplified from an existing plasmid and cloned into the Notl RFLP donor using a Notl site.

[0013] FIG. 4 is a schematic depicting methods of detecting (A) RFLP
integration and restriction enzyme digestion and (B) integration of the GFP
expression cassette using PCR amplification.

[0014] FIG. 5 is a photographic image of fluorescently stained PCR
fragments resolved on an agarose gel. The leftmost lane contains a DNA ladder.
Lanes 1 to 6 contain PCR fragments amplified using mouse Mdrl a-specific primers from a whole or a fraction of a mouse blastocyst. Lanes 1 and 2 were amplified from 5/6 and 1/6 of a blastocyst, respectively. Lane 3 was from one whole blastocyst. Lanes 4 to 6 were from 1/2, 1/3, and 1 /6 of the same blastocyst, respective. Lane 7 contains a positive control PCR fragment amplified using the same primers from extracted mouse toe DNA.

[0015] FIG. 6 is a photographic image of fluorescently stained DNA
fragments resolved on an agarose gel. The leftmost lanes contain a DNA ladder.
(A) Lanes 1 to 39 contain PCR fragments amplified using mMdr1 a-specific primers from 37 mouse embryos cultured in vitro after being microinjected with ZFN RNA against mouse Mdrl a and RFLP donor with Notl site, along with one positive and negative control for PCR amplification. (B) Lanes 1 to 39 contain the PCR fragments in (A) after performing the Surveyor's mutation detection assay.

[0016] FIG. 7 is a photographic image of fluorescently stained DNA
fragments resolved on an agarose gel. The leftmost and rightmost lanes contain a DNA ladder. (A) Lanes contain PCR fragments amplified using mMdrla-specific primers from mouse embryos in FIG 6, and digested with Notl without purifying the PCR product. FIG. 7B is a longer run of the same gel in FIG. 7A.
The uncut PCR products are around 1.8 kb, and the digested products are two bands around 900 bp.

[0017] FIG. 8 is a photographic image of fluorescently stained DNA
fragments resolved on an agarose gel. The leftmost lane contains a DNA ladder.
Lanes 1 to 6 contain some of the PCR fragments from FIG 7 digested with Notl after the PCR products were column purified so that Notl can work in its optimal buffer. Lines 7 and 8 are two of the samples digested with Notl as in FIG 7.
This gel shows Notl digestion in PCR reactions was complete.

[0018] FIG. 9 is a photographic image of fluorescently stained PCR
fragments resolved on an agarose gel. The leftmost lane contains a DNA ladder.
Lanes 1 to 5 contain PCR fragments amplified using PXR-specific primers from 1, 1/2, 1/6, 1/10, 1/30 of a rat blastocyst. Lane 6 is a positive control amplified using the same primers from purified Sprague Dawley genomic DNA.

[0019] FIG. 10 is a photographic image of fluorescently stained DNA fragments resolved on an agarose gel. The leftmost and rightmost lanes contain a DNA ladder. (A) Lanes contain PCR fragments amplified from rat embryos cultured in vitro after microinjection of PXR ZFN mRNA and the Notl RFLP donor, using PXR-specific primers and digested with Notl. (B) Lanes contain the same PCR fragments as in FIG. 10A after performing the Surveyor's mutation detection assay.

[0020] FIG. 11 is a photographic image of fluorescently stained DNA fragments resolved on an agarose gel. The first 4 lanes are PCR amplified from 4 well developed fetus at 12.5 days post conception from embryos injected with mMdr1 a ZFN mRNA with the Notl RFLP donor. The PCR was digested with Notl. Lane 4 is positive one. Lanes 5-8 are 4 decidua, aborted implantations.
All four were negative.

[0021] FIG. 12 is a schematic and photographic image of fluorescently stained DNA fragments resolved on an agarose gel. (A) A
schematic showing the location of the primers used. Panels (B) and (C) show results from primers PF and GR. Panels (D) and (E) show results from primers PR + GF. Expected fragment size is 2.4kb. Two out of forty fetuses were positive for GFP.

[0022] FIG. 13 is a photographic image of DNA fragments resolved on an agarose gel. Lane 8 represents a 13 dpc fetus positive for the Notl site.

[0023] FIG. 14 illustrates ZFN-mediated cleavage of SMAD4 in human and feline cells, as detected by a Cel-1 surveyor nuclease assay. G =
GFP (no ZFN control). Z = SMAD4 ZFN (191160/19159). Arrows denote cleavage products.

[0024] FIG. 15 depicts Cel-1 assays confirming SMAD4 ZFN
activity in cat embryos.

[0025] FIG. 16 illustrates cleavage of Fel dl in AKD cells.
Presented is Cel-1 screening of the Fel dl ZFN pair 17, 18 cleavage of chain 1-exon 1.

[0026] FIG. 17 illustrates cleavage of Fel d1 chain 1-exon 2 in AKD
cells by the Fel dl ZFN pair 7, 9.

[0027] FIG. 18 depicts Cel-1 analysis of the Fel dl ZFN pair 12/13 cleavage of chain 1 -exon 2 in AKD cells.

[0028] FIG. 19 illustrates cleavage of Fel dl locus in cat embryos by ZFN pairs 17, 18 and 12, 13. Lanes 1, 2, 7, and 8 contain samples from individual blastocysts derived from embryos injected with 40 ng/pL of ZFNs.
Lane 3 presents a sample from a blastocyst derived an embryo injected with 20 ng/pL of ZFNs. Lanes 4, 9, and 10 contain samples from individual morulas derived from embryos injected with 40 ng/pL of ZFNs. Lane 3 presents a sample from a morula derived an embryo injected with 20 ng/pL of ZFNs. Lane 6 presents a sample from a control blastocyst.

[0029] FIG. 20 presents the DNA sequence of an edited Fel dl locus comprising a 4541 bp deletion (SEQ ID NO:51) between the regions coding for chain 2 and chain 1.

[0030] FIG. 21 aligns the edited Fel dl locus (designated by red dotted line, labeled "sample 5") comprising the 4541 bp deletion with the sequence of the wild-type Fel dl locus (SEQ ID NO:52). In the edited sample, the binding site for ZFN 13 is truncated (and the binding sire for ZFN 12 is missing), but the binding site for ZFN pair 17, 18 is intact.

[0031] FIG. 22 depicts cleavage of the cauxin locus by cauxin ZFN
pair 1/2 (lane 2), ZFN pair 9/10 (lane 4), and ZFN pair 17/18 (lane 5) in AKD
cells. Lanes 1 and 3 contain samples from control (GFP) cells.

[0032] FIG. 23 illustrates cleavage of the cauxin locus by cauxin ZFN pair 29/30 (lane 2). Lane 2 contains a control (GFP) sample.

[0033] FIG. 24 depicts integration at the TUBA1 B locus. (A) is a schematic showing the chromosome sequence (SEQ ID NO:85) at the target region for integration of the heterologous coding sequence, ZFN binding sites (yellow sequence) on the chromosome target region, the ZFN cut site (yellow arrow), and the integration site (green arrow). (B) presents schematics of the TUBA1 B locus, site of integration, design of the SH2 biosensor, and the proteins expressed after successful integration. (C) presents an image of a Western blot of wild-type and integrated cells.

[0034] FIG. 25 depicts the map of a donor plasmid comprising the SH2 biosensor sequence flanked by TUBAIA sequences at the target region.

[0035] FIG. 26 presents differential interference contrast (DIC) and fluorescence microscopy images of individual isolated cell clones expressing the GFP-2xSH2-Grbl -2A protein. Fluorescent images show a time course of biosensor translocation after exposure to 100 ng/mL of EGF.

[0036] FIG. 27 presents the map of a donor plasmid comprising the SH2 biosensor sequence flanked by the ACTB sequences at the target region.

[0037] FIG. 28 depicts fluorescence microscopy images of individual isolated cell clones expressing GFP-2xSH2-Grbl-2A (upper panels) and RFP-(3-actin (lower panels). Presented is a time course after exposure to 100 ng/mL of EGF.

[0038] FIG. 29 presents the DNA sequences of two edited LRRK2 loci. The upper sequence (SEQ ID NO:92) has a 10 bp deletion in the target sequence of exon 30, and the lower sequence (SEQ ID NO:93) has a 8 bp deletion in the target sequence of exon 30. The exon is shown in green; the target site is presented in yellow, and the deletions are shown in dark blue.

[0039] FIG. 30 presents the DNA sequences of two edited ApoE
loci. The upper sequence (SEQ ID NO:1 14) has a 16 bp deletion in the target sequence of exon 2, and the lower sequence (SEQ ID NO:115) has a 1 bp deletion in the target sequence of exon 2. The exon sequence is shown in green; the target site is presented in yellow, and the deletions are shown in dark blue.

[0040] FIG. 31 shows the DNA sequence of an edited leptin locus.
Presented is a region of the leptin locus (SEQ ID NO:1 16) in which 151 bp are deleted from exon 1 and intron 1. The exon is shown in green; the target site is presented in yellow, and the deletion is shown in dark blue.

[0041] FIG. 32 presents the DNA sequences of edited APP loci in two animals. (A) Shows a region of the rat APP locus (SEQ ID NO:127) in which 292 bp is deleted from exon 9. (B) Presents a region of the rat APP locus (SEQ
ID NO:128) in which there is a 309 bp deletion in exon 9. The exon is shown in green; the target site is presented in yellow, and the deletion is shown in dark blue.

[0042] FIG. 33 presents the DNA sequences of edited Rag1 loci in two animals. The upper sequence (SEQ ID NO:1 31) has a 808 bp deletion in exon 2, and the lower sequence (SEQ ID NO:132) has a 29 bp deletion in exon 2. The exon sequence is shown in green; the target site is presented in yellow, and the deletions are shown in dark blue.

[0043] FIG. 34 presents the DNA sequences of edited Rag2 loci in two animals. The upper sequence (SEQ ID NO:133) has a 13 bp deletion in the target sequence in exon 3, and the lower sequence (SEQ ID NO:134) has a 2 bp deletion in the target sequence in exon 2. The exon sequence is shown in green;
the target site is presented in yellow, and the deletions are shown in dark blue.

[0044] FIG. 35 presents the DNA sequences of edited Mdrl a loci in two animals. The upper sequence (SEQ ID NO:157) has a 20 bp deletion in exon 7, and the lower sequence (SEQ ID NO:158) has a 15 bp deletion and a 3 bp insertion (GCT) in exon 7. The exon sequence is shown in green; the target sequence is presented in yellow, and the deletions are shown in dark blue.

[0045] FIG. 36 illustrates knockout of the Mdrl a gene in rat.
Presented is a Western blot of varying amounts of a colon lysate from an Mdrl a knockout rat and a control cell lysate. The relative locations Mdrl a protein and actin protein are indicated to the left of the image [0046] FIG. 37 presents the DNA sequences of edited Mrpl loci in two animals. The upper sequence (SEQ ID NO:159) has a 43 bp deletion in exon 11, and the lower sequence (SEQ ID NO:160) has a 14 bp deletion in exon 11. The exon sequence is shown in green; the target sequence is presented in yellow, the deletions are shown in dark blue; and overlap between the target sequence and the exon is shown in grey.

[0047] FIG. 38 shows the DNA sequence of an edited Mrp2 locus.
The sequence (SEQ ID NO:161) has a 726 bp deletion in exon 7. The exon is shown in green; the target sequence is presented in yellow, and the deletion is shown in dark blue.

[0048] FIG. 39 presents the DNA sequences of edited BCRP loci in two animals. (A) Shows a region of the rat BCRP locus (SEQ ID NO:162) comprising a 588 bp deletion in exon 7. (B) Presents a region of the rat BCRP
locus (SEQ ID NO:163) comprising a 696 bp deletion in exon 7. The exon sequence is shown in green; the target site is presented in yellow, and the deletions are shown in dark blue.

[0049] FIG. 40 presents target sites and ZFN validation of Mdrl a, and two additional genes, Jag1, and Notch3. (A) shows ZFN target sequences.
The ZFN binding sites are underlined. (B) shows results of a mutation detection assay in NIH 3T3 cells to validate the ZFN mRNA activity. Each ZFN mRNA pair was cotransfected into NIH 3T3 cells. Transfected cells were harvested 24 h later. Genomic DNA was analyzed with the mutation detection assay to detect NHEJ products, indicative of ZFN activity. M, PCR marker; G (lanes 1, 3, and 5):

GFP transfected control; Z (lanes 2, 4, and 6), ZFN transfected samples. Uncut and cleaved bands are marked with respective sizes in base pairs.

[0050] FIG. 41 presents identification of genetically engineered Mdrl a founders using a mutation detection assay. Uncut and cleaved bands are marked with respective sizes in base pairs. Cleaved bands indicate a mutation is present at the target site. M, PCR marker. 1-44, 44 pups born from injected eggs.
The numbers of founders are underlined.

[0051] FIG. 42 presents amplification of large deletions in Mdrl a founders. PCR products were amplified using primers located 800 bp upstream and downstream of the ZFN target site. Bands significantly smaller than the 1.6 kb wild-type band indicate large deletions in the target locus. Four founders that were not identified in Figure 7 are underlined.

[0052] FIG. 43 presents the results of a mutation detection assay at the Mdrl b site in 44 Mdrl a ZFN injected pups. M, PCR marker; WT, toe DNA
from FVB/N mice that were not injected with Mdrl a ZFNs; 3T3, NIH 3T3 cells transfected with Mdrl a ZFNs as a control.

[0053] FIG. 44 presents detection of Mdrl a expression by using RT-PCR in Mdrl a-/- mice. (A) is a schematic illustration of Mdrl a genomic and mRNA structures around the target site. Exons are represented by open rectangles with respective numbers. The size of each exon in base pairs is labeled directly underneath. Intron sequences are represented by broken bars with size in base pairs underneath. The ZFN target site in exon 7 is marked with a solid rectangle. The position of the 396 bp deletion in founder #23 is labeled above intron 6 and exon 7. RT-F and RT-R are the primers used in RT-PCR, located in exons 5 and 9, respectively. In the RT reaction, 40 ng of total RNA
was used as template. Normalization of the input RNA is confirmed by GAPDH
amplification with or without RT.

[0054] FIG. 45 presents the results of band isolation following isolation and purification of the species at the wild-type size in the Mdrl a-/-samples, and then use as a template in a nested PCR.

[0055] FIG. 46 shows the DNA sequences of edited BDNF loci in two animals. The upper sequence (SEQ ID NO:21 1) has a 14 bp deletion in the target sequence in exon 2, and the lower sequence (SEQ ID NO:212) has a 7 bp deletion in the target sequence in exon 2. The exon is shown in green; the target site is presented in yellow, and the deletions are shown in dark blue.

[0056] FIG. 47 presents the DNA sequence of an edited DISC1 locus. Presented is a region of the rat DISC1 (SEQ ID NO:225) in which there is a 20 bp deletion in the target sequence in exon 5. The exon is shown in green;
the target site is presented in yellow, and the deletion is shown in dark blue.

[0057] FIG. 48 illustrates editing of the p53 locus in rats. Presented is a Cel-1 assay in which the presence of cleavage products indicated editing of the p53 gene.

[0058] FIG. 49 illustrates knockout of the p53 gene in rats.
Presented are Western blots of cytoplasmic and nuclear lysates of kidney (K) and liver (L) samples from wild-type (WT 731 RP) and p53 knockout (KO 733RP) animals. The relative locations p53 protein and actin protein are indicated to the right of each image.

DETAILED DESCRIPTION OF THE INVENTION

[0059] The present disclosure provides a method for creating a genetically modified animal or animal cell comprising at least one edited chromosomal sequence. The edited chromosomal sequence may be (1) inactivated, (2) modified, or (3) comprise an integrated sequence. An inactivated chromosomal sequence is altered such that a functional protein is not made or a control sequence no longer functions the same as a wild-type control sequence.
Thus, a genetically modified animal comprising an inactivated chromosomal sequence may be termed a "knock-out" or a "conditional knock-out." Similarly, a genetically modified animal comprising an integrated sequence may be termed a "knock-in" or a "conditional knock-in." As detailed below, a knock-in animal may be a humanized animal. Furthermore, a genetically modified animal comprising a modified chromosomal sequence may comprise a targeted point mutation(s) or other modification such that an altered protein product is produced. A
chromosomal sequence generally is edited using a zinc finger nuclease-mediated process. Briefly, the process comprises introducing into a cell at least one nucleic acid encoding a targeted zinc finger nuclease and, optionally, at least one accessory polynucleotide. The method further comprises incubating the cell to allow expression of the zinc finger nuclease, wherein a double-stranded break introduced into the targeted chromosomal sequence by the zinc finger nuclease is repaired by an error-prone non-homologous end-joining DNA repair process or a homology-directed DNA repair process. In an exemplary embodiment, the cell is an embryo. The method of editing chromosomal sequences using targeted zinc finger nuclease technology as described herein is rapid, precise, and highly efficient.

[0060] Additionally, the invention encompasses an animal or a cell comprising at least one edited chromosomal sequence. A method of the invention, an animal of the invention, a cell of the invention, and applications thereof are described in more detail below.

1. Method for Chromosomal Editing [0061] One aspect of the present invention encompasses a method for chromosomal editing. As used herein, "chromosomal editing" refers to editing a chromosomal sequence such that the sequence is (1) inactivated, (2) modified, or (3) comprises an integrated sequence. Generally speaking, a method for editing a chromosomal sequence comprises: (a) introducing into a cell at least one nucleic acid encoding a zinc finger nuclease that recognizes a target sequence in the chromosomal sequence and is able to cleave a site in the chromosomal sequence, and, optionally, (i) at least one donor polynucleotide comprising a sequence for integration, the sequence flanked by an upstream sequence and a downstream sequence that share substantial sequence identity with either side of the cleavage site, or (ii) at least one exchange polynucleotide comprising a sequence that is substantially identical to a portion of the chromosomal sequence at the cleavage site and which further comprises at least one nucleotide change; and (b) culturing the cell to allow expression of the zinc finger nuclease such that the zinc finger nuclease introduces a double-stranded break into the chromosomal sequence, and wherein the double-stranded break is repaired by (i) a non-homologous end-joining repair process such that a mutation is introduced into the chromosomal sequence, or (ii) a homology-directed repair process such that the sequence in the donor polynucleotide is integrated into the chromosomal sequence or the sequence in the exchange polynucleotide is exchanged with the portion of the chromosomal sequence.

[0062] Components of the zinc finger nuclease-mediated method of editing a chromosomal sequence are described in more detail below.

(a) nucleic acid encoding a zinc finger nuclease [0063] The method comprises, in part, introducing into a cell at least one nucleic acid encoding a zinc finger nuclease. Typically, a zinc finger nuclease comprises a DNA binding domain (i.e., zinc finger) and a cleavage domain (i.e., nuclease). The DNA binding and cleavage domains are described below. The nucleic acid encoding a zinc finger nuclease may comprise DNA or RNA. For example, the nucleic acid encoding a zinc finger nuclease may comprise mRNA. When the nucleic acid encoding a zinc finger nuclease comprises mRNA, the mRNA molecule may be 5' capped. Similarly, when the nucleic acid encoding a zinc finger nuclease comprises mRNA, the mRNA
molecule may be polyadenylated. An exemplary nucleic acid according to the method is a capped and polyadenylated mRNA molecule encoding a zinc finger nuclease. Methods for capping and polyadenylating mRNA are known in the art.

[0064] Generally speaking, a zinc finger nuclease of the invention, once introduced into a cell, creates a double-stranded break in the chromosomal sequence. The double-stranded break may be repaired, in certain embodiments, by a non-homologous end-joining repair process of the cell, such that a mutation is introduced into the chromosomal sequence. In other embodiments, as described below, a homology-directed repair process is used to edit the chromosomal sequence.

(i) zinc finger binding domain [0065] Zinc finger binding domains may be engineered to recognize and bind to any nucleic acid sequence of choice. See, for example, Beerli et al.
(2002) Nat. Biotechnol. 20:135-141; Pabo et al. (2001) Ann. Rev. Biochem.
70:313-340; Isalan et al. (2001) Nat. Biotechnol. 19:656-660; Segal et al.
(2001) Curr. Opin. Biotechnol. 12:632-637; Choo et al. (2000) Curr. Opin. Struct.
Biol.
10:411-416; Zhang et al. (2000) J. Biol. Chem. 275(43):33850-33860; Doyon et al. (2008) Nat. Biotechnol. 26:702-708; and Santiago et al. (2008) Proc. NatI.
Acad. Sci. USA 105:5809-5814. An engineered zinc finger binding domain may have a novel binding specificity compared to a naturally-occurring zinc finger protein. Engineering methods include, but are not limited to, rational design and various types of selection. Rational design includes, for example, using databases comprising doublet, triplet, and/or quadruplet nucleotide sequences and individual zinc finger amino acid sequences, in which each doublet, triplet or quadruplet nucleotide sequence is associated with one or more amino acid sequences of zinc fingers which bind the particular triplet or quadruplet sequence. See, for example, U.S. Patent Nos. 6,453,242 and 6,534,261, the disclosures of which are incorporated by reference herein in their entireties.
As an example, the algorithm described in U.S. Patent No. 6,453,242 may be used to design a zinc finger binding domain to target a preselected sequence.
Alternative methods, such as rational design using a nondegenerate recognition code table may also be used to design a zinc finger binding domain to target a specific sequence (Sera et al. (2002) Biochemistry 41:7074-7081). Publically available web-based tools for identifying potential target sites in DNA
sequences and designing zinc finger binding domains may be found at www.zincfingertools.org and bindr.gdcb.iastate.edu/ZiFiT/, respectively (Mandell et al. (2006) Nuc. Acid Res. 34:W516-W523; Sander et al. (2007) Nuc. Acid Res.
35:W599-W605).

[0066] A zinc finger DNA binding domain may be designed to recognize a DNA sequence ranging from about 3 nucleotides to about 21 nucleotides in length, or from about 8 to about 19 nucleotides in length. In general, the zinc finger binding domains of the zinc finger nucleases disclosed herein comprise at least three zinc finger recognition regions (i.e., zinc fingers).
In one embodiment, the zinc finger binding domain may comprise four zinc finger recognition regions. In another embodiment, the zinc finger binding domain may comprise five zinc finger recognition regions. In still another embodiment, the zinc finger binding domain may comprise six zinc finger recognition regions. A
zinc finger binding domain may be designed to bind to any suitable target DNA
sequence. See for example, U.S. Patent Nos. 6,607,882; 6,534,261 and 6,453,242, the disclosures of which are incorporated by reference herein in their entireties.

[0067] Exemplary methods of selecting a zinc finger recognition region may include phage display and two-hybrid systems, and are disclosed in U.S. Patent. Nos. 5,789,538; 5,925,523; 6,007,988; 6,013,453; 6,410,248;
6,140,466; 6,200,759; and 6,242,568; as well as WO 98/37186; WO 98/53057;
WO 00/27878; WO 01/88197 and GB 2,338,237, each of which is incorporated by reference herein in its entirety. In addition, enhancement of binding specificity for zinc finger binding domains has been described, for example, in WO
02/077227.

[0068] Zinc finger binding domains and methods for design and construction of fusion proteins (and polynucleotides encoding same) are known to those of skill in the art and are described in detail in U.S. Patent Application Publication Nos. 20050064474 and 20060188987, each incorporated by reference herein in its entirety. Zinc finger recognition regions and/or multi-fingered zinc finger proteins may be linked together using suitable linker sequences, including for example, linkers of five or more amino acids in length.
See, U.S. Patent Nos. 6,479,626; 6,903,185; and 7,153,949, the disclosures of which are incorporated by reference herein in their entireties, for non-limiting examples of linker sequences of six or more amino acids in length. The zinc finger binding domain described herein may include a combination of suitable linkers between the individual zinc fingers of the protein.

[0069] In some embodiments, the zinc finger nuclease may further comprise a nuclear localization signal or sequence (NLS). A NLS is an amino acid sequence which facilitates targeting the zinc finger nuclease protein into the nucleus to introduce a double stranded break at the target sequence in the chromosome. Nuclear localization signals are known in the art. See, for example, Makkerh et al. (1996) Current Biology 6:1025-1027.

(ii) cleavage domain [0070] A zinc finger nuclease also includes a cleavage domain.
The cleavage domain portion of the zinc finger nucleases disclosed herein may be obtained from any endonuclease or exonuclease. Non-limiting examples of endonucleases from which a cleavage domain may be derived include, but are not limited to, restriction endonucleases and homing endonucleases. See, for example, 2002-2003 Catalog, New England Biolabs, Beverly, Mass.; and Belfort et al. (1997) Nucleic Acids Res. 25:3379-3388 or www.neb.com. Additional enzymes that cleave DNA are known (e.g., S1 Nuclease; mung bean nuclease;
pancreatic DNase I; micrococcal nuclease; yeast HO endonuclease). See also Linn et al. (eds.) Nucleases, Cold Spring Harbor Laboratory Press, 1993. One or more of these enzymes (or functional fragments thereof) may be used as a source of cleavage domains.

[0071] A cleavage domain also may be derived from an enzyme or portion thereof, as described above, that requires dimerization for cleavage activity. Two zinc finger nucleases may be required for cleavage, as each nuclease comprises a monomer of the active enzyme dimer. Alternatively, a single zinc finger nuclease may comprise both monomers to create an active enzyme dimer. As used herein, an "active enzyme dimer" is an enzyme dimer capable of cleaving a nucleic acid molecule. The two cleavage monomers may be derived from the same endonuclease (or functional fragments thereof), or each monomer may be derived from a different endonuclease (or functional fragments thereof).

[0072] When two cleavage monomers are used to form an active enzyme dimer, the recognition sites for the two zinc finger nucleases are preferably disposed such that binding of the two zinc finger nucleases to their respective recognition sites places the cleavage monomers in a spatial orientation to each other that allows the cleavage monomers to form an active enzyme dimer, e.g., by dimerizing. As a result, the near edges of the recognition sites may be separated by about 5 to about 18 nucleotides. For instance, the near edges may be separated by about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18 nucleotides. It will however be understood that any integral number of nucleotides or nucleotide pairs may intervene between two recognition sites (e.g., from about 2 to about 50 nucleotide pairs or more). The near edges of the recognition sites of the zinc finger nucleases, such as for example those described in detail herein, may be separated by 6 nucleotides. In general, the site of cleavage lies between the recognition sites.

[0073] Restriction endonucleases (restriction enzymes) are present in many species and are capable of sequence-specific binding to DNA (at a recognition site), and cleaving DNA at or near the site of binding. Certain restriction enzymes (e.g., Type IIS) cleave DNA at sites removed from the recognition site and have separable binding and cleavage domains. For example, the Type IIS enzyme Fok I catalyzes double-stranded cleavage of DNA, at 9 nucleotides from its recognition site on one strand and 13 nucleotides from its recognition site on the other. See, for example, U.S. Patent Nos.
5,356,802; 5,436,150 and 5,487,994; as well as Li et al. (1992) Proc. NatI.
Acad.
Sci. USA 89:4275-4279; Li et al. (1993) Proc. NatI. Acad. Sci. USA 90:2764-2768; Kim et al. (1994a) Proc. Natl. Acad. Sci. USA 91:883-887; Kim et al.
(1994b) J. Biol. Chem. 269:31, 978-31, 982. Thus, a zinc finger nuclease may comprise the cleavage domain from at least one Type IIS restriction enzyme and one or more zinc finger binding domains, which may or may not be engineered.
Exemplary Type IIS restriction enzymes are described for example in International Publication WO 07/014,275, the disclosure of which is incorporated by reference herein in its entirety. Additional restriction enzymes also contain separable binding and cleavage domains, and these also are contemplated by the present disclosure. See, for example, Roberts et al. (2003) Nucleic Acids Res. 31:418-420.

[0074] An exemplary Type IIS restriction enzyme, whose cleavage domain is separable from the binding domain, is Fok I. This particular enzyme is active as a dimer (Bitinaite et al. (1998) Proc. NatI. Acad. Sci. USA 95: 10, 10, 575). Accordingly, for the purposes of the present disclosure, the portion of the Fok I enzyme used in a zinc finger nuclease is considered a cleavage monomer. Thus, for targeted double-stranded cleavage using a Fok I cleavage domain, two zinc finger nucleases, each comprising a Fokl cleavage monomer, may be used to reconstitute an active enzyme dimer. Alternatively, a single polypeptide molecule containing a zinc finger binding domain and two Fok I
cleavage monomers may also be used.

[0075] In certain embodiments, the cleavage domain may comprise one or more engineered cleavage monomers that minimize or prevent homodimerization, as described, for example, in U.S. Patent Publication Nos.
20050064474, 20060188987, and 20080131962, each of which is incorporated by reference herein in its entirety. By way of non-limiting example, amino acid residues at positions 446, 447, 479, 483, 484, 486, 487, 490, 491, 496, 498, 499, 500, 531, 534, 537, and 538 of Fok I are all targets for influencing dimerization of the Fok I cleavage half-domains. Exemplary engineered cleavage monomers of Fok I that form obligate heterodimers include a pair in which a first cleavage monomer includes mutations at amino acid residue positions 490 and 538 of Fok I and a second cleavage monomer that includes mutations at amino-acid residue positions 486 and 499.

[0076] Thus, in one embodiment, a mutation at amino acid position 490 replaces Glu (E) with Lys (K); a mutation at amino acid residue 538 replaces Iso (I) with Lys (K); a mutation at amino acid residue 486 replaces GIn (Q) with Glu (E); and a mutation at position 499 replaces Iso (I) with Lys (K).
Specifically, the engineered cleavage monomers may be prepared by mutating positions 490 from E to K and 538 from I to K in one cleavage monomer to produce an engineered cleavage monomer designated "E490K:1538K" and by mutating positions 486 from Q to E and 499 from I to L in another cleavage monomer to produce an engineered cleavage monomer designated "Q486E:1499L." The above described engineered cleavage monomers are obligate heterodimer mutants in which aberrant cleavage is minimized or abolished. Engineered cleavage monomers may be prepared using a suitable method, for example, by site-directed mutagenesis of wild-type cleavage monomers (Fok I) as described in U.S. Patent Publication No. 20050064474 (see Example 5).

[0077] The zinc finger nuclease described above may be engineered to introduce a double stranded break at the targeted site of integration. The double stranded break may be at the targeted site of integration, or it may be up to 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 100, or nucleotides away from the site of integration. In some embodiments, the double stranded break may be up to 1, 2, 3, 4, 5, 10, 15, or 20 nucleotides away from the site of integration. In other embodiments, the double stranded break may be up to 10, 15, 20, 25, 30, 35, 40, 45, or 50 nucleotides away from the site of integration. In yet other embodiments, the double stranded break may be up to 50, 100, or 1000 nucleotides away from the site of integration.

(iii) exemplary zinc finger nuclease [0078] Provided herein are non-limiting examples of zinc finger nucleases that recognize and bind target sequences found in various animal chromosomal sequences. For instance, a zinc finger nuclease of the invention may have an amino acid sequence that is at least 80% identical to a sequence chosen from a zinc finger nuclease having a SEQ ID NO chosen from 53, 54, 57-62, 69-76, 104-113, 123-126, 147-156, 201-210, 219-222, 223-224, 230-233, 240-243. In other embodiments, the sequence identity may be about 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100%.

[0079] Moreover, the zinc finger nucleases encoded by a SEQ ID
NO chosen from 53, 54, 57-62, 69-76, 104-113, 123-126, 147-156, 201-210, 219-222, 223-224, 230-233, 240-243 may recognize and bind a chromosomal sequence having at least about 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% sequence identity to a chromosomal SEQ ID
NO 55, 56, 63-68, 77-84, 86- 91, 94-103, 117-122, 129, 130, 135, 136, 137, 138, 139-146, 164-173, 213-218, 226-229, 234, 235, 236, 237, 238, 239.

(iv) additional methods for targeted cleavage [0080] Any nuclease having a target site in a chromosome may be used in the methods disclosed herein. For example, homing endonucleases and meganucleases have very long recognition sequences, some of which are likely to be present, on a statistical basis, once in a human-sized genome. Any such nuclease having a unique target site in a genome may be used instead of, or in addition to, a zinc finger nuclease, for targeted cleavage of a chromosome.

[0081] Non-limiting examples of homing endonucleases include I-Scel, I-Ceul, PI-Pspl, PI-Sce, I-SceIV, I-Csml, I-Pant, I-Scell, I-Ppol, I-Scelll, I-Crel, I-Tevl, I-Tevll and I-Tevlll. The recognition sequences of these enzymes are known in the art. See also U.S. Patent No. 5,420,032; U.S. Patent No.
6,833,252; Belfort et al. (1997) Nucleic Acids Res. 25:3379-3388; Dujon et al.
(1989) Gene 82:115-118; Perler et al. (1994) Nucleic Acids Res. 22, 1125-1127;
Jasin (1996) Trends Genet. 12:224-228; Gimble et al. (1996) J. Mol. Biol.
263:163-180; Argast et al. (1998) J. Mol. Biol. 280:345-353 and the New England Biolabs catalogue.

[0082] Although the cleavage specificity of most homing endonucleases is not absolute with respect to their recognition sites, the sites are of sufficient length that a single cleavage event per mammalian-sized genome may be obtained by expressing a homing endonuclease in a cell containing a single copy of its recognition site. It has also been reported that the specificity of homing endonucleases and meganucleases may be engineered to bind non-natural target sites. See, for example, Chevalier et al. (2002) Molec. Cell 10:895-905; Epinat et al. (2003) Nucleic Acids Res. 31:2952-2962; Ashworth et al.
(2006) Nature 441:656-659; Paques et al. (2007) Current Gene Therapy 7:49-66.

(b) optional exchange polynucleotide [0083] A method for editing chromosomal sequences may further comprise introducing into a cell at least one exchange polynucleotide comprising a sequence that is substantially identical to the chromosomal sequence at the site of cleavage and which further comprises at least one specific nucleotide change.

[0084] Typically, the exchange polynucleotide will be DNA. The exchange polynucleotide may be a DNA plasmid, a bacterial artificial chromosome (BAC), a yeast artificial chromosome (YAC), a viral vector, a linear piece of DNA, a PCR fragment, a naked nucleic acid, or a nucleic acid complexed with a delivery vehicle such as a liposome or poloxamer. An exemplary exchange polynucleotide may be a DNA plasmid.

[0085] The sequence in the exchange polynucleotide is substantially identical to a portion of the chromosomal sequence at the site of cleavage. In general, the sequence of the exchange polynucleotide will share enough sequence identity with the chromosomal sequence such that the two sequences may be exchanged by homologous recombination. For example, the sequence in the exchange polynucleotide may be at least about 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% identical to a region of the chromosomal sequence.

[0086] Importantly, the sequence in the exchange polynucleotide comprises at least one specific nucleotide change with respect to the sequence of the corresponding chromosomal sequence. For example, one nucleotide in a specific codon may be changed to another nucleotide such that the codon codes for a different amino acid. In one embodiment, the sequence in the exchange polynucleotide may comprise one specific nucleotide change such that the encoded protein comprises one amino acid change. In other embodiments, the sequence in the exchange polynucleotide may comprise two, three, four, or more specific nucleotide changes such that the encoded protein comprises one, two, three, four, or more amino acid changes. In still other embodiments, the sequence in the exchange polynucleotide may comprise a three nucleotide deletion or insertion such that the reading frame of the coding reading is not altered (and a functional protein may be produced). The expressed protein, however, would comprise a single amino acid deletion or insertion.

[0087] The length of the sequence in the exchange polynucleotide that is substantially identical to a portion of the chromosomal sequence at the site of cleavage can and will vary. In general, the sequence in the exchange polynucleotide may range from about 25 bp to about 10,000 bp in length. In various embodiments, the sequence in the exchange polynucleotide may be about 50, 100, 200, 400, 600, 800, 1000, 1200, 1400, 1600, 1800, 2000, 2200, 2400, 2600, 2800, 3000, 3200, 3400, 3600, 3800, 4000, 4200, 4400, 4600, 4800, or 5000 bp in length. In other embodiments, the sequence in the exchange polynucleotide may be about 5500, 6000, 6500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500, or 10,000 bp in length.

[0088] One of skill in the art would be able to construct an exchange polynucleotide as described herein using well-known standard recombinant techniques (see, for example, Sambrook et al., 2001 and Ausubel et al., 1996).

[0089] In the method detailed above for modifying a chromosomal sequence, a double stranded break introduced into the chromosomal sequence by the zinc finger nuclease is repaired, via homologous recombination with the exchange polynucleotide, such that the sequence in the exchange polynucleotide may be exchanged with a portion of the chromosomal sequence. The presence of the double stranded break facilitates homologous recombination and repair of the break. The exchange polynucleotide may be physically integrated or, alternatively, the exchange polynucleotide may be used as a template for repair of the break, resulting in the exchange of the sequence information in the exchange polynucleotide with the sequence information in that portion of the chromosomal sequence. Thus, a portion of the endogenous chromosomal sequence may be converted to the sequence of the exchange polynucleotide.
The changed nucleotide(s) may be at or near the site of cleavage.
Alternatively, the changed nucleotide(s) may be anywhere in the exchanged sequences. As a consequence of the exchange, however, the chromosomal sequence is modified.

(c) optional donor polynucleotide [0090] A method for editing chromosomal sequences may alternatively comprise introducing at least one donor polynucleotide comprising a sequence for integration into a cell. A donor polynucleotide comprises at least three components: the sequence to be integrated that is flanked by an upstream sequence and a downstream sequence, wherein the upstream and downstream sequences share sequence similarity with either side of the site of integration in the chromosome.

[0091] Typically, the donor polynucleotide will be DNA. The donor polynucleotide may be a DNA plasmid, a bacterial artificial chromosome (BAC), a yeast artificial chromosome (YAC), a viral vector, a linear piece of DNA, a PCR
fragment, a naked nucleic acid, or a nucleic acid complexed with a delivery vehicle such as a liposome or poloxamer. An exemplary donor polynucleotide may be a DNA plasmid.

[0092] The donor polynucleotide comprises a sequence for integration. The sequence for integration may be a sequence endogenous to the animal or cell or it may be an exogenous sequence. The sequence for integration may encode a protein or a non-coding RNA (e.g., a microRNA).
Thus, the sequence for integration may be operably linked to an appropriate control sequence or sequences. Alternatively, the sequence for integration may provide a regulatory function. Accordingly, the size of the sequence for integration can and will vary. In general, the sequence for integration may range from about one nucleotide to several million nucleotides.

[0093] The donor polynucleotide also comprises upstream and downstream sequence flanking the sequence to be integrated. The upstream and downstream sequences in the donor polynucleotide are selected to promote recombination between the chromosomal sequence of interest and the donor polynucleotide. The upstream sequence, as used herein, refers to a nucleic acid sequence that shares sequence similarity with the chromosomal sequence upstream of the targeted site of integration. Similarly, the downstream sequence refers to a nucleic acid sequence that shares sequence similarity with the chromosomal sequence downstream of the targeted site of integration. The upstream and downstream sequences in the donor polynucleotide may share about 75%, 80%, 85%, 90%, 95%, or 100% sequence identity with the targeted chromosomal sequence. In other embodiments, the upstream and downstream sequences in the donor polynucleotide may share about 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with the targeted chromosomal sequence. In an exemplary embodiment, the upstream and downstream sequences in the donor polynucleotide may share about 99% or 100% sequence identity with the targeted chromosomal sequence.

[0094] An upstream or downstream sequence may comprise from about 20 bp to about 2500 bp. In various embodiments, an upstream or downstream sequence may comprise about 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, or 2500 bp. An exemplary upstream or downstream sequence may comprise about 200 bp to about 2000 bp, about 600 bp to about 1000 bp, or more particularly about 700 bp to about 1000 bp.

[0095] In some embodiments, the donor polynucleotide may further comprise a marker. Such a marker may make it easy to screen for targeted integrations. Non-limiting examples of suitable markers include restriction sites, fluorescent proteins, or selectable markers.

[0096] One of skill in the art would be able to construct a donor polynucleotide as described herein using well-known standard recombinant techniques (see, for example, Sambrook et al., 2001 and Ausubel et al., 1996).

[0097] In the method detailed above for editing a chromosomal sequence by integrating a sequence, the double stranded break introduced into the chromosomal sequence by the zinc finger nuclease is repaired, via homologous recombination with the donor polynucleotide, such that the sequence is integrated into the chromosome. The presence of a double-stranded break facilitates integration of the sequence. A donor polynucleotide may be physically integrated or, alternatively, the donor polynucleotide may be used as a template for repair of the break, resulting in the introduction of the sequence as well as all or part of the upstream and downstream sequences of the donor polynucleotide into the chromosome. Thus, the endogenous chromosomal sequence may be converted to the sequence of the donor polynucleotide.

(d) introducing nucleic acid into a cell [0098] To mediate zinc finger nuclease genome editing, at least one nucleic acid molecule encoding a zinc finger nuclease and, optionally, at least one exchange polynucleotide or at least one donor polynucleotide is introduced into a cell. As used herein, the term "cell" encompasses any animal cell that comprises a chromosomal sequence. In some embodiments, the term "cell" may refer to an embryo. In certain exemplary embodiments, the embryo is a fertilized one-cell stage embryo. In other exemplary embodiments, the embryo may be an embryo of any stage.

[0099] Suitable methods of introducing the nucleic acids to the embryo or cell may include microinjection, electroporation, sonoporation, biolistics, calcium phosphate-mediated transfection, cationic transfection, liposome transfection, dendrimer transfection, heat shock transfection, nucleofection transfection, magnetofection, lipofection, impalefection, optical transfection, proprietary agent-enhanced uptake of nucleic acids, and delivery via liposomes, immunoliposomes, virosomes, or artificial virions. In one embodiment, the nucleic acids may be introduced into an embryo by microinjection. The nucleic acids may be microinjected into the nucleus or the cytoplasm of the embryo. In another embodiment, the nucleic acids may be introduced into a cell by nucleofection.

[0100] In embodiments in which both a nucleic acid encoding a zinc finger nuclease and an exchange (or donor) polynucleotide are introduced into an embryo or cell, the ratio of exchange (or donor) polynucleotide to nucleic acid encoding a zinc finger nuclease may range from about 1:10 to about 10:1. In various embodiments, the ratio of exchange (or donor) polynucleotide to nucleic acid encoding a zinc finger nuclease may be about 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1. In one embodiment, the ratio may be about 1:1.

[0101] In embodiments in which more than one nucleic acid encoding a zinc finger nuclease and, optionally, more than one exchange (or donor) polynucleotide is introduced into an embryo or cell, the nucleic acids may be introduced simultaneously or sequentially. For example, nucleic acids encoding the zinc finger nucleases, each specific for a distinct recognition sequence, as well as the optional exchange (or donor) polynucleotides, may be introduced at the same time. Alternatively, each nucleic acid encoding a zinc finger nuclease, as well as the optional exchange (or donor) polynucleotides, may be introduced sequentially.

[0102] In one embodiment, at least one nucleic acid molecule encoding a zinc finger nuclease is introduced into a cell. In another embodiment, at least 2, 3, 4, 5, or more than 5 nucleic acid molecules encoding a zinc finger nuclease are introduced into a cell. In each of the above embodiments, one or more corresponding donor or exchange polynucleotides may also be introduced into the cell, in a ratio from about 1:10 to about 10:1 donor or exchange polynucleotides to zinc finger nuclease nucleic acids, as described above.

(e) culturing the cell [0103] A method for editing a chromosomal sequence using a zinc finger nuclease-mediated process as described herein further comprises culturing the cell comprising the introduced nucleic acid(s) to allow expression of the at least one zinc finger nuclease.

[0104] Cells comprising the introduced nucleic acids may be cultured using standard procedures to allow expression of the zinc finger nuclease. Standard cell culture techniques are described, for example, in Santiago et al. (2008) PNAS 105:5809-5814; Moehle et al. (2007) PNAS
104:3055-3060; Urnov et al. (2005) Nature 435:646-651; and Lombardo et al (2007) Nat. Biotechnology 25:1298-1306. Those of skill in the art appreciate that methods for culturing cells are known in the art and can and will vary depending on the cell type or cell species. Routine optimization may be used, in all cases, to determine the best techniques for a particular cell type.

[0105] In one embodiment where the cell is an embryo, the embryo may be cultured in vitro (e.g., in cell culture). Typically, the embryo is cultured for a short period of time at an appropriate temperature and in appropriate media with the necessary 02/CO2 ratio to allow the expression of the zinc finger nuclease. A skilled artisan will appreciate that culture conditions can and will vary depending on the embryo species. Routine optimization may be used, in all cases, to determine the best culture conditions for a particular species of embryo.

In some cases, a cell line may be derived from an in vitro-cultured embryo (e.g., an embryonic stem cell line).

[0106] Preferably, the embryo will be cultured in vivo by transferring the embryo into the uterus of a female host. Generally speaking, the female host is from the same or a similar species as the embryo. Preferably, the female host is pseudo-pregnant. Methods of preparing pseudo-pregnant female hosts are known in the art. Additionally, methods of transferring an embryo into a female host are known. Culturing an embryo in vivo permits the embryo to develop and may result in a live birth of an animal derived from the embryo. Such an animal generally will comprise the disrupted chromosomal sequence(s) in every cell of its body.

[0107] Upon expression of the at least one zinc finger nuclease in a cell, the chromosomal sequence of the cell may be edited. In cases in which the cell comprises an expressed zinc finger nuclease but no exchange (or donor) polynucleotide, the zinc finger nuclease recognizes, binds, and cleaves the target sequence in the chromosomal sequence of interest. The double-stranded break introduced by the zinc finger nuclease is repaired by an error-prone non-homologous end-joining DNA repair process. Consequently, a deletion, or insertion resulting in a missense or nonsense mutation may be introduced in the chromosomal sequence such that the sequence is inactivated.

[0108] In cases in which the embryo or cell comprises an expressed zinc finger nuclease as well as an exchange (or donor) polynucleotide, the zinc finger nuclease recognizes, binds, and cleaves the target sequence in the chromosome. The double-stranded break introduced by the zinc finger nuclease is repaired, via homologous recombination with the exchange (or donor) polynucleotide, such that a portion of the chromosomal sequence is converted to the sequence in the exchange polynucleotide or the sequence in the donor polynucleotide is integrated into the chromosomal sequence. As a consequence, the chromosomal sequence is edited.

[0109] The genetically modified animals disclosed herein may be crossbred to create animals comprising more than one edited chromosomal sequence or to create animals that are homozygous for one or more edited chromosomal sequences. Those of skill in the art will appreciate that many combinations are possible. Moreover, the genetically modified animals disclosed herein may be crossed with other animals to combine the edited chromosomal sequence with other genetic backgrounds. By way of non-limiting example, suitable genetic backgrounds include wild-type, natural mutations giving rise to known phenotypes, targeted chromosomal integration, non-targeted integrations, etc.

(f) types of chromosomal edits [0110] As stated above, a method of the invention may be used to (1) inactivate a chromosomal sequence, (2) modify a chromosomal sequence, or (3) integrate a sequence into a chromosome. Each of these is discussed in more detail below.

i. inactivate a sequence [0111] In one embodiment, an edited chromosomal sequence may be inactivated such that the sequence is not transcribed, the coded protein is not produced, or the sequence does not function as the wild-type sequence does.
For example, a protein coding sequence may be inactivated such that the protein is not produced. Alternatively, a microRNA coding sequence may be inactivated such that the microRNA is not produced. Furthermore, a control sequence may be inactivated such that it no longer functions as a control sequence. As used herein, "control sequence" refers to any nucleic acid sequence that effects the transcription, translation, or accessibility of a nucleic acid sequence. By way of non-limiting example, a promoter, a transcription terminator, and an enhancer are control sequences. The inactivated chromosomal sequence may include a deletion mutation (i.e., deletion of one or more nucleotides), an insertion mutation (i.e., insertion of one or more nucleotides), or a nonsense mutation (i.e., substitution of a single nucleotide for another nucleotide such that a stop codon is introduced). In some embodiments, a chromosomal sequence that is inactivated may be termed a "knock-out." In an interation of the invention, a "knock-out" animal created by a method of the invention does not comprise any exogenous sequence.

ii. modify a sequence [0112] In another embodiment, an edited chromosomal sequence may be modified such that it codes for an altered gene product or the function of the sequence is altered. A chromosomal sequence encoding a protein may be modified to include at least one changed nucleotide such that the codon comprising the changed nucleotide codes for a different amino acid. The resultant protein, therefore, comprises at least one amino acid change.
Moreover, a protein coding sequence may be modified by insertions or deletions such that the reading from of the sequence is not altered and a modified protein is produced. In such embodiments, the modified sequence may result in a phenotype change.

[0113] Alternatively, a chromosomal sequence that functions as a control sequence may be modified. For instance, a promoter may be modified such that it is always active or is regulated by an exogenous signal.

[0114] In yet another embodiment, at least one chromosomal sequence encoding a protein of interest may be edited such that the expression pattern of the protein is altered. For example, regulatory regions controlling the expression of the protein, such as a promoter or transcription factor binding site, may be altered such that the protein of interest is over-produced, or the tissue-specific or temporal expression of the protein is altered, or a combination thereof.

N. Integrate a sequence [0115] In yet another embodiment, an edited chromosomal sequence may comprise an integrated sequence. Such a sequence may encode an endogenous protein, an exogenous or heterologous protein, a wild-type protein, a modified protein, a fusion protein, a microRNA, or the like. An integrated protein coding sequence may be linked to a reporter sequence (the reporter sequence may be linked 5' or 3' to the protein coding sequence). An integrated protein coding sequence may also be placed under control of an endogenous promoter, may be operably linked to an exogenous promoter, or may be fused in-frame with an endogenous protein coding sequence.
Additionally, the integrated sequence may function as a control element.
Accordingly, the integrated sequence may be endogenous or exogenous to the cell. An animal or cell comprising such an integrated sequence may be termed "knock-in." In one iteration of the above embodiments, it should be understood that no selectable marker is present.

[0116] In certain embodiments, a sequence may be integrated to alter the expression pattern of a protein of interest. For instance, a conditional knock-out system may be created.

A. conditional mutations [0117] In certain embodiments, a sequence may be edited to alter the expression pattern of a protein of interest. For instance, a conditional knock-out system may be created.

[0118] As used herein, a "conditional knock-out" system is a model where the expression of a nucleic acid molecule is disrupted in a particular organ, tissue, or cell type, as opposed to the entire animal, and/or in a temporally controlled manner. A conditional knock-out allows, for example, the study of a gene function even when global disruption of the gene is lethal.

[0119] A non-limiting example of a conditional knock-out system includes a Cre-lox recombination system. A Cre-lox recombination system comprises a Cre recombinase enzyme, a site-specific DNA recombinase that can catalyse the recombination of a nucleic acid sequence between specific sites (lox sites) in a nucleic acid molecule. Methods of using this system to produce temporal and tissue specific expression are known in the art. In general, a genetically modified cell is generated with lox sites flanking a chromosomal sequence of interest. A genetically modified animal comprising a cell with the lox-flanked chromosomal sequence of interest may then be crossed with another genetically modified animal expressing Cre recombinase in one or more cells.
Progeny animals comprising one or more cells comprising a lox-flanked chromosomal sequence and one or more cells comprising a Cre recombinase are then produced. In the cells that comprise both a lox-flanked chromosomal sequence and a Cre recombinase, the lox-flanked chromosomal sequence encoding a protein of interest is recombined, leading to deletion or inversion of the chromosomal sequence encoding the protein of interest. Expression of Cre recombinase may be temporally and conditionally regulated to effect temporally and conditionally regulated recombination of the chromosomal sequence encoding the protein of interest.

A. integrations that disrupt an endogenous locus [0120] In another embodiment, a method of the invention may be used to integrate a mutation that disrupts an endogenous locus. For instance, a chromosomal sequence may be disrupted by the substitution of an exogenous sequence for an endogenous sequence, such that the exogenous sequence is under the control of the endogenous promoter. In these embodiments, the disrupted endogenous sequence would not be expressed, but the integrated exogenous sequence would be expressed. The exogenous sequence may be a homolog of the endogenous sequence. For instance, the exogenous sequence may be a human sequence when the endogenous sequence is non-human. In some embodiments, the exogenous sequence may be unrelated to the endogenous sequence it is replacing. For instance, an endogenous sequence may be substituted for an exogenous marker such that when the endogenous promoter is active, the marker is detectable. In some embodiments, the marker may be an enzymatic marker that can amplify the detectable signal of the marker.

[0121] Alternatively, in some embodiments a method of the invention may be used to substitute an endogenous promoter or other regulatory sequence with an exogenous promoter or regulator sequence. In these embodiments, the expression pattern of the locus would be dictated by the exogenous promoter or regulatory sequence, as opposed to the endogenous promoter or regulatory sequence. Such an exogenous promoter or regulatory sequence may be a homolog of the endogenous promoter or regulatory sequence. For instance, the exogenous sequence may be a human sequence when the endogenous sequence is non-human. In some embodiments, the exogenous sequence may be unrelated to the endogenous sequence it is replacing.

C. integration of an exogenous nucleic acid sequence [0122] Alternatively, instead of disrupting a locus, a method of the invention may be used to integrate an exogenous sequence, with or without a promoter, into a chromosomal sequence without disrupting the expression of an endogenous locus. In some embodiments, such integration may be in a "safe harbor" locus, such as Rosa26 locus in the rat (or an equivalent in another animal) or the HPRT locus on the X chromosome in the rat (or an equivalent in another animal).

[0123] In one embodiment, a cassette comprising an exogenous promoter operably linked to an exogenous nucleic acid sequence may be integrated into a safe harbor locus. In certain embodiments, the exogenous promoter may be conditional. For instance, a conditional promoter may be a tissue-specific promoter, an organ specific promoter, or a cell-type specific promoter (such as a stem cell promoter, a B-cell promoter, a hair cell promoter, etc.) or an inducible promoter. An inducible promoter, as used herein, is a promoter that is active only in the presence of a particular substance, such as an antibiotic, a drug, or other exogenous compound. In some embodiments, the integration of a cassette comprising a conditional promoter may be used to track cell lineages.

[0124] In another embodiment, an exogenous nucleic acid sequence may be integrated to serve as a detectable marker for a particular nucleic acid sequence.

D. humanized [0125] In an additional embodiment, the genetically modified animal may be a "humanized" animal comprising at least one chromosomally integrated sequence encoding a functional human protein. The functional human protein may have no corresponding ortholog in the genetically modified animal.
Alternatively, the wild-type animal from which the genetically modified animal is derived may comprise an ortholog corresponding to the functional human protein.
In this case, the orthologous sequence in the "humanized" animal is inactivated such that no endogenous functional protein is made and the "humanized" animal comprises at least one chromosomally integrated sequence encoding the human protein. Those of skill in the art appreciate that "humanized" animals may be generated by crossing a knock-out animal with a knock-in animal comprising the chromosomally integrated sequence.

(g) multiple chromosomal edits [0126] A further embodiment of the above invention comprises performing a method of the invention serially, such that a cell is developed with more than one chromosomal edit. For instance, an embryo with a first edit may be cultured to produce an animal comprising the first genomic edit. An embryo deriving from this animal may then be used in a method of the invention to create a second genomic edit. The same process may be repeated to create an embryo with three, four, five, six, seven, eight, nine, ten or more than ten genomic edits.

[0127] Alternatively, a cell with multiple genomic edits may be developed by simultaneoulsy introducing more than one zinc finger nuclease, each specific for a distinct edit site. A corresponding number of donor and/or exchange polynucleotides may optionally be introduced as well. The number of zinc finger nucleases and optional corresponding donor or exchange polynucleotides introduced into a cell may be two, three, four, five or more than five.

II. Applications Derived From a Method of the Invention [0128] A method of the invention may be used to create an animal or cell comprising an edited chromosomal sequence. Such an animal or cell may be used for several different applications, including, for instance, research applications, livestock applications, companion animal applications, or biomolecule production applications. Non-limiting examples of such applications are detailed in sections (a) - (d) below.

(a) research applications [0129] In certain embodiments, a method of the invention may be used to create an animal or cell that may be used in research applications.
Such applications may include disease models, pharmacological models, developmental models, cellular function models, and humanized models, each of which are detailed below.

i. disease models [0130] A method of the invention may be used to create an animal or cell that may be used as a disease model. As used herein, "disease" refers to a disease, disorder, or indication in a subject. For instance, in one embodiment, a method of the invention may be used to create an animal or cell that comprises a chromosomal edit in one or more nucleic acid sequences associated with a disease. Such a nucleic acid sequence may encode a disease associated protein sequence or may be a disease associated control sequence.

[0131] In one embodiment, an animal or cell created by a method of the invention may be used to study the effects of mutations on the animal or cell and development and/or progression of the disease using measures commonly used in the study of the disease. Alternatively, such an animal or cell may be used to study the effect of a pharmaceutically active compound on the disease.

[0132] In another embodiment, an animal or cell created by a method of the invention may be used to assess the efficacy of a potential gene therapy strategy. That is, a chromosomal sequence encoding a protein associated with a disease may be modified such that the disease development and/or progression is inhibited or reduced. In particular, the method comprises editing a chromosomal sequence encoding a protein associated with the disease such that an altered protein is produced and, as a result, the animal or cell has an altered response. Accordingly, in some embodiments, a genetically modified animal may be compared with an animal predisposed to development of the disease such that the effect of the gene therapy event may be assessed.

[0133] In certain embodiments, a method of the invention may be used to create an animal or cell that maybe used as a disease model for a disease listed in Table A. Such an animal or cell may comprise a chromosomal edit in a gene listed in Table A. In another embodiment, a method of the invention may be used to create an animal or cell that maybe used as a disease model for a disease listed in Table B. Such an animal or cell may comprise a chromosomal edit in a gene listed in Table B. In Table B, a six-digit number following an entry in the Disease/Disorder/Indication column is an OMIM number (Online Mendelian Inheritance in Man, OMIM (TM). McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD), available on the World Wide Web. A number in parentheses after the name of each disorder indicates whether the mutation was positioned by mapping the wildtype gene (1), by mapping the disease phenotype itself (2), or by both approaches (3). For example, a "(3)", includes mapping of the wildtype gene combined with demonstration of a mutation in that gene in association with the disorder."

TABLE A
DISEASE/DISORDERS GENE(S) PTEN; ATM; ATR; EGFR; ERBB2; ERBB3; ERBB4;
Notch1; Notch2; Notch3; Notch4; AKT; AKT2; AKT3; HIF;
HIF1a; HIF3a; Met; HRG; Bc12; PPAR alpha; PPAR
gamma; WT1 (Wilms Tumor); FGF Receptor Family members (5 members: 1, 2, 3, 4, 5); CDKN2a; APC; RB
Neoplasia (retinoblastoma); MEN1; VHL; BRCA1; BRCA2; AR
(Androgen Receptor); TSG101; IGF; IGF Receptor; lgf1 (4 variants); lgf2 (3 variants); lgf 1 Receptor; lgf 2 Receptor;
Bax; Bc12; caspases family (9 members:
1,2,3,4,6,7,8,9,12); Kras; Apc Age-related Macular Abcr; Cc12; Cc2; cp (ceruloplasmin); Timp3; cathepsinD;
Degeneration VIdlr; Ccr2 Neuregulin1 (Nrgl); Erb4 (receptor for Neuregulin);
Complexin1 (Cplxl); Tphl Tryptophan hydroxylase; Tph2 Schizophrenia Tryptophan hydroxylase 2; Neurexin 1; GSK3; GSK3a;
GSK3b 5-HTT (Slc6a4); COMT; DRD (Drdla); SLC6A3; DAOA;
Disorders DTNBP1; Dao (Daol) TABLE A
DISEASE/DISORDERS GENE(S) HTT (Huntington's Dx); SBMA/SMAX1/AR (Kennedy's Dx); FXN/X25 (Friedrich's Ataxia); ATX3 (Machado-Trinucleotide Repeat Joseph's Dx); ATXN1 and ATXN2 (spinocerebellar Disorders ataxias); DMPK (myotonic dystrophy); Atrophin-1 and Atn1 (DRPLA Dx); CBP (Creb-BP - global instability); VLDLR
(Alzheimer's); Atxn7; Atxn10 Fragile X Syndrome FMR2; FXR1; FXR2; mGLUR5 Secretase Related APH-1 (alpha and beta); Presenilin (Psen1); nicastrin Disorders (Ncstn); PEN-2 Others Nos1; Parp1; Nat1; Nat2 Prion - related disorders Prp SOD1; ALS2; STEX; FUS; TARDBP; VEGF (VEGF-a;
ALS VEGF-b; VEGF-c) Prkce (alcohol); Drd2; Drd4; ABAT (alcohol); GRIA2;
Drug addiction Grm5; Grin1; Htr1b; Grin2a; Drd3; Pdyn; Grial (alcohol) Mecp2; BZRAP1; MDGA2; Sema5A; Neurexin 1; Fragile X
Autism (FMR2 (AFF2); FXR1; FXR2; Mglur5) El; CHIP; UCH; UBB; Tau; LRP; PICALM; Clusterin; PS1;
Alzheimer's Disease SORL1; CR1; VIdIr; Ubal; Uba3; CHIP28 (Agp1, Aquaporin 1); Uchll; Uch13; APP

IL-10; IL-1 (IL-1a; IL-1b); IL-13; IL-17 (IL-17a (CTLA8); IL-17b; IL-17c; IL-17d; IL-17f); 11-23; Cx3cr1; ptpn22; TNFa;
Inflammation NOD2/CARD15 for IBD; IL-6; IL-12 (IL-12a; IL-12b);
CTLA4; Cx3cll Parkinson's Disease x-Synuclein; DJ-1; LRRK2; Parkin; PINK1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) 17,20-lyase deficiency, isolated, 202110 (3) CYP17A1, CYP17, P450C17 17-alpha-hydroxylase/17,20-lyase CYP17A1, CYP17, P450C17 deficiency, 202110 (3) 2-methyl-3-hydroxybutyryl-CoA HAD H2, ERAB
dehydrogenase deficiency, 300438 (3) 2-methylbutyrylglycinuria (3) ACADSB
3-beta-hydroxysteroid dehydrogenase, type HSD3B2 II, deficiency (3) 3-hydroxyacyl-CoA dehydrogenase HADHSC, SCHAD
deficiency, 609609 (3) 3-Methyl crotonyl-CoA carboxylase 1 MCCC1, MCCA
deficiency, 210200 (3) 3-Methyl crotonyl-CoA carboxylase 2 MCCC2, MCCB
deficiency, 210210 (3) 3-methylglutaconic aciduria, type I, 250950 AUH
(3) 3-methylglutaconicaciduria, type III, 258501 OPA3, MGA3 (3) 3-M syndrome, 273750 (3) CUL7 6-mercaptopurine sensitivity (3) TPMT
Aarskog-Scott syndrome (3) FGD1, FGDY, AAS
Abacavir hypersensitivity, susceptibility to HLA-B
(3) ABCD syndrome, 600501 (3) EDNRB, HSCR2, ABCDS
Abetalipoproteinemia, 200100 (3) MTP
Abetalipoproteinemia (3) APOB, FLDB
Acampomelic campolelic dysplasia, 114290 SOX9, CMD1, SRA1 (3) Acatalasemia (3) CAT

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Accelerated tumor formation, susceptibility MDM2 to (3) Achalasia-addisonianism-alacrimia AAAS, AAA
syndrome, 231550 (3) Acheiropody, 200500 (3) C7orf2, ACHP, LMBR1 Achondrogenesis-hypochondrogenesis, COL2A1 type II, 200610 (3) Achondrogenesis Ib, 600972 (3) SLC26A2, DTD, DTDST, D5S1708, Achondroplasia, 100800 (3) FGFR3, ACH
Achromatopsia-2, 216900 (3) CNGA3, CNG3, ACHM2 Achromatopsia-3, 262300 (3) CNGB3, ACHM3 Achromatopsia-4 (3) GNAT2, ACHM4 Acid-labile subunit, deficiency of (3) IGFALS, ALS
Acquired long QT syndrome, susceptibility KCNH2, LQT2, HERG
to (3) Acrocallosal syndrome, 200990 (3) GL13, PAPA, PAPB, ACLS
Acrocapitofemoral dysplasia, 607778 (3) IHH, BDA1 Acrodermatitis enteropathica, 201100 (3) SLC39A4, ZIP4 Acrokeratosis verruciformis, 101900 (3) ATP2A2, ATP2B, DAR
Acromegaly, 102200 (3) GNAS, GNAS1, GPSA, POH, PHP1B, PHP1A, AHO
Acromegaly, 102200 (3) SSTR5 Acromesomelic dysplasia, Hunter- GDF5, CDMP1 Thompson type, 201250 (3) Acromesomelic dysplasia, Maroteaux type, NPR2, ANPRB, AMDM
602875 (3) Acyl-CoA dehydrogenase, long chain, ACADL, LCAD
deficiency of (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Acyl-CoA dehydrogenase, medium chain, ACADM, MCAD
deficiency of, 201450 (3) Acyl-CoA dehydrogenase, short-chain, ACADS, SCAD
deficiency of, 201470 (3) Adenocarcinoma of lung, response to EGFR
tyrosine kinase inhibitor in, 211980 (3) Adenocarcinoma of lung, somatic, 211980 BRAF
(3) Adenocarcinoma of lung, somatic, 211980 ERBB2, NGL, NEU, HER2 (3) Adenocarcinoma of lung, somatic, 211980 PRKN, PARK2, PDJ
(3) Adenocarcinoma, ovarian, somatic (3) PRKN, PARK2, PDJ
Adenoma, periampullary (3) APC, GS, FPC
Adenomas, multiple colorectal, 608456 (3) MUTYH
Adenomas, salivary gland pleomorphic, PLAG1, SGPA, PSA
181030 (3) Adenomatous polyposis coli (3) APC, GS, FPC
Adenomatous polyposis coli, attenuated (3) APC, GS, FPC
Adenosine deaminase deficiency, partial, ADA
102700 (3) Adenylosuccinase deficiency, 103050 (3) ADSL
Adiponectin deficiency (3) APM1, GBP28 Adrenal adenoma, sporadic (3) MEN1 Adrenal cortical carcinoma, 202300 (3) TP53, P53, LFS1 Adrenal hyperplasia, congenital, due to 11- CYP11B1, P450C11, FHI
beta-hydroxylase deficiency (3) Adrenal hyperplasia, congenital, due to 21- CYP21A2, CYP21, CA21 H
hydroxylase deficiency (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Adrenal hyperplasia, congenital, due to POR
combined P450C17 and P450C21 deficiency, 201750 (3) Adrenal hypoplasia, congenital, with DAX1, AHC, AHX, NROB1 hypogonadotropic hypogonadism, 300200 (3) Adrenocortical insufficiency without ovarian FTZF1, FTZ1, SF1 defect (3) Adrenocortical tumor, somatic (3) PRKAR1A, TSE1, CNC1, CAR
Adrenocorticotropic hormone deficiency, TBS19 201400 (3) Adrenoleukodystrophy, 300100 (3) ABCD1, ALD, AMN
Adrenoleukodystrophy, neonatal, 202370 PEX10, NALD
(3) Adrenoleukodystrophy, neonatal, 202370 PEX13, ZWS, NALD
(3) Adrenoleukodystrophy, neonatal, 202370 PEX1, ZWS1 (3) Adrenoleukodystrophy, neonatal, 202370 PEX26 (3) Adrenoleukodystrophy, neonatal, 202370 PXR1, PEX5, PTS1R
(3) Adrenomyeloneuropathy, 300100 (3) ABCD1, ALD, AMN
Adult i phenotype with congenital cataract, GCNT2 110800 (3) Adult i phenotype without cataract, 110800 GCNT2 (3) ADULT syndrome, 103285 (3) TP73L, TP63, KET, EEC3, SHFM4, LMS, RHS

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Advanced sleep phase syndrome, familial, PER2, FASPS, KIAA0347 604348 (3) Afibrinogenemia, 202400 (3) FGA
Afibrinogenemia, congenital, 202400 (3) FGB
Agammaglobulinemia, 601495 (3) IGHM, MU
Agammaglobulinemia, autosomal recessive IGLL1, IGO, IGL5, VPREB2 (3) Agammaglobulinemia, non-Bruton type, LRRC8, KIAA1437 601495 (3) Agammaglobulinemia, type 1, X-linked (3) BTK, AGMX1, IMD1, XLA, AT
AGAT deficiency (3) GATM, AGAT
Agenesis of the corpus callosum with SLC12A6, KCC3A, KCC3B, KCC3, peripheral neuropathy, 218000 (3) ACCPN
AICA-ribosiduria due to ATIC deficiency, ATIC, PURH, AICAR
608688 (3) AIDS, delayed/rapid progression to (3) KIR3DL1, NKAT3, NKB1, AMB11, AIDS, rapid progression to, 609423 (3) IFNG
AIDS, resistance to (3) CXCL12, SDF1 Alagille syndrome, 118450 (3) JAG1, AGS, AHD
Albinism, brown oculocutaneous, (3) OCA2, P, PED, D15S12, BOCA
Albinism, ocular, autosomal recessive (3) OCA2, P, PED, D15S12, BOCA
Albinism, oculocutaneous, type IA, 203100 TYR
(3) Albinism, oculocutaneous, type IB, 606952 TYR
(3) Albinism, oculocutaneous, type II (3) OCA2, P, PED, D15S12, BOCA
Albinism, rufous, 278400 (3) TYRP1, CAS2, GP75 Alcohol dependence, susceptibility to, HTR2A
103780 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Alcohol intolerance, acute (3) ALDH2 Alcoholism, susceptibility to, 103780 (3) GABRA2 Aldolase A deficiency (3) ALDOA
Aldosterone to renin ratio raised (3) CYP1 1 B2 Aldosteronism, glucocorticoid-remediable, CYP11B1, P450C11, FHI
103900 (3) Alexander disease, 203450 (3) GFAP
Alexander disease, 203450 (3) NDUFV1, UQOR1 Alkaptonuria, 203500 (3) HGD, AKU
Allan-Herndon-Dudley syndrome, 300523 SLC16A2, DXS128, XPCT
(3) Allergic rhinitis, susceptibility to, 607154 (3) IL13, ALRH
Alopecia universalis, 203655 (3) HR, AU
Alpers syndrome, 203700 (3) POLG, POLG1, POLGA, PEO
Alpha-l-antichymotrypsin deficiency (3) SERPINA3, AACT, ACT
Alpha-actinin-3 deficiency (3) ACTN3 Alpha-methylacetoacetic aciduria, 203750 ACAT1 (3) Alpha-methylacyl-CoA racemase deficiency AMACR
(3) Alpha-thalassemia/mental retardation ATRX, XH2, XNP, MRXS3, SHS
syndrome, 301040 (3) Alpha-thalassemia myelodysplasia ATRX, XH2, XNP, MRXS3, SHS
syndrome, somatic, 300448 (3) Alport syndrome, 301050 (3) COL4A5, ATS, ASLN
Alport syndrome, autosomal recessive, COL4A3 203780 (3) Alport syndrome, autosomal recessive, COL4A4 203780 (3) Alstrom syndrome, 203800 (3) ALMS1, ALSS, KIAA0328 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Alternating hemiplegia of childhood, 104290 ATP1A2, FHM2, MHP2 (3) Alveolar soft-part sarcoma, 606243 (3) ASPCR1, RCC17, ASPL, ASPS
Alzheimer disease-1, APP-related (3) APP, AAA, CVAP, AD1 Alzheimer disease-2, 104310 (3) APOE, AD2 Alzheimer disease-4, 606889 (3) PSEN2, AD4, STM2 Alzheimer disease, late-onset, 104300 (3) APBB2, FE65L1 Alzheimer disease, late-onset, susceptibility NOS3 to, 104300 (3) Alzheimer disease, late-onset, susceptibility PLAU, URK
to, 104300 (3) Alzheimer disease, susceptibility to, 104300 ACE, DCP1, ACE1 (3) Alzheimer disease, susceptibility to, 104300 MPO
(3) Alzheimer disease, susceptibility to, 104300 PACIP1, PAXIPI L, PTIP
(3) Alzheimer disease, susceptibility to (3) A2M
Alzheimer disease, susceptibility to (3) BLMH, BMH
Alzheimer disease, type 3, 607822 (3) PSEN1, AD3 Alzheimer disease, type 3, with spastic PSEN1, AD3 paraparesis and apraxia, 607822 (3) Alzheimer disease, type 3, with spastic PSEN1, AD3 paraparesis and unusual plaques, 607822 (3) Amelogenesis imperfecta 2, hypoplastic ENAM
local, 104500 (3) Amelogenesis imperfecta, 301200 (3) AMELX, AMG, AIH1, AMGX

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Amelogenesis imperfecta, hypomaturation- DLX3, TDO
hypoplastic type, with taurodontism, 104510 (3) Amelogenesis imperfecta, hypoplastic, and ENAM
openbite malocclusion, 608563 (3) Amelogenesis imperfecta, pigmented KLK4, EMSP1, PRSS17 hypomaturation type, 204700 (3) Amish infantile epilepsy syndrome, 609056 SIAT9, ST3GALV
(3) AMP deaminase deficiency, erythrocytic (3) AMPD3 Amyloid neuropathy, familial, several allelic TTR, PALB
types (3) Amyloidosis, 3 or more types (3) APOA1 Amyloidosis, cerebroarterial, Dutch type (3) APP, AAA, CVAP, AD1 Amyloidosis, Finnish type, 105120 (3) GSN
Amyloidosis, hereditary renal, 105200 (3) FGA
Amyloidosis, renal, 105200 (3) LYZ
Amyloidosis, senile systemic (3) TTR, PALB
Amyotrophic lateral sclerosis 8, 608627 (3) VAPB, VAPC, ALS8 Amyotrophic lateral sclerosis, due to SOD1 SOD1, ALS1 deficiency, 105400 (3) Amyotrophic lateral sclerosis, juvenile, ALS2, ALSJ, PLSJ, IAHSP
205100 (3) Amyotrophic lateral sclerosis, susceptibility DCTN1 to, 105400 (3) Amyotrophic lateral sclerosis, susceptibility NEFH
to, 105400 (3) Amyotrophic lateral sclerosis, susceptibility PRPH
to, 105400 (3) Analbuminemia (3) ALB

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Analgesia from kappa-opioid receptor MC1 R
agonist, female-specific (3) Anderson disease, 607689 (3) SARA2, SARI B, CMRD
Androgen insensitivity, 300068 (3) AR, DHTR, TFM, SBMA, KD, SMAX1 Anemia, congenital dyserythropoietic, type I, CDAN1, CDA1 224120 (3) Anemia, Diamond-Blackfan, 105650 (3) RPS19, DBA
Anemia, hemolytic, due to PK deficiency (3) PKLR, PK1 Anemia, hemolytic, due to UMPH1 NT5C3, UMPH1, PSN1 deficiency, 266120 (3) Anemia, hemolytic, Rh-null, regulator type, RHAG, RH50A
268150 (3) Anemia, hypochromic microcytic, 206100 NRAMP2 (3) Anemia, neonatal hemolytic, fatal and near- SPTB
fatal (3) Anemia, sideroblastic/hypochromic (3) ALAS2, ANH1, ASB
Anemia, sideroblastic, with ataxia, 301310 ABCB7, ABC7, ASAT
(3) Aneurysm, familial arterial (3) COL3A1 Angelman syndrome, 105830 (3) MECP2, RTT, PPMX, MRX16, MRX79 Angelman syndrome, 105830 (3) UBE3A, ANCR
Angioedema, hereditary, 106100 (3) C1NH, HAE1, HAE2, SERPING1 Angioedema induced by ACE inhibitors, XPNPEP2 susceptibility to (3) Angiofibroma, sporadic (3) MEN1 Angiotensin I-converting enzyme, benign ACE, DCP1, ACE1 serum increase (3) Anhaptoglobinemia (3) HP
Aniridia, type 11, 106210 (3) PAX6, AN2, MGDA

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Ankylosing spoldylitis, susceptibility to, HLA-B
106300 (3) Anophthalmia 3, 206900 (3) SOX2, ANOP3 Anorexia nervosa, susceptibility to, 606788 HTR2A
(3) Anterior segment anomalies and cataract EYA1, BOR
(3) Anterior segment mesenchymal dysgenesis, FOXE3, FKHL12, ASMD
107250 (3) Anterior segment mesenchymal dysgenesis FOXC1, FKHL7, FREAC3 (3) Anterior segment mesenchymal dysgenesis PITX3 and cataract, 107250 (3) Antithrombin III deficiency (3) AT3 Antley-Bixler syndrome, 207410 (3) POR
Anxiety-related personality traits (3) SLC6A4, HTT, OCD1 Aortic aneurysm, ascending, and dissection FBN1, MFS1, WMS
(3) Apert syndrome, 101200 (3) FGFR2, BEK, CFD1, JWS
Aplasia of lacrimal and salivary glands, FGF10 180920 (3) Aplastic anemia, 609135 (3) IFNG
Aplastic anemia, 609135 (3) TERC, TRC3, TR
Aplastic anemia, susceptibility to, 609135 TERT, TCS1, EST2 (3) Apnea, postanesthetic (3) BCHE, CHE1 ApoA-I and apoC-III deficiency, combined APOA1 (3) Apolipoprotein A-II deficiency (3) APOA2 Apolipoprotein C3 deficiency (3) APOC3 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Apolipoprotein H deficiency (3) APOH
Apparent mineralocorticoid excess, HSD11132, HSD1 1 K
hypertension due to (3) Aquaporin-1 deficiency (3) AQP1, CHIP28, CO
ARC syndrome, 208085 (3) VPS33B
Argininemia, 207800 (3) ARG1 Argininosuccinic aciduria, 207900 (3) ASL
Aromatase deficiency (3) CYP19A1, CYP19, ARO
Aromatic L-amino acid decarboxylase DDC
deficiency, 608643 (3) Arrhythmogenic right ventricular dysplasia 2, RYR2, VTSIP
600996 (3) Arrhythmogenic right ventricular dysplasia 8, DSP, KPPS2, PPKS2 607450 (3) Arrhythmogenic right ventricular dysplasia, PKP2, ARVD9 familial, 9, 609040 (3) Arthrogryposis multiplex congenita, distal, TPM2, TMSB, AMCD1, DA1 type 1, 108120 (3) Arthrogryposis multiplex congenita, distal, TNN12, AMCD2B, DA2B, FSSV
type 2B, 601680 (3) Arthropathy, progressive WISP3, PPAC, PPD
pseudorheumatoid, of childhood, 208230 (3) Arthyrgryposis multiplex congenita, distal, TNNT3, AMCD2B, DA2B, FSSV
type 2B, 601680 (3) Aspartylglucosaminuria (3) AGA
Asperger syndrome, 300494 (3) NLGN3 Asperger syndrome, 300497 (3) NLGN4, KIAA1260, AUTSX2 Asthma, 600807 (3) PHF11, NYREN34 Asthma, atopic, susceptibility to (3) MS4A2, FCER1 B

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Asthma, dimished response to ALOX5 antileukotriene treatment in, 600807 (3) Asthma, nocturnal, susceptibility to (3) ADRB2 Asthma, susceptibility to, 1, 607277 (3) PTGDR, AS1 Asthma, susceptibility to, 2, 608584 (3) GPR154, GPRA, VRR1, PGR14 Asthma, susceptibility to (3) HNMT
Asthma, susceptibility to, 600807 (3) IL12B, NKSF2 Asthma, susceptibility to, 600807 (3) IL13, ALRH
Asthma, susceptibility to, 600807 (3) PLA2G7, PAFAH
Asthma, susceptibility to, 600807 (3) SCGB3A2, UGRP1 Asthma, susceptibility to, 600807 (3) TNF, TNFA
Asthma, susceptibility to, 600807 (3) UGB, CC10, CCSP, SCGB1A1 Ataxia, cerebellar, Cayman type, 601238 (3) ATCAY, CLAC, KIAA1872 Ataxia, early-onset, with oculomotor apraxia APTX, AOA, AOA1 and hypoalbuminemia, 208920 (3) Ataxia, episodic (3) CACNB4, EJM
Ataxia-ocular apraxia-2, 606002 (3) SETX, SCAR1, AOA2 Ataxia-telangiectasia, 208900 (3) ATM, ATA, AT1 Ataxia-telangiectasia-like disorder, 604391 MRE1 1A, MRE1 1, ATLD
(3) Ataxia with isolated vitamin E deficiency, TTPA, TTP1, AVED
277460 (3) Atelosteogenesis II, 256050 (3) SLC26A2, DTD, DTDST, D5S1708, Atelostogenesis, type I, 108720 (3) FLNB, SCT, AOI
Athabaskan brainstem dysgenesis HOXA1, HOX1F, BSAS
syndrome, 601536 (3) Atherosclerosis, susceptibility to (3) ALOX5 Atopy, 147050 (3) SPINK5, LEKTI
Atopy, resistance to, 147050 (3) HAVCR1, HAVCR

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Atopy, susceptibility to, 147050 (3) PLA2G7, PAFAH
Atopy, susceptibility to, 147050 (3) SELP, GRMP
Atopy, susceptibility to (3) IL4R, IL4RA
Atransferrinemia, 209300 (3) TF
Atrial fibrillation, familial, 607554 (3) KCNE2, MIRP1, LQT6 Atrial fibrillation, familial, 607554 (3) KCNQ1, KCNA9, LQT1, KVLQT1, Atrial septal defect-2, 607941 (3) GATA4 Atrial septal defect 3 (3) MYH6, ASD3, MYHCA
Atrial septal defect with atrioventricular NKX2E, CSX
conduction defects, 108900 (3) Atrichia with papular lesions, 209500 (3) HR, AU
Atrioventricular block, idiopathic second- NKX2E, CSX
degree (3) Atrioventricular septal defect, 600309 (3) GJA1, CX43, ODDD, SDTY3, ODOD
Atrioventricular septal defect, partial, with CRELD1, AVSD2 heterotaxy syndrome, 606217 (3) Atrioventricular septal defect, susceptibility CRELD1, AVSD2 to, 2, 606217 (3) Attention deficit-hyperactivity disorder, DRD5, DRD1 B, DRD1 L2 susceptibility to, 143465 (3) Autism, susceptibility to, 209850 (3) GLO1 Autism, X-linked, 300425 (3) MECP2, RTT, PPMX, MRX16, MRX79 Autism, X-linked, 300425 (3) NLGN3 Autism, X-linked, 300495 (3) NLGN4, KIAA1260, AUTSX2 Autoimmune lymphoproliferative syndrome, TNFRSF6, APT1, FAS, CD95, ALPS1A
601859 (3) Autoimmune lymphoproliferative syndrome, TNFRSF6, APT1, FAS, CD95, ALPS1A
type IA, 601859 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Autoimmune lymphoproliferative syndrome, CASP10, MCH4, ALPS2 type II, 603909 (3) Autoimmune lymphoproliferative syndrome, CASP8, MCH5 type 1113, 607271 (3) Autoimmune polyglandular disease, type I, AIRE, APECED
240300 (3) Autoimmune thyroid disease, susceptibility TG, AITD3 to 3, 608175 (3) Autonomic nervous system dysfunction (3) DRD4 Axenfeld anomaly (3) FOXC1, FKHL7, FREAC3 Azoospermia (3) USP9Y, DFFRY
Azoospermia due to perturbations of SYCP3, SCP3, COR1 meiosis, 270960 (3) Bamforth-Lazarus syndrome, 241850 (3) FOXE1, FKHL15, TITF2, TTF2 Bannayan-Riley-Ruvalcaba syndrome, PTEN, MMAC1 153480 (3) Bannayan-Zonana syndrome, 153480 (3) PTEN, MMAC1 Bardet-Biedl syndrome 1, 209900 (3) BBS1 Bardet-Biedl syndrome 1, modifier of, ARL6, BBS3 209900 (3) Bardet-Biedl syndrome, 209900 (3) BBS7 Bardet-Biedl syndrome 2, 209900 (3) BBS2 Bardet-Biedl syndrome 3, 600151 (3) ARL6, BBS3 Bardet-Biedl syndrome 4, 209900 (3) BBS4 Bardet-Biedl syndrome 5, 209900 (3) BBS5 Bardet-Biedl syndrome 6, 209900 (3) MKKS, HMCS, KMS, MKS, BBS6 Bardet-Biedl syndrome 8, 209900 (3) TTC8, BBS8 Bare lymphocyte syndrome, type I, 604571 TAPBP, TPSN
(3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Bare lymphocyte syndrome, type I, due to TAP2, ABCB3, PSF2, RING1 1 TAP2 deficiency, 604571 (3) Bare lymphocyte syndrome, type II, MHC2TA, C2TA
complementation group A, 209920 (3) Bare lymphocyte syndrome, type II, RFX5 complementation group C, 209920 (3) Bare lymphocyte syndrome, type II, RFXAP
complementation group D, 209920 (3) Bare lymphocyte syndrome, type II, RFX5 complementation group E, 209920 (3) Barth syndrome, 302060 (3) TAZ, EFE2, BTHS, CMD3A, LVNCX
Bart-Pumphrey syndrome, 149200 (3) GJB2, CX26, DFNB1, PPK, DFNA3, KID, HID
Bartter syndrome, type 1, 601678 (3) SLC12A1, NKCC2 Bartter syndrome, type 2, 241200 (3) KCNJ1, ROMK1 Bartter syndrome, type 3, 607364 (3) CLCNKB
Bartter syndrome, type 4, 602522 (3) BSND
Bartter syndrome, type 4, digenic, 602522 CLCNKA
(3) Bartter syndrome, type 4, digenic, 602522 CLCNKB
(3) Basal cell carcinoma (3) RASA1, GAP, CMAVM, PKWS
Basal cell carcinoma, somatic, 605462 (3) PTCH2 Basal cell carcinoma, somatic, 605462 (3) PTCH, NBCCS, BCNS, HPE7 Basal cell carcinoma, sporadic (3) SMOH, SMO
Basal cell nevus syndrome, 109400 (3) PTCH, NBCCS, BCNS, HPE7 Basal ganglia disease, adult-onset, 606159 FTL
(3) Basal ganglia disease, biotin-responsive, SLC19A3 607483 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) B-cell non-Hodgkin lymphoma, high-grade BCL7A, BCL7 (3) BCG infection, generalized familial (3) IFNGR1 Beare-Stevenson cutis gyrata syndrome, FGFR2, BEK, CFD1, JWS
123790 (3) Becker muscular dystrophy, 300376 (3) DMD, BMD
Becker muscular dystrophy modifier, MYF6 310200 (3) Beckwith-Wiedemann syndrome, 130650 CDKNIC, KIP2, BWS
(3) Beckwith-Wiedemann syndrome, 130650 H19, D11S813E, ASM1, BWS
(3) Beckwith-Wiedemann syndrome, 130650 KCNQ1 OT1, LIT1 (3) Beckwith-Wiedemann syndrome, 130650 NSD1, ARA267, STO
(3) Benzene toxicity, susceptibility to (3) NQO1, DIA4, NMOR1 Bernard-Soulier syndrome, 231200 (3) GP1 BA
Bernard-Soulier syndrome, type B, 231200 GP1 BB
(3) Bernard-Soulier syndrome, type C (3) GP9 Beryllium disease, chronic, susceptibility to HLA-DPB1 (3) Beta-2-adrenoreceptor agonist, reduced ADRB2 response to (3) Beta-u reidopropionase deficiency (3) UPB1, BUP1 Bethlem myopathy, 158810 (3) COL6A1, OPLL
Bethlem myopathy, 158810 (3) COL6A2 Bethlem myopathy, 158810 (3) COL6A3 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Bietti crystalline corneoretinal dystrophy, CYP4V2, BCD
210370 (3) Bile acid malabsorption, primary (3) SLC10A2, NTCP2 Biotinidase deficiency, 253260 (3) BTD
Bipolar disorder, susceptibility to, 125480 XBP1, XBP2 (3) Birt-Hogg-Dube syndrome, 135150 (3) FLCN, BHD
Bladder cancer, 109800 (3) FGFR3, ACH
Bladder cancer, 109800 (3) KRAS2, RASK2 Bladder cancer, 109800 (3) RB1 Bladder cancer, somatic, 109800 (3) HRAS
Blau syndrome, 186580 (3) CARD15, NOD2, IBD1, CD, ACUG, Bleeding disorder due to defective TBXA2R
thromboxane A2 receptor (3) Bleeding due to platelet ADP receptor P2RX1, P2X1 defect, 600515 (3) Blepharophimosis, epicanthus inversus, and FOXL2, BPES, BPES1, PFRK, POF3 ptosis, type 1, 110100 (3) Blepharophimosis, epicanthus inversus, and FOXL2, BPES, BPES1, PFRK, POF3 ptosis, type 2, 110100 (3) Blepharospasm, primary benign, 606798 (3) DRD5, DRD1 B, DRD1 L2 Blood group, ABO system (3) ABO
Blood group, Auberger system (3) LU, AU, BCAM
Blood group, Colton, 110450 (3) AQP1, CHIP28, CO
Blood group Cromer (3) DAF
Blood group, Diego, 110500 (3) SLC4A1, AE1, EPB3 Blood group, Dombrock (3) ART4, DO
Blood group, Gerbich (3) GYPC, GE, GPC
Blood group GIL, 607457 (3) AQP3 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Blood group, Ii, 110800 (3) GCNT2 Blood group, Indian system (3) CD44, MDU2, MDU3, MIC4 Blood group, Kell (3) KEL
Blood group, Kidd (3) SLC14A1, JK, UTE, UT1 Blood group, Knops system, 607486 (3) CR1, C3BR
Blood group, Landsteiner-Wiener (3) LW
Blood group, Lewis (3) FUT3, LE
Blood group, Lutheran system (3) LU, AU, BCAM
Blood group, MN (3) GYPA, MN, GPA
Blood group, OK, 111380 (3) BSG
Blood group, P system, 111400 (3) A4GALT, PK
Blood group, P system, 111400 (3) B3GALT3, GLCT3, P
Blood group, Rhesus (3) RHCE
Blood group, Ss (3) GYPB, SS, MNS
Blood group, Waldner, 112010 (3) SLC4A1, AE1, EPB3 Blood group, Wright, 112050 (3) SLC4A1, AE1, EPB3 Blood group, XG system (3) XG
Blood group, Yt system, 112100 (3) ACHE, YT
Bloom syndrome, 210900 (3) RECQL3, RECQ2, BLM, BS
Blue-cone monochromacy, 303700 (3) OPN1LW, RCP, CBP, CBBM
Blue-cone monochromacy, 303700 (3) OPN1MW, GCP, CBD, CBBM
Bombay phenotype (3) FUT1, H, HH
Bombay phenotype (3) FUT2, SE
Bone mineral density variability 1, 601884 LRP5, BMND1, LRP7, LR3, OPPG, (3) VBCH2 Borjeson-Forssman-Lehmann syndrome, PHF6, BFLS
301900 (3) Bosley-Salih-Alorainy syndrome, 601536 (3) HOXA1, HOX1F, BSAS
Bothnia retinal dystrophy, 607475 (3) RLBP1 Brachydactyly, type Al, 112500 (3) IHH, BDA1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Brachydactyly, type A2, 112600 (3) BMPR1 B, ALK6 Brachydactyly, type B1, 113000 (3) ROR2, BDB1, BDB, NTRKR2 Brachydactyly, type C, 113100 (3) GDF5, CDMP1 Brachydactyly, type D, 113200 (3) HOXD13, HOX41, SPD
Brachydactyly, type E, 113300 (3) HOXD13, HOX41, SPD
Bradyopsia, 608415 (3) R9AP, RGS9, PERRS
Bradyopsia, 608415 (3) RGS9, PERRS
Branchiootic syndrome (3) EYA1, BOR
Branchiootorenal syndrome, 113650 (3) EYA1, BOR
Branchiootorenal syndrome with cataract, EYA1, BOR
113650 (3) Breast and colorectal cancer, susceptibility CHEK2, RAD53, CHK2, CDS1, LFS2 to (3) Breast cancer, 114480 (3) PIK3CA
Breast cancer, 114480 (3) PPM1 D, WIP1 Breast cancer, 114480 (3) SLC22A1L, BWSCR1A, IMPT1 Breast cancer, 114480 (3) TP53, P53, LFS1 Breast cancer-1 (3) BRCA1, PSCP
Breast cancer 2, early onset (3) BRCA2, FANCD1 Breast cancer (3) TSG101 Breast cancer, early-onset, 114480 (3) BRIP1, BACH1, FANCJ
Breast cancer, invasive intraductal (3) RAD54L, HR54, HRAD54 Breast cancer, lobular (3) CDH1, UVO
Breast cancer, male, susceptibility to, BRCA2, FANCD1 114480 (3) Breast cancer, male, with Reifenstein AR, DHTR, TFM, SBMA, KD, SMAX1 syndrome (3) Breast cancer, somatic, 114480 (3) KRAS2, RASK2 Breast cancer, somatic, 114480 (3) RB1CC1, CC1, KIAA0203 Breast cancer, sporadic (3) PHB

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Breast cancer, susceptibility to, 114480 (3) ATM, ATA, AT1 Breast cancer, susceptibility to, 114480 (3) BARD 1 Breast cancer, susceptibility to, 114480 (3) CHEK2, RAD53, CHK2, CDS1, LFS2 Breast cancer, susceptibility to, 114480 (3) RAD51A, RECA
Breast cancer, susceptibility to (3) XRCC3 Breast-ovarian cancer (3) BRCA1, PSCP
Brody myopathy, 601003 (3) ATP2A1, SERCA1 Bruck syndrome 2, 609220 (3) PLOD2 Brugada syndrome, 601144 (3) SCN5A, LQT3, IVF, HB1, SSS1 Brunner syndrome (3) MAOA
Burkitt lymphoma, 113970 (3) MYC
Buschke-Ollendorff syndrome, 166700 (3) LEMD3, MAN1 Butterfly dystrophy, retinal, 169150 (3) RDS, RP7, PRPH2, PRPH, AVMD, AOFMD
C 1 q deficiency, type A (3) C1QA
Clq deficiency, type B (3) C1QB
Clq deficiency, type C (3) C1QG
Cis deficiency, isolated (3) C1S
C2 deficiency (3) C2 C3b inactivator deficiency (3) IF
C3 deficiency (3) C3 C4 deficiency (3) C4A, C4S
C4 deficiency (3) C4B, C4F
C6 deficiency (3) C6 C7 deficiency (3) C7 C8 deficiency, type II (3) C8B
C9 deficiency (3) C9 C9 deficiency with dermatomyositis (3) C9 Cafe-au-lait spots, multiple, with leukemia, MSH2, COCA1, FCC1, HNPCC1 114030 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Cafe-au-lait spots with glioma or leukemia, MLH1, COCA2, HNPCC2 114030 (3) Caffey disease, 114000 (3) COL1A1 Calcinosis, tumoral, 211900 (3) FGF23, ADHR, HPDR2, PHPTC
Calcinosis, tumoral, 211900 (3) GALNT3 Campomelic dysplasia, 114290 (3) SOX9, CMD1, SRA1 Campomelic dysplasia with autosomal sex SOX9, CMD1, SRA1 reversal, 114290 (3) Cam ptod actyly-a rth ro path y-coxa vara- PRG4, CACP, MSF, SZP, HAPO
pericarditis syndrome, 208250 (3) Camurati-Engelmann disease, 131300 (3) TGFB1, DPD1, CED
Canavan disease, 271900 (3) ASPA
Cancer progression/metastasis (3) FGFR4 Cancer susceptibility (3) MSH6, GTBP, HNPCC5 Capillary malformation-arteriovenous RASA1, GAP, CMAVM, PKWS
malformation, 608354 (3) Carbamoylphosphate synthetase I CPS1 deficiency, 237300 (3) Carbohydrate-deficient glycoprotein PMM2, CDG1 syndrome, type I, 212065 (3) Carbohydrate-deficient glycoprotein MPI, PM11 syndrome, type Ib, 602579 (3) Carbohydrate-deficient glycoprotein MGAT2, CDGS2 syndrome, type 11, 212066 (3) Carboxypeptidase N deficiency, 212070 (3) CPN1, SCPN, CPN
Carcinoid tumor of lung (3) MEN1 Carcinoid tumors, intestinal, 114900 (3) SDHD, PGL1 Cardioencephalomyopathy, fatal infantile, SC02 due to cytochrome c oxidase deficiency, 604377 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Cardiomyopathy, Familial hypertrophic, 8, MYL3, CMH8 608751 (3) Cardiomyopathy, dilated, 115200 (3) ACTC
Cardiomyopathy, dilated, 115200 (3) MYH7, CMH1, MPD1 Cardiomyopathy, dilated, 1A, 115200 (3) LMNA, LMN1, EMD2, FPLD, CMD1A, HGPS, LGMD1 B
Cardiomyopathy, dilated, 1 D, 601494 (3) TNNT2, CMH2, CMD1D
Cardiomyopathy, dilated, 1G, 604145 (3), TTN, CMD1G, TMD, LGMD2J
Tibial muscular dystrophy, tardive, 600334 (3) Cardiomyopathy, dilated, 11, 604765 (3) DES, CMD11 Cardiomyopathy, dilated, 1J,605362(3) EYA4, DFNA10, CMD1J
Cardiomyopathy, dilated, 1L,606685(3) SGCD, SGD, LGMD2F, CMD1 L
Cardiomyopathy, dilated, 1 M, 607482 (3) CSRP3, CRP3, CLP, CMD1M
Cardiomyopathy, dilated, 1N,607487(3) TCAP, LGMD2G, CMD1N
Cardiomyopathy, dilated, with ventricular ABCC9, SUR2 tachycardia, 608569 (3) Cardiomyopathy, dilated, X-linked, 302045 DMD, BMD
(3) Cardiomyopathy, familial hypertrophic, 10, MYL2, CMH10 608758 (3) Cardiomyopathy, familial hypertrophic, 1, MYH7, CMH1, MPD1 192600 (3) Cardiomyopathy, familial hypertrophic, ACTC
192600 (3) Cardiomyopathy, familial hypertrophic, CAV3, LGMD1C
192600 (3) Cardiomyopathy, familial hypertrophic, MYH6, ASD3, MYHCA
192600 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Cardiomyopathy, familial hypertrophic, TNNC1 192600 (3) () Cardiomyopathy, familial hypertrophic, 2, TNNT2, CMH2, CMD1 D
115195 (3) Cardiomyopathy, familial hypertrophic, 3, TPM1, CMH3 115196 (3) Cardiomyopathy, familial hypertrophic (3) TNN13 Cardiomyopathy, familial hypertrophic, 4, MYBPC3, CMH4 115197 (3) Cardiomyopathy, familial hypertrophic, 9 (3) TTN, CMD1G, TMD, LGMD2J
Cardiomyopathy, familial restrictive, 115210 TNN13 (3) Cardiomyopathy, hypertrophic, early-onset COX1 5 fatal (3) Cardiomyopathy, hypertrophic, mid-left MYL2, CMH10 ventricular chamber type, 608758 (3) Cardiomyopathy, hypertrophic, MYLK2, MLCK
midventricular, digenic, 192600 (3) Cardiomyopathy, hypertrophic, with WPW, PRKAG2, WPWS
600858 (3) Cardiomyopathy, idiopathic dilated, 115200 PLN, PLB
(3) Cardiomyopathy, X-linked dilated, 300069 TAZ, EFE2, BTHS, CMD3A, LVNCX
(3) Carney complex, type 1, 160980 (3) PRKAR1A, TSE1, CNC1, CAR
Carney complex variant, 608837 (3) MYH8 Carnitine-acylcarnitine translocase SLC25A20, CACT, CAC
deficiency (3) Carnitine deficiency, systemic primary, SLC22A5, OCTN2, CDSP, SCD
212140 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Carpal tunnel syndrome, familial (3) TTR, PALB
Cartilage-hair hypoplasia, 250250 (3) RMRP, RMRPR, CHH
Cataract, autosomal dominant nuclear (3) CRYAA, CRYA1 Cataract, cerulean, type 2, 601547 (3) CRYBB2, CRYB2 Cataract, congenital (3) PITX3 Cataract, congenital, 604219 (3) BFSP2, CP49, CP47 Cataract, congenital progressive, autosomal CRYAA, CRYA1 recessive (3) Cataract, congenital, with late-onset corneal PAX6, AN2, MGDA
dystrophy (3) Cataract, congenital zonular, with sutural CRYBA1, CRYB1 opacities, 600881 (3) Cataract, Coppock-like, 604307 (3) CRYGC, CRYG3, CCL
Cataract, cortical pulverulent, late-onset (3) LIM2, MP19 Cataract, crystalline aculeiform, 115700 (3) CRYGD, CRYG4 Cataract, juvenile-onset, 604219 (3) BFSP2, CP49, CP47 Cataract, lamellar, 116800 (3) HSF4, CTM
Cataract, Marner type, 116800 (3) HSF4, CTM
Cataract, polymorphic and lamellar, 604219 MIP, AQPO
(3) Cataract, posterior polar 2 (3) CRYAB, CRYA2, CTPP2 Cataract, pulverulent (3) CRYBB1 Cataracts, punctate, progressive juvenile- CRYGD, CRYG4 onset (3) Cataract, sutural, with punctate and CRYBB2, CRYB2 cerulean opacities, 607133 (3) Cataract, variable zonular pulverulent (3) CRYGC, CRYG3, CCL
Cataract, zonular central nuclear, autosomal CRYAA, CRYA1 dominant (3) Cataract, zonular pulverulent-1, 116200 (3) GJA8, CX50, CAE1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Cataract, zonular pulverulent-3, 601885 (3) GJA3, CX46, CZP3, CAE3 Cavernous malformations of CNS and CCM1, CAM, KRIT1 retina, 116860 (3) CD59 deficiency (3) CD59, MIC1 1 CD8 deficiency, familial, 608957 (3) CD8A
Central core disease, 117000 (3) RYR1, MHS, CCO
Central core disease, one form (3) () MYH7, CMH1, MPD1 Central hypoventilation syndrome, 209880 GDNF
(3) Central hypoventilation syndrome, BDNF
congenital, 209880 (3) Central hypoventilation syndrome, EDN3 congenital, 209880 (3) Central hypoventilation syndrome, PMX2B, NBPHOX, PHOX2B
congenital, 209880 (3) Central hypoventilation syndrome, RET, MEN2A
congenital, 209880 (3) Cerebellar ataxia, 604290 (3) CP
Cerebellar ataxia, pure (3) CACNA1A, CACNL1A4, SCA6 Cerebellar hypoplasia, VLDLR-associated, VLDLR, VLDLRCH
224050 (3) Cerebral amyloid angiopathy, 105150 (3) ABCA1, ABC1, HDLDT1, TGD
Cerebral amyloid angiopathy, 105150 (3) CST3 Cerebral arteriopathy with subcortical NOTCH3, CADASIL, CASIL
infarcts and leukoencephalopathy, 125310 (3) Cerebral cavernous malformations-1, CCM1, CAM, KRIT1 116860 (3) Cerebral cavernous malformations-2, C7orf22, CCM2, MGC4067 603284 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Cerebral cavernous malformations 3, PDCD10, TFAR15, CCM3 603285 (3) Cerebral dysgenesis, neuropathy, SNAP29, CEDNIK
ichthyosis, and palmoplantar keratoderma syndrome, 609528 (3) Cerebrooculofacioskeletal syndrome, ERCC2, EM9 214150 (3) Cerebrooculofacioskeletal syndrome, ERCC5, XPG
214150 (3) Cerebrooculofacioskeletal syndrome ERCC6, CKN2, COFS, CSB
214150 (3) Cerebrotendinous xanthomatosis, 213700 CYP27A1, CYP27, CTX
(3) Cerebrovascular disease, occlusive (3) SERPINA3, AACT, ACT
Ceroid lipofuscinosis, neuronal-1, infantile, PPT1, CLN1 256730 (3) Ceroid-lipofuscinosis, neuronal 2, classic CLN2 late infantile, 204500 (3) Ceroid-lipofuscinosis, neuronal-3, juvenile, CLN3, BTS
204200 (3) Ceroid-lipofuscinosis, neuronal-5, variant CLN5 late infantile, 256731 (3) Ceroid-lipofuscinosis, neuronal-6, variant CLN6 late infantile, 601780 (3) Ceroid lipofuscinosis, neuronal 8, 600143 CLN8, EPMR
(3) Ceroid lipofuscinosis, neuronal, variant PPT1, CLN1 juvenile type, with granular osmiophilic deposits (3) Cervical cancer, somatic, 603956 (3) FGFR3, ACH

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) CETP deficiency, 607322 (3) CETP
Chanarin-Dorfman syndrome, 275630 (3) ABHD5, CG158, IECN2, NCIE2 Charcot-Marie-Tooth disease, axonal, type HSPB1, HSP27, CMT2F
2F,606595(3) Charcot-Marie-Tooth disease, dominant MPZ, CMT1 B, CMTD13, CHM, DSS
intermediate 3, 607791 (3) Charcot-Marie-Tooth disease, dominant DNM2 intermediate B, 606482 (3) Charcot-Marie-Tooth disease, foot deformity HOXD10, HOX4D
of (3) Charcot-Marie-Tooth disease, mixed axonal GDAP1, CMT4A, CMT2K, CMT2G
and demyelinating type, 214400 (3) Charcot-Marie-Tooth disease, type 1A, PMP22, CMT1A, CMT1 E, DSS
118220 (3) Charcot-Marie-Tooth disease, type 1 B, MPZ, CMT1 B, CMTD13, CHM, DSS
118200 (3) Charcot-Marie-Tooth disease, type 1C, LITAF, CMT1 C
601098 (3) Charcot-Marie-Tooth disease, type 1 D, EGR2, KROX20 607678 (3) Charcot-Marie-Tooth disease, type 1 E, PMP22, CMT1A, CMT1 E, DSS
118300 (3) Charcot-Marie-Tooth disease, type 1 F, NEFL, CMT2E, CMT1 F
607734 (3) Charcot-Marie-Tooth disease, type 2A1, KIF1 B, CMT2A, CMT2A1 118210 (3) Charcot-Marie-Tooth disease, type 2A2, MFN2, KIAA0214, CMT2A2 609260 (3) Charcot-Marie-Tooth disease, type 2B, RAB7, CMT2B, PSN
600882 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Charcot-Marie-Tooth disease, type 2D, GARS, SMAD1, CMT2D
601472 (3) Charcot-Marie-Tooth disease, type 2E, NEFL, CMT2E, CMT1 F
607684 (3) Charcot-Marie-Tooth disease, type 2G, GDAP1, CMT4A, CMT2K, CMT2G
607706 (3) Charcot-Marie-Tooth disease, type 21, MPZ, CMT1 B, CMTD13, CHM, DSS
607677 (3) Charcot-Marie-Tooth disease, type 2J, MPZ, CMT1 B, CMTD13, CHM, DSS
607736 (3) Charcot-Marie-Tooth disease, type 2K, GDAP1, CMT4A, CMT2K, CMT2G
607831 (3) Charcot-Marie-Tooth disease, type 4A, GDAP1, CMT4A, CMT2K, CMT2G
214400 (3) Charcot-Marie-Tooth disease, type 4B1, MTMR2, CMT4B1 601382 (3) Charcot-Marie-Tooth disease, type 4B2, SBF2, MTMR13, CMT4B2 604563 (3) Charcot-Marie-Tooth disease, type 4B2, SBF2, MTMR13, CMT4B2 with early-onset glaucoma, 607739 (3) Charcot-Marie-Tooth disease, type 4C, KIAA1985 601596 (3) Charcot-Marie-Tooth disease, type 4D, NDRG1, HMSNL, CMT4D
601455 (3) Charcot-Marie-Tooth neuropathy, X-linked GJB1, CX32, CMTX1 dominant, 1, 302800 (3) CHARGE syndrome, 214800 (3) CHD7 Char syndrome, 169100 (3) TFAP2B, CHAR
Chediak-Higashi syndrome, 214500 (3) CHS1, LYST
Cherubism, 118400 (3) SH3BP2, CRPM

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) CHILD syndrome, 308050 (3) NSDHL
Chitotriosidase deficiency (3) CHIT
Chloride diarrhea, congenital, Finnish type, SLC26A3, DRA, CLD
214700 (3) Cholelithiasis, 600803 (3) ABCB4, PGY3, MDR3 Cholestasis, benign recurrent intrahepatic, ATP8B1, FIC1, BRIC, PFIC1 243300 (3) Cholestasis, familial intrahepatic, of ABCB4, PGY3, MDR3 pregnancy, 147480 (3) Cholestasis, progressive familial ATP8B1, FIC1, BRIC, PFIC1 intrahepatic 1, 211600 (3) Cholestasis, progressive familial ABCB11, BSEP, SPGP, PFIC2 intrahepatic 2, 601847 (3) Cholestasis, progressive familial ABCB4, PGY3, MDR3 intrahepatic 3, 602347 (3) Cholestasis, progressive familial HSD3B7, PFIC4 intrahepatic 4, 607765 (3) Cholesteryl ester storage disease (3) LIPA
Chondrocalcinosis 2, 118600 (3) ANKH, HANK, ANK, CMDJ, CCAL2, CPPDD
Chondrodysplasia, Grebe type, 200700 (3) GDF5, CDMP1 Chondrodysplasia punctata, rhizomelic, type GNPAT, DHAPAT
2,222765(3) Chondrodysplasia punctata, X-linked EBP, CDPX2, CPXD, CPX
dominant, 302960 (3) Chondrodysplasia punctata, X-linked ARSE, CDPX1, CDPXR
recessive, 302950 (3) Chondrosarcoma, 215300 (3) EXT1 Chondrosarcoma, extraskeletal myxoid (3) CSMF
Chondrosarcoma, extraskeletal myxoid (3) EWSR1, EWS

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Chorea, hereditary benign, 118700 (3) TITF1, NKX2A, TTF1 Choreoacanthocytosis, 200150 (3) VPS13A, CHAC
Choreoathetosis, hypothyroidism, and TITF1, NKX2A, TTF1 respiratory distress (3) Choroideremia, 303100 (3) CHM, TCD
Chromosome 22q13.3 deletion syndrome, PSAP2, PROSAP2, KIAA1650 606232 (3) Chronic granulomatous disease, autosomal, CYBA
due to deficiency of CYBA, 233690 (3) Chronic granulomatous disease due to NCF1 deficiency of NCF-1, 233700 (3) Chronic granulomatous disease due to NCF2 deficiency of NCF-2, 233710 (3) Chronic granulomatous disease, X-linked, CYBB, CGD
306400 (3) Chronic infections, due to opsonin defect (3) MBL2, MBL, MBP1 Chudley-Lowry syndrome, 309490 (3) ATRX, XH2, XNP, MRXS3, SHS
Chylomicronemia syndrome, familial (3) LPL, LIPD
Chylomicron retention disease, 246700 (3) SARA2, SARI B, CMRD
Chylomicron retention disease with SARA2, SARI B, CMRD
Marinesco-Sjogren syndrome, 607692 (3) Ciliary dyskinesia, primary, 1, 242650 (3) DNAI1, CILD1, ICS, PCD
Ciliary dyskinesia, primary, 3 608644 (3) DNAH5, HL1, PCD, CILD3 CINCA syndrome, 607115 (3) CIAS1, C1orf7, FCU, FCAS
Cirrhosis, cryptogenic (3) KRT18 Cirrhosis, cryptogenic (3) KRT8 Cirrhosis, noncryptogenic, susceptibility to, KRT18 215600 (3) Cirrhosis, noncryptogenic, susceptibility to, KRT8 215600 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Cirrhosis, North American Indian childhood CIRHIA, NAIC, TEX292, KIAA1988 type, 604901 (3) Citrullinemia, 215700 (3) ASS
Citrullinemia, adult-onset type II, 603471 (3) SLC25A13, CTLN2 Citrullinemia, type II, neonatal-onset, SLC25A13, CTLN2 605814 (3) Cleft lip/palate ectodermal dysplasia HVEC, PVRL1, PVRR1, PRR1 syndrome, 225000 (3) Cleft lip/palate, nonsyndromic, 608874 (3) MSX1, HOX7, HYD1, OFC5 Cleft palate with ankyloglossia, 303400 (3) TBX22, CPX
Cleidocranial dysplasia, 119600 (3) RUNX2, CBFA1, PEBP2A1, AML3 Coats disease, 300216 (3) NDP, ND
Cockayne syndrome, type A, 216400 (3) ERCC8, CKN1, CSA
Cockayne syndrome, type B, 133540 (3) ERCC6, CKN2, COFS, CSB
Codeine sensitivity (3) CYP2D@, CYP2D, P450C2D
Coffin-Lowry syndrome, 303600 (3) RPS6KA3, RSK2, MRX19 Cohen syndrome, 216550 (3) COH1 Colchicine resistance (3) ABCB1, PGY1, MDR1 Cold-induced autoinflammatory syndrome, CIAS1, C1orf7, FCU, FCAS
familial, 120100 (3) Cold-induced sweating syndrome, 272430 CRLF1, CISS
(3) Coloboma, ocular, 120200 (3) PAX6, AN2, MGDA
Coloboma, ocular, 120200 (3) SHH, HPE3, HLP3, SMMCI
Colon adenocarcinoma (3) RAD54B
Colon adenocarcinoma (3) RAD54L, HR54, HRAD54 Colon cancer (3) BCL10 Colon cancer (3) PTPN12, PTPG1 Colon cancer (3) TGFBR2, HNPCC6 Colon cancer, advanced (3) SRC, ASV, SRC1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Colon cancer, hereditary nonpolypopsis, MLH3, HNPCC7 type 7 (3) Colon cancer, somatic, 114500 (3) PTPRJ, DEP1 Colonic adenoma recurrence, reduced risk ODC1 of, 114500 (3) Colonic aganglionosis, total, with small RET, MEN2A
bowel involvement (3) Colorblindness, deutan (3) OPN1MW, GCP, CBD, CBBM
Colorblindness, protan (3) OPN1LW, RCP, CBP, CBBM
Colorblindness, tritan (3) OPN1SW, BCP, CBT
Colorectal adenomatous polyposis, MUTYH
autosomal recessive, with pilomatricomas, 132600 (3) Colorectal cancer, 114500 (3) AXIN2 Colorectal cancer, 114500 (3) BUB1 B, BUBR1 Colorectal cancer, 114500 (3) EP300 Colorectal cancer, 114500 (3) PDGFRL, PDGRL, PRLTS
Colorectal cancer, 114500 (3) PIK3CA
Colorectal cancer, 114500 (3) TP53, P53, LFS1 Colorectal cancer (3) APC, GS, FPC
Colorectal cancer (3) BAX
Colorectal cancer (3) CTNNB1 Colorectal cancer (3) DCC
Colorectal cancer (3) MCC
Colorectal cancer (3) NRAS
Colorectal cancer, hereditary nonpolyposis, MSH2, COCA1, FCC1, HNPCC1 type 1, 120435 (3) Colorectal cancer, hereditary nonpolyposis, MLH1, COCA2, HNPCC2 type 2, 609310 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Colorectal cancer, hereditary nonpolyposis, PMS1, PMSL1, HNPCC3 type 3 (3) Colorectal cancer, hereditary nonpolyposis, PMS2, PMSL2, HNPCC4 type 4 (3) Colorectal cancer, hereditary nonpolyposis, MSH6, GTBP, HNPCC5 type 5 (3) Colorectal cancer, hereditary nonpolyposis, TGFBR2, HNPCC6 type 6 (3) Colorectal cancer, somatic, 109800 (3) FGFR3, ACH
Colorectal cancer, somatic, 114500 (3) FLCN, BHD
Colorectal cancer, somatic, 114500 (3) MLH3, HNPCC7 Colorectal cancer, somatic (3) BRAF
Colorectal cancer, somatic (3) DLC1 Colorectal cancer, sporadic, 114500 (3) PLA2G2A, PLA2B, PLA2L, MOM1 Colorectal cancer, susceptibility to (3) CCND1, PRAD1, BCL1 Colorectal cancer with chromosomal BUB1 instability (3) Combined C6/C7 deficiency (3) C6 Combined factor V and VIII deficiency, LMAN1, ERGIC53, F5F8D, MCFD1 227300 (3) Combined hyperlipemia, familial (3) LPL, LIPD
Combined immunodeficiency, X-linked, IL2RG, SCIDX1, SCIDX, IMD4 moderate, 312863 (3) Combined oxidative phosphorylation GFM1, EFG1, GFM
deficiency, 609060 (3) Combined SAP deficiency (3) PSAP, SAP1 Complex I, mitochondrial respiratory chain, NDUFS6 deficiency of, 252010 (3) Complex V, mitochondrial respiratory chain, ATPAF2, ATP12 deficiency of, 604273 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Cone dystrophy-1, 304020 (3) RPGR, RP3, CRD, RP15, COD1 Cone dystrophy-3, 602093 (3) GUCAIA, GCAP
Cone-rod dystrophy, 300029 (3) RPGR, RP3, CRD, RP15, COD1 Cone-rod dystrophy 3 (3) ABCA4, ABCR, STGD1, FFM, RP19 Cone-rod dystrophy (3) AIPL1, LCA4 Cone-rod dystrophy 6, 601777(3) GUCY2D, GUC2D, LCA1, CORD6 Cone-rod dystrophy 9, 608194 (3) RPGRIP1, LCA6, CORD9 Cone-rod retinal dystrophy-2, 120970 (3) CRX, CORD2, CRD
Congenital bilateral absence of vas CFTR, ABCC7, CF, MRP7 deferens, 277180 (3) Congenital cataracts, facial dysmorphism, CTDP1, FCP1, CCFDN
and neuropathy, 604168 (3) Congenital disorder of glycosylation, type Ic, ALG6 603147(3) Congenital disorder of glycosylation, type Id, ALG3, NOT56L, CDGS4 601110(3) Congenital disorder of glycosylation, type le, DPM1, MPDS, CDGIE
608799 (3) Congenital disorder of glycosylation, type If, MPDU1, SL15, CDGIF
609180(3) Congenital disorder of glycosylation, type Ig, ALG12 607143(3) Congenital disorder of glycosylation, type Ih, ALG8 608104(3) Congenital disorder of glycosylation, type Ii, ALG2, CDGII
607906 (3) Congenital disorder of glycosylation, type II, DIBD1, ALG9 608776 (3) Congenital disorder of glycosylation, type SLC35C1, FUCT1 Ilc, 266265 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Congenital disorder of glycosylation, type B4GALT1, GGTB2, GT1, GTB
Ild, 607091 (3) Congenital disorder of glycosylation, type COG7, CDG2E
Ile, 608779 (3) Congenital disorder of glycosylation, type Ij, DPAGT2, DGPT
608093 (3) Congenital disorder of glycosylation, type Ik, ALG1, HMAT1, HMT1 608540 (3) Congestive heart failure, susceptibility to (3) ADRA2C, ADRA2L2 Congestive heart failure, susceptibility to (3) ADRB1, ADRB1 R, RHR
Conjunctivitis, ligneous, 217090 (3) PLG
Conotruncal anomaly face syndrome, TBX1, DGS, CTHM, CAFS, TGA, 217095 (3) DORV, VCFS, DGCR
Contractural arachnodactyly, congenital (3) FBN2, CCA
Convulsions, familial febrile, 4, 604352 (3) MASS1, VLGR1, KIAA0686, FEB4, COPD, rate of decline of lung function in, MMP1, CLG
606963 (3) Coproporphyria (3) CPO
Corneal clouding, autosomal recessive (3) APOA1 Corneal dystrophy, Avellino type, 607541 TGFBI, CSD2, CDGG1, CSD, BIGH3, (3) CDG2 Corneal dystrophy, gelatinous drop-like, TACSTD2, TROP2, M1S1 204870 (3) Corneal dystrophy, Groenouw type I, TGFBI, CSD2, CDGG1, CSD, BIGH3, 121900 (3) CDG2 Corneal dystrophy, hereditary polymorphous VSX1, RINX, PPCD, PPD, KTCN
posterior, 122000 (3) Corneal dystrophy, hereditary polymorphous COL8A2, FECD, PPCD2 posterior, 2, 122000 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Corneal dystrophy, lattice type I, 122200 (3) TGFBI, CSD2, CDGG1, CSD, BIGH3, Corneal dystrophy, lattice type IIIA, 608471 TGFBI, CSD2, CDGG1, CSD, BIGH3, (3) CDG2 Corneal dystrophy, Reis-Bucklers type, TGFBI, CSD2, CDGG1, CSD, BIGH3, 608470 (3) CDG2 Corneal dystrophy, Thiel-Behnke type, TGFBI, CSD2, CDGG1, CSD, BIGH3, 602082 (3) CDG2 Corneal fleck dystrophy, 121850 (3) PIP5K3, CFD
Cornea plana congenita, recessive, 217300 KERA, CNA2 (3) Cornelia de Lange syndrome, 122470 (3) NIPBL, CDLS
Coronary artery disease, autosomal MEF2A, ADCAD1 dominant, 1, 608320 (3) Coronary artery disease in familial ABCA1, ABC1, HDLDT1, TGD
hypercholesterolemia, protection against, 143890 (3) Coronary artery disease, susceptibility to (3) KL
Coronary artery disease, susceptibility to (3) POW, PON, ESA
Coronary artery disease, susceptibility to (3) PON2 Coronary artery spasm, susceptibility to (3) PON1, PON, ESA
Coronary heart disease, susceptibility to (3) MMP3, STMY1 Coronary spasms, susceptibility to (3) NOS3 Corpus callosum, agenesis of, with mental IGBP1 retardation, ocular coloboma and micrognathia, 300472 (3) Cortisol resistance (3) NR3C1, GCR, GRL
Cortisone reductase deficiency, 604931 (3) GDH
Cortisone reductase deficiency, 604931 (3) HSD11B1, HSD11, HSD11L
Costello syndrome, 218040 (3) HRAS

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Coumarin resistance, 122700 (3) CYP2A6, CYP2A3, CYP2A, P450C2A
Cowden disease, 158350 (3) PTEN, MMAC1 Cowden-like syndrome, 158350 (3) BMPR1A, ACVRLK3, ALK3 CPT deficiency, hepatic, type IA, 255120 (3) CPT1A
CPT deficiency, hepatic, type II, 600649 (3) CPT2 CPT II deficiency, lethal neonatal, 608836 CPT2 (3) Cramps, familial, potassium-aggravated (3) SCN4A, HYPP, NAC1A
Craniofacial anomalies, empty sella turcica, VSX1, RINX, PPCD, PPD, KTCN
corneal endothelial changes, and abnormal retinal and auditory bipolar cells (3) Craniofacial-deafness-hand syndrome, PAX3, WS1, HUP2, CDHS
122880 (3) Craniofacial-skeletal-dermatologic dysplasia FGFR2, BEK, CFD1, JWS
(3) Craniofrontonasal dysplasia, 304110 (3) EFNB1, EPLG2, CFNS, CFND
Craniometaphyseal dysplasia, 123000 (3) ANKH, HANK, ANK, CMDJ, CCAL2, CPPDD
Craniosynostosis, nonspecific (3) FGFR2, BEK, CFD1, JWS
Craniosynostosis, type 2, 604757 (3) MSX2, CRS2, HOX8 CRASH syndrome, 303350 (3) L1 CAM, CAML1, HSAS1 Creatine deficiency syndrome, X-linked, SLC6A8, CRTR
300352 (3) Creatine phosphokinase, elevated serum, CAV3, LGMD1C
123320 (3) Creatine phosphokinase, elevated serum, CAV3, LGMD1C
123320 (3) Creutzfeldt-Jakob disease, 123400 (3) PRNP, PRIP
Creutzfeldt-Jakob disease, variant, HLA-DQB1 resistance to, 123400 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Crigler-Najjar syndrome, type I, 218800 (3) UGT1A1, UGT1, GNT1 Crigler-Najjar syndrome, type II, 606785 (3) UGT1A1, UGT1, GNT1 Crohn disease, susceptibility to, 266600 (3) CARD15, NOD2, IBD1, CD, ACUG, Crohn disease, susceptibility to, 266600 (3) DLG5, PDLG, KIAA0583 Crouzon syndrome, 123500 (3) FGFR2, BEK, CFD1, JWS
Crouzon syndrome with acanthosis FGFR3, ACH
nigricans (3) Cryptorchidism, bilateral, 219050 (3) LGR8, GREAT
Cryptorchidism, idiopathic, 219050 (3) INSL3 Currarino syndrome, 176450 (3) HLXB9, HOXHB9, SCRA1 Cutis laxa, AD, 123700 (3) ELN
Cutis laxa, autosomal dominant, 123700 (3) FBLN5, ARMD3 Cutis laxa, autosomal recessive, 219100 (3) FBLN5, ARMD3 Cutis laxa, neonatal (3) ATP7A, MNK, MK, OHS
Cyclic ichthyosis with epidermolytic KRT1 hyperkeratosis, 607602 (3) Cylindromatosis, familial, 132700 (3) CYLD1, CDMT, EAC
Cystathioninuria, 219500 (3) CTH
Cystic fibrosis, 219700 (3) CFTR, ABCC7, CF, MRP7 Cystinosis, atypical nephropathic (3) CTNS
Cystinosis, late-onset juvenile or adolescent CTNS
nephropathic, 219900 (3) Cystinosis, nephropathic, 219800 (3) CTNS
Cystinosis, ocular nonnephropathic, 219750 CTNS
(3) Cystinuria, 220100 (3) SLC3A1, ATR1, D2H, NBAT
Cystinuria, type II (3) SLC7A9, CSNU3 Cystinuria, type III (3) SLC7A9, CSNU3 D-2-hydroxyglutaric aciduria, 600721 (3) D2HGD

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Darier disease, 124200 (3) ATP2A2, ATP2B, DAR
D-bifunctional protein deficiency, 261515 (3) HSD17B4 Deafness, autosomal dominant 10, 601316 EYA4, DFNA10, CMD1J
(3) Deafness, autosomal dominant 1, 124900 DIAPH1, DFNA1, LFHL1 (3) Deafness, autosomal dominant 11, MYO7A, USH1B, DFNB2, DFNA11 neurosensory, 601317 (3) Deafness, autosomal dominant 12, 601842 TECTA, DFNA8, DFNA12, DFNB21 (3) Deafness, autosomal dominant 13, 601868 COL11A2, STL3, DFNA13 (3) Deafness, autosomal dominant 15, 602459 POU4F3, BRN3C
(3) Deafness, autosomal dominant 17, 603622 MYH9, MHA, FTNS, DFNA17 (3) Deafness, autosomal dominant 20/26, ACTG1, DFNA20, DFNA26 604717 (3) Deafness, autosomal dominant 22, 606346 MYO6, DFNA22, DFNB37 (3) Deafness, autosomal dominant 2, 600101 GJB3, CX31, DFNA2 (3) Deafness, autosomal dominant 2, 600101 KCNQ4, DFNA2 (3) Deafness, autosomal dominant 28, 608641 TFCP2L3, DFNA28 (3) Deafness, autosomal dominant 3, 601544 GJB2, CX26, DFNB1, PPK, DFNA3, (3) KID, HID
Deafness, autosomal dominant 3, 601544 GJB6, CX30, DFNA3, HED, ED2 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Deafness, autosomal dominant 36, 606705 TMC1, DFNB7, DFNB11, DFNA36 (3) Deafness, autosomal dominant 36, with DSPP, DPP, DG11, DFNA39, DTDP2 dentinogenesis, 605594 (3) Deafness, autosomal dominant 40 (3) CRYM, DFNA40 Deafness, autosomal dominant 4, 600652 MYH14, KIAA2034, DFNA4 (3) Deafness, autosomal dominant 5 (3) DFNA5 Deafness, autosomal dominant 8, 601543 TECTA, DFNA8, DFNA12, DFNB21 (3) Deafness, autosomal dominant 9, 601369 COCH, DFNA9 (3) Deafness, autosomal dominant MYO1A
nonsyndromic sensorineural, 607841 (3) Deafness, autosomal dominant, with GJB3, CX31, DFNA2 peripheral neuropathy (3) Deafness, autosomal recessive 10, TMPRSS3, ECHOS1, DFNB8, DFNB10 congenital, 605316 (3) Deafness, autosomal recessive 1, 220290 GJB2, CX26, DFNB1, PPK, DFNA3, (3) KID, HID
Deafness, autosomal recessive 12, 601386 CDH23, USH1D
(3) Deafness, autosomal recessive 12, modifier ATP2B2, PMCA2 of, 601386 (3) Deafness, autosomal recessive 16, 603720 STRC, DFNB16 (3) Deafness, autosomal recessive 18, 602092 USH1C, DFNB18 (3) Deafness, autosomal recessive 21, 603629 TECTA, DFNA8, DFNA12, DFNB21 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Deafness, autosomal recessive 22, 607039 OTOA, DFNB22 (3) Deafness, autosomal recessive 23, 609533 PCDH15, DFNB23 (3) Deafness, autosomal recessive 29 (3) CLDN14, DFNB29 Deafness, autosomal recessive 2, MYO7A, USH1B, DFNB2, DFNA11 neurosensory, 600060 (3) Deafness, autosomal recessive 30, 607101 MYO3A, DFNB30 (3) Deafness, autosomal recessive 31, 607084 WHRN, CIP98, KIAA1526, DFNB31 (3) Deafness, autosomal recessive 3, 600316 MYO15A, DFNB3 (3) Deafness, autosomal recessive 36, 609006 ESPN
(3) Deafness, autosomal recessive 37, 607821 MYO6, DFNA22, DFNB37 (3) Deafness, autosomal recessive (3) GJB3, CX31, DFNA2 Deafness, autosomal recessive 4, 600791 SLC26A4, PDS, DFNB4 (3) Deafness, autosomal recessive 61 (3) PRES, DFNB61, SLC26A5 Deafness, autosomal recessive 6, 600971 TMIE, DFNB6 (3) Deafness, autosomal recessive 7, 600974 TMC1, DFNB7, DFNB11, DFNA36 (3) Deafness, autosomal recessive 8, childhood TMPRSS3, ECHOS1, DFNB8, DFNB10 onset, 601072 (3) Deafness, autosomal recessive 9, 601071 OTOF, DFNB9, NSRD9 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Deafness, congenital heart defects, and JAG1, AGS, AHD
posterior embryotoxon (3) Deafness, nonsyndromic (3) () KIAA1199 Deafness, nonsyndromic neurosensory, GJB6, CX30, DFNA3, HED, ED2 digenic (3) Deafness, sensorineural, with hypertrophic MYO6, DFNA22, DFNB37 cardiomyopathy, 606346 (3) Deafness, X-linked 1, progressive (3) TIMM8A, DFN1, DDP, MTS, DDP1 Deafness, X-linked 3, conductive, with POU3F4, DFN3 stapes fixation, 304400 (3) Debrisoquine sensitivity (3) CYP2D@, CYP2D, P450C2D
Dejerine-Sottas disease, 145900 (3) PMP22, CMT1A, CMT1 E, DSS
Dejerine-Sottas neuropathy, 145900 (3) EGR2, KROX20 Dejerine-Sottas neuropathy, autosomal PRX, CMT4F
recessive, 145900 (3) Dejerine-Sottas syndrome, 145900 (3) MPZ, CMT1 B, CMTDI3, CHM, DSS
Delayed sleep phase syndrome, AANAT, SNAT
susceptibility to (3) Dementia, familial British, 176500 (3) ITM2B, BRI, ABRI, FBD
Dementia, familial Danish, 117300 (3) ITM2B, BRI, ABRI, FBD
Dementia, frontotemporal, 600274 (3) PSEN1, AD3 Dementia, frontotemporal, with MAPT, MTBT1, DDPAC, MSTD
parkinsonism, 600274 (3) Dementia, Lewy body, 127750 (3) SNCA, NACP, PARK1, PARK4 Dementia, Lewy body, 127750 (3) SNCB
Dementia, Pick disease-like, 172700 (3) MAPT, MTBT1, DDPAC, MSTD
Dementia, vascular, susceptibility to (3) TNF, TNFA
Dengue fever, protection against (3) CD209, CDSIGN
Dental anomalies, isolated (3) RUNX2, CBFA1, PEBP2A1, AML3 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Dentatorubro-palIidol uysian atrophy, 125370 DRPLA
(3) Dent disease, 300009 (3) CLCN5, CLCK2, NPHL2, DENTS
Dentin dysplasia, type II, 125420 (3) DSPP, DPP, DG11, DFNA39, DTDP2 Dentinogenesis imperfecta, Shields type 11, DSPP, DPP, DG11, DFNA39, DTDP2 125490 (3) Dentinogenesis imperfecta, Shields type 111, DSPP, DPP, DG11, DFNA39, DTDP2 125500 (3) Dent syndrome, 300009 (3) OCRL, LOCR, OCRL1, NPHL2 Denys-Drash syndrome, 194080 (3) WT1 Dermatofibrosarcoma protuberans (3) PDGFB, SIS
De Sanctis-Cacchione syndrome, 278800 ERCC6, CKN2, COFS, CSB
(3) Desmoid disease, hereditary, 135290 (3) APC, GS, FPC
Desmosterolosis, 602398 (3) DHCR24, KIAA0018 Diabetes insipidus, nephrogenic, 304800 (3) AVPR2, DIR, D11, ADHR
Diabetes insipidus, nephrogenic, autosomal AQP2 dominant, 125800 (3) Diabetes insipidus, nephrogenic, autosomal AQP2 recessive, 222000 (3) Diabetes insipidus, neurohypophyseal, AVP, AVRP, VP
125700 (3) Diabetes mellitus, 125853 (3) ABCC8, SUR, PHHI, SUR1 Diabetes mellitus, insulin-dependent, TCF1, HNF1A, MODY3 222100 (3) Diabetes mellitus, insulin-dependent, 5, SUMO4, IDDM5 600320 (3) Diabetes mellitus, insulin-dependent, PTPN8, PEP, PTPN22, LYP
susceptibility to, 222100 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Diabetes mellitus, insulin-resistant, with INSR
acanthosis nigricans (3) Diabetes mellitus, insulin-resistant, with PPARG, PPARG1, PPARG2 acanthosis nigricans and hypertension, 604367 (3) Diabetes mellitus, neonatal-onset, 606176 GCK
(3) Diabetes mellitus, noninsulin-dependent, GCGR
125853 (3) Diabetes mellitus, noninsulin-dependent, GPD2 125853 (3) Diabetes mellitus, noninsulin-dependent, HNF4A, TCF14, MODY1 125853 (3) Diabetes mellitus, noninsulin-dependent, I RS2 125853 (3) Diabetes mellitus, noninsulin-dependent, MAPK81P1, 1131 125853 (3) Diabetes mellitus, noninsulin-dependent, NEUROD1, NIDDM
125853 (3) Diabetes mellitus, noninsulin-dependent, TCF2, HNF2 125853 (3) Diabetes mellitus, noninsulin-dependent, 2, TCF1, HNF1A, MODY3 125853 (3) Diabetes mellitus, noninsulin-dependent (3) IRS1 Diabetes mellitus, noninsulin-dependent (3) SLC2A2, GLUT2 Diabetes mellitus, noninsulin-dependent (3) SLC2A4, GLUT4 Diabetes mellitus, noninsulin-dependent, CAPN10 601283 (3) Diabetes mellitus, non-insulin-dependent, ENPP1, PDNP1, NPPS, M6S1, PCA1 susceptibility to, 125853 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Diabetes mellitus, noninsulin-dependent, RETN, RSTN, FIZZ3 susceptibility to, 125853 (3) Diabetes mellitus, permanent neonatal, with PTF1A
cerebellar agenesis, 609069 (3) Diabetes mellitus, permanent neonatal, with KCNJ11, BIR, PHHI
neurologic features, 606176 (3) Diabetes mellitus, type II, 125853 (3) AKT2 Diabetes mellitus, type II, susceptibility to, IPF1 125853 (3) Diabetes mellitus, type I, susceptibility to, FOXP3, IPEX, AIID, XPID, PIDX
222100 (3) Diabetes, permanent neonatal, 606176 (3) KCNJ11, BIR, PHHI
Diabetic nephropathy, susceptibility to, ACE, DCP1, ACE1 603933 (3) Diabetic retinopathy, NIDDM-related, VEGF
susceptibility to, 125853 (3) Diastrophic dysplasia, 222600 (3) SLC26A2, DTD, DTDST, D5S1708, Diastrophic dysplasia, broad bone- SLC26A2, DTD, DTDST, D5S1708, platyspondylic variant (3) EDM4 DiGeorge syndrome, 188400 (3) TBX1, DGS, CTHM, CAFS, TGA, DORV, VCFS, DGCR
Dihydropyrimidinuria (3) DPYS, DHP
Dilated cardiomyopathy with woolly hair and DSP, KPPS2, PPKS2 keratoderma, 605676 (3) Dimethylglycine dehydrogenase deficiency, DMGDH, DMGDHD
605850 (3) Disordered steroidogenesis, isolated (3) POR
Dissection of cervical arteries (3) COL1A1 DNA ligase I deficiency (3) LIG1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) DNA topoisomerase I, camptothecin- TOP1 resistant (3) DNA topoisomerase II, resistance to TOP2A, TOP2 inhibition of, by amsacrine (3) Dopamine-beta-hydroxylase activity levels, DBH
plasma (3) Dopamine beta-hydroxylase deficiency, DBH
223360 (3) Dosage-sensitive sex reversal, 300018 (3) DAX1, AHC, AHX, NROB1 Double-outlet right ventricle, 217095 (3) CFC1, CRYPTIC, HTX2 Down syndrome, risk of, 190685 (3) MTR
Doyne honeycomb degeneration of retina, EFEMP1, FBNL, DHRD
126600 (3) Drug addiction, susceptibility to (3) FAAH
Duane-radial ray syndrome, 607323 (3) SALL4, HSAL4 Dubin-Johnson syndrome, 237500 (3) ABCC2, CMOAT
Duchenne muscular dystrophy, 310200 (3) DMD, BMD
Dyggve-Melchior-Clausen disease, 223800 DYM, FLJ90130, DMC, SMC
(3) Dysalbuminemic hyperthyroxinemia (3) ALB
Dysautonomia, familial, 223900 (3) IKBKAP, IKAP
Dyschromatosis symmetrica hereditaria, ADAR, DRADA, DSH, DSRAD
127400 (3) Dyserythropoietic anemia with GATA1, GF1, ERYF1, NFE1 thrombocytopenia, 300367 (3) Dysfibrinogenemia, alpha type, causing FGA
bleeding diathesis (3) Dysfibrinogenemia, alpha type, causing FGA
recurrent thrombosis (3) Dysfibrinogenemia, beta type (3) FGB

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Dysfibrinogenemia, gamma type (3) FGG
Dyskeratosis congenita-1, 305000 (3) DKC1, DKC
Dyskeratosis congenita, autosomal TERC, TRC3, TR
dominant, 127550 (3) Dyslexia, susceptibility to, 1, 127700 (3) DYX1C1, DYXC1, DYX1 Dyslexia, susceptibility to, 2, 600202 (3) KIAA0319, DYX2, DYLX2, DLX2 Dysprothrombinemia (3) F2 Dyssegmental dysplasia, Silverman- HSPG2, PLC, SJS, SJA, SJS1 Handmaker type, 224410 (3) Dystonia-12, 128235 (3) ATP1A3, DYT12, RDP
Dystonia-1, torsion, 128100 (3) DYT1, TOR1A
Dystonia, DOPA-responsive, 128230 (3) GCH1, DYT5 Dystonia, early-onset atypical, with DYT1, TOR1A
myoclonic features (3) Dystonia, myoclonic, 159900 (3) DRD2 Dystonia, myoclonic, 159900 (3) SGCE, DYT11 Dystonia, primary cervical (3) DRD5, DRD1 B, DRD1 L2 Dystransthyretinemic hyperthyroxinemia(3) TTR, PALB
EBD, Bart type, 132000 (3) COL7A1 EBD, localisata variant (3) COL7A1 Ectodermal dysplasia-1, anhidrotic, 305100 ED1, EDA, HED
(3) Ectodermal dysplasia 2, hidrotic, 129500 (3) GJB6, CX30, DFNA3, HED, ED2 Ectodermal dysplasia, anhidrotic, 224900 EDARADD
(3) Ectodermal dysplasia, anhidrotic, IKBKG, NEMO, FIP3, IP2 lymphedema and immunodeficiency, 300301 (3) Ectodermal dysplasia, anhidrotic, with T-cell NFKBIA, IKBA
immunodeficiency (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Ectodermal dysplasia, hypohidrotic, EDAR, DL, ED3, EDA3 autosomal dominant, 129490 (3) Ectodermal dysplasia, hypohidrotic, EDAR, DL, ED3, EDA3 autosomal recessive, 224900 (3) Ectodermal dysplasia, hypohidrotic, with IKBKG, NEMO, FIP3, IP2 immune deficiency, 300291 (3) Ectodermal dysplasia, Margarita Island type, HVEC, PVRL1, PVRR1, PRR1 225060 (3) Ectodermal dysplasia/skin fragility PKP1 syndrome, 604536 (3) Ectopia lentis, familial, 129600 (3) FBN1, MFS1, WMS
Ectopia pupillae, 129750 (3) PAX6, AN2, MGDA
Ectrodactyly, ectodermal dysplasia, and TP73L, TP63, KET, EEC3, SHFM4, cleft lip/palate syndrome 3, 604292 (3) LMS, RHS
Ehlers-Danlos due to tenascin X deficiency, TNXB, TNX, TNXB1, TNXBS, TNXB2 606408 (3) Ehlers-Danlos syndrome, hypermobility TNXB, TNX, TNXB1, TNXBS, TNXB2 type, 130020 (3) Ehlers-Danlos syndrome, progeroid form, B4GALT7, XGALT1, XGPT1 130070 (3) Ehlers-Danlos syndrome, type I, 130000 (3) COL1A1 Ehlers-Danlos syndrome, type I, 130000 (3) COL5A1 Ehlers-Danlos syndrome, type I, 130000 (3) COL5A2 Ehlers-Danlos syndrome, type II, 130010 (3) COL5A1 Ehlers-Danlos syndrome, type III, 130020 COL3A1 (3) Ehlers-Danlos syndrome, type IV, 130050 COL3A1 (3) Ehlers-Danlos syndrome, type VI, 225400 PLOD, PLOD1 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Ehlers-Danlos syndrome, type VII, 130060 COL1A1 (3) Ehlers-Danlos syndrome, type VIIA2, COL1A2 130060 (3) Ehlers-Danlos syndrome, type VI IC, 225410 ADAMTS2, NPI
(3) Elite sprint athletic performance (3) ACTN3 Elliptocytosis-1 (3) EPB41, EL1 Elliptocytosis-2 (3) SPTA1 Elliptocytosis-3 (3) SPTB
Elliptocytosis, Malaysian-Melanesian type SLC4A1, AE1, EPB3 (3) Ellis-van Creveld syndrome, 225500 (3) EVC
Ellis-van Creveld syndrome, 225500 (3) LBN, EVC2 Emery-Dreifuss muscular dystrophy, EMD, EDMD, STA
310300 (3) Emery-Dreifuss muscular dystrophy, AD, LMNA, LMN1, EMD2, FPLD, CMD1A, 181350 (3) HGPS, LGMD1 B
Emery-Dreifuss muscular dystrophy, AR, LMNA, LMN1, EMD2, FPLD, CMD1A, 604929 (3) HGPS, LGMD1 B
Emphysema (3) PI, AAT
Emphysema-cirrhosis (3) PI, AAT
Encephalopathy, familial, with neuroserpin SERPINI1, P112 inclusion bodies, 604218 (3) Encephalopathy, progressive mitochondrial, COX10 with proximal renal tubulopathy due to cytochrome c oxidase deficiency (3) Enchondromatosis, Ollier type, 166000 (3) PTHR1, PTHR
Endometrial carcinoma (3) CDH1, UVO
Endometrial carcinoma (3) MSH3 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Endometrial carcinoma (3) MSH6, GTBP, HNPCC5 Endometrial carcinoma (3) PTEN, MMAC1 Endotoxin hyporesponsiveness (3) TLR4 Endplate acetylcholinesterase deficiency, COLQ, EAD
603034 (3) Enhanced S-cone syndrome, 268100 (3) NR2E3, PNR, ESCS
Enlarged vestibular aqueduct, 603545 (3) SLC26A4, PDS, DFNB4 Enolase-beta deficiency (3) ENO3 Enterokinase deficiency, 226200 (3) PRSS7, ENTK
Eosinophil peroxidase deficiency, 261500 EPX
(3) Epidermodysplasia verruciformis, 226400 EVER1, EV1 (3) Epidermodysplasia verruciformis, 226400 EVER2, EV2 (3) Epidermolysis bullosa dystrophica, AD, COL7A1 131750 (3) Epidermolysis bullosa dystrophica, AR, COL7A1 226600 (3) Epidermolysis bullosa, generalized atrophic COL17A1, BPAG2 benign, 226650 (3) Epidermolysis bullosa, generalized atrophic ITGB4 benign, 226650 (3) Epidermolysis bullosa, generalized atrophic LAMA3, LOCS
benign, 226650 (3) Epidermolysis bullosa, generalized atrophic LAMB3 benign, 226650 (3) Epidermolysis bullosa, generalized atrophic LAMC2, LAMNB2, LAMB2T
benign, 226650 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Epidermolysis bullosa, Herlitz junctional LAMB3 type, 226700 (3) Epidermolysis bullosa, Herlitz junctional LAMC2, LAMNB2, LAMB2T
type, 226700 (3) Epidermolysis bullosa, junctional, Herlitz LAMA3, LOCS
type, 226700 (3) Epidermolysis bullosa, junctional, with ITGB4 pyloric atresia, 226730 (3) Epidermolysis bullosa, junctional, with ITGA6 pyloric stenosis, 226730 (3) Epidermolysis bullosa, lethal acantholytic, DSP, KPPS2, PPKS2 609638 (3) Epidermolysis bullosa of hands and feet, ITGB4 131800 (3) Epidermolysis bullosa, pretibial, 131850 (3) COL7A1 Epidermolysis bullosa pruriginosa, 604129 COL7A1 (3) Epidermolysis bullosa simplex, Koebner, KRT14 Dowling-Meara, and Weber-Cockayne types, 131900, 131760, 131800 (3) Epidermolysis bullosa simplex, Koebner, KRT5 Dowling-Meara, and Weber-Cockayne types, 131900, 131760, 131800 (3) Epidermolysis bullosa simplex, Ogna type, PLEC1, PLTN, EBS1 131950 (3) Epidermolysis bullosa simplex, recessive, KRT14 601001 (3) Epidermolysis bullosa simplex with mottled KRT5 pigmentation, 131960 (3) Epidermolytic hyperkeratosis, 113800 (3) KRT10 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Epidermolytic hyperkeratosis, 113800 (3) KRT1 Epidermolytic palmoplantar keratoderma, KRT9, EPPK
144200 (3) Epilepsy, benign, neonatal, type 1, 121200 KCNQ2, EBN1 (3) Epilepsy, benign neonatal, type 2, 121201 KCNQ3, EBN2, BFNC2 (3) Epilepsy, childhood absence, 607681 (3) GABRG2, GEFSP3, CAE2, ECA2 Epilepsy, childhood absence, 607682 (3) CLCN2, EGMA, ECA3, EG13 Epilepsy, childhood absence, evolving to JRK, JH8 juvenile myoclonic epilepsy (3) Epilepsy, generalized idiopathic, 600669 (3) CACNB4, EJM
Epilepsy, generalized, with febrile seizures GABRG2, GEFSP3, CAE2, ECA2 plus, 604233 (3) Epilepsy, generalized, with febrile seizures SCN1A, GEFSP2, SMEI
plus, type 2, 604233 (3) Epilepsy, idopathic generalized, ME2 susceptibility to, 600669 (3) Epilepsy, juvenile absence, 607631 (3) CLCN2, EGMA, ECA3, EG13 Epilepsy, juvenile myoclonic, 606904 (3) CACNB4, EJM
Epilepsy, juvenile myoclonic, 606904 (3) CLCN2, EGMA, ECA3, EG13 Epilepsy, juvenile myoclonic, 606904 (3) GABRA1, EJM
Epilepsy, myoclonic, Lafora type, 254780 EPM2A, MELF, EPM2 (3) Epilepsy, myoclonic, Lafora type, 254780 NHLRC1, EPM2A, EPM2B
(3) Epilepsy, neonatal myoclonic, with SLC25A22, GC1 suppression-burst pattern, 609304 (3) Epilepsy, nocturnal frontal lobe, 1, 600513 CHRNA4, ENFL1 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Epilepsy, nocturnal frontal lobe, 3, 605375 CHRNB2, EFNL3 (3) Epilepsy, partial, with auditory features, LGI1, EPT, ETL1 600512 (3) Epilepsy, progressive myoclonic 1, 254800 CSTB, STFB, EPM1 (3) Epilepsy, progressive myoclonic 2B, 254780 NHLRC1, EPM2A, EPM2B
(3) Epilepsy, severe myoclonic, of infancy, SCN1A, GEFSP2, SMEI
607208 (3) Epilepsy with grand mal seizures on CLCN2, EGMA, ECA3, EG13 awakening, 607628 (3) Epilepsy, X-linked, with variable learning SYN1 disabilities and behavior disorders, 300491 (3) Epiphyseal dysplasia, multiple 1, 132400 (3) COMP, EDM1, MED, PSACH
Epiphyseal dysplasia, multiple, 226900 (3) SLC26A2, DTD, DTDST, D5S1708, Epiphyseal dysplasia, multiple, 3, 600969 COL9A3, EDM3, IDD
(3) Epiphyseal dysplasia, multiple, 5, 607078 MATN3, EDM5, HOA
(3) Epiphyseal dysplasia, multiple, COL9A1- COL9A1, MED
related (3) Epiphyseal dysplasia, multiple, type 2, COL9A2, EDM2 600204 (3) Epiphyseal dysplasia, multiple, with COL9A3, EDM3, IDD
myopathy (3) Episodic ataxia/myokymia syndrome, KCNA1, AEMK, EA1 160120 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Episodic ataxia, type 2, 108500 (3) CACNAIA, CACNL1A4, SCA6 Epithelial ovarian cancer, somatic, 604370 OPCML
(3) Epstein syndrome, 153650 (3) MYH9, MHA, FTNS, DFNA17 Erythermalgia, primary, 133020 (3) SCN9A, NENA, PN1 Erythremias, alpha-(3) HBA1 Erythremias, beta-(3) HBB
Erythrocytosis (3) HBA2 Erythrocytosis, familial, 133100 (3) EPOR
Erythrokeratoderma, progressive symmetric, LOR
602036 (3) Erythrokeratodermia variabilis, 133200 (3) GJB3, CX31, DFNA2 Erythrokeratodermia variabilis with GJB4, CX30.3 erythema gyratum repens, 133200 (3) Esophageal cancer, 133239 (3) TGFBR2, HNPCC6 Esophageal carcinoma, somatic, 133239 (3) RNF6 Esophageal squamous cell carcinoma, LZTS1, F37, FEZ1 133239 (3) Esophageal squamous cell carcinoma, WWOX, FOR
133239 (3) Estrogen resistance (3) ESR1, ESR
Ethylmalonic encephalopathy, 602473 (3) ETHE1, HSCO, D83198 Ewing sarcoma (3) EWSR1, EWS
Exertional myoglobinuria due to deficiency LDHA, LDH1 of LDH-A (3) Exostoses, multiple, type 1, 133700 (3) EXT1 Exostoses, multiple, type 2, 133701 (3) EXT2 Exudative vitreoretinopathy, 133780 (3) FZD4, EVR1 Exudative vitreoretinopathy, dominant, LRP5, BMND1, LRP7, LR3, OPPG, 133780 (3) VBCH2 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Exudative vitreoretinopathy, recessive, LRP5, BMND1, LRP7, LR3, OPPG, 601813 (3) VBCH2 Exudative vitreoretinopathy, X-linked, NDP, ND
305390 (3) Eye anomalies, multiplex (3) PAX6, AN2, MGDA
Ezetimibe, nonresponse to (3) NPC1 L1 Fabry disease (3) GLA
Facioscapulohumeral muscular dystrophy- FSHMD1A, FSHD1A
1A (3) Factor H and factor H-like 1 (3) HF1, CFH, HUS
Factor V and factor VIII, combined MCFD2 deficiency of, 227300 (3) Factor VII deficiency (3) F7 Factor X deficiency (3) F10 Factor XI deficiency, autosomal dominant F11 (3) Factor XI deficiency, autosomal recessive F11 (3) Factor XII deficiency (3) F12, HAF
Factor XIIIA deficiency (3) F13A1, F13A
Factor XIIIB deficiency (3) F13B
Familial Mediterranean fever, 249100 (3) MEFV, MEF, FMF
Fanconi anemia, complementation group A, FANCA, FACA, FA1, FA, FAA
227650 (3) Fanconi anemia, complementation group B, FAAP95, FAAP90, FLJ34064, FANCB
300514 (3) Fanconi anemia, complementation group C FANCC, FACC
(3) Fanconi anemia, complementation group BRCA2, FANCD1 D1,605724(3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Fanconi anemia, complementation group D2 FANCD2, FANCD, FACD, FAD
(3) Fanconi anemia, complementation group E FANCE, FACE
(3) Fanconi anemia, complementation group F FANCF
(3) Fanconi anemia, complementation group G XRCC9, FANCG
(3) Fanconi anemia, complementation group J, BRIP1, BACH1, FANCJ
609054 (3) Fanconi anemia, complementation group L PHF9, FANCL
(3) Fanconi anemia, complementation group M FANCM, KIAA1596 (3) Fanconi-Bickel syndrome, 227810 (3) SLC2A2, GLUT2 Farber lipogranulomatosis (3) ASAH, AC
Fatty liver, acute, of pregnancy (3) HAD HA, MTPA
Favism (3) G6PD, G6PD1 Fechtner syndrome, 153640 (3) MYH9, MHA, FTNS, DFNA17 Feingold syndrome, 164280 (3) MYCN, NMYC, ODED, MODED
Fertile eunuch syndrome, 228300 (3) GNRHR, LHRHR
Fibrocalculous pancreatic diabetes, SPINK1, PSTI, PCTT, TATI
susceptibility to (3) Fibromatosis, gingival, 135300 (3) SOS1, GINGF, GF1, HGF
Fibromatosis, juvenile hyaline, 228600 (3) ANTXR2, CMG2, JHF, ISH
Fibrosis of extraocular muscles, congenital, KIF21A, KIAA1708, FEOM1, CFEOM1 1,135700(3) Fibrosis of extraocular muscles, congenital, PHOX2A, ARIX, CFEOM2 2,602078(3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Fibular hypoplasia and complex GDF5, CDMP1 brachydactyly, 228900 (3) Fish-eye disease, 136120 (3) LCAT
Fish-odor syndrome, 602079 (3) FMO3 Fitzgerald factor deficiency (3) KNG
Fluorouracil toxicity, sensitivity to (3) DPYD, DPD
Focal cortical dysplasia, Taylor balloon cell TSC1, LAM
type, 607341 (3) Follicle-stimulating hormone deficiency, FSHB
isolated, 229070 (3) Forebrain defects (3) TDGF1 Foveal hypoplasia, isolated, 136520 (3) PAX6, AN2, MGDA
Foveomacular dystrophy, adult-onset, with RDS, RP7, PRPH2, PRPH, AVMD, choroidal neovascularization, 608161 (3) AOFMD
Fragile X syndrome (3) FMR1, FRAXA
Fraser syndrome, 219000 (3) FRAS1 Fraser syndrome, 219000 (3) FREM2 Frasier syndrome, 136680 (3) WT1 Friedreich ataxia, 229300 (3) FRDA, FARR
Friedreich ataxia with retained reflexes, FRDA, FARR
229300 (3) Frontometaphyseal dysplasia, 304120 (3) FLNA, FLN1, ABPX, NHBP, OPD1, OPD2, FMD, MNS
Fructose-bisphosphatase deficiency (3) FBP1 Fructose intolerance (3) ALDOB
Fructosuria (3) KHK
Fuchs endothelial corneal dystrophy, COL8A2, FECD, PPCD2 136800 (3) Fucosidosis (3) FUCA1 Fucosyltransferase-6 deficiency (3) FUT6 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Fumarase deficiency, 606812 (3) FH
Fundus albipunctatus, 136880 (3) RDH5 Fundus albipunctatus, 136880 (3) RLBP1 Fundus flavimaculatus, 248200 (3) ABCA4, ABCR, STGD1, FFM, RP19 G6PD deficiency (3) G6PD, G6PD1 GABA-transaminase deficiency (3) ABAT, GABAT
Galactokinase deficiency with cataracts, GALK1 230200 (3) Galactose epimerase deficiency, 230350 (3) GALE
Galactosemia, 230400 (3) GALT
Galactosialidosis (3) PPGB, GSL, NGBE, GLB2, CTSA
GAMT deficiency (3) GAMT
Gardner syndrome (3) APC, GS, FPC
Gastric cancer, 137215 (3) APC, GS, FPC
Gastric cancer, 137215 (3) IRF1, MAR
Gastric cancer, familial diffuse, 137215 (3) CDH1, UVO
Gastric cancer risk after H. pylori infection, 11-1 13 137215 (3) Gastric cancer risk after H. pylori infection, IL1 RN
137215 (3) Gastric cancer, somatic, 137215 (3) CASP10, MCH4, ALPS2 Gastric cancer, somatic, 137215 (3) ERBB2, NGL, NEU, HER2 Gastric cancer, somatic, 137215 (3) FGFR2, BEK, CFD1, JWS
Gastric cancer, somatic, 137215 (3) KLF6, COPEB, BCD1, ZF9 Gastric cancer, somatic, 137215 (3) MUTYH
Gastrointestinal stromal tumor, somatic, KIT, PBT
606764 (3) Gastrointestinal stromal tumor, somatic, PDGFRA
606764 (3) Gaucher disease, 230800 (3) GBA

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Gaucher disease, variant form (3) PSAP, SAP1 Gaucher disease with cardiovascular GBA
calcification, 231005 (3) Gaze palsy, horizontal, with progressive ROBO3, RBIG1, RIG1, HGPPS
scoliosis, 607313 (3) Generalized epilepsy and paroxysmal KCNMA1, SLO
dyskinesia, 609446 (3) Generalized epilepsy with febrile seizures SCN1 B, GEFSP1 plus, 604233 (3) Germ cell tumor (3) BCL10 Germ cell tumors, 273300 (3) KIT, PBT
Gerstmann-Straussler disease, 137440 (3) PRNP, PRIP
Giant axonal neuropathy-1, 256850 (3) GAN, GAN1 Giant-cell fibroblastoma (3) PDGFB, SIS
Giant cell hepatitis, neonatal, 231100 (3) CYP7B1 Giant platelet disorder, isolated (3) GP1 BB
Gilbert syndrome, 143500 (3) UGT1A1, UGT1, GNT1 Gitelman syndrome, 263800 (3) SLC12A3, NCCT, TSC
Glanzmann thrombasthenia, type A, 273800 ITGA2B, GP2B, CD41 B
(3) Glanzmann thrombasthenia, type B (3) ITGB3, GP3A
Glaucoma 1A, primary open angle, juvenile- MYOC, TIGR, GLC1A, JOAG, GPOA
onset, 137750 (3) Glaucoma 1A, primary open angle, MYOC, TIGR, GLC1A, JOAG, GPOA
recessive (3) Glaucoma 1 E, primary open angle, adult- OPTN, GLC1 E, FIP2, HYPL, NRP
onset, 137760 (3) Glaucoma 3A, primary congenital, 231300 CYP1 B1, GLC3A
(3) Glaucoma, early-onset, digenic (3) CYP1B1, GLC3A

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Glaucoma, early-onset, digenic (3) MYOC, TIGR, GLC1A, JOAG, GPOA
Glaucoma, normal tension, susceptibility to, OPA1, NTG, NPG
606657 (3) Glaucoma, normal tension, susceptibility to, OPTN, GLC1 E, FIP2, HYPL, NRP
606657 (3) Glaucoma, primary open angle, adult-onset, CYP1 B1, GLC3A
137760 (3) Glaucoma, primary open angle, juvenile- CYP1 B1, GLC3A
onset, 137750 (3) Glioblastoma, early-onset, 137800 (3) MSH2, COCA1, FCC1, HNPCC1 Glioblastoma multiforme, somatic, 137800 DMBT1 (3) Glioblastoma, somatic, 137800 (3) ERBB2, NGL, NEU, HER2 Glioblastoma, somatic, 137800 (3) LGI1, EPT, ETL1 Glioblastoma, susceptibility to, 137800 (3) PPARG, PPARG1, PPARG2 Glomerulocystic kidney disease, TCF2, HNF2 hypoplastic, 137920 (3) Glomerulosclerosis, focal segmental, 1, ACTN4, FSGS1, FSGS
603278 (3) Glomerulosclerosis, focal segmental, 2, TRPC6, TRP6, FSGS2 603965 (3) Glomerulosclerosis, focal segmental, 3, CD2AP, CMS
607832 (3) Glomuvenous malformations, 138000 (3) GLML, GVM, VMGLOM
Glucocorticoid deficiency 2, 607398 (3) MRAP, FALP, C21 orf61 Glucocorticoid deficiency, due to ACTH MC2R
unresponsiveness, 202200 (3) Glucose/galactose malabsorption, 606824 SLC5A1, SGLT1 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Glucose transport defect, blood-brain SLC2A1, GLUT1 barrier, 606777 (3) Glucosidase I deficiency, 606056 (3) GCS1 Glutamate formiminotransferase deficiency, FTCD
229100 (3) Glutaricaciduria, type I, 231670 (3) GCDH
Glutaricaciduria, type IIA, 231680 (3) ETFA, GA2, MADD
Glutaricaciduria, type IIB, 231680 (3) ETFB, MADD
Glutaricaciduria, type IIC, 231680 (3) ETFDH, MADD
Glutathione synthetase deficiency, 266130 GSS, GSHS
(3) Glycerol kinase deficiency, 307030 (3) GK
Glycine encephalopathy, 605899 (3) AMT, NKH, GCE
Glycine encephalopathy, 605899 (3) GCSH, NKH
Glycine encephalopathy, 605899 (3) GLDC, HYGN1, GCSP, GCE, NKH
Glycine N-methyltransferase deficiency, GNMT
606664 (3) Glycogenosis, hepatic, autosomal (3) PHKG2 Glycogenosis, X-linked hepatic, type I (3) PHKA2, PHK
Glycogenosis, X-linked hepatic, type II (3) PHKA2, PHK
Glycogen storage disease I (3) G6PC, G6PT
Glycogen storage disease Ib, 232220 (3) G6PT1 Glycogen storage disease Ic, 232240 (3) G6PT1 Glycogen storage disease II, 232300 (3) GAA
Glycogen storage disease Ilb, 300257 (3) LAMP2, LAMPB
Glycogen storage disease Illa (3) AGL, GDE
Glycogen storage disease Illb (3) AGL, GDE
Glycogen storage disease IV, 232500 (3) GBE1 Glycogen storage disease, type 0, 240600 GYS2 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Glycogen storage disease VI (3) PYGL
Glycogen storage disease VII (3) PFKM
GM1-gangliosidosis (3) GLB1 GM2-gangliosidosis, AB variant (3) GM2A
GM2-gangliosidosis, several forms, 272800 HEXA, TSD
(3) Gnthodiaphyseal dysplasia, 166260 (3) TMEM16E, GDD1 Goiter, congenital (3) TPO, TPX
Goiter, nonendemic, simple (3) TG, AITD3 Gold berg-Sh pri ntzen megacolon syndrome, KIAA1 279 609460 (3) Gonadal dysgenesis, 46XY, partial, with DHH
minifascicular neuropathy, 607080 (3) Gonadal dysgenesis, XY type (3) SRY, TDF
GRACILE syndrome, 603358 (3) BCS1L, FLNMS, GRACILE
Graft-versus-host disease, protection IL10, CSIF
against (3) Graves disease, susceptibility to, 275000 (3) CTLA4 Graves disease, susceptibility to, 3, 275000 GC, DBP
(3) Greenberg dysplasia, 215140 (3) LBR, PHA
Greig cephalopolysyndactyly syndrome, GLI3, PAPA, PAPB, ACLS
175700 (3) Griscelli syndrome, type 1, 214450 (3) MYO5A, MYH12, GS1 Griscelli syndrome, type 2, 607624 (3) RAB27A, RAM, GS2 Griscelli syndrome, type 3, 609227 (3) MLPH
Growth hormone deficient dwarfism (3) GHRHR
Growth hormone insensitivity with STAT5B
immunodeficiency, 245590 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Growth retardation with deafness and IGF1 mental retardation due to IGF1 deficiency, 608747 (3) Guttmacher syndrome, 176305 (3) HOXA13, HOX1J
Gyrate atrophy of choroid and retina with OAT
ornithinemia, B6 responsive or unresponsive (3) Hailey-Hailey disease, 169600 (3) ATP2C1, BCPM, HHD
Haim-Munk syndrome, 245010 (3) CTSC, CPPI, PALS, PLS, HMS
Hand-foot-uterus syndrome, 140000 (3) HOXA13, HOX1J
Harderoporphyrinuria (3) CPO
HARP syndrome, 607236 (3) PANK2, NBIA1, PKAN, HARP
Hartnup disorder, 234500 (3) SLC6A19, HND
Hay-Wells syndrome, 106260 (3) TP73L, TP63, KET, EEC3, SHFM4, LMS, RHS
HDL deficiency, familial, 604091 (3) ABCA1, ABC1, HDLDT1, TGD
HDL response to hormone replacement, ESR1, ESR
augmented (3) Hearing loss, low-frequency sensorineural, WFS1, WFRS, WFS, DFNA6 600965 (3) Heart block, nonprogressive, 113900 (3) SCN5A, LQT3, IVF, HB1, SSS1 Heart block, progressive, type I, 113900 (3) SCN5A, LQT3, IVF, HB1, SSS1 Heinz body anemia (3) HBA2 Heinz body anemias, alpha-(3) HBA1 Heinz body anemias, beta-(3) HBB
HELLP syndrome, maternal, of pregnancy HAD HA, MTPA
(3) Hemangioblastoma, cerebellar, somatic (3) VHL
Hemangioma, capillary infantile, somatic, FLT4, VEGFR3, PCL
602089 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Hemangioma, capillary infantile, somatic, KDR
602089 (3) Hematopoiesis, cyclic, 162800 (3) ELA2 Hematuria, familial benign (3) COL4A4 Heme oxygenase-1 deficiency (3) HMOX1 Hemiplegic migraine, familial, 141500 (3) CACNAIA, CACNL1A4, SCA6 Hemochromatosis (3) HFE, HLA-H, HFE1 Hemochromatosis, juvenile, 602390 (3) HAMP, LEAP1, HEPC, HFE2 Hemochromatosis, juvenile, digenic, 602390 HAMP, LEAP1, HEPC, HFE2 (3) Hemochromatosis, type 2A, 602390 (3) HJV, HFE2A
Hemochromatosis, type 3, 604250 (3) TFR2, HFE3 Hemochromatosis, type 4, 606069 (3) SLC40A1, SLC11A3, FPN1, IREG1, Hemoglobin H disease (3) HBA2 Hemolytic anemia due to adenylate kinase AK1 deficiency (3) Hemolytic anemia due to band 3 defect SLC4A1, AE1, EPB3 defect (3) Hemolytic anemia due to BPGM
bisphosphoglycerate mutase deficiency (3) Hemolytic anemia due to G6PD deficiency G6PD, G6PD1 (3) Hemolytic anemia due to gamma- GCLC, GLCLC
glutamylcysteine synthetase deficiency, 230450 (3) Hemolytic anemia due to glucosephosphate GPI
isomerase deficiency (3) Hemolytic anemia due to glutathione GSS, GSHS
synthetase deficiency, 231900 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Hemolytic anemia due to hexokinase HK1 deficiency (3) Hemolytic anemia due to PGK deficiency (3) PGK1, PGKA
Hemolytic anemia due to triosephosphate TP11 isomerase deficiency (3) Hemolytic-uremic syndrome, 235400 (3) HF1, CFH, HUS
Hemophagocytic lymphohistiocytosis, PRF1, HPLH2 familial, 2, 603553 (3) Hemophagocytic lymphohistiocytosis, UNC13D, MUNC13-4, HPLH3, HLH3, familial, 3, 608898 (3) FHL3 Hemophilia A (3) F8, F8C, HEMA
Hemophilia B (3) F9, HEMB
Hemorrhagic diathesis due to P1, AAT
\'antithrombinV Pittsburgh (3) Hemorrhagic diathesis due to factor V F5 deficiency (3) Hemosiderosis, systemic, due to CP
aceruloplasminemia, 604290 (3) Hepatic adenoma, 142330 (3) TCF1, HNF1A, MODY3 Hepatic failure, early onset, and neurologic SCOD1, SCO1 disorder (3) Hepatic lipase deficiency (3) LIPC
Hepatoblastoma (3) CTNNB1 Hepatocellular cancer, 114550 (3) PDGFRL, PDGRL, PRLTS
Hepatocellular carcinoma, 114550 (3) AXIN1, AXIN
Hepatocellular carcinoma, 114550 (3) CTNNBI
Hepatocellular carcinoma, 114550 (3) TP53, P53, LFS1 Hepatocellular carcinoma (3) IGF2R, MPRI
Hepatocellular carcinoma, childhood type, MET
114550 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Hepatocellular carcinoma, somatic, 114550 CASP8, MCH5 (3) Hereditary hemorrhagic telangiectasia-1, ENG, END, HHT1, ORW
187300 (3) Hereditary hemorrhagic telangiectasia-2, ACVRL1, ACVRLK1, ALK1, HHT2 600376 (3) Hereditary persistence of alpha-fetoprotein AFP, HPAFP
(3) Hermansky-Pudlak syndrome, 203300 (3) HPS1 Hermansky-Pudlak syndrome, 203300 (3) HPS3 Hermansky-Pudlak syndrome, 203300 (3) HPS4 Hermansky-pudlak syndrome, 203300 (3) HPS5, RU2, KIAA1017 Hermansky-Pudlak syndrome, 203300 (3) HPS6, RU
Hermansky-Pudlak syndrome, 608233 (3) AP3B1, ADTB3A, HPS2 Hermansky-Pudlak syndrome 7, 203300 (3) DTNBP1, HPS7 Heterotaxy, visceral, 605376 (3) CFC1, CRYPTIC, HTX2 Heterotaxy, X-linked visceral, 306955 (3) ZIC3, HTX1, HTX
Heterotopia, periventricular, 300049 (3) FLNA, FLN1, ABPX, NHBP, OPD1, OPD2, FMD, MNS
Heterotopia, periventricular, ED variant, FLNA, FLN1, ABPX, NHBP, OPD1, 300537 (3) OPD2, FMD, MNS
Heterotopia, periventricular nodular, with FLNA, FLN1, ABPX, NHBP, OPD1, frontometaphyseal dysplasia, 300049 (3) OPD2, FMD, MNS
Hex A pseudodeficiency, 272800 (3) HEXA, TSD
High-molecular-weight kininogen deficiency KNG
(3) Hirschsprung disease, 142623 (3) EDN3 Hirschsprung disease, 142623 (3) GDNF
Hirschsprung disease, 142623 (3) NRTN, NTN
Hirschsprung disease, 142623 (3) RET, MEN2A

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Hirschsprung disease-2, 600155 (3) EDNRB, HSCR2, ABCDS
Hirschsprung disease, cardiac defects, and ECE1 autonomic dysfunction (3) Hirschsprung disease, short-segment, PMX2B, NBPHOX, PHOX2B
142623 (3) Histidinemia, 235800 (3) HAL, HSTD
Histiocytoma (3) TP53, P53, LFS1 HIV-1 disease, delayed progression of (3) CCL5, SCYA5, D17S136E, TCP228 HIV-1 disease, rapid progression of (3) CCL5, SCYA5, D17S136E, TCP228 HIV-1, susceptibility to (3) IL10, CSIF
HIV infection, susceptibility/resistance to (3) CMKBR2, CCR2 HIV infection, susceptibility/resistance to (3) CMKBR5, CCCKR5 HMG-CoA lyase deficiency (3) HMGCL
HMG-CoA synthase-2 deficiency, 605911 HMGCS2 (3) Holocarboxylase synthetase deficiency, HLCS, HCS
253270 (3) Holoprosencephaly-2, 157170 (3) SIX3, HPE2 Holoprosencephaly-3, 142945 (3) SHH, HPE3, HLP3, SMMCI
Holoprosencephaly-4, 142946 (3) TGIF, HPE4 Holoprosencephaly-5, 609637 (3) ZIC2, HPE5 Holoprosencephaly-7 (3) PTCH, NBCCS, BCNS, HPE7 Holt-Oram syndrome, 142900 (3) TBX5 Homocysteine, total plasma, elevated (3) CTH
Homocystinuria, B6-responsive and CBS
nonresponsive types (3) Homocystinuria due to MTHFR deficiency, MTHFR
236250 (3) Homocystinuria-megaloblastic anemia, cbl E MTRR
type, 236270 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Homozygous 2p16 deletion syndrome, SLC3A1, ATR1, D2H, NBAT
606407 (3) Hoyeraal-Hreidarsson syndrome, 300240 DKC1, DKC
(3) HPFH, deletion type (3) HBB
HPFH, nondeletion type A (3) HBG1 HPFH, nondeletion type G (3) HBG2 HPRT-related gout, 300323 (3) HPRT1, HPRT
H. pylori infection, susceptibility to, 600263 IFNGR1 (3) Huntington disease (3) HD, IT15 Huntington disease-like 1, 603218 (3) PRNP, PRIP
Huntington disease-like 2, 606438 (3) JPH3, JP3, HDL2 Huntington disease-like-4, 607136 (3) TBP, SCA17 Hyalinosis, infantile systemic, 236490 (3) ANTXR2, CMG2, JHF, ISH
Hydrocephalus due to aqueductal stenosis, L1 CAM, CAML1, HSAS1 307000 (3) Hydrocephalus with congenital idiopathic L1 CAM, CAML1, HSAS1 intestinal pseudoobstruction, 307000 (3) Hydrocephalus with Hirschsprung disease L1 CAM, CAML1, HSAS1 and cleft palate, 142623 (3) Hyperalphalipoproteinemia, 143470 (3) CETP
Hyperammonemia with hypoornithinemia, PYCS, GSAS
hypocitrullinemia, hypoargininemia, and hypoprolinemia (3) Hyperandrogenism, nonclassic type, due to CYP21A2, CYP21, CA21 H
21-hydroxylase deficiency (3) Hyperapobetalipoproteinemia, susceptibility PPARA, PPAR
to (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Hyperbilirubinemia, familial transcient UGT1A1, UGT1, GNT1 neonatal, 237900 (3) Hypercalciuria, absorptive, susceptibility to, SAC, HCA2 143870 (3) Hypercholanemia, familial, 607748 (3) BRAT
Hypercholanemia, familial, 607748 (3) EPHX1 Hypercholanemia, familial, 607748 (3) TJP2, Z02 Hypercholesterolemia, due to ligand- APOB, FLDB
defective apo B, 144010 (3) Hypercholesterolemia, familial, 143890 (3) LDLR, FHC, FH
Hypercholesterolemia, familial, 3, 603776 PCSK9, NARC1, HCHOLA3, FH3 (3) Hypercholesterolemia, familial, autosomal ARH, FHCB2, FHCB1 recessive, 603813 (3) Hypercholesterolemia, familial, due to LDLR EPHX2 defect, modifier of, 143890 (3) Hypercholesterolemia, familial, modification APOA2 of, 143890 (3) Hypercholesterolemia, susceptibility to, GSBS
143890 (3) Hypercholesterolemia, susceptibility to, ITIH4, PK120, ITIHL1 143890 (3) Hyperekplexia and spastic paraparesis (3) GLRA1, STHE
Hyperekplexia, autosomal recessive, GLRB
149400 (3) Hypereosinophilic syndrome, idiopathic, PDGFRA
resistant to imatinib, 607685 (3) Hyperferritinemia-cataract syndrome, FTL
600886 (3) Hyper-IgD syndrome, 260920 (3) MVK, MVLK

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Hyperinsulinism, familial, 602485 (3) GCK
Hyperinsulinism-hyperammonemia GLUD1 syndrome, 606762 (3) Hyperkalemic periodic paralysis, 170500 (3) SCN4A, HYPP, NAC1A
Hyperkeratotic cutaneous capillary-venous CCM1, CAM, KRIT1 malformations associated with cerebral capillary malformations, 116860 (3) Hyperlipidemia, familial combined, USF1, HYPLIP1 susceptibility to, 602491 (3) Hyperlipoproteinemia, type Ib, 207750 (3) APOC2 Hyperlipoproteinemia, type III (3) APOE, AD2 Hyperlysinemia, 238700 (3) AASS
Hypermethioninemia, persistent, autosomal MAT1A, MATA1, SAMS1 dominant, due to methionine adenosyltransferase I/III deficiency (3) Hypermethioninemia with deficiency of S- AHCY, SAHH
adenosylhomocysteine hydrolase (3) Hyperornithinemia-hyperammonemia- SLC25A15, ORNT1, HHH
homocitrullinemia syndrome, 238970 (3) Hyperostosis, endosteal, 144750 (3) LRP5, BMND1, LRP7, LR3, OPPG, Hyperoxaluria, primary, type 1, 259900 (3) AGXT, SPAT
Hyperoxaluria, primary, type II, 260000 (3) GRHPR, GLXR
Hyperparathyroidism, AD, 145000 (3) MEN1 Hyperparathyroidism, familial primary, HRPT2, C1orf28 145000 (3) Hyperparathyroidism-jaw tumor syndrome, HRPT2, C1orf28 145001 (3) Hyperparathyroidism, neonatal, 239200 (3) CASR, HHC1, PCAR1, FIH

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Hyperphenylalaninemia due to pterin-4a- PCBD, DCOH
carbinolamine dehydratase deficiency, 264070 (3) Hyperphenylalaninemia, mild (3) PAH, PKU1 Hyperproinsulinemia, familial (3) INS
Hyperprolinemia, type I, 239500 (3) PRODH, PRODH2, SCZD4 Hyperprolinemia, type II, 239510 (3) ALDH4A1, ALDH4, P5CDH
Hyperproreninemia (3) REN
Hyperprothrombinemia (3) F2 Hypertension, diastolic, resistance to, KCNMB1 608622 (3) Hypertension, early-onset, autosomal NR3C2, MLR, MCR
dominant, with exacerbation in pregnancy, 605115 (3) Hypertension, essential, 145500 (3) AGTR1, AGTR1A, AT2R1 Hypertension, essential, 145500 (3) PTGIS, CYP8A1, PGIS, CYP8 Hypertension, essential, salt-sensitive, ADD1 145500 (3) Hypertension, essential, susceptibility to, AGT, SERPINA8 145500 (3) Hypertension, essential, susceptibility to, ECE1 145500 (3) Hypertension, essential, susceptibility to, GNB3 145500 (3) Hypertension, insulin resistance-related, RETN, RSTN, FIZZ3 susceptibility to, 125853 (3) Hypertension, mild low-renin (3) HSD11132, HSD11 K
Hypertension, pregnancy-induced, 189800 NOS3 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Hypertension, salt-sensitive essential, CYP3A5, P450PCN3 susceptibility to, 145500 (3) Hypertension, susceptibility to, 145500 (3) NOS3 Hyperthroidism, congenital (3) TSHR
Hyperthyroidism, congenital (3) TPO, TPX
Hypertriglyceridemia, one form (3) APOA1 Hypertriglyceridemia, susceptibility to, APOA5 145750 (3) Hypertriglyceridemia, susceptibility to, LIPI, LPDL, PRED5 145750 (3) Hypertriglyceridemia, susceptibility to, RP1, ORP1 145750 (3) Hypertrypsinemia, neonatal (3) CFTR, ABCC7, CF, MRP7 Hyperuricemic nephropathy, familial UMOD, HNFJ, FJHN, MCKD2, juvenile, 162000 (3) ADMCKD2 Hypoaldosteronism, congenital, due to CMO CYP1 1 B2 I deficiency, 203400 (3) Hypoaldosteronism, congenital, due to CMO CYP1 1 B2 II deficiency (3) Hypoalphalipoproteinemia (3) APOA1 Hypobetalipoproteinemia (3) APOB, FLDB
Hypocalcemia, autosomal dominant, CASR, HHC1, PCAR1, FIH
146200 (3) Hypocalcemia, autosomal dominant, with CASR, HHC1, PCAR1, FIH
Bartter syndrome (3) Hypocalciuric hypercalcemia, type I, 145980 CASR, HHC1, PCAR1, FIH
(3) Hypoceruloplasminemia, hereditary, 604290 CP
(3) Hypochondroplasia, 146000 (3) FGFR3, ACH

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Hypochromic microcytic anemia (3) HBA2 Hypodontia, 106600 (3) PAX9 Hypodontia, autosomal dominant, 106600 MSX1, HOX7, HYD1, OFC5 (3) Hypodontia with orofacial cleft, 106600 (3) MSX1, HOX7, HYD1, OFC5 Hypofibrinogenemia, gamma type (3) FGG
Hypoglobulinemia and absent B cells (3) BLNK, SLP65 Hypoglycemia of infancy, leucine-sensitive, ABCC8, SUR, PHHI, SUR1 240800 (3) Hypoglycemia of infancy, persistent ABCC8, SUR, PHHI, SUR1 hyperinsulinemic, 256450 (3) Hypogonadism, hypergonadotropic (3) LHB
Hypogonadotropic hypogonadism, 146110 GPR54 (3) Hypogonadotropic hypogonadism, 146110 NELF
(3) Hypogonadotropic hypogonadism (3) GNRHR, LHRHR
Hypogonadotropic hypogonadism (3) LHCGR
Hypohaptoglobinemia (3) HP
Hypokalemic periodic paralysis, 170400 (3) CACNA1S, CACNL1A3, CCHL1A3 Hypokalemic periodic paralysis, 170400 (3) KCNE3, HOKPP
Hypokalemic periodic paralysis, 170400 (3) SCN4A, HYPP, NAC1A
Hypolactasia, adult type, 223100 (3) LCT, LAC, LPH
Hypolactasia, adult type, 223100 (3) MCM6 Hypomagnesemia-2, renal, 154020 (3) FXYD2, ATP1G1, HOMG2 Hypomagnesemia, primary, 248250 (3) CLDN16, PCLN1 Hypomagnesemia with secondary TRPM6, CHAK2 hypocalcemia, 602014 (3) Hypoparathyroidism, autosomal dominant(3) PTH

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Hypoparathyroidism, autosomal recessive PTH
(3) Hypoparathyroidism, familial isolated, GCMB
146200 (3) Hypoparathyroidism-retardation- TBCE, KCS, KCS1, HRD
dysmorphism syndrome, 241410 (3) Hypoparathyroidism, sensorineural GATA3, HDR
deafness, and renal dysplasia, 146255 (3) Hypophosphatasia, childhood, 241510 (3) ALPL, HOPS, TNSALP
Hypophosphatasia, infantile, 241500 (3) ALPL, HOPS, TNSALP
Hypophosphatemia, type III (3) CLCN5, CLCK2, NPHL2, DENTS
Hypophosphatemia, X-linked, 307800 (3) PHEX, HYP, HPDR1 Hypophosphatemic rickets, autosomal FGF23, ADHR, HPDR2, PHPTC
dominant, 193100 (3) Hypoplastic enamel pitting, localized, ENAM
608563 (3) Hypoplastic left heart syndrome, 241550 (3) GJA1, CX43, ODDD, SDTY3, ODOD
Hypoprothrombinemia (3) F2 Hypothyroidism, autoimmune, 140300 (3) CTLA4 Hypothyroidism, congenital, 274400 (3) SLC5A5, NIS
Hypothyroidism, congenital, due to DUOX2 DUOX2, THOX2 deficiency, 607200 (3) Hypothyroidism, congenital, due to thyroid PAX8 dysgenesis or hypoplasia, 218700 (3) Hypothyroidism, congenital, due to TSH TSHR
resistance, 275200 (3) Hypothyroidism, hereditary congenital (3) TG, AITD3 Hypothyroidism, nongoitrous (3) TSHB
Hypothyroidism, subclinical (3) TSHR

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Hypotrichosis, congential, with juvenile CDH3, CDHP, PCAD, HJMD
macular dystrophy, 601553 (3) Hypotrichosis, localized, autosomal DSG4, LAH
recessive, 607903 (3) Hypotrichosis-lymphedema-telangiectasia SOX18, HLTS
syndrome, 607823 (3) Hypotrichosis simplex of scalp, 146520 (3) CDSN, HTSS
Hypouricemia, renal, 220150 (3) SLC22A12, OAT4L, URAT1 Hystrix-like ichthyosis with deafness, GJB2, CX26, DFNB1, PPK, DFNA3, 602540 (3) KID, HID
Ichthyosiform erythroderma, congenital, TGM1, ICR2, L11 242100 (3) Ichthyosiform erythroderma, congenital, ALOX12B
nonbullous, 1, 242100 (3) Ichthyosiform erythroderma, congenital, ALOXE3 nonbullous, 1, 242100 (3) Ichthyosis bullosa of Siemens, 146800 (3) KRT2A, KRT2E
Ichthyosis, congenital, autosomal recessive ICHYN
(3) Ichthyosis, cyclic, with epidermolytic KRT10 hyperkeratosis, 607602 (3) Ichthyosis, harlequin, 242500 (3) ABCA12, ICR2B, L12 Ichthyosis histrix, Curth-Macklin type, KRT1 146590 (3) Ichthyosis, lamellar 2, 601277 (3) ABCA12, ICR2B, L12 Ichthyosis, lamellar, autosomal recessive, TGM1, ICR2, L11 242300 (3) Ichthyosis, X-linked (3) STS, ARSC1, ARSC, SSDD
ICOS deficiency, 607594 (3) ICOS, AILIM
IgE levels QTL, 147050 (3) PHF1 1, NYREN34 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) IgG2 deficiency, selective (3) IGHG2 IgG receptor I, phagocytic, familial FCGR1A, IGFR1, CD64 deficiency of (3) Immunodeficiency-centromeric instability- DNMT3B, ICF
facial anomalies syndrome, 242860 (3) Immunodeficiency due to defect in CD3- CD3E
epsilon (3) Immunodeficiency due to defect in CD3- CD3G
gamma (3) Immunodeficiency with hyper-IgM, type 2, AICDA, AID, HIGM2 605258 (3) Immunodeficiency with hyper-IgM, type 3, TNFRSF5, CD40 606843 (3) Immunodeficiency with hyper IgM, type 4, UNG, DGU, HIGM4 608106 (3) Immunodeficiency, X-linked, with hyper-IgM, TNFSF5, CD40LG, HIGM1, IGM
308230 (3) Immunodysregulation, polyendocrinopathy, FOXP3, IPEX, AIID, XPID, PIDX
and enteropathy, X-linked, 304790 (3) Immunoglobulin A deficiency, 609529 (3) TNFRSF14B, TACI
Inclusion body myopathy-3, 605637 (3) MYH2 Inclusion body myopathy, autosomal GNE, GLCNE, IBM2, DMRV, NM
recessive, 600737 (3) Inclusion body myopathy with early-onset VCP, IBMPFD
Paget disease and frontotemporal dementia, 167320 (3) Incontinentia pigmenti, type II, 308300 (3) IKBKG, NEMO, FIP3, IP2 Infantile spasm syndrome, 308350 (3) ARX, ISSX, PRTS, MRXS1, MRX36, TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Infundibular hypoplasia and hypopituitarism SOX3, MRGH
(3) Inosine triphosphatase deficiency (3) ITPA
Insensitivity to pain, congenital, with NTRK1, TRKA, MTC
anhidrosis, 256800 (3) Insomnia (3) () GABRB3 Insomnia, fatal familial, 600072 (3) PRNP, PRIP
Insulin resistance, severe, digenic, 604367 PPARG, PPARG1, PPARG2 (3) Insulin resistance, severe, digenic, 604367 PPP1R3A, PPP1R3 (3) Insulin resistance, susceptibility to (3) PTPN1, PTP1B
Interleukin-2 receptor, alpha chain, IL2RA, IL2R
deficiency of (3) Intervertebral disc disease, susceptibility to, COL9A2, EDM2 603932 (3) Intervertebral disc disease, susceptibility to, COL9A3, EDM3, IDD
603932 (3) Intrauterine and postnatal growth retardation IGF1 R
(3) Intrauterine and postnatal growth retardation IGF2 (3) Intrinsic factor deficiency, 261000 (3) GIF, IF
IRAK4 deficiency, 607676 (3) IRAK4, REN64 Iridogoniodysgenesis, 601631 (3) FOXC1, FKHL7, FREAC3 Iridogoniodysgenesis syndrome-2, 137600 PITX2, IDG2, RIEG1, RGS, IGDS2 (3) Iris hypoplasia and glaucoma (3) FOXC1, FKHL7, FREAC3 Iron deficiency anemia, susceptibility to (3) TF
Iron overload, autosomal dominant (3) FTH1, FTHL6 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Isolated growth hormone deficiency, Illig GH1, GHN
type with absent GH and Kowarski type with bioinactive GH (3) Isovaleric acidemia, 243500 (3) IVD
Jackson-Weiss syndrome, 123150 (3) FGFR1, FLT2, KAL2 Jackson-Weiss syndrome, 123150 (3) FGFR2, BEK, CFD1, JWS
Jensen syndrome, 311150 (3) TIMM8A, DFN1, DDP, MTS, DDP1 Jervell and Lange-Nielsen syndrome, KCNE1, JLNS, LQT5 220400 (3) Jervell and Lange-Nielsen syndrome, KCNQ1, KCNA9, LQT1, KVLQT1, 220400 (3) ATFB1 Joubert syndrome, 213300 (3) NPHP1, NPH1, SLSN1 Joubert syndrome-3, 608629 (3) AH11 Juberg-Marsidi syndrome, 309590 (3) ATRX, XH2, XNP, MRXS3, SHS
Juvenile polyposis/hereditary hemorrhagic MADH4, DPC4, SMAD4, JIP
telangiectasia syndrome, 175050 (3) Kallikrein, decreased urinary activity of (3) KLK1, KLKR
Kallmann syndrome 2, 147950 (3) FGFR1, FLT2, KAL2 Kallmann syndrome (3) KAL1, KMS, ADMLX
Kanzaki disease, 609242 (3) NAGA
Kaposi sarcoma, susceptibility to, 148000 IL6, IFNB2, BSF2 (3) Kappa light chain deficiency (3) IGKC
Kartagener syndrome, 244400 (3) DNAH11, DNAHC11 Kartagener syndrome, 244400 (3) DNAH5, HL1, PCD, CILD3 Kartagener syndrome, 244400 (3) DNA11, CILD1, ICS, PCD
Kenny-Caffey syndrome-1, 244460 (3) TBCE, KCS, KCS1, HRD
Keratitis, 148190 (3) PAX6, AN2, MGDA
Keratitis-ichthyosis-deafness syndrome, GJB2, CX26, DFNB1, PPK, DFNA3, 148210(3) KID, HID

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Keratoconus, 148300 (3) VSX1, RINX, PPCD, PPD, KTCN
Keratoderma, palmoplantar, with deafness, GJB2, CX26, DFNB1, PPK, DFNA3, 148350 (3) KID, HID
Keratosis follicularis spinulosa decalvans, SAT, SSAT, KFSD
308800 (3) Keratosis palmoplantaria striata, 148700 (3) KRT1 Keratosis palmoplantaris striata I, 148700 DSG1 (3) Keratosis palmoplantaris striata II (3) DSP, KPPS2, PPKS2 Keratosis palmoplantaris striata III, 607654 KRT1 (3) Ketoacidosis due to SCOT deficiency (3) SCOT, OXCT
Keutel syndrome, 245150 (3) MGP, NTI
Kindler syndrome, 173650 (3) KIND1, URP1, C20orf42 Kininogen deficiency (3) KNG
Klippel-Trenaunay syndrome, 149000 (3) VG5Q, HUS84971, FLJ10283 Kniest dysplasia, 156550 (3) COL2A1 Knobloch syndrome, 267750 (3) COL18A1, KNO
Krabbe disease, 245200 (3) GALC
L-2-hydroxyglutaric aciduria, 236792 (3) L2HGDH, C14orf160 Lactate dehydrogenase-B deficiency (3) LDHB
Lacticacidemia due to PDX1 deficiency, PDX1 245349 (3) Langer mesomelic dysplasia, 249700 (3) SHOX, GCFX, SS, PHOG
Langer mesomelic dysplasia, 249700 (3) SHOXY
Laron dwarfism, 262500 (3) GHR
Larson syndrome, 150250 (3) FLNB, SCT, AOI
Laryngoonychocutaneous syndrome, LAMA3, LOCS
245660 (3) Lathosterolosis, 607330 (3) SC5DL, ERG3 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) LCHAD deficiency (3) HADHA, MTPA
Lead poisoning, susceptibility to (3) ALAD
Leanness, inherited (3) AGRP, ART, AGRT
Leber congenital amaurosis, 204000 (3) CRB1, RP12 Leber congenital amaurosis, 204000 (3) CRX, CORD2, CRD
Leber congenital amaurosis, 204000 (3) RPGRIP1, LCA6, CORD9 Leber congenital amaurosis-2, 204100 (3) RPE65, RP20 Leber congenital amaurosis, 604393 (3) AIPL1, LCA4 Leber congenital amaurosis, type I, 204000 GUCY2D, GUC2D, LCA1, CORD6 (3) Leber congenital amaurosis, type III, RDH12, LCA3 604232 (3) Left-right axis malformations (3) ACVR2B
Left-right axis malformations (3) EBAF, TGFB4, LEFTY2, LEFTA, LEFTYA
Left ventricular noncompaction, familial DTNA, D18S892E, DRP3, LVNC1 isolated, 1, 604169 (3) Left ventricular noncompaction with DTNA, D18S892E, DRP3, LVNC1 congenital heart defects, 606617 (3) Legionaire disease, susceptibility to, 608556 TLR5, TIL3 (3) Leigh syndrome, 256000 (3) BCS1L, FLNMS, GRACILE
Leigh syndrome, 256000 (3) DLD, LAD, PHE3 Leigh syndrome, 256000 (3) NDUFS3 Leigh syndrome, 256000 (3) NDUFS4, AQDQ
Leigh syndrome, 256000 (3) NDUFS7, PSST
Leigh syndrome, 256000 (3) NDUFS8 Leigh syndrome, 256000 (3) NDUFV1, UQOR1 Leigh syndrome, 256000 (3) SDHA, SDH2, SDHF

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Leigh syndrome, due to COX deficiency, SURF1 256000 (3) Leigh syndrome due to cytochrome c COX15 oxidase deficiency, 256000 (3) Leigh syndrome, French-Canadian type, LRPPRC, LRP130, LSFC
220111 (3) Leigh syndrome, X-linked, 308930 (3) PDHA1, PHE1A
Leiomyomatosis and renal cell cancer, FH
605839 (3) Leiomyomatosis, diffuse, with Alport COL4A6 syndrome, 308940 (3) Leopard syndrome, 151100 (3) PTPN11, PTP2C, SHP2, NS1 Leprechaunism, 246200 (3) INSR
Leprosy, susceptibility to, 607572 (3) PRKN, PARK2, PDJ
Leri-Weill dyschondrosteosis, 127300 (3) SHOX, GCFX, SS, PHOG
Leri-Weill dyschondrosteosis, 127300 (3) SHOXY
Lesch-Nyhan syndrome, 300322, (3) HPRT1, HPRT
Leukemia-1, T-cell acute lymphocytic (3) TALI, TCL5, SCL
Leukemia-2, T-cell acute lymphoblastic (3) TAL2 Leukemia, acute lymphoblastic (3) FLT3 Leukemia, acute lymphoblastic (3) NBS1, NBS
Leukemia, acute lymphoblastic (3) ZNFN1A1, IK1, LYF1 Leukemia, acute lymphoblastic, HOXD4, HOX4B
susceptibility to (3) Leukemia, acute lymphocytic (3) BCR, CIVIL, PHL, ALL
Leukemia, acute myeloblastic (3) ARNT
Leukemia, acute myelogenous (3) KRAS2, RASK2 Leukemia, acute myelogenous, 601626 (3) GMPS
Leukemia, acute myeloid, 601626 (3) AF10 Leukemia, acute myeloid, 601626 (3) ARHGEF12, LARG, KIAA0382 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Leukemia, acute myeloid, 601626 (3) CALM, CLTH
Leukemia, acute myeloid, 601626 (3) CEBPA, CEBP
Leukemia, acute myeloid, 601626 (3) CHIC2, BTL
Leukemia, acute myeloid, 601626 (3) FLT3 Leukemia, acute myeloid, 601626 (3) KIT, PBT
Leukemia, acute myeloid, 601626 (3) LPP
Leukemia, acute myeloid, 601626 (3) NPM1 Leukemia, acute myeloid, 601626 (3) NUP214, D9S46E, CAN, CAIN
Leukemia, acute myeloid, 601626 (3) RUNX1, CBFA2, AML1 Leukemia, acute myeloid, 601626 (3) WHSC1L1, NSD3 Leukemia, acute myeloid, reduced survival FLT3 in (3) Leukemia, acute myelomonocytic (3) AF1Q
Leukemia, acute promyelocytic, NPM/RARA NPM1 type (3) Leukemia, acute promyelocytic, NUMA1 NUMA/RARA type (3) Leukemia, acute promyelocytic, ZNF145, PLZF
PL2F/RARA type (3) Leukemia, acute promyelocytic, PML/RARA PML, MYL
type (3) Leukemia, acute promyeloyctic, STAT5B
STAT5B/RARA type (3) Leukemia, acute T-cell lymphoblastic (3) AF10 Leukemia, acute T-cell lymphoblastic (3) CALM, CLTH
Leukemia, chronic lymphatic, susceptibility ARL1 1, ARLTS1 to, 151400 (3) Leukemia, chronic lymphatic, susceptibility P2RX7, P2X7 to, 151400 (3) Leukemia, chronic myeloid, 608232 (3) BCR, CIVIL, PHL, ALL

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Leukemia, juvenile myelomonocytic, 607785 GRAF
(3) Leukemia, juvenile myelomonocytic, 607785 NF1, VRNF, WSS, NFNS
(3) Leukemia, juvenile myelomonocytic, 607785 PTPN1 1, PTP2C, SHP2, NS1 (3) Leukemia/lymphoma, B-cell, 2 (3) BCL2 Leukemia/lymphoma, chronic B-cell, 151400 CCND1, PRAD1, BCL1 (3) Leukemia/lymphoma, T-cell (3) TCRA
Leukemia, megakaryoblastic, of Down GATA1, GF1, ERYF1, NFE1 syndrome, 190685 (3) Leukemia, megakaryoblastic, with or without GATA1, GF1, ERYF1, NFE1 Down syndrome, 190685 (3) Leukemia, Philadelphia chromosome- ABL1 positive, resistant to imatinib (3) Leukemia, post-chemotherapy, susceptibility NQO1, DIA4, NMOR1 to (3) Leukemia, T-cell acute lymphoblastic (3) NUP214, D9S46E, CAN, CAIN
Leukocyte adhesion deficiency, 116920 (3) ITGB2, CD18, LCAMB, LAD
Leukoencephalopathy with vanishing white EIF2B1, EIF2BA
matter, 603896 (3) Leukoencephalopathy with vanishing white EIF2B2 matter, 603896 (3) Leukoencephalopathy with vanishing white EIF2B3 matter, 603896 (3) Leukoencephalopathy with vanishing white EIF2B5, LVWM, CACH, CLE
matter, 603896 (3) Leukoencephaly with vanishing white EIF2B4 matter, 603896 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Leydig cell adenoma, with precocious LHCGR
puberty (3) Lhermitte-Duclos syndrome (3) PTEN, MMAC1 Liddle syndrome, 177200 (3) SCNN1 B
Liddle syndrome, 177200 (3) SCNNIG, PHA1 Li Fraumeni syndrome, 151623 (3) CDKN2A, MTS1, P16, MLM, CMM2 Li-Fraumeni syndrome, 151623 (3) TP53, P53, LFS1 Li-Fraumeni syndrome, 609265 (3) CHEK2, RAD53, CHK2, CDS1, LFS2 LIG4 syndrome, 606593 (3) LIG4 Limb-mammary syndrome, 603543 (3) TP73L, TP63, KET, EEC3, SHFM4, LMS, RHS
Lipodystrophy, congenital generalized, type AGPAT2, LPAAB, BSCL, BSCL1 1,608594(3) Lipodystrophy, congenital generalized, type BSCL2, SPG17 2,269700(3) Lipodystrophy, familial partial, 151660 (3) LMNA, LMN1, EMD2, FPLD, CMD1A, HGPS, LGMD1 B
Lipodystrophy, familial partial, 151660 (3) PPARG, PPARG1, PPARG2 Lipodystrophy, familial partial, with PPARGC1A, PPARGC1 decreased subcutaneous fat of face and neck (3) Lipoid adrenal hyperplasia, 201710 (3) STAR
Lipoid congenital adrenal hyperplasia, CYP1 1A, P450SCC
201710 (3) Lipoid proteinosis, 247100 (3) ECM1 Lipoma (3) HMGA2, HMGIC, BABL, LIPO
Lipoma (3) LPP
Lipoma, sporadic (3) MEN1 Lipomatosis, mutiple, 151900 (3) HMGA2, HMGIC, BABL, LIPO
Lipoprotein lipase deficiency (3) LPL, LIPD

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Lissencephaly-1, 607432 (3) PAFAH1B1, LIS1 Lissencephaly syndrome, Norman-Roberts RELN, RL
type, 257320 (3) Lissencephaly, X-linked, 300067 (3) DCX, DBCN, LISX
Lissencephaly, X-linked with ambiguous ARX, ISSX, PRTS, MRXS1, MRX36, genitalia, 300215 (3) MRX54 Listeria monocytogenes, susceptibility to (3) CDH1, UVO
Loeys-Dietz syndrome, 609192 (3) TGFBR1 Loeys-Dietz syndrome, 609192 (3) TGFBR2, HNPCC6 Longevity, exceptional, 152430 (3) CETP
Longevity, reduced, 152430 (3) AKAP10 Long QT syndrome-1, 192500 (3) KCNQ1, KCNA9, LQT1, KVLQTI, Long QT syndrome-2 (3) KCNH2, LQT2, HERG
Long QT syndrome-3, 603830 (3) SCN5A, LQT3, IVF, HB1, SSS1 Long QT syndrome 4, 600919 (3) ANK2, LQT4 Long QT syndrome-5 (3) KCNE1, JLNS, LQT5 Long QT syndrome-6 (3) KCNE2, MIRP1, LQT6 Long QT syndrome-7, 170390 (3) KCNJ2, HHIRK1, KIR2.1, IRK1, LQT7 Lower motor neuron disease, progressive, DCTN1 without sensory symptoms, 607641 (3) Lowe syndrome, 309000 (3) OCRL, LOCR, OCRL1, NPHL2 Low renin hypertension, susceptibility to (3) CYP1 1 B2 LPA deficiency, congenital (3) LPA
Lumbar disc disease, susceptibility to, CILP
603932 (3) Lung cancer, 211980 (3) KRAS2, RASK2 Lung cancer, 211980 (3) PPP2R1B
Lung cancer, 211980 (3) SLC22A1L, BWSCR1A, IMPT1 Lung cancer, somatic, 211980 (3) MAP3K8, COT, EST, TPL2 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Lupus nephritis, susceptibility to (3) FCGR2A, IGFR2, CD32 Lymphangioleiomyomatosis, 606690 (3) TSC1, LAM
Lymphangioleiomyomatosis, somatic, TSC2, LAM
606690 (3) Lymphedema and ptosis, 153000 (3) FOXC2, FKHL14, MFH1 Lymphedema-distichiasis syndrome, FOXC2, FKHL14, MFH1 153400 (3) Lymphedema-distichiasis syndrome with FOXC2, FKHL14, MFH1 renal disease and diabetes mellitus (3) Lymphedema, hereditary I, 153100 (3) FLT4, VEGFR3, PCL
Lymphedema, hereditary II, 153200 (3) FOXC2, FKHL14, MFH1 Lymphocytic leukemia, acute T-cell (3) RAP1 GDS1 Lymphoma, B-cell non-Hodgkin, somatic (3) ATM, ATA, AT1 Lymphoma, diffuse large cell (3) BCL8 Lymphoma, follicular (3) BCL10 Lymphoma, MALT (3) BCL10 Lymphoma, mantle cell (3) ATM, ATA, AT1 Lymphoma, non-Hodgkin (3) RAD54B
Lymphoma, non-Hodgkin (3) RAD54L, HR54, HRAD54 Lymphoma, progression of (3) FCGR2B, CD32 Lymphoma, somatic (3) MAD1L1, TXBP181 Lymphoma, T-cell (3) MSH2, COCA1, FCC1, HNPCC1 Lymphoproliferative syndrome, X-linked, SH2D1A, LYP, IMD5, XLP, XLPD
308240 (3) Lynch cancer family syndrome II, 114400 MSH2, COCA1, FCC1, HNPCC1 (3) Lysinuric protein intolerance, 222700 (3) SLC7A7, LPI
Machado-Joseph disease, 109150 (3) ATXN3, MJD, SCA3 Macrocytic anemia, refractory, of 5q- IRF1, MAR
syndrome, 153550 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Macrothrombocytopenia, 300367 (3) GATA1, GF1, ERYF1, NFE1 Macular corneal dystrophy, 217800 (3) CHST6, MCDC1 Macular degeneration, age-related, 1, HF1, CFH, HUS
603075 (3) Macular degeneration, age-related, 1, HMCN1, FBLN6, FIBL6 603075 (3) Macular degeneration, age-related, 3, FBLN5, ARMD3 608895 (3) Macular degeneration, juvenile, 248200 (3) CNGB3, ACHM3 Macular degeneration, X-linked atrophic (3) RPGR, RP3, CRD, RP15, COD1 Macular dystrophy (3) RDS, RP7, PRPH2, PRPH, AVMD, AOFMD
Macular dystrophy, age-related, 2, 153800 ABCA4, ABCR, STGD1, FFM, RP19 (3) Macular dystrophy, autosomal dominant, ELOVL4, ADMD, STGD2, STGD3 chromosome 6-linked, 600110 (3) Macular dystrophy, vitelliform, 608161 (3) RDS, RP7, PRPH2, PRPH, AVMD, AOFMD
Macular dystrophy, vitelliform type, 153700 VMD2 (3) Maculopathy, bull's-eye, 153870 (3) VMD2 Major depressive disorder and accelerated FKBP5, FKBP51 response to antidepressant drug treatment, 608616 (3) Malaria, cerebral, reduced risk of, 248310 CD36 (3) Malaria, cerebral, susceptibility to, 248310 CD36 (3) Malaria, cerebral, susceptibility to (3) ICAM1 Malaria, cerebral, susceptibility to (3) TNF, TNFA

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Malaria, resistance to, 248310 (3) GYPC, GE, GPC
Malaria, resistance to, 248310 (3) NOS2A, NOS2 Malignant hyperthermia susceptibility 1, RYR1, MHS, CCO
145600 (3) Malignant hyperthermia susceptibility 5, CACNA1S, CACNL1A3, CCHL1A3 601887 (3) Malonyl-CoA decarboxylase deficiency, MLYCD, MCD
248360 (3) MALT lymphoma (3) MALT1, MLT
Mandibuloacral dysplasia with type B ZMPSTE24, FACE1, STE24, MADB
lipodystrophy, 608612 (3) Mannosidosis, alpha-, types I and II, 248500 MAN2B1, MANB
(3) Mannosidosis, beta, 248510 (3) MANBA, MANB1 Maple syrup urine disease, type la, 248600 BCKDHA, MSUD1 (3) Maple syrup urine disease, type lb (3) BCKDHB, E113 Maple syrup urine disease, type II (3) DBT, BCATE2 Maple syrup urine disease, type III, 248600 DLD, LAD, PHE3 (3) Marfan syndrome, 154700 (3) FBN1, MFS1, WMS
Marfan syndrome, atypical (3) COL1A2 Maroteaux-Lamy syndrome, several forms ARSB, MPS6 (3) Marshall syndrome, 154780 (3) COL11A1, STL2 MASA syndrome, 303350 (3) L1CAM, CAML1, HSAS1 MASP2 deficiency (3) MASP2 MASS syndrome, 604308 (3) FBN1, MFS1, WMS
Mast cell leukemia (3) KIT, PBT

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Mastocytosis with associated hematologic KIT, PBT
disorder (3) Mast syndrome, 248900 (3) ACP33, MAST, SPG21 May-Hegglin anomaly, 155100 (3) MYH9, MHA, FTNS, DFNA17 McArdle disease, 232600 (3) PYGM
McCune-Albright syndrome, 174800 (3) GNAS, GNAS1, GPSA, POH, PHP1B, PHP1A, AHO
McKusick-Kaufman syndrome, 236700 (3) MKKS, HMCS, KMS, MKS, BBS6 McLeod syndrome (3) XK
McLeod syndrome with neuroacanthosis (3) XK
Medullary cystic kidney disease 2, 603860 UMOD, HNFJ, FJHN, MCKD2, (3) ADMCKD2 Medullary thyroid carcinoma, 155240 (3) RET, MEN2A
Medullary thyroid carcinoma, familial, NTRK1, TRKA, MTC
155240 (3) Medulloblastoma, 155255 (3) PTCH2 Medulloblastoma, desmoplastic, 155255 (3) SUFU, SUFUXL, SUFUH
Meesmann corneal dystrophy, 122100 (3) KRT12 Meesmann corneal dystrophy, 122100 (3) KRT3 Megakaryoblastic leukemia, acute (3) MKL1, AMKL, MAL
Megalencephalic leukoencephalopathy with MLC1, LVM, VL
subcortical cysts, 604004 (3) Megaloblastic anemia-1, Finnish type, CUBN, IFCR, MGA1 261100 (3) Megaloblastic anemia-1, Norwegian type, AMN
261100 (3) Melanoma (3) CDK4, CMM3 Melanoma and neural system tumor CDKN2A, MTS1, P16, MLM, CMM2 syndrome, 155755 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Melanoma, cutaneous malignant, 2, 155601 CDKN2A, MTS1, P16, MLM, CMM2 (3) Melanoma, cutaneous malignant, XRCC3 susceptibility to (3) Melanoma, malignant sporadic (3) STK1 1, PJS, LKB1 Melanoma, melignant, somatic (3) BRAF
Meleda disease, 248300 (3) SLURP1, MDM
Melnick-Needles syndrome, 309350 (3) FLNA, FLN1, ABPX, NHBP, OPD1, OPD2, FMD, MNS
Melorheostosis with osteopoikilosis, 155950 LEMD3, MAN1 (3) Memory impairment, susceptibility to (3) BDNF
Meniere disease 156000 (3) () COCH, DFNA9 Meningioma, 607174 (3) MN1, MGCR
Meningioma, 607174 (3) PTEN, MMAC1 Meningioma, NF2-related, somatic, 607174 NF2 (3) Meningioma, SIS-related (3) PDGFB, SIS
Meningococcal disease, susceptibility to (3) MBL2, MBL, MBP1 Menkes disease, 309400 (3) ATP7A, MNK, MK, OHS
Mental retardation, nonsyndromic, PRSS12, BSSP3 autosomal recessive, 249500 (3) Mental retardation, nonsyndromic, CRBN, MRT2A
autosomal recessive, 2A, 607417 (3) Mental retardation, X-linked, 300425 (3) NLGN4, KIAA1260, AUTSX2 Mental retardation, X-linked, 300458 (3) MECP2, RTT, PPMX, MRX16, MRX79 Mental retardation, X-linked 30, 300558 (3) PAK3, MRX30, MRX47 Mental retardation, X-linked, 34, 300426 (3) IL1RAPL, MRX34 Mental retardation, X-linked 36, 300430 (3) ARX, ISSX, PRTS, MRXS1, MRX36, TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Mental retardation, X-linked (3) SLC6A8, CRTR
Mental retardation, X-linked-44, 300501 (3) FTSJ1, JM23, SPB1, MRX44, MRX9 Mental retardation, X-linked 45, 300498 (3) ZNF81, MRX45 Mental retardation, X-linked 54, 300419 (3) ARX, ISSX, PRTS, MRXS1, MRX36, Mental retardation, X-linked 58, 300218 (3) TM4SF2, MXS1, A15 Mental retardation, X-linked, 60, 300486 (3) OPHN1 Mental retardation, X-linked-9, 309549 (3) FTSJ1, JM23, SPB1, MRX44, MRX9 Mental retardation, X-linked, FRAXE type FMR2, FRAXE, MRX2 (3) Mental retardation, X-linked, JARID1C- SMCX, MRXJ, DXS1272E, XE169, related, 300534 (3) JARID1C
Mental retardation, X-linked nonspecific, GDI1, RABGD1A, MRX41, MRX48 309541 (3) Mental retardation, X-linked nonspecific, 63, FACL4, ACS4, MRX63 300387 (3) Mental retardation, X-linked nonspecific, RPS6KA3, RSK2, MRX19 type 19 (3) Mental retardation, X-linked nonspecific, ARHGEF6, MRX46, COOL2 type 46, 300436 (3) Mental retardation, X-linked nonsyndromic AGTR2 (3) Mental retardation, X-linked nonsyndromic FGD1, FGDY, AAS
(3) Mental retardation, X-linked nonsyndromic ZNF41 (3) Meesmann corneal dystrophy, 122100 (3) KRT12 Meesmann corneal dystrophy, 122100 (3) KRT3 Megakaryoblastic leukemia, acute (3) MKL1, AMKL, MAL

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Megalencephalic leukoencephalopathy with MLC1, LVM, VL
subcortical cysts, 604004 (3) Megaloblastic anemia-1, Finnish type, CUBN, IFCR, MGA1 261100(3) Megaloblastic anemia-1, Norwegian type, AMN
261100(3) Melanoma (3) CDK4, CMM3 Melanoma and neural system tumor CDKN2A, MTS1, P16, MLM, CMM2 syndrome, 155755 (3) Melanoma, cutaneous malignant, 2, 155601 CDKN2A, MTS1, P16, MLM, CMM2 (3) Melanoma, cutaneous malignant, XRCC3 susceptibility to (3) Melanoma, malignant sporadic (3) STK11, PJS, LKB1 Melanoma, melignant, somatic (3) BRAF
Meleda disease, 248300 (3) SLURPI, MDM
Melnick-Needles syndrome, 309350 (3) FLNA, FLN1, ABPX, NHBP, OPD1, OPD2, FMD, MNS
Melorheostosis with osteopoikilosis, 155950 LEMD3, MAN1 (3) Memory impairment, susceptibility to (3) BDNF
Meniere disease 156000 (3) () COCH, DFNA9 Meningioma, 607174 (3) MN1, MGCR
Meningioma, 607174 (3) PTEN, MMAC1 Meningioma, NF2-related, somatic, 607174 NF2 (3) Meningioma, SIS-related (3) PDGFB, SIS
Meningococcal disease, susceptibility to (3) MBL2, MBL, MBP1 Menkes disease, 309400 (3) ATP7A, MNK, MK, OHS

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Mental retardation, nonsyndromic, PRSS12, BSSP3 autosomal recessive, 249500 (3) Mental retardation, nonsyndromic, CRBN, MRT2A
autosomal recessive, 2A, 607417 (3) Mental retardation, X-linked, 300425 (3) NLGN4, KIAA1260, AUTSX2 Mental retardation, X-linked, 300458 (3) MECP2, RTT, PPMX, MRX16, MRX79 Mental retardation, X-linked 30, 300558 (3) PAK3, MRX30, MRX47 Mental retardation, X-linked, 34, 300426 (3) IL1RAPL, MRX34 Mental retardation, X-linked 36, 300430 (3) ARX, ISSX, PRTS, MRXS1, MRX36, Mental retardation, X-linked (3) SLC6A8, CRTR
Mental retardation, X-linked-44, 300501 (3) FTSJ1, JM23, SPB1, MRX44, MRX9 Mental retardation, X-linked 45, 300498 (3) ZNF81, MRX45 Mental retardation, X-linked 54, 300419 (3) ARX, ISSX, PRTS, MRXS1, MRX36, Mental retardation, X-linked 58, 300218 (3) TM4SF2, MXS1, A15 Mental retardation, X-linked, 60, 300486 (3) OPHN1 Mental retardation, X-linked-9, 309549 (3) FTSJ1, JM23, SPB1, MRX44, MRX9 Mental retardation, X-linked, FRAXE type FMR2, FRAXE, MRX2 (3) Mental retardation, X-linked, JARIDIC- SMCX, MRXJ, DXS1272E, XE169, related, 300534 (3) JARID1C
Mental retardation, X-linked nonspecific, GDI1, RABGD1A, MRX41, MRX48 309541 (3) Mental retardation, X-linked nonspecific, 63, FACL4, ACS4, MRX63 300387 (3) Mental retardation, X-linked nonspecific, RPS6KA3, RSK2, MRX19 type 19 (3) Mental retardation, X-linked nonspecific, ARHGEF6, MRX46, COOL2 type 46, 300436 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Mental retardation, X-linked nonsyndromic AGTR2 (3) Mental retardation, X-linked nonsyndromic FGD1, FGDY, AAS
(3) Mental retardation, X-linked nonsyndromic ZNF41 (3) Mental retardation, X-linked nonsyndromic, DLG3, NEDLG, SAP102, MRX
DLG3-related (3) Mental retardation, X-linked, Snyder- SMS, SRS, MRSR
Robinson type, 309583 (3) Mental retardation, X-linked, with isolated SOX3, MRGH
growth hormone deficiency, 300123 (3) Mental retardation, X-linked, with MECP2, RTT, PPMX, MRX16, MRX79 progressive spasticity, 300279 (3) Mental retardation, X-linked, with seizures SLC6A8, CRTR
and carrier manifestations, 300397 (3) Mephenytoin poor metabolizer (3) CYP2C, CYP2C19 Merkel cell carcinoma, somatic (3) SDHD, PGL1 Mesangial sclerosis, isolated diffuse, WT1 256370 (3) Mesothelioma (3) BCL10 Metachromatic leukodystrophy, 250100 (3) ARSA
Metachromatic leukodystrophy due to PSAP, SAP1 deficiency of SAP-1 (3) Metaphyseal chondrodysplasia, Murk PTHR1, PTHR
Jansen type, 156400 (3) Metaphyseal chondrodysplasia, Schmid COL1OA1 type (3) Metaphyseal dysplasia without RMRP, RMRPR, CHH
hypotrichosis, 250460 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Methemoglobinemia due to cytochrome b5 CYB5 deficiency (3) Methemoglobinemias, alpha-(3) HBA1 Methemoglobinemias, beta-(3) HBB
Methemoglobinemia, type I (3) DIA1 Methemoglobinemia, type 11 (3) DIA1 Methionine adenosyltransferase deficiency, MAT1A, MATA1, SAMS1 autosomal recessive (3) Methylcobalamin deficiency, cblG type, MTR
250940 (3) Methylmalonate semialdehyde ALDH6A1, MMSDH
dehydrogenase deficiency (3) Methylmalonic aciduria, mut(0) type, 251000 MUT, MCM
(3) Methylmalonic aciduria, vitamin B12- MMAA
responsive, 251100 (3) Methylmalonic aciduria, vitamin B12- MMAB
responsive, due to defect in synthesis of adenosylcobalamin, cb1B complementation type, 251110 (3) Mevalonicaciduria (3) MVK, MVLK
MHC class 11 deficiency, complementation RFXANK
group B, 209920 (3) Microcephaly, Amish type, 607196 (3) SLC25A19, DNC, MUP1, MCPHA
Microcephaly, autosomal recessive 1, MCPH1 251200 (3) Microcephaly, primary autosomal recessive, CDK5RAP2, KIAA1633, MCPH3 3,604804(3) Microcephaly, primary autosomal recessive, ASPM, MCPH5 5,608716(3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Microcephaly, primary autosomal recessive, CEMPJ, CPAP, MCPH6 6,608393(3) Microcoria-congenital nephrosis syndrome, LAMB2, LAMS
609049 (3) Micropenis (3) LHCGR
Microphthalmia, cataracts, and iris CHX10, HOX10 abnormalities (3) Microphthalmia, SIX6-related (3) SIX6 Microphthalmia with associated anomalies BCOR, KIAA1575, MAA2, ANOP2 2, 300412 (3) Migraine, familial hemiplegic, 2, 602481 (3) ATP1A2, FHM2, MHP2 Migraine, resistance to, 157300 (3) EDNRA
Migraine, susceptibility to, 157300 (3) ESR1, ESR
Migraine without aura, susceptibility to, TNF, TNFA
157300 (3) Miller-Dieker lissencephaly, 247200 (3) YWHAE, MDCR, MDS
Mitochondrial complex I deficiency, 252010 NDUFS1 (3) Mitochondrial complex I deficiency, 252010 NDUFS2 (3) Mitochondrial complex I deficiency, 252010 NDUFS4, AQDQ
(3) Mitochondrial complex I deficiency, 252010 NDUFV1, UQOR1 (3) Mitochondrial complex III deficiency, 124000 BCS1L, FLNMS, GRACILE
(3) Mitochondrial complex III deficiency, 124000 UQCRB, UQBP, QPC
(3) Mitochondrial DNA depletion myopathy, TK2 251880 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Mitochondrial DNA depletion syndrome, SUCLA2 251880 (3) Mitochondrial DNA-depletion syndrome, DGUOK, DGK
hepatocerebral form, 251880 (3) Mitochondrial myopathy and sideroblastic PUS1, MLASA
anemia, 600462 (3) Mitochondrial respiratory chain complex II SDHA, SDH2, SDHF
deficiency, 252011 (3) Miyoshi myopathy, 254130 (3) DYSF, LGMD2B
MODY5 with nephron agenesis (3) TCF2, HNF2 MODY5 with non-diabetic renal disease and TCF2, HNF2 Mullerian aplasia (3) MODY, one form, 125850 (3) INS
MODY, type I, 125850 (3) HNF4A, TCF14, MODY1 MODY, type II, 125851 (3) GCK
MODY, type III, 600496 (3) TCF1, HNF1A, MODY3 MODY, type IV (3) IPF1 MODY, type V, 604284 (3) TCF2, HNF2 Mohr-Tranebjaerg syndrome, 304700 (3) TIMM8A, DFN1, DDP, MTS, DDP1 Molybdenum cofactor deficiency, type A, MOCS1, MOCOD
252150 (3) Molybdenum cofactor deficiency, type B, MOCS2, MPTS
252150 (3) Molybdenum cofactor deficiency, type C, GPH, KIAA1385, GEPH
252150 (3) Monilethrix, 158000 (3) KRTHB1, HB1 Monilethrix, 158000 (3) KRTHB6, HB6 Morning glory disc anomaly (3) PAX6, AN2, MGDA
Mowat-Wilson syndrome, 235730 (3) ZFHX1B, SMADIP1, SIP1 Moyamoya disease 3 (3) MYMY3 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Muckle-Wells syndrome, 191900 (3) CIAS1, C1orf7, FCU, FCAS
Mucoepidermoid salivary gland carcinoma MAML2, MAM3 (3) Mucoepidermoid salivary gland carcinoma MECT1, KIAA0616 (3) Mucolipidosis IIIA, 252600 (3) GNPTAB, GNPTA
Mucolipidosis IIIC, 252605 (3) GNPTAG
Mucolipidosis IV, 252650 (3) MCOLN1, ML4 Mucopolysaccharidosis Ih, 607014 (3) IDUA, IDA
Mucopolysaccharidosis Ih/s, 607015 (3) IDUA, IDA
Mucopolysaccharidosis II (3) IDS, MPS2, SIDS
Mucopolysaccharidosis Is, 607016 (3) IDUA, IDA
Mucopolysaccharidosis IVA (3) GALNS, MPS4A
Mucopolysaccharidosis IVB (3) GLB1 Mucopolysaccharidosis type IIID, 252940 GNS, G6S
(3) Mucopolysaccharidosis type IX, 601492 (3) HYAL1 Mucopolysaccharidosis VII (3) GUSB, MPS7 Muenke syndrome, 602849 (3) FGFR3, ACH
Muir-Torre syndrome, 158320 (3) MLH1, COCA2, HNPCC2 Muir-Torre syndrome, 158320 (3) MSH2, COCA1, FCC1, HNPCC1 Mulibrey nanism, 253250 (3) TRIM37, MUL, KIAA0898 Multiple cutaneous and uterine FH
leiomyomata, 150800 (3) Multiple endocrine neoplasia I (3) MEN1 Multiple endocrine neoplasia IIA, 171400 (3) RET, MEN2A
Multiple endocrine neoplasia IIB, 162300 (3) RET, MEN2A
Multiple malignancy syndrome (3) TP53, P53, LFS1 Multiple myeloma (3) IRF4, LSIRF
Multiple myeloma, resistance to, 254500 (3) LIG4 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Multiple sclerosis, susceptibility to, 126200 MHC2TA, C2TA
(3) Multiple sclerosis, susceptibility to, 126200 PTPRC, CD45, LCA
(3) Multiple sulfatase deficiency, 272200 (3) SUMF1, FGE
Muscle-eye-brain disease, 253280 (3) POMGNT1, MEB
Muscle glycogenosis (3) PHKA1 Muscle hypertrophy (3) GDF8, MSTN
Muscular dystrophy, congenital, 1 C (3) FKRP, MDC1C, LGMD21 Muscular dystrophy, congenital, due to LAMA2, LAMM
partial LAMA2 deficiency, 607855 (3) Muscular dystrophy, congenital merosin- LAMA2, LAMM
deficient, 607855 (3) Muscular dystrophy, congenital, type 1 D, LARGE, KIAA0609, MDC1 D
608840 (3) Muscular dystrophy, Fukuyama congenital, FCMD
253800 (3) Muscular dystrophy, limb-girdle, type 1A, TTID, MYOT
159000 (3) Muscular dystrophy, limb-girdle, type 2A, CAPN3, CANP3 253600 (3) Muscular dystrophy, limb-girdle, type 2B, DYSF, LGMD2B
253601 (3) Muscular dystrophy, limb-girdle, type 2C, SGCG, LGMD2C, DMDA1, SCG3 253700 (3) Muscular dystrophy, limb-girdle, type 2D, SGCA, ADL, DAG2, LGMD2D, DMDA2 608099 (3) Muscular dystrophy, limb-girdle, type 2E, SGCB, LGMD2E
604286 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Muscular dystrophy, limb-girdle, type 2F, SGCD, SGD, LGMD2F, CMD1 L
601287 (3) Muscular dystrophy, limb-girdle, type 2G, TCAP, LGMD2G, CMD1 N
601954 (3) Muscular dystrophy, limb-girdle, type 2H, TRIM32, HT2A, LGMD2H
254110 (3) Muscular dystrophy, limb-girdle, type 21, FKRP, MDC1 C, LGMD21 607155 (3) Muscular dystrophy, limb-girdle, type 2J, TTN, CMD1G, TMD, LGMD2J
608807 (3) Muscular dystrophy, limb-girdle, type 2K, POMT1 609308 (3) Muscular dystrophy, limb-girdle, type IC, CAV3, LGMD1 C
607801 (3) Muscular dystrophy, rigid spine, 1, 602771 SEPN1, SELN, RSMD1 (3) Muscular dystrophy with epidermolysis PLEC1, PLTN, EBS1 bullosa simplex, 226670 (3) Myasthenia, familial infantile, 1, 605809 (3) CMS1A1, FIM1 Myasthenic syndrome (3) SCN4A, HYPP, NAC1A
Myasthenic syndrome, congenital, CHRNB1, ACHRB, SCCMS, CMS2A, associated with acetylcholine receptor CMS1 D
deficiency, 608931 (3) Myasthenic syndrome, congenital, CHRNE, SCCMS, CMS2A, FCCMS, associated with acetylcholine receptor CMS1 E, CMS1 D
deficiency, 608931 (3) Myasthenic syndrome, congenital, RAPSN, CMS1 D, CMS1 E
associated with acetylcholine receptor deficiency, 608931 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Myasthenic syndrome, congenital, CHAT, CMS1A2 associated with episodic apnea, 254210 (3) Myasthenic syndrome, congenital, RAPSN, CMS1 D, CMS1 E
associated with facial dysmorphism and acetylcholine receptor deficiency, 608931 (3) Myasthenic syndrome, fast-channel CHRNA1, ACHRD, CMS2A, SCCMS, congenital, 608930 (3) FCCMS
Myasthenic syndrome, fast-channel CHRND, ACHRD, SCCMS, CMS2A, congenital, 608930 (3) FCCMS
Myasthenic syndrome, fast-channel CHRNE, SCCMS, CMS2A, FCCMS, congenital, 608930 (3) CMS1 E, CMS1 D
Myasthenic syndrome, slow-channel CHRNA1, ACHRD, CMS2A, SCCMS, congenital, 601462 (3) FCCMS
Myasthenic syndrome, slow-channel CHRNB1, ACHRB, SCCMS, CMS2A, congenital, 601462 (3) CMS1 D
Myasthenic syndrome, slow-channel CHRND, ACHRD, SCCMS, CMS2A, congenital, 601462 (3) FCCMS
Myasthenic syndrome, slow-channel CHRNE, SCCMS, CMS2A, FCCMS, congenital, 601462 (3) CMS1E, CMS1D
Mycobacterial and salmonella infections, IL12RB1 susceptibility to, 209950 (3) Mycobacterial infection, atypical, familial IFNGR1 disseminated, 209950 (3) Mycobacterial infection, atypical, familial IFNGR2, IFNGT1, IFGR2 disseminated, 209950 (3) Mycobacterial infection, atypical, familial STAT1 disseminated, 209950 (3) Mycobacterium tuberculosis, suceptibility to NRAMP1, NRAMP
infection by, 607948 (3) Myelodysplasia syndrome-1 (3) MDS1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Myelodysplastic syndrome (3) FACL6, ACS2 Myelodysplastic syndrome, preleukemic (3) IRF1, MAR
Myelofibrosis, idiopathic, 254450 (3) JAK2 Myelogenous leukemia, acute (3) FACL6, ACS2 Myelogenous leukemia, acute (3) IRF1, MAR
Myeloid leukemia, acute, M4Eo subtype (3) CBFB
Myeloid malignancy, predisposition to (3) CSF1 R, FMS
Myelokathexis, isolated (3) CXCR4, D2S201 E, NPY3R, WHIM
Myelomonocytic leukemia, chronic (3) PDGFRB, PDGFR
Myeloperoxidase deficiency, 254600 (3) MPO
Myeloproliferative disorder with eosinophilia, PDGFRB, PDGFR
131440 (3) Myoadenylate deaminase deficiency (3) AMPD1 Myocardial infarction, decreased F7 susceptibility to (3) Myocardial infarction susceptibility (3) APOE, AD2 Myocardial infarction, susceptibility to (3) ACE, DCP1, ACE1 Myocardial infarction, susceptibility to (3) ALOX5AP, FLAP
Myocardial infarction, susceptibility to (3) LGALS2 Myocardial infarction, susceptibility to (3) LTA, TNFB
Myocardial infarction, susceptibility to (3) OLR1, LOX1 Myocardial infarction, susceptibility to (3) THBD, THRM
Myocardial infarction, susceptibility to, GCLM, GLCLR
608446 (3) Myocardial infarction, susceptibility to, TNFSF4, GP34, OX4OL
608446 (3) Myoclonic epilepsy, juvenile, 1, 254770 (3) EFHC1, FLJ10466, EJM1 Myoclonic epilepsy, severe, of infancy, GABRG2, GEFSP3, CAE2, ECA2 607208 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Myoclonic epilepsy with mental retardation ARX, ISSX, PRTS, MRXS1, MRX36, and spasticity, 300432 (3) MRX54 Myoglobinuria/hemolysis due to PGK PGK1, PGKA
deficiency (3) Myokymia with neonatal epilepsy, 606437 KCNQ2, EBN1 (3) Myoneurogastrointestinal ECGF1 encephalomyopathy syndrome, 603041 (3) Myopathy, actin, congenital, with cores (3) ACTA1, ASMA, NEM3, NEM1 Myopathy, actin, congenital, with excess of ACTA1, ASMA, NEM3, NEM1 thin myofilaments, 161800 (3) Myopathy, cardioskeletal, desmin-related, CRYAB, CRYA2, CTPP2 with cataract, 608810 (3) Myopathy, centronuclear, 160150 (3) MYF6 Myopathy, congenital (3) ITGA7 Myopathy, desmin-related, cardioskeletal, DES, CMD11 601419 (3) Myopathy, distal, with anterior tibial onset, DYSF, LGMD2B
606768 (3) Myopathy, distal, with decreased caveolin 3 CAV3, LGMD1C
(3) Myopathy due to CPT II deficiency, 255110 CPT2 (3) Myopathy due to phosphoglycerate mutase PGAM2, PGAMM
deficiency (3) Myopathy, Laing distal, 160500 (3) MYH7, CMH1, MPD1 Myopathy, myosin storage, 608358 (3) MYH7, CMH1, MPD1 Myopathy, nemaline, 3, 161800 (3) ACTA1, ASMA, NEM3, NEM1 Myotilinopathy, 609200 (3) TTID, MYOT

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Myotonia congenita, atypical, SCN4A, HYPP, NAC1A
acetazolamide-responsive, 608390 (3) Myotonia congenita, dominant, 160800 (3) CLCN1 Myotonia congenita, recessive, 255700 (3) CLCN1 Myotonia levior, recessive (3) CLCN1 Myotonic dystrophy, 160900 (3) DMPK, DM, DMK
Myotonic dystrophy, type 2, 602668 (3) ZNF9, CNBP1, DM2, PROMM
Myotubular myopathy, X-linked, 310400 (3) MTM1, MTMX
Myxoid liposarcoma (3) DDIT3, GADD153, CHOP10 Myxoma, intracardiac, 255960 (3) PRKAR1A, TSE1, CNC1, CAR
N-acetylglutamate synthase deficiency, NAGS
237310 (3) Nail-patella syndrome, 161200 (3) LMX1B, NPS1 Nail-patella syndrome with open-angle LMX1 B, NPS1 glaucoma, 137750 (3) Nance-Horan syndrome, 302350 (3) NHS
Narcolepsy, 161400 (3) HCRT, OX
Nasopharyngeal carcinoma, 161550 (3) TP53, P53, LFS1 Nasu-Hakola disease, 221770 (3) TREM2 Nasu-Hakola disease, 221770 (3) TYROBP, PLOSL, DAP12 Naxos disease, 601214 (3) JUP, DP3, PDGB
Nemaline myopathy, 161800 (3) TPM2, TMSB, AMCD1, DA1 Nemaline myopathy 1, autosomal dominant, TPM3, NEM1 161800 (3) Nemaline myopathy 2, autosomal recessive, NEB, NEM2 256030 (3) Nemaline myopathy, Amish type, 605355 TNNT1, ANM
(3) Neonatal ichthyosis-sclerosing cholangitis CLDN1, SEMP1 syndrome, 607626 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Nephrogenic syndrome of inappropriate AVPR2, DIR, D11, ADHR
antidiuresis, 300539 (3) Nephrolithiasis, type I, 310468 (3) CLCN5, CLCK2, NPHL2, DENTS
Nephrolithiasis, uric acid, susceptibility to, ZNF365, UAN
605990 (3) Nephronophthisis 2, infantile, 602088 (3) INVS, INV, NPHP2, NPH2 Nephronophthisis 4, 606966 (3) NPHP4, SLSN4 Nephronophthisis, adolescent, 604387 (3) NPHP3, NPH3 Nephronophthisis, juvenile, 256100 (3) NPHP1, NPH1, SLSN1 Nephropathy, chronic hypocomplementemic HF1, CFH, HUS
(3) Nephropathy with pretibial epidermolysis CD151, PETA3, SFA1 bullosa and deafness, 609057 (3) Nephrosis-1, congenital, Finnish type, NPHS1, NPHN
256300 (3) Nephrotic syndrome, steroid-resistant, PDCN, NPHS2, SRN1 600995 (3) Netherton syndrome, 256500 (3) SPIN KS, LEKTI
Neural tube defects, maternal risk of, MTHFD, MTHFC
601634 (3) Neuroblastoma, 256700 (3) NME1, NM23 Neuroblastoma, 256700 (3) PMX2B, NBPHOX, PHOX2B
Neurodegeneration, pantothenate kinase- PANK2, NBIA1, PKAN, HARP
associated, 234200 (3) Neuroectodermal tumors, supratentorial PMS2, PMSL2, HNPCC4 primitive, with cafe-au-lait spots, 608623 (3) Neurofibromatosis, familial spinal, 162210 NF1, VRNF, WSS, NFNS
(3) Neurofibromatosis-Noonan syndrome, NF1, VRNF, WSS, NFNS
601321 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Neurofibromatosis, type 1 (3) NF1, VRNF, WSS, NFNS
Neurofibromatosis, type 2, 101000 (3) NF2 Neurofibromatosis, type I, with leukemia, MSH2, COCA1, FCC1, HNPCC1 162200 (3) Neurofibrosarcoma (3) MXI1 Neuropathy, congenital hypomyelinating, 1, EGR2, KROX20 605253 (3) Neuropathy, congenital hypomyelinating, MPZ, CMT1 B, CMTD13, CHM, DSS
605253 (3) Neuropathy, distal hereditary motor, 608634 HSPB1, HSP27, CMT2F
(3) Neuropathy, distal hereditary motor, type 11, HSPB8, H11, E21G1, DHMN2 158590 (3) Neuropathy, hereditary sensory and SPTLC1, LBC1, SPT1, HSN1, HSAN
autonomic, type 1, 162400 (3) Neuropathy, hereditary sensory and NGFB, HSAN5 autonomic, type V, 608654 (3) Neuropathy, hereditary sensory, type 11, HSN2 201300 (3) Neuropathy, recurrent, with pressure PMP22, CMT1A, CMT1E, DSS
palsies, 162500 (3) Neutropenia, alloimmune neonatal (3) FCGR3A, CD16, IGFR3 Neutropenia, congenital, 202700 (3) ELA2 Neutropenia, severe congenital, 202700 (3) GF11, ZNF163 Neutropenia, severe congenital, X-linked, WAS, IMD2, THC
300299 (3) Neutrophil immunodeficiency syndrome, RAC2 608203 (3) Nevo syndrome, 601451 (3) PLOD, PLOD1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Nevus, epidermal, epidermolytic KRT10 hyperkeratotic type, 600648 (3) Newfoundland rod-cone dystrophy, 607476 RLBP1 (3) Nicotine addiction, protection from (3) CYP2A6, CYP2A3, CYP2A, P450C2A
Nicotine addiction, susceptibility to, 188890 CHRNA4, ENFL1 (3) Nicotine dependence, susceptibility to, GPR51, GABBR2 188890 (3) Niemann-Pick disease, type A, 257200 (3) SMPD1, NPD
Niemann-Pick disease, type B, 607616 (3) SMPD1, NPD
Niemann-Pick disease, type C1, 257220 (3) NPC1, NPC
Niemann-pick disease, type C2, 607625 (3) NPC2, HE1 Niemann-Pick disease, type D, 257220 (3) NPC1, NPC
Night blindness, congenital stationary (3) GNAT1 Night blindness, congenital stationary, type CSNB1, NYX
1,310500(3) Night blindness, congenital stationary, type PDE6B, PDEB, CSNB3 3,163500(3) Night blindness, congenital stationary, X- CACNA1 F, CSNB2 linked, type 2, 300071 (3) Night blindness, congenital stationery, RHO, RP4, OPN2 rhodopsin-related (3) Nijmegen breakage syndrome, 251260 (3) NBS1, NBS
Nonaka myopathy, 605820 (3) GNE, GLCNE, IBM2, DMRV, NM
Noncompaction of left ventricular TAZ, EFE2, BTHS, CMD3A, LVNCX
myocardium, isolated, 300183 (3) Non-Hodgkin lymphoma, somatic, 605027 CASP10, MCH4, ALPS2 (3) Nonsmall cell lung cancer (3) IRF1, MAR

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Nonsmall cell lung cancer, response to EGFR
tyrosine kinase inhibitor in, 211980 (3) Nonsmall cell lung cancer, somatic (3) BRAF
Noonan syndrome 1, 163950 (3) PTPN11, PTP2C, SHP2, NS1 Norrie disease (3) NDP, ND
Norum disease, 245900 (3) LCAT
Norwalk virus infection, resistance to (3) FUT2, SE
Nucleoside phosphorylase deficiency, NP
immunodeficiency due to (3) Obesity, adrenal insufficiency, and red hair POMC
(3) Obesity, autosomal dominant, 601665 (3) MC4R
Obesity, hyperphagia, and developmental AKR1C2, DDH2, DD2, HAKRD
delay (3) Obesity, hyperphagia, and developmental NTRK2, TRKB
delay (3) Obesity, late-onset, 601665 (3) AGRP, ART, AGRT
Obesity, mild, early-onset, 601665 (3) NR0B2, SHP
Obesity, morbid, with hypogonadism (3) LEP, OB
Obesity, morbid, with hypogonadism (3) LEPR, OBR
Obesity, resistance to (3) PPARG, PPARG1, PPARG2 Obesity, severe, 601665 (3) PPARG, PPARG1, PPARG2 Obesity, severe, 601665 (3) SIM1 Obesity, severe, and type II diabetes, UCP3 601665 (3) Obesity, severe, due to leptin deficiency (3) LEP, OB
Obesity, severe, susceptibility to, 601665 (3) MC3R
Obesity, susceptibility to, 300306 (3) SLC6A14, OBX
Obesity, susceptibility to, 601665 (3) ADRB2 Obesity, susceptibility to, 601665 (3) ADRB3 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Obesity, susceptibility to, 601665 (3) CART
Obesity, susceptibility to, 601665 (3) ENPP1, PDNP1, NPPS, M6S1, PCA1 Obesity, susceptibility to, 601665 (3) GHRL
Obesity, susceptibility to, 601665 (3) UCP1 Obesity, susceptibility to, 601665 (3) UCP2 Obestiy with impaired prohormone PCSK1, NEC1, PC1, PC3 processing, 600955 (3) Obsessive-compulsive disorder 1, 164230 SLC6A4, HTT, OCD1 (3) Obsessive-compulsive disorder, protection BDNF
against, 164230 (3) Obsessive-compulsive disorder, HTR2A
susceptibility to, 164230 (3) Occipital horn syndrome, 304150 (3) ATP7A, MNK, MK, OHS
Ocular albinism, Nettleship-Falls type (3) OA1 Oculocutaneous albinism, type II, modifier of MC1 R
(3) Oculocutaneous albinism, type IV, 606574 MATP, AIM1 (3) Oculodentodigital dysplasia, 164200 (3) GJA1, CX43, ODDD, SDTY3, ODOD
Oculofaciocardiodental syndrome, 300166 BCOR, KIAA1575, MAA2, ANOP2 (3) Oculopharyngeal muscular dystorphy, PABPN1, PABP2, PAB2 164300 (3) Oculopharyngeal muscular dystrophy, PABPN1, PABP2, PAB2 autosomal recessive, 257950 (3) Odontohypophosphatasia, 146300 (3) ALPL, HOPS, TNSALP
Oguchi disease-1, 258100 (3) SAG
Oguchi disease-2, 258100 (3) RHOK, RK, GRK1 Oligodendroglioma, 137800 (3) PTEN, MMAC1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Oligodontia, 604625 (3) PAX9 Oligodontia-colorectal cancer syndrome, AXIN2 608615 (3) Omenn syndrome, 603554 (3) DCLRE1C, ARTEMIS, SCIDA
Omenn syndrome, 603554 (3) RAG1 Omenn syndrome, 603554 (3) RAG2 Opitz G syndrome, type I, 300000 (3) MID1, OGS1, BBBG1, FXY, OSX
Opremazole poor metabolizer (3) CYP2C, CYP2C19 Optic atrophy 1, 165500 (3) OPA1, NTG, NPG
Optic atrophy and cataract, 165300 (3) OPA3, MGA3 Optic nerve coloboma with renal disease, PAX2 120330 (3) Optic nerve hypoplasia/aplasia, 165550 (3) PAX6, AN2, MGDA
Oral-facial-digital syndrome 1, 311200 (3) OFD1, CXorf5 Ornithine transcarbamylase deficiency, OTC
311250 (3) Orofacial cleft 6, 608864 (3) IRF6, VWS, LPS, PIT, PPS, OFC6 Orolaryngeal cancer, multiple, (3) CDKN2A, MTS1, P16, MLM, CMM2 Oroticaciduria (3) UMPS, OPRT
Orthostatic intolerance, 604715 (3) SLC6A2, NAT1, NET1 OSMED syndrome, 215150 (3) COL11A2, STL3, DFNA13 Osseous heteroplasia, progressive, 166350 GNAS, GNAS1, GPSA, POH, PHP1 B, (3) PHP1A, AHO
Ossification of posterior longitudinal ENPP1, PDNP1, NPPS, M6S1, PCA1 ligament of spine, 602475 (3) Osteoarthritis, hand, susceptibility to, MATN3, EDM5, HOA
607850 (3) Osteoarthritis of hip, female-specific, FRZB, FRZB1, SRFP3 susceptibility to, 165720 (3) Osteoarthritis, susceptibility to, 165720 (3) ASPN, PLAP1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Osteoarthrosis, 165720 (3) COL2A1 Osteogenesis imperfecta, 3 clinical forms, COL1A2 166200, 166210, 259420 (3) Osteogenesis imperfecta, type I, 166200 (3) COL1A1 Osteogenesis imperfecta, type II, 166210 COL1A1 (3) Osteogenesis imperfecta, type III, 259420 COL1A1 (3) Osteogenesis imperfecta, type IV, 166220 COL1A1 (3) Osteolysis, familial expansile, 174810 (3) TNFRSF11A, RANK, ODFR, OFE
Osteolysis, idiopathic, Saudi type, 605156 MMP2, CLG4A, MONA
(3) Osteopetrosis, autosomal dominant, type I, LRP5, BMND1, LRP7, LR3, OPPG, 607634 (3) VBCH2 Osteopetrosis, autosomal dominant, type II, CLCN7, CLC7, OPTA2 166600 (3) Osteopetrosis, autosomal recessive, OSTM1, GL
259700 (3) Osteopetrosis, recessive, 259700 (3) CLCN7, CLC7, OPTA2 Osteopetrosis, recessive, 259700 (3) TCIRG1, TIRC7, OC116, OPTB1 Osteopoikilosis, 166700 (3) LEMD3, MAN1 Osteoporosis, 166710 (3) COL1A1 Osteoporosis, 166710 (3) LRP5, BMND1, LRP7, LR3, OPPG, Osteoporosis (3) CALCA, CALC1 Osteoporosis, hypophosphatemic, (3) SLC17A2, NPT2 Osteoporosis, idiopathic, 166710 (3) COL1A2 Osteoporosis, postmenopausal, CALCR, CRT
susceptibility, 166710 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Osteoporosis-pseudoglioma syndrome, LRP5, BMND1, LRP7, LR3, OPPG, 259770 (3) VBCH2 Osteoporosis, susceptibility to, 166710 (3) RIL
Osteosarcoma (3) TP53, P53, LFS1 Osteosarcoma, somatic, 259500 (3) CHEK2, RAD53, CHK2, CDS1, LFS2 Otopalatodigital syndrome, type I, 311300 FLNA, FLN1, ABPX, NHBP, OPD1, (3) OPD2, FMD, MNS
Otopalatodigital syndrome, type II, 304120 FLNA, FLN1, ABPX, NHBP, OPD1, (3) OPD2, FMD, MNS
Ovarian cancer (3) BRCA1, PSCP
Ovarian cancer (3) MSH2, COCA1, FCC1, HNPCC1 Ovarian cancer, 604370 (3) PIK3CA
Ovarian cancer, endometrial type (3) MSH6, GTBP, HNPCC5 Ovarian cancer, somatic, (3) ERBB2, NGL, NEU, HER2 Ovarian carcinoma (3) CDH1, UVO
Ovarian carcinoma (3) RRAS2, TC21 Ovarian carcinoma, endometrioid type (3) CTNNB1 Ovarian dysgenesis 1, 233300 (3) FSHR, ODG1 Ovarian dysgenesis 2, 300510 (3) BMP15, GDF9B, ODG2 Ovarian hyperstimulation syndrome, FSHR, ODG1 gestational, 608115 (3) Ovarian sex cord tumors (3) FSHR, ODG1 Ovarioleukodystrophy, 603896 (3) EIF2B2 Ovarioleukodystrophy, 603896 (3) EIF2B4 Ovarioleukodystrophy, 603896 (3) EIF2B5, LVWM, CACH, CLE
Pachyonychia congenita, Jackson-Lawler KRT17, PC2, PCHC1 type, 167210 (3) Pachyonychia congenita, Jackson-Lawler KRT6B, PC2 type, 167210 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Pachyonychia congenita, Jadassohn- KRT16 Lewandowsky type, 167200 (3) Pachyonychia congenita, Jadassohn- KRT6A
Lewandowsky type, 167200 (3) Paget disease, juvenile, 239000 (3) TNFRSF11 B, OPG, OCIF
Paget disease of bone, 602080 (3) SQSTM1, P62, PDB3 Paget disease of bone, 602080 (3) TNFRSF11A, RANK, ODFR, OFE
Pallidopontonigral degeneration, 168610 (3) MAPT, MTBT1, DDPAC, MSTD
Pallister-Hall syndrome, 146510 (3) GI-13, PAPA, PAPB, ACLS
Palmoplantar keratoderma, KRT16 nonepidermolytic, 600962 (3) Palmoplantar verrucous nevus, unilateral, KRT16 144200 (3) Pancreatic agenesis, 260370 (3) IPF1 Pancreatic cancer, 260350 (3) ARMET, ARP
Pancreatic cancer, 260350 (3) BRCA2, FANCD1 Pancreatic cancer, 260350 (3) TP53, P53, LFS1 Pancreatic cancer (3) MADH4, DPC4, SMAD4, JIP
Pancreatic cancer/melanoma syndrome, CDKN2A, MTS1, P16, MLM, CMM2 606719 (3) Pancreatic cancer, somatic (3) ACVR1 B, ACVRLK4, ALK4 Pancreatic cancer, sporadic (3) STK11, PJS, LKB1 Pancreatic carcinoma, somatic, 260350 (3) KRAS2, RASK2 Pancreatic carcinoma, somatic (3) RBBP8, RIM
Pancreatitis, hereditary, 167800 (3) PRSS1, TRY1 Pancreatitis, hereditary, 167800 (3) SPINK1, PSTI, PCTT, TATI
Pancreatitis, idiopathic (3) CFTR, ABCC7, CF, MRP7 Papillary serous carcinoma of the BRCA1, PSCP
peritoneum (3) Papillon-Lefevre syndrome, 245000 (3) CTSC, CPPI, PALS, PLS, HMS

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Paraganglioma, familial malignant, 168000 SDHB, SDH1, SDHIP
(3) Paragangliomas, familial central nervous SDHD, PGL1 system, 168000 (3) Paragangliomas, familial nonchromaffin, 1, SDHD, PGL1 with and without deafness, 168000 (3) Paragangliomas, familial nonchromaffin, 3, SDHC, PGL3 605373 (3) Paraganglioma, sporadic corotid body, SDHD, PGL1 168000 (3) Paramyotonia congenita, 168300 (3) SCN4A, HYPP, NAC1A
Parathyroid adenoma, sporadic (3) MEN1 Parathyroid adenoma with cystic changes, HRPT2, C1orf28 145001 (3) Parathyroid carcinoma, 608266 (3) HRPT2, Clorf28 Parietal foramina 1, 168500 (3) MSX2, CRS2, HOX8 Parietal foramina 2, 168500 (3) ALX4, PFM2, FPP
Parietal foramina with cleidocranial MSX2, CRS2, HOX8 dysplasia, 168550 (3) Parkes Weber syndrome, 608355 (3) RASA1, GAP, CMAVM, PKWS
Parkinson disease, 168600 (3) NR4A2, NURR1, NOT, TINUR
Parkinson disease, 168600 (3) SNCAIP
Parkinson disease, 168600 (3) TBP, SCA17 Parkinson disease 4, autosomal dominant SNCA, NACP, PARK1, PARK4 Lewy body, 605543 (3) Parkinson disease 7, autosomal recessive DJ1, PARK7 early-onset, 606324 (3) Parkinson disease-8, 607060 (3) LRRK2, PARK8 Parkinson disease, early onset, 605909 (3) PINK1, PARK6 Parkinson disease, familial, 168600 (3) UCHL1, PARKS

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Parkinson disease, familial, 168601 (3) SNCA, NACP, PARK1, PARK4 Parkinson disease, juvenile, type 2, 600116 PRKN, PARK2, PDJ
(3) Parkinson disease, resistance to, 168600 DBH
(3) Parkinson disease, susceptibility to, 168600 NDUFV2 (3) Paroxysmal nocturnal hemoglobinuria (3) PIGA
Paroxysmal nonkinesigenic dyskinesia, MR1, TAHCCP2, KIPP1184, BRP17, 118800 (3) PNKD, FPD1, PDC, DYT8 Partington syndrome, 309510 (3) ARX, ISSX, PRTS, MRXS1, MRX36, PCWH, 609136 (3) SOX10, WS4 Pelger-Huet anomaly, 169400 (3) LBR, PHA
Pelizaeus-Merzbacher disease, 312080 (3) PLP1, PMD
Pelizaeus-Merzbacher-like disease, GJA12, CX47, PMLDAR
autosomal recessive, 608804 (3) Pendred syndrome, 274600 (3) SLC26A4, PDS, DFNB4 Perineal hypospadias (3) AR, DHTR, TFM, SBMA, KD, SMAX1 Periodic fever, familial, 142680 (3) TNFRSF1A, TNFR1, TNFAR, FPF
Periodontitis, juvenile, 170650 (3) CTSC, CPPI, PALS, PLS, HMS
Periventricular heterotopia with ARFGEF2, BIG2 microcephaly, 608097 (3) Peroxisomal biogenesis disorder, PEX6, PXAAA1, PAF2 complementation group 4 (3) Peroxisomal biogenesis disorder, PEX6, PXAAA1, PAF2 complementation group 6 (3) Peroxisome biogenesis factor 12 (3) PEX12 Persistent hyperinsulinemic hypoglycemia of KCNJ11, BIR, PHHI
infancy, 256450 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Persistent Mullerian duct syndrome, type I, AMH, MIF
261550 (3) Persistent Mullerian duct syndrome, type II, AMHR2, AMHR
261550 (3) Peters anomaly, 603807 (3) PAX6, AN2, MGDA
Peters anomaly, 604229 (3) CYP1B1, GLC3A
Peutz-Jeghers syndrome, 175200 (3) STK11, PJS, LKB1 Pfeiffer syndrome, 101600 (3) FGFR1, FLT2, KAL2 Pfeiffer syndrome, 101600 (3) FGFR2, BEK, CFD1, JWS
Phenylketonuria (3) PAH, PKU1 Phenylketonuria due to dihydropteridine QDPR, DHPR
reductase deficiency (3) Phenylketonuria due to PTS deficiency (3) PTS
Phenylthiocarbamide tasting, 171200 (3) TAS2R38, T2R61, PTC
Pheochromocytoma, 171300 (3) SDHD, PGL1 Pheochromocytoma, 171300 (3) VHL
Pheochromocytoma, extraadrenal, and SDHB, SDH1, SDHIP
cervical paraganglioma, 115310 (3) Phosphoglycerate dehydrogenase PHGDH
deficiency, 601815 (3) Phosphoribosyl pyrophosphate synthetase- PRPS1 related gout (3) Phosphorylase kinase deficiency of liver and PHKB
muscle, autosomal recessive, 261750 (3) Phosphoserine phosphatase deficiency (3) PSP
Pick disease, 172700 (3) PSEN1, AD3 Piebaldism (3) KIT, PBT
Pigmentation of hair, skin, and eyes, MATP, AIM1 variation in (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Pigmented adrenocortical disease, primary PRKAR1A, TSE1, CNC1, CAR
isolated, 160980 (3) Pigmented paravenous chorioretinal CRB1, RP12 atrophy, 172870 (3) Pilomatricoma, 132600 (3) CTNNB1 Pituitary ACTH-secreting adenoma (3) GNA12, GNA12B, GIP
Pituitary ACTH secreting adenoma (3) GNAS, GNAS1, GPSA, POH, PHP1 B, PHP1A, AHO
Pituitary adenoma, nonfunctioning (3) THRA, ERBA1, THRA1 Pituitary anomalies with holoprosencephaly- GL12 like features (3) Pituitary hormone deficiency, combined (3) POU1F1, PIT1 Pituitary hormone deficiency, combined (3) PROP1 Pituitary hormone deficiency, combined, HESX1, RPX
HESX1-related, 182230 (3) Pituitary hormone deficiency, combined, LHX3 with rigid cervical spine, 262600 (3) Pituitary tumor, invasive (3) PRKCA, PKCA
Placental abruption (3) NOS3 Placental steroid sulfatase deficiency (3) STS, ARSC1, ARSC, SSDD
Plasmin inhibitor deficiency (3) PLI, SERPINF2 Plasminogen Tochigi disease (3) PLG
Platelet-activating factor acetylhydrolase PLA2G7, PAFAH
deficiency (3) Platelet ADP receptor defect (3) P2RY12, P2Y12 Platelet disorder, familial, with associated RUNX1, CBFA2, AML1 myeloid malignancy, 601399 (3) Platelet glycoprotein IV deficiency, 608404 CD36 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Pneumonitis, desquamative interstitial, SFTPC, SFTP2 263000 (3) Pneumothorax, primary spontaneous, FLCN, BHD
173600 (3) Polycystic kidney and hepatic disease, FCYT, PKHD1, ARPKD
263200 (3) Polycystic kidney disease, adult type I, PKD1 173900 (3) Polycystic kidney disease, adult, type 11 (3) PKD2, PKD4 Polycystic kidney disease, infantile severe, PKDTS
with tuberous sclerosis (3) Polycystic liver disease, 174050 (3) PRKCSH, G19P1, PCLD
Polycystic liver disease, 174050 (3) SEC63 Polycythemia, benign familial, 263400 (3) VHL
Polycythemia vera, 263300 (3) JAK2 Polydactyly, postaxial, types Al and B, GI-13, PAPA, PAPB, ACLS
174200 (3) Polydactyly, preaxial, type IV, 174700 (3) GI-13, PAPA, PAPB, ACLS
Polymicrogyria, bilateral frontoparietal, GPR56, TM7XN1, BFPP
606854 (3) Polyposis, juvenile intestinal, 174900 (3) BMPR1A, ACVRLK3, ALK3 Polyposis, juvenile intestinal, 174900 (3) MADH4, DPC4, SMAD4, JIP
Popliteal pterygium syndrome, 119500 (3) IRF6, VWS, LPS, PIT, PPS, OFC6 Porencephaly, 175780 (3) COL4A1 Porphyria, acute hepatic (3) ALAD
Porphyria, acute intermittent (3) HMBS, PBGD, UPS
Porphyria, acute intermittent, nonerythroid HMBS, PBGD, UPS
variant (3) Porphyria, congenital erythropoietic, 263700 UROS
(3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Porphyria cutanea tarda (3) UROD
Porphyria, hepatoerythropoietic (3) UROD
Porphyria variegata, 176200 (3) HFE, HLA-H, HFE1 Porphyria variegata, 176200 (3) PPOX
PPM-X syndrome, 300055 (3) MECP2, RTT, PPMX, MRX16, MRX79 Prader-Willi syndrome, 176270 (3) NDN
Prader-Willi syndrome, 176270 (3) SNRPN
Precocious puberty, male, 176410 (3) LHCGR
Preeclampsia/eclampsia 4 (3) STOX1, PEE4 Preeclampsia, susceptibility to, 189800 (3) EPHX1 Preeclampsia, susceptibility to (3) AGT, SERPINA8 Prekallikrein deficiency (3) KLKB1, KLK3 Premature chromosome condensation with MCPH1 microcephaly and mental retardation, 606858 (3) Premature ovarian failure, 300511 (3) DIAPH2, DIA, POF2 Premature ovarian failure 3, 608996 (3) FOXL2, BPES, BPES1, PFRK, POF3 Primary lateral sclerosis, juvenile, 606353 ALS2, ALSJ, PLSJ, IAHSP
(3) Prion disease with protracted course, PRNP, PRIP
606688 (3) Progressive external ophthalmoplegia with ClOorf2, TWINKLE, PEO1, PEO
mitochondrial DNA deletions, 157640 (3) Progressive external ophthalmoplegia with POLG, POLG1, POLGA, PEO
mitochondrial DNA deletions, 157640 (3) Progressive external ophthalmoplegia with SLC25A4, ANTI, T1, PEO3 mitochondrial DNA deletions, 157640 (3) Proguanil poor metabolizer (3) CYP2C, CYP2C19 Prolactinoma, hyperparathyroidism, MEN1 carcinoid syndrome (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Prolidase deficiency (3) PEPD
Properdin deficiency, X-linked, 312060 (3) PFC, PFD
Propionicacidemia, 606054 (3) PCCA
Propionicacidemia, 606054 (3) PCCB
Prostate cancer 1, 176807, 601518 (3) RNASEL, RNS4, PRCA1, HPC1 Prostate cancer, 176807 (3) BRCA2, FANCD1 Prostate cancer, 176807 (3) PTEN, MMAC1 Prostate cancer (3) AR, DHTR, TFM, SBMA, KD, SMAX1 Prostate cancer, familial, 176807 (3) CHEK2, RAD53, CHK2, CDS1, LFS2 Prostate cancer, hereditary, 176807 (3) MSR1 Prostate cancer, progression and EPHB2, EPHT3, DRT, ERK
metastasis of, 176807 (3) Prostate cancer, somatic, 176807 (3) KLF6, COPEB, BCD1, ZF9 Prostate cancer, somatic, 176807 (3) MAD1L1, TXBP181 Prostate cancer, susceptibility to, 176807 AR, DHTR, TFM, SBMA, KD, SMAX1 (3) Prostate cancer, susceptibility to, 176807 ATBF1 (3) Prostate cancer, susceptibility to, 176807 ELAC2, HPC2 (3) Prostate cancer, susceptibility to, 176807 MXI1 (3) Protein S deficiency (3) PROS1 Proteinuria, low molecular weight, with CLCN5, CLCK2, NPHL2, DENTS
hypercalciuric nephrocalcinosis (3) Protoporphyria, erythropoietic (3) FECH, FCE
Protoporphyria, erythropoietic, recessive, FECH, FCE
with liver failure (3) Proud syndrome, 300004 (3) ARX, ISSX, PRTS, MRXS1, MRX36, TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Pseudoachondroplasia, 177170 (3) COMP, EDM1, MED, PSACH
Pseudohermaphroditism, male, with HSD17B3, EDH17B3 gynecomastia, 264300 (3) Pseudohermaphroditism, male, with Leydig LHCGR
cell hypoplasia (3) Pseudohypoaldosteronism, type I, 264350 SCNN1A
(3) Pseudohypoaldosteronism, type I, 264350 SCNN1B
(3) Pseudohypoaldosteronism, type I, 264350 SCNN1G, PHA1 (3) Pseudohypoaldosteronism type I, autosomal NR3C2, MLR, MCR
dominant, 177735 (3) Pseudohypoaldosteronism type II (3) WNK4, PRKWNK4, PHA2B
Pseudohypoaldosteronism, type IIC, 145260 WNK1, PRKWNK1, KDP, PHA2C
(3) Pseudohypoparathyroidism, type la, 103580 GNAS, GNAS1, GPSA, POH, PHP1 B, (3) PHP1A, AHO
Pseudohypoparathyroidism, type Ib, 603233 GNAS, GNAS1, GPSA, POH, PHP1 B, (3) PHP1A, AHO
Pseudovaginal perineoscrotal hypospadias, SRD5A2 264600 (3) Pseudovitamin D deficiency rickets 1 (3) CYP27B1, PDDR, VDD1 Pseudoxanthoma elasticum, autosomal ABCC6, ARA, ABC34, MLP1, PXE
dominant, 177850 (3) Pseudoxanthoma elasticum, autosomal ABCC6, ARA, ABC34, MLP1, PXE
recessive, 264800 (3) Psoriasis, susceptibility to, 177900 (3) PSORS6 Psoriatic arthritis, susceptibility to, 607507 CARD15, NOD2, IBD1, CD, ACUG, (3) PSORAS1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Pulmonary alveolar proteinosis, 265120 (3) CSF2RB
Pulmonary alveolar proteinosis, 265120 (3) SFTPC, SFTP2 Pulmonary alveolar proteinosis, congenital, SFTPB, SFTB3 265120 (3) Pulmonary fibrosis, idiopathic, familial, SFTPC, SFTP2 178500 (3) Pulmonary fibrosis, idiopathic, susceptibility SFTPA1, SFTP1 to, 178500 (3) Pulmonary hypertension, familial primary, BMPR2, PPH1 178600 (3) Pycnodysostosis, 265800 (3) CTSK
Pyloric stenosis, infantile hypertrophic, NOS1 susceptibility to, 179010 (3) Pyogenic sterile arthritis, pyoderma PSTPIP1, PSTPIP, CD2BP1, PAPAS
gangrenosum, and acne, 604416 (3) Pyropoikilocytosis (3) SPTA1 Pyruvate carboxylase deficiency, 266150 (3) PC
Pyruvate dehydrogenase deficiency (3) PDHA1, PHE1A
Pyruvate dehydrogenase El-beta deficiency PDHB
(3) Rabson-Mendenhall syndrome, 262190 (3) INSR
Radioulnar synostosis with amegakaryocytic HOXA1 1, HOX1 I
thrombocytopenia, 605432 (3) RAPADILINO syndrome, 266280 (3) RECQL4, RTS, RECQ4 Rapid progression to AIDS from HIV1 CX3CR1, GPR13, V28 infection (3) Rapp-Hodgkin syndrome, 129400 (3) TP73L, TP63, KET, EEC3, SHFM4, LMS, RHS
Red hair/fair skin (3) MC1 R
Refsum disease, 266500 (3) PEX7, RCDP1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Refsum disease, 266500 (3) PHYH, PAHX
Refsum disease, infantile, 266510 (3) PEX1, ZWS1 Refsum disease, infantile form, 266510 (3) PEX26 Refsum disease, infantile form, 266510 (3) PXMP3, PAF1, PMP35, PEX2 Renal carcinoma, chromophobe, somatic, FLCN, BHD
144700 (3) Renal cell carcinoma, 144700 (3) TRC8, RCA1, HRCA1 Renal cell carcinoma, clear cell, somatic, OGG1 144700 (3) Renal cell carcinoma, papillary, 1, 605074 PRCC, RCCP1 (3) Renal cell carcinoma, papillary, 1, 605074 TFE3 (3) Renal cell carcinoma, papillary, familial and MET
sporadic, 605074 (3) Renal cell carcinoma, somatic (3) VHL
Renal glucosuria, 233100 (3) SLC5A2, SGLT2 Renal hypoplasia, isolated (3) PAX2 Renal tubular acidosis, distal, 179800, SLC4A1, AE1, EPB3 602722 (3) Renal tubular acidosis, distal, autosomal ATP6VOA4, ATP6N 1 B, VPP2, RTA1 C, recessive, 602722 (3) RTADR
Renal tubular acidosis-osteopetrosis CA2 syndrome (3) Renal tubular acidosis, proximal, with ocular SLC4A4, NBC1, KNBC, SLC4A5 abnormalities, 604278 (3) Renal tubular acidosis with deafness, ATP6B1, VPP3 267300 (3) Renal tubular dysgenesis, 267430 (3) ACE, DCP1, ACE1 Renal tubular dysgenesis, 267430 (3) AGTR1, AGTR1A, AT2R1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Renal tubular dysgenesis, 267430 (3) AGT, SERPINA8 Renal tubular dysgenesis, 267430 (3) REN
Renpenning syndrome, 309500 (3) PQBP1, NPW38, SHS, MRX55, MRXS3, RENS1, MRXS8 Response to morphine-6-glucuronide (3) OPRM1 Resting heart rate, 607276 (3) ADRB1, ADRB1R, RHR
Restrictive dermopathy, lethal, 275210 (3) ZMPSTE24, FACE1, STE24, MADB
Retinal degeneration, autosomal recessive, NRL, D14S46E, RP27 clumped pigment type (3) Retinal degeneration, autosomal recessive, PROM1, PROML1, AC133 prominin-related (3) Retinal degeneration, late-onset, autosomal CIQTNF5, CTRP5, LORD
dominant, 605670 (3) Retinal dystrophy, early-onset severe (3) LRAT
Retinitis pigmentosa-10, 180105 (3) IMPDH1 Retinitis pigmentosa-11, 600138 (3) PRPF31, PRP31 Retinitis pigmentosa-1, 180100 (3) RP1, ORP1 Retinitis pigmentosa-12, autosomal CRB1, RP12 recessive, 600105 (3) Retinitis pigmentosa-13, 600059 (3) PRPF8, PRPC8, RP13 Retinitis pigmentosa-14, 600132 (3) TULP1, RP14 Retinitis pigmentosa-17, 600852 (3) CA4, RP17 Retinitis pigmentosa-18, 601414 (3) HPRP3, RP18 Retinitis pigmentosa-19, 601718 (3) ABCA4, ABCR, STGD1, FFM, RP19 Retinitis pigmentosa-20 (3) RPE65, RP20 Retinitis pigmentosa-2 (3) RP2 Retinitis pigmentosa-26, 608380 (3) CERKL
Retinitis pigmentosa-27 (3) NRL, D14S46E, RP27 Retinitis pigmentosa-30, 607921 (3) FSCN2, RFSN
Retinitis pigmentosa-3, 300389 (3) RPGR, RP3, CRD, RP15, COD1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Retinitis pigmentosa-4, autosomal dominant RHO, RP4, OPN2 (3) Retinitis pigmentosa-7, 608133 (3) RDS, RP7, PRPH2, PRPH, AVMD, AOFMD
Retinitis pigmentosa-9, 180104 (3) RP9 Retinitis pigmentosa, AR, 268000 (3) RLBP1 Retinitis pigmentosa, AR, without hearing USH2A
loss, 268000 (3) Retinitis pigmentosa, autosomal dominant RGR
(3) Retinitis pigmentosa, autosomal recessive, CNGB1, CNCG3L, CNCG2 268000 (3) Retinitis pigmentosa, autosomal recessive CNGA1, CNCG1 (3) Retinitis pigmentosa, autosomal recessive PDE6A, PDEA
(3) Retinitis pigmentosa, autosomal recessive PDE6B, PDEB, CSNB3 (3) Retinitis pigmentosa, autosomal recessive RGR
(3) Retinitis pigmentosa, autosomal recessive RHO, RP4, OPN2 (3) Retinitis pigmentosa, digenic (3) ROM1, ROSP1 Retinitis pigmentosa, digenic, 608133 (3) RDS, RP7, PRPH2, PRPH, AVMD, AOFMD
Retinitis pigmentosa, juvenile (3) AIPL1, LCA4 Retinitis pigmentosa, late onset, 268000 (3) NR2E3, PNR, ESCS
Retinitis pigmentosa, late-onset dominant, CRX, CORD2, CRD
268000 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Retinitis pigmentosa, MERTK-related, MERTK
268000 (3) Retinitis pigmentosa, X-linked with deafness RPGR, RP3, CRD, RP15, COD1 and sinorespiratory infections, 300455 (3) Retinitis pigmentosa, X-linked, with RPGR, RP3, CRD, RP15, COD1 recurrent respiratory infections, 300455 (3) Retinitis punctata albescens, 136880 (3) RDS, RP7, PRPH2, PRPH, AVMD, AOFMD
Retinitis punctata albescens, 136880 (3) RLBP1 Retinoblastoma (3) RB1 Retinol binding protein, deficiency of (3) RBP4 Retinoschisis (3) RS1, XLRS1 Rett syndrome, 312750 (3) MECP2, RTT, PPMX, MRX16, MRX79 Rett syndrome, atypical, 312750 (3) CDKL5, STK9 Rett syndrome, preserved speech variant, MECP2, RTT, PPMX, MRX16, MRX79 312750 (3) Rhabdoid predisposition syndrome, familial SMARCB1, SNF5, IN11, RDT
(3) Rhabdoid tumors (3) SMARCB1, SNF5, IN11, RDT
Rhabdomyosarcoma, 268210 (3) SLC22A1L, BWSCR1A, IMPT1 Rhabdomyosarcoma, alveolar, 268220 (3) FOXO1A, FKHR
Rhabdomyosarcoma, alveolar, 268220 (3) PAX3, WS1, HUP2, CDHS
Rhabdomyosarcoma, alveolar, 268220 (3) PAX7 Rheumatoid arthritis, progression of, IL10, CSIF
180300 (3) Rheumatoid arthritis, susceptibility to, MHC2TA, C2TA
180300 (3) Rheumatoid arthritis, susceptibility to, NFKBIL1 180300 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Rheumatoid arthritis, susceptibility to, PAD14, PAD15, PAD
180300 (3) Rheumatoid arthritis, susceptibility to, PTPN8, PEP, PTPN22, LYP
180300 (3) Rheumatoid arthritis, susceptibility to, RUNX1, CBFA2, AML1 180300 (3) Rheumatoid arthritis, susceptibility to, SLC22A4, OCTN1 180300 (3) Rheumatoid arthritis, systemic juvenile, MIF
susceptibility to, 604302 (3) Rhizomelic chondrodysplasia punctata, type PEX7, RCDP1 1, 215100 (3) Rhizomelic chondrodysplasia punctata, type AGPS, ADHAPS
3, 600121 (3) Rh-mod syndrome (3) RHAG, RH50A
Rh-negative blood type (3) RHD
Rh-null disease, amorph type (3) RHCE
Ribose 5-phosphate isomerase deficiency, RPIA, RPI
608611 (3) Rickets due to defect in vitamin D 25- CYP2R1 hydroxylation, 600081 (3) Rickets, vitamin D-resistant, type IIA, VDR
277440 (3) Rickets, vitamin D-resistant, type IIB, VDR
277420 (3) Rieger anomaly (3) FOXC1, FKHL7, FREAC3 Rieger syndrome, 180500 (3) PITX2, IDG2, RIEG1, RGS, IGDS2 Ring dermoid of cornea, 180550 (3) PITX2, IDG2, RIEG1, RGS, IGDS2 Rippling muscle disease, 606072 (3) CAV3, LGMD1C
Roberts syndrome, 268300 (3) ESCO2 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Robinow syndrome, autosomal recessive, ROR2, BDB1, BDB, NTRKR2 268310 (3) Rokitansky-Kuster-Hauser syndrome, WNT4 277000 (3) Rothmund-Thomson syndrome, 268400 (3) RECQL4, RTS, RECQ4 Roussy-Levy syndrome, 180800 (3) MPZ, CMT1 B, CMTD13, CHM, DSS
Roussy-Levy syndrome, 180800 (3) PMP22, CMT1A, CMT1E, DSS
Rubenstein-Taybi syndrome, 180849 (3) CREBBP, CBP, RSTS
Rubinstein-Taybi syndrome, 180849 (3) EP300 Saethre-Chotzen syndrome, 101400 (3) FGFR2, BEK, CFD1, JWS
Saethre-Chotzen syndrome, 101400 (3) TWIST, ACS3, SCS
Saethre-Chotzen syndrome with eyelid TWIST, ACS3, SCS
anomalies, 101400 (3) Salivary adenoma (3) HMGA2, HMGIC, BABL, LIPO
Salla disease, 604369 (3) SLC17A5, SIASD, SLD
Sandhoff disease, infantile, juvenile, and HEXB
adult forms, 268800 (3) Sanfilippo syndrome, type A, 252900 (3) SGSH, MPS3A, SFMD
Sanfilippo syndrome, type B (3) NAGLU
Sarcoidosis, early-onset, 181000 (3) CARD15, NOD2, IBD1, CD, ACUG, Sarcoidosis, susceptibility to, 181000 (3) BTNL2 Sarcoidosis, susceptibility to, 181000 (3) HLA-DR1 B
Sarcoma, synovial (3) SSX1, SSRC
Sarcoma, synovial (3) SSX2 SARS, progression of (3) ACE, DCP1, ACE1 Schimke immunoosseous dysplasia, SMARCAL1, HARP, SIOD
242900 (3) Schindler disease, type 1, 609241 (3) NAGA
Schindler disease, type III, 609241 (3) NAGA

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Schizencephaly, 269160 (3) EMX2 Schizoaffective disorder, susceptibility to, DISC1 181500 (3) Schizophrenia 5, 603175 (3) TRAR4 Schizophrenia, chronic (3) APP, AAA, CVAP, AD1 Schizophrenia, susceptibility to, 181500 (3) COMT
Schizophrenia, susceptibility to, 181500 (3) DISC1 Schizophrenia, susceptibility to, 181500 (3) HTR2A
Schizophrenia, susceptibility to, 181500 (3) RTN4R, NOGOR
Schizophrenia, susceptibility to, 181500 (3) SYN2 Schizophrenia, susceptibility to, 181510 (3) EPN4, EPNR, KIAA0171, SCZD1 Schizophrenia, susceptibility to, 4 600850 PRODH, PRODH2, SCZD4 (3) Schwannomatosis, 162091 (3) NF2 Schwartz-Jampel syndrome, type 1, 255800 HSPG2, PLC, SJS, SJA, SJS1 (3) SCID, autosomal recessive, T-negative/B- JAK3, JAKL
positive type (3) Sclerosteosis, 269500 (3) SOST
Scurvy (3) GULOP, GULO
Sea-blue histiocyte disease, 269600 (3) APOE, AD2 Seasonal affective disorder, susceptibility to, HTR2A
608516 (3) Sebastian syndrome, 605249 (3) MYH9, MHA, FTNS, DFNA17 Seckel syndrome 1, 210600 (3) ATR, FRP1, SCKL
Segawa syndrome, recessive (3) TH, TYH
Seizures, afebrile, 604233 (3) SCN2A1, SCN2A
Seizures, benign familial neonatal-infantile, SCN2A1, SCN2A
607745 (3) Selective T-cell defect (3) ZAP70, SRK, STD

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Self-healing collodion baby, 242300 (3) TGM1, ICR2, LI1 SEMD, Pakistani type (3) PAPSS2, ATPSK2 Senior-Loken syndrome-1, 266900 (3) NPHP1, NPH1, SLSN1 Senior-Loken syndrome 4, 606996 (3) NPHP4, SLSN4 Senior-Loken syndrome 5, 609254 (3) IQCB1, NPHP5, KIAA0036 Sensory ataxic neuropathy, dysarthria, and POLG, POLG1, POLGA, PEO
ophthalmoparesis, 157640 (3) Sepiapterin reductase deficiency (3) SPR
Sepsis, susceptibility to (3) CASP12, CASP12P1 Septic shock, susceptibility to (3) TNF, TNFA
Septooptic dysplasia, 182230 (3) HESX1, RPX
Sertoli cell-only syndrome, susceptibility to, USP26 305700 (3) Severe combined immunodeficiency, DCLREIC, ARTEMIS, SCIDA
Athabascan type, 602450 (3) Severe combined immunodeficiency, B cell- RAG1 negative, 601457 (3) Severe combined immunodeficiency, B cell- RAG2 negative, 601457 (3) Severe combined immunodeficiency due to ADA
ADA deficiency, 102700 (3) Severe combined immunodeficiency due to PTPRC, CD45, LCA
PTPRC deficiency (3) Severe combined immunodeficiency, T-cell IL7R
negative, B-cell/natural killer cell-positive type, 600802 (3) Severe combined immunodeficiency, T- CD3D, T3D
negative/B-positive type, 600802 (3) Severe combined immunodeficiency, X- IL2RG, SCIDX1, SCIDX, IMD4 linked, 300400 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Sex reversal, XY, with adrenal failure (3) FTZF1, FTZ1, SF1 Sezary syndrome (3) BCL10 Shah-Waardenburg syndrome, 277580 (3) EDN3 Short stature, autosomal dominant, with GHR
normal serum growth hormone binding protein (3) Short stature, idiopathic (3) GHR
Short stature, idiopathic familial, 604271 (3) SHOX, GCFX, SS, PHOG
Short stature, idiopathic familial, 604271 (3) SHOXY
Short stature, pituitary and cerebellar LHX4 defects, and small sella turcica, 606606 (3) Shprintzen-Goldberg syndrome, 182212 (3) FBN1, MFS1, WMS
Shwachman-Diamond syndrome, 260400 SBDS, SDS
(3) Sialic acid storage disorder, infantile, SLC17A5, SIASD, SLD
269920 (3) Sialidosis, type I, 256550 (3) NEU1, NEU, SIAL1 Sialidosis, type II, 256550 (3) NEU1, NEU, SIAL1 Sialuria, 269921 (3) GNE, GLCNE, IBM2, DMRV, NM
Sickle cell anemia (3) HBB
Sick sinus syndrome, 608567 (3) SCN5A, LQT3, IVF, HB1, SSS1 Silver spastic paraplegia syndrome, 270685 BSCL2, SPG17 (3) Simpson-Golabi-Behmel syndrome, type 1, GPC3, SDYS, SGBS1 312870 (3) Sitosterolemia, 210250 (3) ABCG5 Sitosterolemia, 210250 (3) ABCG8 Situs ambiguus (3) NODAL
Situs inversus viscerum, 270100 (3) DNAH11, DNAHC11 Sjogren-Larsson syndrome, 270200 (3) ALDH3A2, ALDH10, SLS, FALDH

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Skin fragility-woolly hair syndrome, 607655 DSP, KPPS2, PPKS2 (3) Slow acetylation (3) NAT2, AAC2 Slowed nerve conduction velocity, AD, ARHGEF10, KIAA0294 608236 (3) Small patella syndrome, 147891 (3) TBX4 SMED Strudwick type, 184250 (3) COL2A1 Smith-Fineman-Myers syndrome, 309580 ATRX, XH2, XNP, MRXS3, SHS
(3) Smith-Lemli-Opitz syndrome, 270400 (3) DHCR7, SLOS
Smith-Magenis syndrome, 182290 (3) RAI1, SMCR, SMS
Smith-McCort dysplasia, 607326 (3) DYM, FLJ90130, DMC, SMC
Solitary median maxillary central incisor, SHH, HPE3, HLP3, SMMCI
147250 (3) Somatotrophinoma (3) GNAS, GNAS1, GPSA, POH, PHP1B, PHP1A, AHO
Sorsby fundus dystrophy, 136900 (3) TIMP3, SFD
Sotos syndrome, 117550 (3) NSD1, ARA267, STO
Spastic ataxia, Charlevoix-Saguenay type, SACS, ARSACS
270550 (3) Spastic paralysis, infantile onset ascending, ALS2, ALSJ, PLSJ, IAHSP
607225 (3) Spastic paraplegia 10, 604187 (3) KIF5A, NKHC, SPG10 Spastic paraplegia-13, 605280 (3) HSPD1, SPG13, HSP60 Spastic paraplegia-2, 312920 (3) PLP1, PMD
Spastic paraplegia-3A, 182600 (3) SPG3A
Spastic paraplegia-4, 182601 (3) SPG4, SPAST
Spastic paraplegia-6, 600363 (3) NIPA1, SPG6 Spastic paraplegia-7, 607259 (3) PGN, SPG7, CMAR, CAR
Specific granule deficiency, 245480 (3) CEBPE, CRP1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Speech-language disorder-1, 602081 (3) FOXP2, SPCH1, TNRC10, CAGH44 Spermatogenic failure, susceptibility to (3) DAZL, DAZH, SPGYLA
Spherocytosis-1 (3) SPTB
Spherocytosis-2 (3) ANK1, SPH2 Spherocytosis, hereditary (3) SLC4A1, AE1, EPB3 Spherocytosis, hereditary, Japanese type EPB42 (3) Spherocytosis, recessive (3) SPTA1 Spina bifida, 601634 (3) MTHFD, MTHFC
Spina bifida, risk of, 601634, 182940(3) MTR
Spina bifida, risk of, 601634, 182940(3) MTRR
Spinal and bulbar muscular atrophy of AR, DHTR, TFM, SBMA, KD, SMAX1 Kennedy, 313200 (3) Spinal muscrular atrophy, late-onset, Finkel VAPB, VAPC, ALS8 type, 182980 (3) Spinal muscular atrophy-1, 253300 (3) SMN1, SMA1, SMA2, SMA3, SMA4 Spinal muscular atrophy-2, 253550 (3) SMN1, SMA1, SMA2, SMA3, SMA4 Spinal muscular atrophy-3, 253400 (3) SMN1, SMA1, SMA2, SMA3, SMA4 Spinal muscular atrophy-4, 271150 (3) SMN1, SMA1, SMA2, SMA3, SMA4 Spinal muscular atrophy, distal, type V, BSCL2, SPG17 600794 (3) Spinal muscular atrophy, distal, type V, GARS, SMAD1, CMT2D
600794 (3) Spinal muscular atrophy, juvenile (3) HEXB
Spinal muscular atrophy with respiratory IGHMBP2, SMUBP2, CATF1, SMARDI
distress, 604320 (3) Spinocerebellar ataxia-10 (3) ATXN10, SCA10 Spinocerebellar ataxia-1, 164400 (3) ATXN1, ATX1, SCA1 Spinocerebellar ataxia 12, 604326 (3) PPP2R2B
Spinocerebellar ataxia 14, 605361 (3) PRKCG, PKCC, PKCG, SCA14 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Spinocerebellar ataxia 17, 607136 (3) TBP, SCA17 Spinocerebellar ataxia-2, 183090 (3) ATXN2, ATX2, SCA2 Spinocerebellar ataxia 25 (3) SCA25 Spinocerebellar ataxia-27, 609307 (3) FGF14, FHF4, SCA27 Spinocerebellar ataxia 4, pure Japanese PLEKHG4 type, 117210 (3) Spinocerebellar ataxia-6, 183086 (3) CACNAIA, CACNL1A4, SCA6 Spinocerebellar ataxia-7, 164500 (3) ATXN7, SCA7, OPCA3 Spinocerebellar ataxia 8, 608768 (3) SCA8 Spinocerebellar ataxia, autosomal recessive TDP1 with axonal neuropathy, 607250 (3) Split hand/foot malformation, type 3, 600095 SHFM3, DAC
(3) Split-hand/foot malformation, type 4, 605289 TP73L, TP63, KET, EEC3, SHFM4, (3) LMS, RHS
Spondylocarpotarsal synostosis syndrome, FLNB, SCT, AOI
272460 (3) Spondylocostal dysostosis, autosomal DLL3, SCDO1 recessive, 1, 277300 (3) Spondylocostal dysostosis, autosomal MESP2 recessive 2, 608681 (3) Spondyloepimeta physeaI dysplasia, 608728 MATN3, EDM5, HOA
(3) Spondyloepiphyseal dysplasia, Kimberley AGC1, CSPG1, MSK16, SEDK
type, 608361 (3) Spondyloepiphyseal dysplasia, Omani type, CHST3, C6ST, C6ST1 608637 (3) Spondyloepiphyseal dysplasia tarda, SEDL, SEDT
313400 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Spondyloepiphyseal dysplasia tarda with WISP3, PPAC, PPD
progressive arthropathy, 208230 (3) Spondylometaphyseal dysplasia, Japanese COL1OA1 type (3) Squamous cell carcinoma, burn scar- TNFRSF6, APT1, FAS, CD95, ALPS1A
related, somatic (3) Squamous cell carcinoma, head and neck, ING1 601400 (3) Squamous cell carcinoma, head and neck, TNFRSF10B, DR5, TRAILR2 601400 (3) Stapes ankylosis syndrome without NOG, SYM1, SYNS1 symphalangism, 184460 (3) Stargardt disease-1, 248200 (3) ABCA4, ABCR, STGD1, FFM, RP19 Stargardt disease 3, 600110 (3) ELOVL4, ADMD, STGD2, STGD3 Startle disease, autosomal recessive (3) GLRA1, STHE
Startle disease/hyperekplexia, autosomal GLRA1, STHE
dominant, 149400 (3) STAT1 deficiency, complete (3) STAT1 Statins, attenuated cholesterol lowering by HMGCR
(3) Steatocystoma multiplex, 184500 (3) KRT17, PC2, PCHC1 Stem-cell leukemia/lymphoma syndrome (3) ZNF198, SCLL, RAMP, FIM
Stevens-Johnson syndrome, HLA-B
carbamazepine-induced, susceptibility to, 608579 (3) Stickler syndrome, type I, 108300 (3) COL2A1 Stickler syndrome, type II, 604841 (3) COL11A1, STL2 Stickler syndrome, type III, 184840 (3) COL11A2, STL3, DFNA13 Stomach cancer, 137215 (3) KRAS2, RASK2 Stroke, susceptibility to, 1, 606799 (3) PDE4D, DPDE3, STRK1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Stroke, susceptibility to, 601367 (3) ALOX5AP, FLAP
Stuve-Wiedemann syndrome/Schwartz- LIFR, STWS, SWS, SJS2 Jampel type 2 syndrome, 601559 (3) Subcortical laminal heteropia, X-linked, DCX, DBCN, LISX
300067 (3) Subcortical laminar heterotopia (3) PAFAH1 B1, LIS1 Succinic semialdehyde dehydrogenase SSADH
deficiency (3) Sucrose intolerance (3) SI
Sudden infant death with dysgenesis of the TSPYL1, TSPYL, SIDDT
testes syndrome, 608800 (3) Sulfite oxidase deficiency, 272300 (3) SUOX
Superoxide dismutase, elevated SOD3 extracellular (3) Supranuclear palsy, progressive, 601104 (3) MAPT, MTBT1, DDPAC, MSTD
Supranuclear palsy, progressive atypical, MAPT, MTBT1, DDPAC, MSTD
260540 (3) Supravalvar aortic stenosis, 185500 (3) ELN
Surfactant deficiency, neonatal, 267450 (3) ABCA3, ABC3 Surfactant protein C deficiency (3) SFTPC, SFTP2 Sutherland-Haan syndrome-like, 300465 (3) ATRX, XH2, XNP, MRXS3, SHS
Sweat chloride elevation without CF (3) CFTR, ABCC7, CF, MRP7 Symphalangism, proximal, 185800 (3) NOG, SYM1, SYNS1 Syndactyly, type III, 186100 (3) GJA1, CX43, ODDD, SDTY3, ODOD
Synostoses syndrome, multiple, 1, 186500 NOG, SYM1, SYNS1 (3) Synpolydactyly, 3/3'4, associated with FBLN1 metacarpal and metatarsal synostoses, 608180 (3) Synpolydactyly, type II, 186000 (3) HOXD13, HOX41, SPD

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Synpolydactyly with foot anomalies, 186000 HOXD13, HOX41, SPD
(3) Systemic lupus erythematosus, TNFSF6, APT1LG1, FASL
susceptibility, 152700 (3) Systemic lupus erythematosus, DNASE1, DNL1 susceptibility to, 152700 (3) Systemic lupus erythematosus, PTPN8, PEP, PTPN22, LYP
susceptibility to, 152700 (3) Systemic lupus erythematosus, PDCD1, SLEB2 susceptibility to, 2, 605218, 152700 (3) Tall stature, susceptibility to (3) MCM6 Tangier disease, 205400 (3) ABCA1, ABC1, HDLDT1, TGD
Tarsal-carpal coalition syndrome, 186570 NOG, SYM1, SYNS1 (3) Tauopathy and respiratory failure (3) MAPT, MTBT1, DDPAC, MSTD
Tay-Sachs disease, 272800 (3) HEXA, TSD
T-cell acute lymphoblastic leukemia (3) BAX
T-cell immunodeficiency, congenital WHN
alopecia, and nail dystrophy (3) T-cell prolymphocytic leukemia, sporadic (3) ATM, ATA, AT1 Temperature-sensitive apoptosis, cellular DAD1 (3) Tetra-amelia, autosomal recessive, 273395 WNT3, INT4 (3) Tetralogy of Fallot, 187500 (3) JAG1, AGS, AHD
Tetralogy of Fallot, 187500 (3) ZFPM2, FOG2 Tetrology of Fallot, 187500 (3) NKX2E, CSX
Thalassemia, alpha-(3) HBA2 Thalassemia-beta, dominant inclusion-body, HBB
603902 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Thalassemia, delta-(3) HBD
Thalassemia due to Hb Lepore (3) HBD
Thalassemia, Hispanic gamma-delta-beta LCRB
(3) Thalassemias, alpha-(3) HBA1 Thalassemias, beta-(3) HBB
Thanatophoric dysplasia, types I and II, FGFR3, ACH
187600 (3) Thiamine-responsive megaloblastic anemia SLC19A2, THTR1 syndrome, 249270 (3) Thrombocythemia, essential, 187950 (3) JAK2 Thrombocythemia, essential, 187950 (3) THPO, MGDF, MPLLG, TPO
Thrombocytopenia-2, 188000 (3) FLJ14813, THC2 Thrombocytopenia, congenital MPL, TPOR, MPLV
amegakaryocytic, 604498 (3) Thrombocytopenia, X-linked, 313900 (3) WAS, IMD2, THC
Thrombocytopenia, X-linked, intermittent, WAS, IMD2, THC
313900 (3) Thromboembolism susceptibility due to F5 factor V Leiden (3) Thrombophilia due to factor V Liverpool (3) F5 Thrombophilia due to heparin cofactor II HCF2, HC2, SERPIND1 deficiency (3) Thrombophilia due to HRG deficiency (3) HRG
Thrombophilia due to protein C deficiency PROC
(3) Thrombophilia due to thrombomodulin THBD, THRM
defect (3) Thrombophilia, dysfibrinogenemic (3) FGB
Thrombophilia, dysfibrinogenemic (3) FGG

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Thrombosis, hyperhomocysteinemic (3) CBS
Thrombotic thrombocytopenic purpura, ADAMTS13, VWFCP, TTP
familial, 274150 (3) Thrombycytosis, susceptibility to, 187950 MPL, TPOR, MPLV
(3) Thymine-uraciluria (3) DPYD, DPD
Thyroid adenoma, hyperfunctioning (3) TSHR
Thyroid carcinoma (3) TP53, P53, LFS1 Thyroid carcinoma, follicular, 188470 (3) MINPP1, HIPER1 Thyroid carcinoma, follicular, 188470 (3) PTEN, MMAC1 Thyroid carcinoma, follicular, somatic, HRAS
188470 (3) Thyroid carcinoma, papillary, 188550 (3) GOLGA5, RFG5, PTC5 Thyroid carcinoma, papillary, 188550 (3) NCOA4, ELE1, PTC3 Thyroid carcinoma, papillary, 188550 (3) PCM1, PTC4 Thyroid carcinoma, papillary, 188550 (3) PRKAR1A, TSE1, CNC1, CAR
Thyroid carcinoma, papillary, 188550 (3) TIF1G, RFG7, PTC7 Thyroid carcinoma, papillary, 188550 (3) TRIM24, TIF1, TIF1A, PTC6 Thyroid hormone organification defect IIA, TPO, TPX
274500 (3) Thyroid hormone resistance, 188570 (3) THRB, ERBA2, THR1 Thyroid hormone resistance, autosomal THRB, ERBA2, THR1 recessive, 274300 (3) Thyrotoxic periodic paralysis, susceptibility CACNA1S, CACNL1A3, CCHL1A3 to, 188580 (3) Thyrotropin-releasing hormone resistance, TRHR
generalized (3) Thyroxine-binding globulin deficiency (3) TBG
Tietz syndrome, 103500 (3) MITF, WS2A
Timothy syndrome, 601005 (3) CACNA1C, CACNL1A1, CCHL1A1, TS

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Toenail dystrophy, isolated, 607523 (3) COL7A1 Tolbutamide poor metabolizer (3) CYP2C9 Total iodide organification defect, 274500 TPO, TPX
(3) Townes-Brocks branchiootorenal-like SALL1, HSAL1, TBS
syndrome, 107480 (3) Townes-Brocks syndrome, 107480 (3) SALL1, HSAL1, TBS
Transaldolase deficiency, 606003 (3) TALDO1 Transcobalamin II deficiency (3) TCN2, TC2 Transient bullous of the newborn, 131705 COL7A1 (3) Transposition of great arteries, dextro- CFC1, CRYPTIC, HTX2 looped, 217095 (3) Transposition of the great arteries, dextro- THRAP2, PROSIT240, TRAP240L, looped, 608808 (3) KIAA1025 Treacher Collins mandibulofacial TCOF1, MFD1 dysostosis, 154500 (3) Tremor, familial essential, 2, 602134 (3) HS1BP3, FLJ14249, ETM2 Trichodontoosseous syndrome, 190320 (3) DLX3, TDO
Trichorhinophalangeal syndrome, type I, TRPS1 190350 (3) Trichorhinophalangeal syndrome, type III, TRPS1 190351 (3) Trichothiodystrophy (3) ERCC3, XPB
Trichothiodystrophy, 601675 (3) ERCC2, EM9 Trichothiodystrophy, complementation TGF2H5, TTDA, TFB5, C6orf175 group A, 601675 (3) Trichothiodystrophy, non photosensitive 1, TTDN1, C7orfl1, ABHS
234050 (3) Trifunctional protein deficiency, type 1 (3) HADHA, MTPA

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Trifunctional protein deficiency, type II (3) HADHB
Trismus-pseudocomptodactyly syndrome, MYH8 158300 (3) Tropical calcific pancreatitis, 608189 (3) SPINK1, PSTI, PCTT, TATI
Troyer syndrome, 275900 (3) SPG20 TSC2 angiomyolipomas, renal, modifier of, IFNG
191100 (3) Tuberculosis, susceptibility to (3) IFNGR1 Tuberculosis, susceptibility to, 607948 (3) IFNG
Tuberous sclerosis-1, 191100 (3) TSC1, LAM
Tuberous sclerosis-2, 191100 (3) TSC2, LAM
Turcot syndrome, 276300 (3) APC, GS, FPC
Turcot syndrome with glioblastoma, 276300 MLH1, COCA2, HNPCC2 (3) Turcot syndrome with glioblastoma, 276300 PMS2, PMSL2, HNPCC4 (3) Twinning, dizygotic, 276400 (3) FSHR, ODG1 Tyrosinemia, type I (3) FAH
Tyrosinemia, type II (3) TAT
Tyrosinemia, type III (3) HPD
Ullrich congenital muscular dystrophy, COL6A1, OPLL
254090 (3) Ullrich congenital muscular dystrophy, COL6A3 254090 (3) Ullrich scleroatonic muscular dystrophy, COL6A2 254090 (3) Ulnar-mammary syndrome, 181450 (3) TBX3 Unipolar depression, susceptibility to, TPH2, NTPH
608516 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Unna-Thost disease, nonepidermolytic, KRT1 600962 (3) Urolithiasis, 2,8-dihydroxyadenine (3) APRT
Urolithiasis, hypophosphatemic (3) SLC17A2, NPT2 Usher syndrome, type 1 B (3) MYO7A, USH1 B, DFNB2, DFNA11 Usher syndrome, type 1 C, 276904 (3) USH1 C, DFNB18 Usher syndrome, type 1 D, 601067 (3) CDH23, USH1D
Usher syndrome, type 1 F, 602083 (3) PCDH15, DFNB23 Usher syndrome, type 1 G, 606943 (3) SANS, USH 1 G
Usher syndrome, type 2A, 276901 (3) USH2A
Usher syndrome, type 3, 276902 (3) USH3A, USH3 Usher syndrome, type IIC, 605472 (3) MASS1, VLGR1, KIAA0686, FEB4, Uterine leiomyoma (3) HMGA2, HMGIC, BABL, LIPO
UV-induced skin damage, vulnerability to (3) MC1 R
van Buchem disease, type 2, 607636 (3) LRP5, BMND1, LRP7, LR3, OPPG, van der Woude syndrome, 119300 (3) IRF6, VWS, LPS, PIT, PPS, OFC6 VATER association with hydrocephalus, PTEN, MMAC1 276950 (3) Velocardiofacial syndrome, 192430 (3) TBX1, DGS, CTHM, CAFS, TGA, DORV, VCFS, DGCR
Venous malformations, multiple cutaneous TEK, TIE2, VMCM
and mucosal, 600195 (3) Venous thrombosis, susceptibility to (3) SERPINA10, ZPI
Ventricular fibrillation, idiopathic, 603829 (3) SCN5A, LQT3, IVF, HB1, SSS1 Ventricular tachycardia, idiopathic, 192605 GNAI2, GNAI2B, GIP
(3) Ventricular tachycardia, stress-induced CASQ2 polymorphic, 604772 (3) TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Ventricular tachycardia, stress-induced RYR2, VTSIP
polymorphic, 604772 (3) Vertical talus, congenital, 192950 (3) HOXD10, HOX4D
Viral infections, recurrent (3) FCGR3A, CD16, IGFR3 Viral infection, susceptibility to (3) OAS1, OIAS
Virilization, maternal and fetal, from CYP19A1, CYP19, ARO
placental aromatase deficiency (3) Vitamin K-dependent clotting factors, VKORC1, VKOR, VKCFD2, FLJO0289 combined deficiency of, 2, 607473 (3) Vitamin K-dependent coagulation defect, GGCX
277450 (3) Vitelliform macular dystrophy, adult-onset, VMD2 608161 (3) VLCAD deficiency, 201475 (3) ACADVL, VLCAD
Vohwinkel syndrome, 124500 (3) GJB2, CX26, DFNB1, PPK, DFNA3, KID, HID
Vohwinkel syndrome with ichthyosis, LOR
604117 (3) von Hippel-Lindau disease, modification of, CCND1, PRAD1, BCL1 193300 (3) von Hippel-Lindau syndrome, 193300 (3) VHL
von Willebrand disease (3) VWF, F8VWF
Waardenburg-Shah syndrome, 277580 (3) EDNRB, HSCR2, ABCDS
Waardenburg-Shah syndrome, 277580 (3) SOX10, WS4 Waardenburg syndrome/albinism, digenic, TYR
103470 (3) Waardenburg syndrome/ocular albinism, MITF, WS2A
digenic, 103470 (3) Waardenburg syndrome, type I, 193500 (3) PAX3, WS1, HUP2, CDHS

TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Waardenburg syndrome, type IIA, 193510 MITF, WS2A
(3) Waardenburg syndrome, type III, 148820 (3) PAX3, WS1, HUP2, CDHS
Waardenburg syndrome, typ IID, 608890 (3) SNAI2, SLUG, WS2D
Wagner syndrome, 143200 (3) COL2A1 WAGR syndrome, 194072 (3) WT1 Walker-Warburg syndrome, 236670 (3) FCMD
Walker-Warburg syndrome, 236670 (3) POMT1 Warburg micro syndrome 1, 600118 (3) RAB3GAP, WARBM1, P130 Warfarin resistance, 122700 (3) VKORC1, VKOR, VKCFD2, FLJO0289 Warfarin sensitivity, 122700 (3) CYP2C9 Warfarin sensitivity (3) F9, HEMB
Watson syndrome, 193520 (3) NF1, VRNF, WSS, NFNS
Weaver syndrome, 277590 (3) NSD1, ARA267, STO
Wegener-like granulomatosis (3) TAP2, ABCB3, PSF2, RING1 1 Weill-Marchesani syndrome, dominant, FBN1, MFS1, WMS
608328 (3) Weill-Marchesani syndrome, recessive, ADAMTS10, WMS
277600 (3) Weissenbacher-Zweymuller syndrome, COL1 1A2, STL3, DFNA13 277610 (3) Werner syndrome, 277700 (3) RECQL2, RECQ3, WRN
Wernicke-Korsakoff syndrome, susceptibility TKT
to, 277730 (3) Weyers acrodental dysostosis, 193530 (3) EVC
WHIM syndrome, 193670 (3) CXCR4, D2S201 E, NPY3R, WHIM
White sponge nevus, 193900 (3) KRT13 White sponge nevus, 193900 (3) KRT4, CYK4 Williams-Beuren syndrome, 194050 (3) ELN
Wilms tumor, 194070 (3) BRCA2, FANCD1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Wilms tumor, somatic, 194070 (3) GPC3, SDYS, SGBS1 Wilms tumor susceptibility-5, 601583 (3) POU6F2, WTSL, WT5 Wilms tumor, type 1, 194070 (3) WT1 Wilson disease, 277900 (3) ATP7B, WND
Wiskott-Aldrich syndrome, 301000 (3) WAS, IMD2, THC
Witkop syndrome, 189500 (3) MSX1, HOX7, HYD1, OFC5 Wolcott-Rallison syndrome, 226980 (3) EIF2AK3, PEK, PERK, WRS
Wolff-Parkinson-White syndrome, 194200 PRKAG2, WPWS
(3) Wolfram syndrome, 222300 (3) WFS1, WFRS, WFS, DFNA6 Wolman disease (3) LIPA
Xanthinuria, type I, 278300 (3) XDH
Xeroderma pigmentosum, group A (3) XPA
Xeroderma pigmentosum, group B (3) ERCC3, XPB
Xeroderma pigmentosum, group C (3) XPC, XPCC
Xeroderma pigmentosum, group D, 278730 ERCC2, EM9 (3) Xeroderma pigmentosum, group E, DDB- DDB2 negative subtype, 278740 (3) Xeroderma pigmentosum, group F, 278760 ERCC4, XPF
(3) Xeroderma pigmentosum, group G, 278780 ERCC5, XPG
(3) Xeroderma pigmentosum, variant type, POLH, XPV
278750 (3) X-inactivation, familial skewed, 300087 (3) XIC, XCE, XIST, SXI1 XLA and isolated growth hormone BTK, AGMX1, IMD1, XLA, AT
deficiency, 307200 (3) Yellow nail syndrome, 153300 (3) FOXC2, FKHL14, MFH1 TABLE B
DISEASE/DISORDER/INDICATION GENE(S) Yemenite deaf-blind hypopigmentation SOX10, WS4 syndrome, 601706 (3) Zellweger syndrome-1, 214100 (3) PEX1, ZWS1 Zellweger syndrome, 214100 (3) PEX10, NALD
Zellweger syndrome, 214100 (3) PEX13, ZWS, NALD
Zellweger syndrome, 214100 (3) PEX14 Zellweger syndrome, 214100 (3) PEX26 Zellweger syndrome, 214100 (3) PXF, HK33, D1S2223E, PEX19 Zellweger syndrome, 214100 (3) PXR1, PEX5, PTS1R
Zellweger syndrome-2 (3) ABCD3, PXMP1, PMP70 Zellweger syndrome-3 (3) PXMP3, PAF1, PMP35, PEX2 Zellweger syndrome, complementation PEX16 group 9 (3) Zellweger syndrome, complementation PEX3 group G, 214100 (3) Zlotogora-Ogur syndrome, 225000 (3) HVEC, PVRL1, PVRR1, PRR1 [0134] Further non-limiting examples of disease models created by a method of the invention include a Parkinson's disease model, an addiction model, an inflammation model, a cardiovascular disease model, an Alzheimer's disease model, an autism spectrum disorder model, a macular degeneration model, a schizophrenia model, a tumor suppression model, a trinucleotide repeat disorder model, a neurotransmission disorder model, a secretase-associated disorder model, an ALS model, a prion disease model, on ABC transporter protein - associated disorder model, and an immunodeficiency model. Each is discussed in more detail below.

A. Parkinsons disease [0135] In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with Parkinsons disease (PD) has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0136] In some embodiments, one or more chromosomal sequences encoding a protein or control sequence associated with PD may be edited. A PD-associated protein or control sequence may typically be selected based on an experimental association of the PD-associated protein or control sequence to PD. By way of non-limiting example, the production rate or circulating concentration of a PD-related protein may be elevated or depressed in a population having PD relative to a population not having PD. Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art. By way of non-limiting example, proteins associated with Parkinson's disease include but are not limited to a-synuclein, DJ-1, LRRK2, PINK1, Parkin, UCHL1, Synphilin-1, and NURR1.
[0137] In certain embodiments, an animal created by a method of the invention may be used to study the effects of mutations on the animal and development and/or progression of PD using measures commonly used in the study of PD. Methods for measuring and studying progression of PD in animals are known in the art. Commonly used measures in the study of PD may include without limit, amyloidogenesis or protein aggregation, dopamine response, neurodegeneration, development of mitochondrial related dysfunction phenotypes, as well as functional, pathological or biochemical assays. Other relevant indicators regarding development or progression of PD include coordination, balance, gait, motor impairment, tremors and twitches, rigidity, hypokinesia, and cognitive impairments. Such assays may be made in comparison to wild type littermates.

B. addiction [0138] Addiction, as used herein, is defined as a chronic disease of brain reward, motivation, memory, and related neuronal circuitry contained within various brain structures. Specific examples of brain structures that may experience dysfunction associated with an addiction disorder include nucleus accumbens, ventral pallidum, dorsal thalamus, prefrontal cortex, striatum, substantia nigra, pontine reticular formation, amygdala, and ventral tegmental area. Dysfunction in these neural circuits may lead to various biological, psychological, social and behavioral symptoms of addiction.
[0139] Biological symptoms of addiction may include overproduction or underproduction of one or more addiction-related proteins;
redistribution of one or more addiction-related proteins within the brain; the development of tolerance, reverse tolerance, or other changes in sensitivity to the effects of an addictive substance or a neurotransmitter within the brain;
high blood pressure; and withdrawal symptoms such as insomnia, restlessness, loss of appetite, depression, weakness, irritability, anger, pain, and craving.
[0140] Psychological symptoms of addiction may vary depending on the particular addictive substance and the duration of the addiction. Non-limiting examples of psychological symptoms of addiction include mood swings, paranoia, insomnia, psychosis, schizophrenia, tachycardia panic attacks, cognitive impairments, and drastic changes in the personality that can lead to aggressive, compulsive, criminal and/or erratic behaviors.
[0141] Social symptoms of addiction may include low self-esteem, verbal hostility, ignorance of interpersonal means, focal anxiety such as fear of crowds, rigid interpersonal behavior, grossly bizarre behavior, rebelliousness, and diminished recognition of significant problems with an individual's behaviors and interpersonal relationships.
[0142] Non-limiting examples of behavioral symptoms of addiction include impairment in behavioral control, inability to consistently abstain from the use of addictive substances, cycles of relapse and remission, risk-taking behavior, pleasure-seeking behavior, novelty-seeking behavior, relief-seeking behavior, and reward-seeking behavior.
[0143] Addictions may be substance addictions typically associated with the ingestion of addictive substances. Addictive substances may include psychoactive substances capable of crossing the blood-brain barrier and temporarily altering the chemical milieu of the brain. Non-limiting examples of addictive substances include alcohol; opioid compounds such as opium and heroin; sedative, hypnotic, or anxiolytic compounds such as benzodiazepine and barbiturate compounds; cocaine and related compounds; cannabis and related compounds; amphetamine and amphetamine-like compounds; hallucinogen compounds; inhalants such as glue or aerosol propellants; phencyclidine or phencyclidine-like compounds; and nicotine. In addition, addictions may be behavioral addictions associated with compulsions that are not substance-related, such as problem gambling and computer addiction.
[0144] In one embodiment, a method of the invention may be used to create an animal or cell in which at least one addiction-related chromosomal sequence has been edited. Suitable edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0145] Addiction-related nucleic acid sequences are a diverse set of sequences associated with susceptibility for developing an addiction, the presence of an addiction, the severity of an addiction or any combination thereof.
An addiction-related nucleic acid sequence may typically be selected based on an experimental association of the addiction-related nucleic acid sequence to an addiction disorder. An addiction-related nucleic acid sequence may encode an addiction-related protein or may be an addiction-related control sequence. By way of non-limiting example, the production rate or circulating concentration of an addiction-related protein may be elevated or depressed in a population having an addiction disorder relative to a population lacking the addiction disorder.
Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art.

[0146] Non-limiting examples of addiction-related proteins include ABAT (4-aminobutyrate aminotransferase); ACN9 (ACN9 homolog (S.
cerevisae)); ADCYAP1 (Adenylate cyclase activating polypeptide 1); ADH1 B
(Alcohol dehydrogenase IB (class I), beta polypeptide); ADH1C (Alcohol dehydrogenase 1 C (class I), gamma polypeptide); ADH4 (Alcohol dehydrogenase 4); ADH7 (Alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide); ADORA1 (Adenosine Al receptor); ADRA1A (Adrenergic, alpha-1A-, receptor); ALDH2 (Aldehyde dehydrogenase 2 family); ANKK1 (Ankyrin repeat, Tagl Al allele); ARC (Activity-regulated cytoskeleton-associated protein);
ATF2 (Corticotrophin-releasing factor); AVPR1A (Arginine vasopressin receptor 1A); BDNF (Brain-derived neurotrophic factor); BMAL1 (Aryl hydrocarbon receptor nuclear translocator-like); CDK5 (Cyclin-dependent kinase 5); CHRM2 (Cholinergic receptor, muscarinic 2); CHRNA3 (Cholinergic receptor, nicotinic, alpha 3); CHRNA4 (Cholinergic receptor, nicotinic, alpha 4); CHRNA5 (Cholinergic receptor, nicotinic, alpha 5); CHRNA7 (Cholinergic receptor, nicotinic, alpha 7); CHRNB2 (Cholinergic receptor, nicotinic, beta 2); CLOCK
(Clock homolog (mouse)); CNR1 (Cannabinoid receptor 1); CNR2 (Cannabinoid receptor type 2); COMT (Catechol-O-methyltransferase); CREB1 (cAMP
Responsive element binding protein 1); CREB2 (Activating transcription factor 2);
CRHR1 (Corticotropin releasing hormone receptor 1); CRY1 (Cryptochrome 1);
CSNK1 E (Casein kinase 1, epsilon); CSPG5 (Chondroitin sulfate proteoglycan 5); CTNNB1 (Catenin (cadherin-associated protein), beta 1, 88kDa); DBI
(Diazepam binding inhibitor); DDN (Dendrin); DRD1 (Dopamine receptor D1);
DRD2 (Dopamine receptor D2); DRD3 (Dopamine receptor D3); DRD4 (Dopamine receptor D4); EGR1 (Early growth response 1); ELTD1 (EGF, latrophilin and seven transmembrane domain containing 1); FAAH (Fatty acid amide hydrolase); FOSB (FBJ murine osteosarcoma viral oncogene homolog);
FOSB (FBJ murine osteosarcoma viral oncogene homolog B); GABBR2 (Gamma-aminobutyric acid (GABA) B receptor, 2); GABRA2 (Gamma-aminobutyric acid (GABA) A receptor, alpha 2); GABRA4 (Gamma-aminobutyric acid (GABA) A receptor, alpha 4); GABRA6 (Gamma-aminobutyric acid (GABA) A receptor, alpha 6); GABRB3 (Gamma-aminobutyric acid (GABA) A receptor, alpha 3); GABRE (Gamma-aminobutyric acid (GABA) A receptor, epsilon);
GABRG1 (Gamma-aminobutyric acid (GABA) A receptor, gamma 1); GAD1 (Glutamate decarboxylase 1); GAD2 (Glutamate decarboxylase 2); GAL (Galanin prepropeptide); GDNF (Glial cell derived neurotrophic factor); GRIA1 (Glutamate receptor, ionotropic, AMPA 1); GRIA2 (Glutamate receptor, ionotropic, AMPA 2);
GRIN1 (Glutamate receptor, ionotropic, N-methyl D-aspartate 1); GRIN2A
(Glutamate receptor, ionotropic, N-methyl D-aspartate 2A); GRM2 (Glutamate receptor, metabotropic 2, mGluR2); GRM5 (Metabotropic glutamate receptor 5);
GRM6 (Glutamate receptor, metabotropic 6); GRM8 (Glutamate receptor, metabotropic 8); HTR1 B (5-Hydroxytryptamine (serotonin) receptor 1 B); HTR3A
(5-Hydroxytryptamine (serotonin) receptor 3A); IL1 (Interleukin 1); U5 (Interleukin 15); ILIA (Interleukin 1 alpha); IL1 B (Interleukin 1 beta);

(Potassium large conductance calcium-activated channel, subfamily M, alpha member 1); LGALS1 (lectin galactoside-binding soluble 1); MAOA (Monoamine oxidase A); MAOB (Monoamine oxidase B); MAPK1 (Mitogen-activated protein kinase 1); MAPK3 (Mitogen-activated protein kinase 3); MBP (Myelin basic protein); MC2R (Melanocortin receptor type 2); MGLL (Monoglyceride lipase);
MOBP (Myelin-associated oligodendrocyte basic protein); NPY (Neuropeptide Y);
NR4A1 (Nuclear receptor subfamily 4, group A, member 1); NR4A2 (Nuclear receptor subfamily 4, group A, member 2); NRXN1 (Neurexin 1); NRXN3 (Neurexin 3); NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2); NTRK2 (Tyrosine kinase B neurotrophin receptor); OPRD1 (delta-Opioid receptor);
OPRK1 (kappa-Opioid receptor); OPRM1 (mu-Opioid receptor); PDYN
(Dynorphin); PENK (Enkephalin); PER2 (Period homolog 2 (Drosophila));
PKNOX2 (PBX/knotted 1 homeobox 2); PLP1 (Proteolipid protein 1); POMC
(Proopiomelanocortin); PRKCE (Protein kinase C, epsilon); PROKR2 (Prokineticin receptor 2); RGS9 (Regulator of G-protein signaling 9); RIMS2 (Regulating synaptic membrane exocytosis 2); SCN9A (sodium channel voltage-gated type IX alpha subunit); SLC1 7A6 (Solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 6); SLC17A7 (Solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 7); SLC1A2 (Solute carrier family 1 (glial high affinity glutamate transporter), member 2); SLC1A3 (Solute carrier family 1 (glial high affinity glutamate transporter), member 3); SLC29A1 (solute carrier family 29 (nucleoside transporters), member 1); SLC4A7 (Solute carrier family 4, sodium bicarbonate cotransporter, member 7); SLC6A3 (Solute carrier family 6 (neurotransmitter transporter, dopamine), member 3); SLC6A4 (Solute carrier family 6 (neurotransmitter transporter, serotonin), member 4); SNCA
(Synuclein, alpha (non A4 component of amyloid precursor)); TFAP2B (Transcription factor AP-2 beta); and TRPV1 (Transient receptor potential cation channel, subfamily V, member 1).
[0147] Preferred addiction-related proteins may include ABAT (4-aminobutyrate aminotransferase), DRD2 (Dopamine receptor D2), DRD3 (Dopamine receptor D3), DRD4 (Dopamine receptor D4), GRIA1 (Glutamate receptor, ionotropic, AMPA 1), GRIA2 (Glutamate receptor, ionotropic, AMPA 2), GRIN1 (Glutamate receptor, ionotropic, N-methyl D-aspartate 1), GRIN2A
(Glutamate receptor, ionotropic, N-methyl D-aspartate 2A), GRM5 (Metabotropic glutamate receptor 5), HTR1 B (5-Hydroxytryptamine (serotonin) receptor 1 B), PDYN (Dynorphin), PRKCE (Protein kinase C, epsilon), LGALS1 (lectin galactoside-binding soluble 1), TRPV1 (transient receptor potential cation channel subfamily V member 1), SCN9A (sodium channel voltage-gated type IX
alpha subunit), OPRD1 (opioid receptor delta 1), OPRK1 (opioid receptor kappa 1), OPRM1 (opioid receptor mu 1), and any combination thereof.
[0148] In certain embodiments, an animal created by a method of the invention may be used as a model for indications of addiction disorders by comparing the measurements of an assay obtained from a genetically modified animal comprising at least one edited chromosomal sequence encoding an addiction-related protein to the measurements of the assay using a wild-type animal. Non-limiting examples of assays used to assess for indications of an addictive disorder include behavioral assays, physiological assays, whole animal assays, tissue assays, cell assays, biomarker assays, and combinations thereof.
The indications of addiction disorders may occur spontaneously, or may be promoted by exposure to exogenous agents such as addictive substances or addiction-related proteins. Alternatively, the indications of addiction disorders may be induced by withdrawal of an addictive substance or other compound such as an exogenously administered addiction-related protein.
[0149] An additional aspect of the present disclosure encompasses a method of assessing the efficacy of a treatment for inhibiting addictive behaviors and/or reducing withdrawal symptoms of a genetically modified animal comprising at least one edited chromosomal sequence associated with addiction.
Treatments for addiction that may be assessed include the administering of one or more novel candidate therapeutic compounds, a novel combination of established therapeutic compounds, a novel therapeutic method, and any combination thereof. Novel therapeutic methods may include various drug delivery mechanisms, nanotechnology applications in drug therapy, surgery, and combinations thereof.
[0150] Behavioral testing of a genetically modified animal comprising at least one edited addiction-related protein and/or a wild-type animal may be used to assess the side effects of a therapeutic compound or combination of therapeutic agents. The genetically modified animal and optionally a wild-type animal may be treated with the therapeutic compound or combination of therapeutic agents and subjected to behavioral testing. The behavioral testing may assess behaviors including but not limited to learning, memory, anxiety, depression, addiction, and sensory-motor functions.
[0151] An additional aspect provides a method for assessing the therapeutic potential of an agent in an animal that may include contacting a genetically modified animal comprising at least one edited chromosomal sequence encoding an addiction-related protein, and comparing results of a selected parameter to results obtained from a wild-type animal with no contact with the same agent. Selected parameters include but are not limited to a) spontaneous behaviors; b) performance during behavioral testing; c) physiological anomalies; d) abnormalities in tissues or cells; e) biochemical function; and f) molecular structures.

C. inflammation [0152] In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with inflammation has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0153] In each of the above embodiments, one or more chromosomal sequences associated with inflammation may be edited. An inflammation-related chromosomal sequence may typically be selected based on an experimental association of the inflammation-related sequence to an inflammation disorder. An inflammation-related sequence may encode an inflammation-related protein or may be an inflammation-related control sequence. For example, the production rate or circulating concentration of an inflammation-related protein may be elevated or depressed in a population having an inflammation disorder relative to a population lacking the inflammation disorder. Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art.
[0154] Non-limiting examples of inflammation-related proteins whose chromosomal sequence may be edited include the monocyte chemoattractant protein-1 (MCP1) encoded by the Ccr2 gene, the C-C
chemokine receptor type 5 (CCR5) encoded by the Ccr5 gene, the IgG receptor IIB (FCGR2b, also termed CD32) encoded by the Fcgr2b gene, the Fc epsilon R1g (FCER1g) protein encoded by the Fcerlg gene, the forkhead box Ni transcription factor (FOXN1) encoded by the FOXN1 gene, Interferon-gamma (IFN-y) encoded by the IFNg gene, interleukin 4 (IL-4) encoded by the IL-4 gene, perforin-1 encoded by the PRF-1 gene, the cyclooxygenase 1 protein (COX1) encoded by the COX1 gene, the cyclooxygenase 2 protein (COX2) encoded by the COX2 gene, the T-box transcription factor (TBX21) protein encoded by the TBX21 gene, the SH2-B PH domain containing signaling mediator 1 protein (SH2BPSM1) encoded by the SH2B1 gene (also termed SH2BPSM1), the fibroblast growth factor receptor 2 (FGFR2) protein encoded by the FGFR2 gene, the solute carrier family 22 member 1 (SLC22A1) protein encoded by the OCT1 gene (also termed SLC22A1), the peroxisome proliferator-activated receptor alpha protein (PPAR-alpha, also termed the nuclear receptor subfamily 1, group C, member 1; NR1 Cl) encoded by the PPARA gene, the phosphatase and tensin homolog protein (PTEN) encoded by the PTEN gene, interleukin 1 alpha (IL-1 a) encoded by the IL-1A gene, interleukin 1 beta (IL-113) encoded by the IL-1B gene, interleukin 6 (IL-6) encoded by the IL-6 gene, interleukin 10 (IL-10) encoded by the IL-10 gene, interleukin 12 alpha (IL-12a) encoded by the IL-12A
gene, interleukin 12 beta (IL-1213) encoded by the IL-12B gene, interleukin 13 (IL-13) encoded by the IL-13 gene, interleukin 17A(IL-17A, also termed CTLA8) encoded by the IL-17A gene, interleukin 17B(IL-17B) encoded by the IL-17B
gene, interleukin 17C (IL-17C) encoded by the IL-17C gene interleukin 17D (IL-17D) encoded by the IL-17D gene interleukin 17F (IL-17F) encoded by the IL-17F gene, interleukin 23 (IL-23) encoded by the IL-23 gene, the chemokine (C-X3-C motif) receptor 1 protein (CX3CR1) encoded by the CX3CR1 gene, the chemokine (C-X3-C motif) ligand 1 protein (CX3CL1) encoded by the CX3CL1 gene, the recombination activating gene 1 protein (RAG1) encoded by the RAG1 gene, the recombination activating gene 2 protein (RAG2) encoded by the RAG2 gene, the protein kinase, DNA-activated, catalytic polypeptidel (PRKDC) encoded by the PRKDC (DNAPK) gene, the protein tyrosine phosphatase non-receptor type 22 protein (PTPN22) encoded by the PTPN22 gene, tumor necrosis factor alpha (TNFa) encoded by the TNFA gene, the nucleotide-binding oligomerization domain containing 2 protein (NOD2) encoded by the NOD2 gene (also termed CARD15), or the cytotoxic T-lymphocyte antigen 4 protein (CTLA4, also termed CD152) encoded by the CTLA4 gene.
[0155] In certain embodiments, an animal created by a method of the invention may be used to study the effects of mutations on the animal and development and/or progression of inflammation using measures commonly used in the study of inflammation. Alternatively, an animal created by a method of the invention may be used to study the effects of the mutations on the progression of a disease state or disorder associated with inflammation-related proteins using measures commonly used in the study of said disease state or disorder. Non-limiting examples of measures that may be used include spontaneous behaviors of the genetically modified animal, performance during behavioral testing, physiological anomalies, differential responses to a compound, abnormalities in tissues or cells, and biochemical or molecular differences between genetically modified animals and wild type animals.

D. cardiovascular disease [0156] Cardiovascular diseases generally include high blood pressure, heart attacks, heart failure, and stroke and TIA. In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with cardiovascular disease has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0157] Any chromosomal sequence involved in cardiovascular disease or the protein encoded by any chromosomal sequence involved in cardiovascular disease may be utilized in a method of the invention. A
cardiovascular-related sequence may typically be selected based on an experimental association of the cardiovascular-related sequence to the development of cardiovascular disease. A cardiovascular-related nucleic acid sequence may encode a cardiovascular-related protein or may be a cardiovascular-related control sequence. For example, the production rate or circulating concentration of a cardiovascular-related protein may be elevated or depressed in a population having a cardiovascular disorder relative to a population lacking the cardiovascular disorder. Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art.
[0158] By way of example, the chromosomal sequence may comprise, but is not limited to, IL1B (interleukin 1, beta), XDH (xanthine dehydrogenase), TP53 (tumor protein p53), PTGIS (prostaglandin 12 (prostacyclin) synthase), MB (myoglobin),IL4 (interleukin 4), ANGPT1 (angiopoietin 1), ABCG8 (ATP-binding cassette, sub-family G (WHITE), member 8), CTSK (cathepsin K), PTGIR (prostaglandin 12 (prostacyclin) receptor (IP)), KCNJ1 1 (potassium inwardly-rectifying channel, subfamily J, member 11), INS
(insulin), CRP (C-reactive protein, pentraxin-related), PDGFRB (platelet-derived growth factor receptor, beta polypeptide), CCNA2 (cyclin A2), PDGFB (platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog)), KCNJ5 (potassium inwardly-rectifying channel, subfamily J, member 5), KCNN3 (potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3), CAPN10 (calpain 10), PTGES (prostaglandin E synthase), ADRA2B (adrenergic, alpha-2B-, receptor), ABCG5 (ATP-binding cassette, sub-family G (WHITE), member 5), PRDX2 (peroxiredoxin 2), CAPN5 (calpain 5), PARP14 (poly (ADP-ribose) polymerase family, member 14), MEX3C
(mex-3 homolog C (C. elegans)), ACE angiotensin I converting enzyme (peptidyl-dipeptidase A) 1), TNF (tumor necrosis factor (TNF superfamily, member 2)), (interleukin 6 (interferon, beta 2)), STN (statin), SERPINE1 (serpin peptidase inhibitor, Glade E (nexin, plasminogen activator inhibitor type 1), member 1), ALB
(albumin), ADIPOQ (adiponectin, C1 Q and collagen domain containing), APOB
(apolipoprotein B (including Ag(x) antigen)), APOE (apolipoprotein E), LEP
(leptin), MTHFR (5,10-m ethyl enetetrahydrofolate reductase (NADPH)), APOA1 (apolipoprotein A-I), EDN1 (endothelin 1), NPPB (natriuretic peptide precursor B), NOS3 (nitric oxide synthase 3 (endothelial cell)), PPARG (peroxisome proliferator-activated receptor gamma), PLAT (plasminogen activator, tissue), PTGS2 (prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)), CETP (cholesteryl ester transfer protein, plasma), AGTR1 (angiotensin II receptor, type 1), HMGCR (3-hydroxy-3-methylglutaryl-Coenzyme A reductase), IGF1 (insulin-like growth factor 1 (somatomedin C)), SELE
(selectin E), REN (renin), PPARA (peroxisome proliferator-activated receptor alpha), PON1 (paraoxonase 1), KNG1 (kininogen 1), CCL2 (chemokine (C-C
motif) ligand 2), LPL (lipoprotein lipase), VWF (von Willebrand factor), F2 (coagulation factor II (thrombin)), ICAM1 (intercellular adhesion molecule 1), TGFB1 (transforming growth factor, beta 1), NPPA (natriuretic peptide precursor A), IL10 (interleukin 10), EPO (erythropoietin), SOD1 (superoxide dismutase 1, soluble), VCAM1 (vascular cell adhesion molecule 1), IFNG (interferon, gamma), LPA (lipoprotein, Lp(a)), MPO (myeloperoxidase), ESR1 (estrogen receptor 1), MAPK1 (mitogen-activated protein kinase 1), HP (haptoglobin), F3 (coagulation factor III (thromboplastin, tissue factor)), CST3 (cystatin C), COG2 (component of oligomeric golgi complex 2), MMP9 (matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)), SERPINC1 (serpin peptidase inhibitor, Glade C (antithrombin), member 1), F8 (coagulation factor VIII, procoagulant component), HMOX1 (heme oxygenase (decycling) 1), APOC3 (apolipoprotein C-III), IL8 (interleukin 8), PROM (prokineticin 1), CBS
(cystathionine-beta-synthase), NOS2 (nitric oxide synthase 2, inducible), TLR4 (toll-like receptor 4), SELP (selectin P (granule membrane protein 140kDa, antigen CD62)), ABCA1 (ATP-binding cassette, sub-family A (ABC1), member 1), AGT (angiotensinogen (serpin peptidase inhibitor, Glade A, member 8)), LDLR
(low density lipoprotein receptor), GPT (glutamic-pyruvate transaminase (alanine aminotransferase)), VEGFA (vascular endothelial growth factor A), NR3C2 (nuclear receptor subfamily 3, group C, member 2), IL18 (interleukin 18 (interferon-gamma-inducing factor)), NOS1 (nitric oxide synthase 1 (neuronal)), NR3C1 (nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor)), FGB (fibrinogen beta chain), HGF (hepatocyte growth factor (hepapoietin A; scatter factor)), IL1A (interleukin 1, alpha), RETN
(resistin), AKT1 (v-akt murine thymoma viral oncogene homolog 1), LIPC (lipase, hepatic), HSPD1 (heat shock 60kDa protein 1 (chaperonin)), MAPK14 (mitogen-activated protein kinase 14), SPP1 (secreted phosphoprotein 1), ITGB3 (integrin, beta 3 (platelet glycoprotein Ilia, antigen CD61)), CAT (catalase), UTS2 (urotensin 2), THBD (thrombomodulin), F10 (coagulation factor X), CP (ceruloplasmin (ferroxidase)), TNFRSF1 1 B (tumor necrosis factor receptor superfamily, member 11 b), EDNRA (endothelin receptor type A), EGFR (epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)), MMP2 (matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)), PLG (plasminogen), NPY (neuropeptide Y), RHOD (ras homolog gene family, member D), MAPK8 (mitogen-activated protein kinase 8), MYC (v-myc myelocytomatosis viral oncogene homolog (avian)), FN1 (fibronectin 1), CMA1 (chymase 1, mast cell), PLAU (plasminogen activator, urokinase), GNB3 (guanine nucleotide binding protein (G protein), beta polypeptide 3), ADRB2 (adrenergic, beta-2-, receptor, surface), APOA5 (apolipoprotein A-V), SOD2 (superoxide dismutase 2, mitochondrial), F5 (coagulation factor V
(proaccelerin, labile factor)), VDR (vitamin D (1,25- dihydroxyvitamin D3) receptor), ALOX5 (arachidonate 5-lipoxygenase), HLA-DRB1 (major histocompatibility complex, class II, DR beta 1), PARP1 (poly (ADP-ribose) polymerase 1), CD40LG (CD40 ligand), PON2 (paraoxonase 2), AGER
(advanced glycosylation end product-specific receptor), IRS1 (insulin receptor substrate 1), PTGS1 (prostaglandin-endoperoxide synthase 1 (prostaglandin G/H
synthase and cyclooxygenase)), ECE1 (endothelin converting enzyme 1), F7 (coagulation factor VII (serum prothrombin conversion accelerator)), IL1 RN
(interleukin 1 receptor antagonist), EPHX2 (epoxide hydrolase 2, cytoplasmic), IGFBP1 (insulin-like growth factor binding protein 1), MAPK10 (mitogen-activated protein kinase 10), FAS (Fas (TNF receptor superfamily, member 6)), ABCB1 (ATP-binding cassette, sub-family B (MDR/TAP), member 1), JUN (jun oncogene), IGFBP3 (insulin-like growth factor binding protein 3), CD14 (CD14 molecule), PDE5A (phosphodiesterase 5A, cGMP-specific), AGTR2 (angiotensin II receptor, type 2), CD40 (CD40 molecule, TNF receptor superfamily member 5), LCAT (lecithin-cholesterol acyltransferase), CCR5 (chemokine (C-C motif) receptor 5), MMP1 (matrix metallopeptidase 1 (interstitial collagenase)), (TIMP metallopeptidase inhibitor 1), ADM (adrenomedullin), DYT10 (dystonia 10), STAT3 (signal transducer and activator of transcription 3 (acute-phase response factor)), MMP3 (matrix metallopeptidase 3 (stromelysin 1, progelatinase)), ELN (elastin), USF1 (upstream transcription factor 1), CFH
(complement factor H), HSPA4 (heat shock 70kDa protein 4), MMP1 2 (matrix metallopeptidase 12 (macrophage elastase)), MME (membrane metallo-endopeptidase), F2R (coagulation factor II (thrombin) receptor), SELL
(selectin L), CTSB (cathepsin B), ANXA5 (annexin A5), ADRB1 (adrenergic, beta-l-, receptor), CYBA (cytochrome b-245, alpha polypeptide), FGA (fibrinogen alpha chain), GGT1 (gamma-glutamyltransferase 1), LIPG (lipase, endothelial), HIF1A
(hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)), CXCR4 (chemokine (C-X-C motif) receptor 4), PROC (protein C
(inactivator of coagulation factors Va and Villa)), SCARB1 (scavenger receptor class B, member 1), CD79A (CD79a molecule, immunoglobulin-associated alpha), PLTP (phospholipid transfer protein), ADD1 (adducin 1 (alpha)), FGG
(fibrinogen gamma chain), SAA1 (serum amyloid Al), KCNH2 (potassium voltage-gated channel, subfamily H (eag-related), member 2), DPP4 (dipeptidyl-peptidase 4), G6PD (glucose-6-phosphate dehydrogenase), NPR1 (natriuretic peptide receptor A/guanylate cyclase A (atrionatriuretic peptide receptor A)), VTN
(vitronectin), KIAA0101 (KIAA0101), FOS (FBJ murine osteosarcoma viral oncogene homolog), TLR2 (toll-like receptor 2), PPIG (peptidylprolyl isomerase G (cyclophilin G)), IL1 R1 (interleukin 1 receptor, type I), AR (androgen receptor), CYP1A1 (cytochrome P450, family 1, subfamily A, polypeptide 1), SERPINA1 (serpin peptidase inhibitor, ciade A (alpha-1 antiproteinase, antitrypsin), member 1), MTR (5-methyltetrahydrofolate-homocysteine methyltransferase), RBP4 (retinol binding protein 4, plasma), APOA4 (apolipoprotein A-IV), CDKN2A
(cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)), FGF2 (fibroblast growth factor 2 (basic)), EDNRB (endothelin receptor type B), (integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor)), CABIN1 (calcineurin binding protein 1), SHBG (sex hormone-binding globulin), HMGB1 (high-mobility group box 1), HSP90B2P (heat shock protein 90kDa beta (Grp94), member 2 (pseudogene)), CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4), GJA1 (gap junction protein, alpha 1, 43kDa), CAV1 (caveolin 1, caveolae protein, 22kDa), ESR2 (estrogen receptor 2 (ER beta)), LTA
(lymphotoxin alpha (TNF superfamily, member 1)), GDF15 (growth differentiation factor 15), BDNF (brain-derived neurotrophic factor), CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6), NGF (nerve growth factor (beta polypeptide)), SP1 (Spl transcription factor), TGIF1 (TGFB-induced factor homeobox 1), SRC (v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian)), EGF (epidermal growth factor (beta-urogastrone)), PIK3CG
(phosphoinositide-3-kinase, catalytic, gamma polypeptide), HLA-A (major histocompatibility complex, class I, A), KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1), CNR1 (cannabinoid receptor 1 (brain)), FBN1 (fibrillin 1), CHKA (choline kinase alpha), BEST1 (bestrophin 1), APP
(amyloid beta (A4) precursor protein), CTNNB1 (catenin (cadherin-associated protein), beta 1, 88kDa), IL2 (interleukin 2), CD36 (CD36 molecule (thrombospondin receptor)), PRKAB1 (protein kinase, AMP-activated, beta 1 non-catalytic subunit), TPO (thyroid peroxidase), ALDH7A1 (aldehyde dehydrogenase 7 family, member Al), CX3CR1 (chemokine (C-X3-C motif) receptor 1), TH (tyrosine hydroxylase), F9 (coagulation factor IX), GH1 (growth hormone 1), TF (transferrin), HFE (hemochromatosis), IL17A (interleukin 17A), PTEN (phosphatase and tensin homolog), GSTM1 (glutathione S-transferase mu 1), DMD (dystrophin), GATA4 (GATA binding protein 4), F13A1 (coagulation factor XIII, Al polypeptide), TTR (transthyretin), FABP4 (fatty acid binding protein 4, adipocyte), PON3 (paraoxonase 3), APOC1 (apolipoprotein C-I), INSR (insulin receptor), TNFRSF1 B (tumor necrosis factor receptor superfamily, member 1 B), HTR2A (5-hydroxytryptamine (serotonin) receptor 2A), CSF3 (colony stimulating factor 3 (granulocyte)), CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9), TXN (thioredoxin), CYP1 1 B2 (cytochrome P450, family 11, subfamily B, polypeptide 2), PTH (parathyroid hormone), CSF2 (colony stimulating factor 2 (granulocyte-macrophage)), KDR (kinase insert domain receptor (a type III receptor tyrosine kinase)), PLA2G2A (phospholipase A2, group IIA (platelets, synovial fluid)), B2M (beta-2-microglobulin), THBS1 (thrombospondin 1), GCG (glucagon), RHOA (ras homolog gene family, member A), ALDH2 (aldehyde dehydrogenase 2 family (mitochondrial)), TCF7L2 (transcription factor 7-like 2 (T-cell specific, HMG-box)), BDKRB2 (bradykinin receptor B2), NFE2L2 (nuclear factor (erythroid-derived 2)-like 2), NOTCH1 (Notch homolog 1, translocation-associated (Drosophila)), UGT1A1 (UDP
glucuronosyltransferase 1 family, polypeptide Al), IFNA1 (interferon, alpha 1), PPARD (peroxisome proliferator-activated receptor delta), SIRT1 (sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae)), GNRH1 (gonadotropin-releasing hormone 1 (luteinizing-releasing hormone)), PAPPA
(pregnancy-associated plasma protein A, pappalysin 1), ARR3 (arrestin 3, retinal (X-arrestin)), NPPC (natriuretic peptide precursor C), AHSP (alpha hemoglobin stabilizing protein), PTK2 (PTK2 protein tyrosine kinase 2), IL13 (interleukin 13), MTOR (mechanistic target of rapamycin (serine/threonine kinase)), ITGB2 (integrin, beta 2 (complement component 3 receptor 3 and 4 subunit)), GSTT1 (glutathione S-transferase theta 1), IL6ST (interleukin 6 signal transducer (gp130, oncostatin M receptor)), CPB2 (carboxypeptidase B2 (plasma)), CYP1A2 (cytochrome P450, family 1, subfamily A, polypeptide 2), HNF4A (hepatocyte nuclear factor 4, alpha), SLC6A4 (solute carrier family 6 (neurotransmitter transporter, serotonin), member 4), PLA2G6 (phospholipase A2, group VI
(cytosolic, calcium-independent)), TNFSF1 1 (tumor necrosis factor (ligand) superfamily, member 11), SLC8A1 (solute carrier family 8 (sodium/calcium exchanger), member 1), F2RL1 (coagulation factor II (thrombin) receptor-like 1), AKR1A1 (aldo-keto reductase family 1, member Al (aldehyde reductase)), ALDH9A1 (aldehyde dehydrogenase 9 family, member Al), BGLAP (bone gamma-carboxyglutamate (gla) protein), MTTP (microsomal triglyceride transfer protein), MTRR (5-methyltetrahydrofolate-homocysteine methyltransferase reductase), SULT1A3 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 3), RAGE (renal tumor antigen), C4B (complement component 4B
(Chido blood group), P2RY12 (purinergic receptor P2Y, G-protein coupled, 12), RNLS (renalase, FAD-dependent amine oxidase), CREB1 (cAMP responsive element binding protein 1), POMC (proopiomelanocortin), RAC1 (ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)), LMNA
(lamin A/C), CD59 (CD59 molecule, complement regulatory protein), SCN5A
(sodium channel, voltage-gated, type V, alpha subunit), CYP1 B1 (cytochrome P450, family 1, subfamily B, polypeptide 1), MIF (macrophage migration inhibitory factor (glycosylation-inhibiting factor)), MMP1 3 (matrix metallopeptidase 13 (collagenase 3)), TIMP2 (TIMP metallopeptidase inhibitor 2), CYP19A1 (cytochrome P450, family 19, subfamily A, polypeptide 1), CYP21A2 (cytochrome P450, family 21, subfamily A, polypeptide 2), PTPN22 (protein tyrosine phosphatase, non-receptor type 22 (lymphoid)), MYH14 (myosin, heavy chain 14, non-muscle), MBL2 (mannose-binding lectin (protein C) 2, soluble (opsonic defect)), SELPLG (selectin P ligand), AOC3 (amine oxidase, copper containing 3 (vascular adhesion protein 1)), CTSL1 (cathepsin L1), PCNA
(proliferating cell nuclear antigen), IGF2 (insulin-like growth factor 2 (somatomedin A)), ITGB1 (integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12)), CAST (calpastatin), CXCL12 (chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)), IGHE
(immunoglobulin heavy constant epsilon), KCNE1 (potassium voltage-gated channel, Isk-related family, member 1), TFRC (transferrin receptor (p90, CD71)), COL1A1 (collagen, type I, alpha 1), COL1A2 (collagen, type I, alpha 2), IL2RB
(interleukin 2 receptor, beta), PLA2G10 (phospholipase A2, group X), ANGPT2 (angiopoietin 2), PROCR (protein C receptor, endothelial (EPCR)), NOX4 (NADPH oxidase 4), HAMP (hepcidin antimicrobial peptide), PTPN1 1 (protein tyrosine phosphatase, non-receptor type 11), SLC2A1 (solute carrier family 2 (facilitated glucose transporter), member 1), IL2RA (interleukin 2 receptor, alpha), CCL5 (chemokine (C-C motif) ligand 5), IRF1 (interferon regulatory factor 1), CFLAR (CASP8 and FADD-like apoptosis regulator), CALCA (calcitonin-related polypeptide alpha), EIF4E (eukaryotic translation initiation factor 4E), GSTP1 (glutathione S-transferase pi 1), JAK2 (Janus kinase 2), CYP3A5 (cytochrome P450, family 3, subfamily A, polypeptide 5), HSPG2 (heparan sulfate proteoglycan 2), CCL3 (chemokine (C-C motif) ligand 3), MYD88 (myeloid differentiation primary response gene (88)), VIP (vasoactive intestinal peptide), SOAT1 (sterol 0-acyltransferase 1), ADRBK1 (adrenergic, beta, receptor kinase 1), NR4A2 (nuclear receptor subfamily 4, group A, member 2), MMP8 (matrix metallopeptidase 8 (neutrophil collagenase)), NPR2 (natriuretic peptide receptor B/guanylate cyclase B (atrionatriuretic peptide receptor B)), GCH1 (GTP
cyclohydrolase 1), EPRS (glutamyl-prolyl-tRNA synthetase), PPARGC1A
(peroxisome proliferator-activated receptor gamma, coactivator 1 alpha), F12 (coagulation factor XII (Hageman factor)), PECAM1 (platelet/endothelial cell adhesion molecule), CCL4 (chemokine (C-C motif) ligand 4), SERPINA3 (serpin peptidase inhibitor, Glade A (alpha-1 antiproteinase, antitrypsin), member 3), CASR (calcium-sensing receptor), GJA5 (gap junction protein, alpha 5, 40kDa), FABP2 (fatty acid binding protein 2, intestinal), TTF2 (transcription termination factor, RNA polymerase II), PROS1 (protein S (alpha)), CTF1 (cardiotrophin 1), SGCB (sarcoglycan, beta (43kDa dystrophin-associated glycoprotein)), YME1 L1 (YME1 -like 1 (S. cerevisiae)), CAMP (cathelicidin antimicrobial peptide), ZC3H12A (zinc finger CCCH-type containing 12A), AKR1 131 (aldo-keto reductase family 1, member 131 (aldose reductase)), DES (desmin), MMP7 (matrix metallopeptidase 7 (matrilysin, uterine)), AHR (aryl hydrocarbon receptor), (colony stimulating factor 1 (macrophage)), HDAC9 (histone deacetylase 9), CTGF (connective tissue growth factor), KCNMA1 (potassium large conductance calcium-activated channel, subfamily M, alpha member 1), UGT1A (UDP
glucuronosyltransferase 1 family, polypeptide A complex locus), PRKCA (protein kinase C, alpha), COMT (catechol-O-methyltransferase), S100B (S100 calcium binding protein B), EGR1 (early growth response 1), PRL (prolactin), U5 (interleukin 15), DRD4 (dopamine receptor D4), CAMK2G (calcium/calmodulin-dependent protein kinase II gamma), SLC22A2 (solute carrier family 22 (organic cation transporter), member 2), CCL1 1 (chemokine (C-C motif) ligand 11), PGF
(8321 placental growth factor), THPO (thrombopoietin), GP6 (glycoprotein VI
(platelet)), TACR1 (tachykinin receptor 1), NTS (neurotensin), HNF1A (HNF1 homeobox A), SST (somatostatin), KCND1 (potassium voltage-gated channel, Shal-related subfamily, member 1), LOC646627 (phospholipase inhibitor), TBXAS1 (thromboxane A synthase 1 (platelet)), CYP2J2 (cytochrome P450, family 2, subfamily J, polypeptide 2), TBXA2R (thromboxane A2 receptor), ADH1C (alcohol dehydrogenase 1C (class I), gamma polypeptide), ALOX12 (arachidonate 12-lipoxygenase), AHSG (alpha-2-HS-glycoprotein), BHMT
(betaine-homocysteine methyltransferase), GJA4 (gap junction protein, alpha 4, 37kDa), SLC25A4 (solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4), ACLY (ATP citrate lyase), ALOX5AP
(arachidonate 5-lipoxygenase-activating protein), NUMA1 (nuclear mitotic apparatus protein 1), CYP27B1 (cytochrome P450, family 27, subfamily B, polypeptide 1), CYSLTR2 (cysteinyl leukotriene receptor 2), SOD3 (superoxide dismutase 3, extracellular), LTC4S (leukotriene C4 synthase), UCN (urocortin), GHRL (ghrelin/obestatin prepropeptide), APOC2 (apolipoprotein C-II), CLEC4A
(C-type lectin domain family 4, member A), KBTBD10 (kelch repeat and BTB
(POZ) domain containing 10), TNC (tenascin C), TYMS (thymidylate synthetase), SHC1 (SHC (Src homology 2 domain containing) transforming protein 1), LRP1 (low density lipoprotein receptor-related protein 1), SOCS3 (suppressor of cytokine signaling 3), ADH1 B (alcohol dehydrogenase 1 B (class I), beta polypeptide), KLK3 (kallikrein-related peptidase 3), HSD1 1 B1 (hydroxysteroid (11-beta) dehydrogenase 1), VKORC1 (vitamin K epoxide reductase complex, subunit 1), SERPINB2 (serpin peptidase inhibitor, Glade B (ovalbumin), member 2), TNS1 (tensin 1), RNF19A (ring finger protein 19A), EPOR (erythropoietin receptor), ITGAM (integrin, alpha M (complement component 3 receptor 3 subunit)), PITX2 (paired-like homeodomain 2), MAPK7 (mitogen-activated protein kinase 7), FCGR3A (Fc fragment of IgG, low affinity Ilia, receptor (CD16a)), LEPR (leptin receptor), ENG (endoglin), GPX1 (glutathione peroxidase 1), GOT2 (glutamic-oxaloacetic transaminase 2, mitochondrial (aspartate aminotransferase 2)), HRH1 (histamine receptor H1), NR112 (nuclear receptor subfamily 1, group I, member 2), CRH (corticotropin releasing hormone), HTR1A
(5-hydroxytryptamine (serotonin) receptor 1A), VDAC1 (voltage-dependent anion channel 1), HPSE (heparanase), SFTPD (surfactant protein D), TAP2 (transporter 2, ATP-binding cassette, sub-family B (MDR/TAP)), RNF123 (ring finger protein 123), PTK2B (PTK2B protein tyrosine kinase 2 beta), NTRK2 (neurotrophic tyrosine kinase, receptor, type 2), IL6R (interleukin 6 receptor), ACHE (acetylcholinesterase (Yt blood group)), GLP1 R (glucagon-like peptide 1 receptor), GHR (growth hormone receptor), GSR (glutathione reductase), NQO1 (NAD(P)H dehydrogenase, quinone 1), NR5A1 (nuclear receptor subfamily 5, group A, member 1), GJB2 (gap junction protein, beta 2, 26kDa), SLC9A1 (solute carrier family 9 (sodium/hydrogen exchanger), member 1), MAOA (monoamine oxidase A), PCSK9 (proprotein convertase subtilisin/kexin type 9), FCGR2A (Fc fragment of IgG, low affinity Ila, receptor (CD32)), SERPINF1 (serpin peptidase inhibitor, Glade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1), EDN3 (endothelin 3), DHFR (dihydrofolate reductase), GAS6 (growth arrest-specific 6), SMPD1 (sphingomyelin phosphodiesterase 1, acid lysosomal), UCP2 (uncoupling protein 2 (mitochondrial, proton carrier)), TFAP2A
(transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha)), C4BPA (complement component 4 binding protein, alpha), SERPINF2 (serpin peptidase inhibitor, Glade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 2), TYMP (thymidine phosphorylase), ALPP (alkaline phosphatase, placental (Regan isozyme)), CXCR2 (chemokine (C-X-C motif) receptor 2), SLC39A3 (solute carrier family 39 (zinc transporter), member 3), ABCG2 (ATP-binding cassette, sub-family G (WHITE), member 2), ADA
(adenosine deaminase), JAK3 (Janus kinase 3), HSPAIA (heat shock 70kDa protein 1A), FASN (fatty acid synthase), FGF1 (fibroblast growth factor 1 (acidic)), F11 (coagulation factor XI), ATP7A (ATPase, Cu++ transporting, alpha polypeptide), CR1 (complement component (3b/4b) receptor 1 (Knops blood group)), GFAP (glial fibrillary acidic protein), ROCK1 (Rho-associated, coiled-coil containing protein kinase 1), MECP2 (methyl CpG binding protein 2 (Rett syndrome)), MYLK (myosin light chain kinase), BCHE (butyrylcholinesterase), LIPE (lipase, hormone-sensitive), PRDX5 (peroxiredoxin 5), ADORA1 (adenosine Al receptor), WRN (Werner syndrome, RecQ helicase-like), CXCR3 (chemokine (C-X-C motif) receptor 3), CD81 (CD81 molecule), SMAD7 (SMAD
family member 7), LAMC2 (laminin, gamma 2), MAP3K5 (mitogen-activated protein kinase kinase kinase 5), CHGA (chromogranin A (parathyroid secretory protein 1)), IAPP (islet amyloid polypeptide), RHO (rhodopsin), ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1), PTHLH (parathyroid hormone-like hormone), NRG1 (neuregulin 1), VEGFC (vascular endothelial growth factor C), ENPEP (glutamyl aminopeptidase (aminopeptidase A)), CEBPB
(CCAAT/enhancer binding protein (C/EBP), beta), NAGLU (N-acetylglucosaminidase, alpha-), F2RL3 (coagulation factor II (thrombin) receptor-like 3), CX3CL1 (chemokine (C-X3-C motif) ligand 1), BDKRB1 (bradykinin receptor B1), ADAMTS13 (ADAM metallopeptidase with thrombospondin type 1 motif, 13), ELANE (elastase, neutrophil expressed), ENPP2 (ectonucleotide pyrophosphatase/phosphodiesterase 2), CISH (cytokine inducible SH2-containing protein), GAST (gastrin), MYOC (myocilin, trabecular meshwork inducible glucocorticoid response), ATP1A2 (ATPase, Na+/K+ transporting, alpha 2 polypeptide), NF1 (neurofibromin 1), GJB1 (gap junction protein, beta 1, 32kDa), MEF2A (myocyte enhancer factor 2A), VCL (vinculin), BMPR2 (bone morphogenetic protein receptor, type II (serine/threonine kinase)), TUBB
(tubulin, beta), CDC42 (cell division cycle 42 (GTP binding protein, 25kDa)), KRT18 (keratin 18), HSF1 (heat shock transcription factor 1), MYB (v-myb myeloblastosis viral oncogene homolog (avian)), PRKAA2 (protein kinase, AMP-activated, alpha 2 catalytic subunit), ROCK2 (Rho-associated, coiled-coil containing protein kinase 2), TFPI (tissue factor pathway inhibitor (lipoprotein-associated coagulation inhibitor)), PRKG1 (protein kinase, cGMP-dependent, type I), BMP2 (bone morphogenetic protein 2), CTNND1 (catenin (cadherin-associated protein), delta 1), CTH (cystathionase (cystathionine gamma-lyase)), CTSS (cathepsin S), VAV2 (vav 2 guanine nucleotide exchange factor), NPY2R
(neuropeptide Y receptor Y2), IGFBP2 (insulin-like growth factor binding protein 2, 36kDa), CD28 (CD28 molecule), GSTA1 (glutathione S-transferase alpha 1), PPIA (peptidylprolyl isomerase A (cyclophilin A)), APOH (apolipoprotein H
(beta-2-glycoprotein I)), S100A8 (S100 calcium binding protein A8), IL11 (interleukin 11), ALOX15 (arachidonate 15-lipoxygenase), FBLN1 (fibulin 1), NR1 H3 (nuclear receptor subfamily 1, group H, member 3), SCD (stearoyl-CoA desaturase (delta-9-desaturase)), GIP (gastric inhibitory polypeptide), CHGB (chromogranin B
(secretogranin 1)), PRKCB (protein kinase C, beta), SRD5A1 (steroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 1)), HSD1 1 B2 (hydroxysteroid (11-beta) dehydrogenase 2), CALCRL
(calcitonin receptor-like), GALNT2 (UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 2 (GaINAc-T2)), ANGPTL4 (angiopoietin-like 4), KCNN4 (potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4), PIK3C2A
(phosphoinositide-3-kinase, class 2, alpha polypeptide), HBEGF (heparin-binding EGF-like growth factor), CYP7A1 (cytochrome P450, family 7, subfamily A, polypeptide 1), HLA-DRB5 (major histocompatibility complex, class II, DR beta 5), BNIP3 (BCL2/adenovirus E1 B 19kDa interacting protein 3), GCKR
(glucokinase (hexokinase 4) regulator), S100A12 (S100 calcium binding protein A12), PADI4 (peptidyl arginine deiminase, type IV), HSPA14 (heat shock 70kDa protein 14), CXCR1 (chemokine (C-X-C motif) receptor 1), H19 (H19, imprinted maternally expressed transcript (non-protein coding)), KRTAP19-3 (keratin associated protein 19-3), IDDM2 (insulin-dependent diabetes mellitus 2), RAC2 (ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2)), RYR1 (ryanodine receptor 1 (skeletal)), CLOCK (clock homolog (mouse)), NGFR (nerve growth factor receptor (TNFR superfamily, member 16)), DBH (dopamine beta-hydroxylase (dopamine beta-monooxygenase)), CHRNA4 (cholinergic receptor, nicotinic, alpha 4), CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), PRKAG2 (protein kinase, AMP-activated, gamma 2 non-catalytic subunit), CHAT (choline acetyltransferase), PTGDS
(prostaglandin D2 synthase 21 kDa (brain)), NR1 H2 (nuclear receptor subfamily 1, group H, member 2), TEK (TEK tyrosine kinase, endothelial), VEGFB
(vascular endothelial growth factor B), MEF2C (myocyte enhancer factor 2C), MAPKAPK2 (mitogen-activated protein kinase-activated protein kinase 2), TNFRSF11A (tumor necrosis factor receptor superfamily, member 11a, NFKB
activator), HSPA9 (heat shock 70kDa protein 9 (mortalin)), CYSLTR1 (cysteinyl leukotriene receptor 1), MAT1A (methionine adenosyltransferase I, alpha), OPRL1 (opiate receptor-like 1), IMPA1 (inositol(myo)-1 (or 4)-monophosphatase 1), CLCN2 (chloride channel 2), DLD (dihydrolipoamide dehydrogenase), PSMA6 (proteasome (prosome, macropain) subunit, alpha type, 6), PSMB8 (proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7)), CHI3L1 (chitinase 3-like 1 (cartilage glycoprotein-39)), ALDH1 B1 (aldehyde dehydrogenase 1 family, member B1), PARP2 (poly (ADP-ribose) polymerase 2), STAR (steroidogenic acute regulatory protein), LBP (lipopolysaccharide binding protein), ABCC6 (ATP-binding cassette, sub-family C (CFTR/MRP), member 6), RGS2 (regulator of G-protein signaling 2, 24kDa), EFNB2 (ephrin-B2), GJB6 (gap junction protein, beta 6, 30kDa), APOA2 (apolipoprotein A-II), AMPD1 (adenosine monophosphate deaminase 1), DYSF (dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive)), FDFT1 (farnesyl-diphosphate farnesyltransferase 1), EDN2 (endothelin 2), CCR6 (chemokine (C-C motif) receptor 6), GJB3 (gap junction protein, beta 3, 31 kDa), IL1 RL1 (interleukin receptor-like 1), ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1), BBS4 (Bardet-Biedl syndrome 4), CELSR2 (cadherin, EGF LAG seven-pass G-type receptor 2 (flamingo homolog, Drosophila)), F11 R (F11 receptor), RAPGEF3 (Rap guanine nucleotide exchange factor (GEF) 3), HYAL1 (hyaluronoglucosaminidase 1), ZNF259 (zinc finger protein 259), ATOX1 (ATX1 antioxidant protein 1 homolog (yeast)), ATF6 (activating transcription factor 6), KHK (ketohexokinase (fructokinase)), SAT1 (spermidine/spermine N1-acetyltransferase 1), GGH (gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)), TIMP4 (TIMP metallopeptidase inhibitor 4), SLC4A4 (solute carrier family 4, sodium bicarbonate cotransporter, member 4), PDE2A (phosphodiesterase 2A, cGMP-stimulated), PDE3B (phosphodiesterase 3B, cGMP-inhibited), FADS1 (fatty acid desaturase 1), FADS2 (fatty acid desaturase 2), TMSB4X (thymosin beta 4, X-linked), TXNIP (thioredoxin interacting protein), LIMS1 (LIM and senescent cell antigen-like domains 1), RHOB (ras homolog gene family, member B), LY96 (lymphocyte antigen 96), FOXO1 (forkhead box 01), PNPLA2 (patatin-like phospholipase domain containing 2), TRH (thyrotropin-releasing hormone), GJC1 (gap junction protein, gamma 1, 45kDa), SLC17A5 (solute carrier family 17 (anion/sugar transporter), member 5), FTO (fat mass and obesity associated), GJD2 (gap junction protein, delta 2, 36kDa), PSRC1 (proline/serine-rich coiled-coil 1), CASP12 (caspase 12 (gene/pseudogene)), GPBARI (G protein-coupled bile acid receptor 1), PXK (PX
domain containing serine/threonine kinase), IL33 (interleukin 33), TRIB1 (tribbles homolog 1 (Drosophila)), PBX4 (pre-B-cell leukemia homeobox 4), NUPR1 (nuclear protein, transcriptional regulator, 1), 15-Sep(15 kDa selenoprotein), CILP2 (cartilage intermediate layer protein 2), TERC (telomerase RNA
component), GGT2 (gamma-glutamyltransferase 2), MT-CO1 (mitochondrially encoded cytochrome c oxidase I), and UOX (urate oxidase, pseudogene).
[0159] In an additional embodiment, the chromosomal sequence may further be selected from Pont (paraoxonase 1), LDLR (LDL receptor), ApoE
(Apolipoprotein E), Apo B-100 (Apolipoprotein B-100), ApoA
(Apolipoprotein(a)), ApoA1 (Apolipoprotein Al), CBS (Cystathione B-synthase), Glycoprotein Ilb/Ilb, MTHRF (5,10-m ethyl enetetrahydrofolate reductase (NADPH), and combinations thereof. In one iteration, the chromosomal sequences and proteins encoded by chromosomal sequences involved in cardiovascular disease may be chosen from Cacnal C, Sodl, Pten, Ppar(alpha), Apo E, Leptin, and combinations thereof.
[0160] In certain embodiments, an animal created by a method of the invention may be used to study the effects of mutations on the animal and development and/or progression of cardiovascular disease using measures commonly used in the study of cardiovascular disease. For instance, suitable disease measures may include behavioral, electrophysiological, neurochemical, biochemical, or cellular dysfunctions which can be evaluated using any of a number of well-known diagnostic tests or assays.

E. Alzheimer's disease [0161] In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with Alheimer's disease (AD) has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0162] In some embodiments, one or more chromosomal sequences associated with AD may be edited. The AD-related nucleic acid sequence may typically be selected based on an experimental association of the AD-related nucleic acid sequence to an AD disorder. An AD-related nucleic acid sequence may encode an AD-related protein or may be an AD-related control sequence. For example, the production rate or circulating concentration of an AD-related protein may be elevated or depressed in a population having an AD
disorder relative to a population lacking the AD disorder. Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art.
[0163] By way of non-limiting example, proteins associated with AD
include but are not limited to the very low density lipoprotein receptor protein (VLDLR) encoded by the VLDLR gene, the ubiquitin-like modifier activating enzyme 1 (UBA1) encoded by the UBAI gene, the NEDD8-activating enzyme El catalytic subunit protein (UBE1 C) encoded by the UBA3 gene, the aquaporin 1 protein (AQP1) encoded by the AQPI gene, the ubiquitin carboxyl-terminal esterase L1 protein (UCHL1) encoded by the UCHLI gene, the ubiquitin carboxyl-terminal hydrolase isozyme L3 protein (UCHL3) encoded by the UCHL3 gene, the ubiquitin B protein (UBB) encoded by the UBB gene, the microtubule-associated protein tau (MAPT) encoded by the MAPT gene, the protein tyrosine phosphatase receptor type A protein (PTPRA) encoded by the PTPRA gene, the phosphatidylinositol binding clathrin assembly protein (PICALM) encoded by the P/CALM gene, the clusterin protein (also known as apoplipoprotein J) encoded by the CLU gene, the presenilin 1 protein encoded by the PSENI gene, the presenilin 2 protein encoded by the PSEN2 gene, the sortilin-related receptor L(DLR class) A repeats-containing protein (SORL1) protein encoded by the SORLI gene, the amyloid precursor protein (APP) encoded by the APP gene, the Apolipoprotein E precursor (APOE) encoded by the APOE gene, or the brain-derived neurotrophic factor (BDNF) encoded by the BDNF gene, or combinations thereof.
[0164] In certain embodiments, an animal created by a method of the invention may be used to study the effects of mutations on the animal and development and/or progression of AD using measures commonly used in the study of AD. Commonly used measures in the study of AD include without limit, learning and memory, anxiety, depression, addiction, and sensory-motor functions, as well as functional, pathological, metabolic, or biochemical assays.
Those of skill in the art are familiar with other suitable measures or indicators of AD. In general, such measures may be made in comparison to wild type littermates.
[0165] Other measures of behavior may include assessments of spontaneous behavior. Spontaneous behavior may be assessed using any one or more methods of spontaneous behavioral observations known in the art. In general, any spontaneous behavior within a known behavioral repertoire of an animal may be observed, including movement, posture, social interaction, rearing, sleeping, blinking, eating, drinking, urinating, defecating, mating, and aggression. An extensive battery of observations for quantifying the spontaneous behavior of mice and rats is well-known in the art, including but not limited to home-cage observations such as body position, respiration, tonic involuntary movement, unusual motor behavior such as pacing or rocking, catatonic behavior, vocalization, palpebral closure, mating frequency, running wheel behavior, nest building, and frequency of aggressive interactions.
[0166] In another embodiment, the animals of the invention may be used to study the effects of the mutations on the progression of a disease state or disorder other than AD, but which is also associated with AD-related proteins, using measures commonly used in the study of said disease state or disorder.
Non limiting examples of disease states or disorders other than AD that may be associated with AD-related proteins include dementia, congenital cerebellar ataxia, mental retardation such as learning and memory defects, lissencephaly, tauopathy or fibrilization, amyloidosis, neurodegeneration, Parkinsonism, progressive supranuclear palsy, Pick disease, male infertility, prostate and breast cancer, squamous cell carcinoma, lymphoma, leukemia, and atherosclerosis.
[0167] Yet another aspect encompasses a method for assessing the efficacy of a potential gene therapy strategy. That is, a chromosomal sequence encoding a protein associated with AD may be modified such that the genetically modified animal may have an altered response to the development and/or progression of AD as compared to a non treated animal. Stated another way, a mutated gene that predisposes an animal to AD may be "corrected"
through gene therapy.

F. autism spectrum disorder [0168] In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with autism spectrum disorder (ASD) has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0169] In each of the above embodiments, one or more chromosomal sequences associated with ASD may be edited. An ASD
associated protein or control sequence may typically be selected based on an experimental association of the protein or control sequence to an incidence or indication of an ASD. For example, the production rate or circulating concentration of a protein associated with ASD may be elevated or depressed in a population having an ASD relative to a population lacking the ASD.
Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art.
[0170] The identity of the protein associated with ASD whose chromosomal sequence is edited can and will vary. In preferred embodiments, the proteins associated with ASD whose chromosomal sequence is edited may be the benzodiazapine receptor (peripheral) associated protein 1 (BZRAP1) encoded by the BZRAPI gene, the AF4/FMR2 family member 2 protein (AFF2) encoded by the AFF2 gene (also termed MFR2), the fragile X mental retardation autosomal homolog 1 protein (FXR1) encoded by the FXR1 gene, the fragile X
mental retardation autosomal homolog 2 protein (FXR2) encoded by the FXR2 gene, the MAM domain containing glycosylphosphatidylinositol anchor 2 protein (MDGA2) encoded by the MDGA2 gene, the methyl CpG binding protein 2 (MECP2) encoded by the MECP2 gene, the metabotropic glutamate receptor 5 (MGLUR5) encoded by the MGLUR5-1 gene (also termed GRM5), the neurexin 1 protein encoded by the NRXN1 gene, or the semaphorin-5A protein (SEMA5A) encoded by the SEMA5A gene.
[0171] The edited or integrated chromosomal sequence may be modified to encode an altered protein associated with ASD. Non-limiting examples of mutations in proteins associated with ASD include the L18Q
mutation in neurexin 1 where the leucine at position 18 is replaced with a glutamine, the R451 C mutation in neuroligin 3 where the arginine at position is replaced with a cysteine, the R87W mutation in neuroligin 4 where the arginine at position 87 is replaced with a tryptophan, and the 1425V mutation in serotonin transporter where the isoleucine at position 425 is replaced with a valine. A
number of other mutations and chromosomal rearrangements in ASD-related chromosomal sequences have been associated with ASD and are known in the art. See, for example, Freitag et al. (2010) Eur. Child. Adolesc. Psychiatry 19:169-178, and Bucan et al. (2009) PLoS Genetics 5: el000536, the disclosure of which is incorporated by reference herein in its entirety.
[0172] In certain embodiments, an animal created by a method of the invention may be used to study the effects of mutations on the animal and development and/or progression of ASD using measures commonly used in the study of ASD.

G. macular degeneration [0173] In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with macular degeneration (MD) has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0174] In each of the above embodiments, one or more chromosomal sequences associated with MD may be edited. A MD-associated protein or control sequence may typically be selected based on an experimental association of the protein associated with MD to an MD disorder. For example, the production rate or circulating concentration of a protein associated with MD
may be elevated or depressed in a population having an MD disorder relative to a population lacking the MD disorder. Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art.
[0175] The identity of the protein associated with MD whose chromosomal sequence is edited can and will vary. In preferred embodiments, the proteins associated with MD whose chromosomal sequence is edited may be the ATP-binding cassette, sub-family A (ABC1) member 4 protein (ABCA4) encoded by the ABCR gene, the apolipoprotein E protein (APOE) encoded by the APOE gene, the chemokine (C-C motif) Ligand 2 protein (CCL2) encoded by the CCL2 gene, the chemokine (C-C motif) receptor 2 protein (CCR2) encoded by the CCR2 gene, the ceruloplasmin protein (CP) encoded by the CP gene, the cathepsin D protein (CTSD) encoded by the CTSD gene, or the metalloproteinase inhibitor 3 protein (TIMP3) encoded by the TIMP3 gene.
[0176] In certain embodiments, a genetically modified animal created by a method of the invention may be used to study the effects of mutations on the progression of MD using measures commonly used in the study of MD. Alternatively, the genetically modified animals of the invention may be used to study the effects of the mutations on the progression of a disease state or disorder associated with proteins associated with MD using measures commonly used in the study of said disease state or disorder. Non-limiting examples of measures that may be used include drusen accumulation, lipofuscin accumulation, thickening of Bruch's membrane, retinal degeneration, choroidal neovascularization, differential responses to a compound, abnormalities in tissues or cells, biochemical or molecular differences between genetically modified animals and wild type animals or a combination thereof.

H. schizophrenia [0177] In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with schizophrenia has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0178] In each of the above embodiments, one or more chromosomal sequences associated with schizophrenia may be edited. A
schizophrenia-associated protein or control sequence may typically be selected based on an experimental association of the protein associated with schizophrenia to the development or progression of schizophrenia. For example, the production rate or circulating concentration of a protein associated with schizophrenia may be elevated or depressed in a population having schizophrenia relative to a population not having schizophrenia. Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art. Exemplary non-limiting examples of chromosomal sequences associated with schizophrenia include NRG1, ErbB4, CPLX1, TPH1, TPH2, NRXN1, GSK3A, BDNF, DISC1, GSK3B, and combinations thereof, each of which is described in more detail below.
[0179] In certain embodiments, an animal created by a method of the invention may be used to study the effects of mutations on the animal and development and/or progression of MD using measures commonly used in the study of MD.
[0180] The incidence or indication of the schizophrenia or related disorder may occur spontaneously in the genetically modified animal.
Alternatively, the incidence or indication of the schizophrenia or related disorder may be promoted by exposure to a disruptive agent. Non-limiting examples of disruptive agents include a protein associated with schizophrenia such as any of those described above, a drug, a toxin, a chemical, an activated retrovirus, and an environmental stress. Non-limiting examples of environmental stresses include forced swimming, cold swimming, platform shaker stimuli, loud noises, and immobilization stress.

1. tumor sumpresion [0181] Tumor suppression genes are genes whose protein products protect a cell from one step on the path to cancer. A mutation in a tumor suppressor gene may cause a loss or reduction in the protective function of its protein product, thereby increasing the probability that a tumor will form, leading to cancer, usually in combination with other genetic changes. The proteins encoded by tumor suppressor genes have a dampening or repressive effect on the regulation of the cell cycle or promote apoptosis, and sometimes both.

Tumor suppressor proteins are involved in the repression of genes essential for the continuing cell cycle; coupling the cell cycle to DNA damage so that the cell cycle can continue; initiating apoptosis in the cell if the damage cannot be repaired; and cell adhesion to prevent tumors from dispersing, blocking a loss of contact inhibition, and inhibiting metastasis.
[0182] In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with tumor suppresion has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0183] In each of the above embodiments, one or more chromosomal sequences associated with tumor suppression may be edited. A
tumor suppression-associated protein or control sequence may typically selected based on an experimental association of the protein of interest with a cancer.
For example, the production rate or circulating concentration of a protein associated with tumor suppression may be elevated or depressed in a population having cancer relative to a population not having cancer. Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art.
[0184] By way of example, proteins involved in tumor suppression may comprise, but are not limited to, TNF (tumor necrosis factor (TNF
superfamily, member 2)), TP53 (tumor protein p53), ERBB2 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)), FN1 (fibronectin 1), TSC1 (tuberous sclerosis 1), PTGS2 (prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)), PTEN (phosphatase and tensin homolog), PCNA
(proliferating cell nuclear antigen), COL18A1 (collagen, type XVIII, alpha 1), TSSC4 (tumor suppressing subtransferable candidate 4), JUN (jun oncogene), MAPK8 (mitogen-activated protein kinase 8), TGFB1 (transforming growth factor, beta 1), IL6 (interleukin 6 (interferon, beta 2)), IFNG (interferon, gamma), (breast cancer 1, early onset), TSPAN32 (tetraspanin 32), BCL2 (B-cell CLL/lymphoma 2), NF2 (neurofibromin 2 (merlin)), GJB1 (gap junction protein, beta 1, 32kDa), MAPK1 (mitogen-activated protein kinase 1), CD44 (CD44 molecule (Indian blood group)), PGR (progesterone receptor), TNS1 (tensin 1), PROK1 (prokineticin 1), SIAH1 (seven in absentia homolog 1 (Drosophila)), ENG
(endoglin), TP73 (tumor protein p73), APC (adenomatous polyposis coli), BAX
(BCL2-associated X protein), SRC (v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian)), VHL (von Hippel-Lindau tumor suppressor), FHIT
(fragile histidine triad gene), NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1), IFNA1 (interferon, alpha 1), TGFBR1 (transforming growth factor, beta receptor 1), PRKCD (protein kinase C, delta), TGIF1 (TGFB-induced factor homeobox 1), DLC1 (deleted in liver cancer 1), SLC22A1 8 (solute carrier family 22, member 18), VEGFA (vascular endothelial growth factor A), MME (membrane metallo-endopeptidase), IL3 (interleukin 3 (colony-stimulating factor, multiple)), MK167 (antigen identified by monoclonal antibody Ki-67), HSPD1 (heat shock 60kDa protein 1 (chaperonin)), HSPB1 (heat shock 27kDa protein 1), HSP90B2P (heat shock protein 90kDa beta (Grp94), member 2 (pseudogene)), MBL2 (mannose-binding lectin (protein C) 2, soluble (opsonic defect)), ZFYVE9 (zinc finger, FYVE domain containing 9), TERT (telomerase reverse transcriptase), PML (promyelocytic leukemia), SKP2 (S-phase kinase-associated protein 2 (p45)), CYCS (cytochrome c, somatic), MAPK10 (mitogen-activated protein kinase 10), PAX7 (paired box 7), YAP1 (Yes-associated protein 1), PARP1 (poly (ADP-ribose) polymerase 1), MIR34A (microRNA 34a), PRKCA
(protein kinase C, alpha), FAS (Fas (TNF receptor superfamily, member 6)), SYK
(spleen tyrosine kinase), GSK3B (glycogen synthase kinase 3 beta), PRKCE
(protein kinase C, epsilon), CYP1 9A1 (cytochrome P450, family 19, subfamily A, polypeptide 1), ABCB1 (ATP-binding cassette, sub-family B (MDR/TAP), member 1), NFKBIA (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), RUNX1 (runt-related transcription factor 1), PRKCG (protein kinase C, gamma), RELA (v-ref reticuloendotheliosis viral oncogene homolog A
(avian)), PLAU (plasminogen activator, urokinase), BTK (Bruton agammaglobulinemia tyrosine kinase), PRKCB (protein kinase C, beta), CSF1 (colony stimulating factor 1 (macrophage)), POMC (proopiomelanocortin), CEBPB (CCAAT/enhancer binding protein (C/EBP), beta), ROCK1 (Rho-associated, coiled-coil containing protein kinase 1), KDR (kinase insert domain receptor (a type III receptor tyrosine kinase)), NPM1 (nucleophosmin (nucleolar phosphoprotein B23, numatrin)), ROCK2 (Rho-associated, coiled-coil containing protein kinase 2), PRKAB1 (protein kinase, AMP-activated, beta 1 non-catalytic subunit), BAK1 (BCL2-antagonist/killer 1), AURKA (aurora kinase A), NTN1 (netrin 1), FLT1 (fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)), NBN (nibrin), DNM3 (dynamin 3), PRDM10 (PR domain containing 10), PAX5 (paired box 5), EIF4G1 (eukaryotic translation initiation factor 4 gamma, 1), KAT2B (K(lysine) acetyltransferase 2B), TIMP3 (TIMP metallopeptidase inhibitor 3), CCL22 (chemokine (C-C motif) ligand 22), GRIN2B (glutamate receptor, ionotropic, N-methyl D-aspartate 2B), CD81 (CD81 molecule), CCL27 (chemokine (C-C motif) ligand 27), MAPK1 1 (mitogen-activated protein kinase 11), DKK1 (dickkopf homolog 1 (Xenopus laevis)), HYAL1 (hyaluronoglucosaminidase 1), CTSL1 (cathepsin L1), PKD1 (polycystic kidney disease 1 (autosomal dominant)), BUB1 B (budding uninhibited by benzimidazoles 1 homolog beta (yeast)), MPP1 (membrane protein, palmitoylated 1, 55kDa), SIAH2 (seven in absentia homolog 2 (Drosophila)), DUSP13 (dual specificity phosphatase 13), CCL21 (chemokine (C-C motif) ligand 21), RTN4 (reticulon 4), SMO (smoothened homolog (Drosophila)), CCL19 (chemokine (C-C motif) ligand 19), CSTF2 (cleavage stimulation factor, 3V pre-RNA, subunit 2, 64kDa), RSF1 (remodeling and spacing factor 1), EZH2 (enhancer of zeste homolog 2 (Drosophila)), AK1 (adenylate kinase 1), CKM
(creatine kinase, muscle), HYAL3 (hyaluronoglucosaminidase 3), ALOX15B
(arachidonate 15-lipoxygenase, type B), PAG1 (phosphoprotein associated with glycosphingolipid microdomains 1), MIR21 (microRNA 21), S100A2 (S100 calcium binding protein A2), HYAL2 (hyaluronoglucosaminidase 2), CSTF1 (cleavage stimulation factor, 3\' pre-RNA, subunit 1, 50kDa), PCGF2 (polycomb group ring finger 2), THSD1 (thrombospondin, type I, domain containing 1), HOPX (HOP homeobox), SLC5A8 (solute carrier family 5 (iodide transporter), member 8), EMB (embigin homolog (mouse)), PAX9 (paired box 9), ARMCX3 (armadillo repeat containing, X-linked 3), ARMCX2 (armadillo repeat containing, X-linked 2), ARMCX1 (armadillo repeat containing, X-linked 1), RASSF4 (Ras association (RaIGDS/AF-6) domain family member 4), MIR34B (microRNA 34b), MIR205 (microRNA 205), RB1 (retinoblastoma 1), DYT10 (dystonia 10), CDKN2A (cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)), CDKN1A (cyclin-dependent kinase inhibitor 1A (p21, Cip1)), CCND1 (cyclin D1), AKT1 (v-akt murine thymoma viral oncogene homolog 1), MYC (v-myc myelocytomatosis viral oncogene homolog (avian)), CTNNB1 (catenin (cadherin-associated protein), beta 1, 88kDa), MDM2 (Mdm2 p53 binding protein homolog (mouse)), SERPINB5 (serpin peptidase inhibitor, Glade B (ovalbumin), member 5), EGF (epidermal growth factor (beta-urogastrone)), FOS (FBJ murine osteosarcoma viral oncogene homolog), NOS2 (nitric oxide synthase 2, inducible), CDK4 (cyclin-dependent kinase 4), SOD2 (superoxide dismutase 2, mitochondrial), SMAD3 (SMAD family member 3), CDKN1 B (cyclin-dependent kinase inhibitor 1 B (p27, Kip1)), SOD1 (superoxide dismutase 1, soluble), CCNA2 (cyclin A2), LOX (lysyl oxidase), SMAD4 (SMAD family member 4), HGF
(hepatocyte growth factor (hepapoietin A; scatter factor)), THBS1 (thrombospondin 1), CDK6 (cyclin-dependent kinase 6), ATM (ataxia telangiectasia mutated), STAT3 (signal transducer and activator of transcription 3 (acute-phase response factor)), HIF1A (hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)), IGF1 R (insulin-like growth factor 1 receptor), MTOR (mechanistic target of rapamycin (serine/threonine kinase)), TSC2 (tuberous sclerosis 2), CDC42 (cell division cycle 42 (GTP binding protein, 25kDa)), ODC1 (ornithine decarboxylase 1), SPARC (secreted protein, acidic, cysteine-rich (osteonectin)), HDAC1 (histone deacetylase 1), CDK2 (cyclin-dependent kinase 2), BARD1 (BRCA1 associated RING domain 1), CDH1 (cadherin 1, type 1, E-cadherin (epithelial)), EGR1 (early growth response 1), INSR (insulin receptor), IRF1 (interferon regulatory factor 1), PHB
(prohibitin), PXN (paxillin), HSPA4 (heat shock 70kDa protein 4), TYR (tyrosinase (oculocutaneous albinism IA)), CAV1 (caveolin 1, caveolae protein, 22kDa), CDKN2B (cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)), FOXO3 (forkhead box 03), HDAC9 (histone deacetylase 9), FBXW7 (F-box and WD
repeat domain containing 7), FOXO1 (forkhead box 01), E2F1 (E2F transcription factor 1), STK1 1 (serine/threonine kinase 11), BMP2 (bone morphogenetic protein 2), HSP90AAl (heat shock protein 90kDa alpha (cytosolic), class A
member 1), HNF4A (hepatocyte nuclear factor 4, alpha), CAMK2G
(calcium/calmodulin-dependent protein kinase II gamma), TP53BP1 (tumor protein p53 binding protein 1), CRYAB (crystallin, alpha B), HMGCR (3-hydroxy-3-methylglutaryl-Coenzyme A reductase), PLAUR (plasminogen activator, urokinase receptor), MCL1 (myeloid cell leukemia sequence 1 (BCL2-related)), NOTCH1 (Notch homolog 1, translocation-associated (Drosophila)), RASSF1 (Ras association (RaIGDS/AF-6) domain family member 1), GSN (gelsolin), CADM1 (cell adhesion molecule 1), ATF2 (activating transcription factor 2), IFNB1 (interferon, beta 1, fibroblast), DAPK1 (death-associated protein kinase 1), CHFR (checkpoint with forkhead and ring finger domains), KITLG (KIT ligand), NDUFA13 (NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 13), DPP4 (dipeptidyl-peptidase 4), GLB1 (galactosidase, beta 1), IKZF1 (IKAROS family zinc finger 1 (Ikaros)), ST5 (suppression of tumorigenicity 5), TGFA
(transforming growth factor, alpha), EIF4EBP1 (eukaryotic translation initiation factor 4E
binding protein 1), TGFBR2 (transforming growth factor, beta receptor II
(70/8OkDa)), EIF2AK2 (eukaryotic translation initiation factor 2-alpha kinase 2), GJA1 (gap junction protein, alpha 1, 43kDa), MYD88 (myeloid differentiation primary response gene (88)), IF127 (interferon, alpha-inducible protein 27), RBMX (RNA binding motif protein, X-linked), EPHA1 (EPH receptor Al), TWSG1 (twisted gastrulation homolog 1 (Drosophila)), H2AFX (H2A histone family, member X), LGALS3 (lectin, galactoside-binding, soluble, 3), MUC3A (mucin 3A, cell surface associated), ILK (integrin-linked kinase), APAF1 (apoptotic peptidase activating factor 1), MAOA (monoamine oxidase A), ERBB3 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian)), EIF2S1 (eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa), PER2 (period homolog (Drosophila)), IGFBP7 (insulin-like growth factor binding protein 7), KDM5B
(lysine (K)-specific demethylase 5B), SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4), NME1 (non-metastatic cells 1, protein (NM23A) expressed in), F2RL1 (coagulation factor II (thrombin) receptor-like 1), ZFP36 (zinc finger protein 36, C3H type, homolog (mouse)), HSPA8 (heat shock 70kDa protein 8), WNT5A
(wingless-type MMTV integration site family, member 5A), ITGB4 (integrin, beta 4), RARB (retinoic acid receptor, beta), VEGFC (vascular endothelial growth factor C), CCL20 (chemokine (C-C motif) ligand 20), EPHB2 (EPH receptor B2), CSNK2A1 (casein kinase 2, alpha 1 polypeptide), PSMD9 (proteasome (prosome, macropain) 26S subunit, non-ATPase, 9), SERPINB2 (serpin peptidase inhibitor, Glade B (ovalbumin), member 2), RHOB (ras homolog gene family, member B), DUSP6 (dual specificity phosphatase 6), CDKN1C (cyclin-dependent kinase inhibitor 1C (p57, Kip2)), SLIT2 (slit homolog 2 (Drosophila)), CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)), UBC (ubiquitin C), STS (steroid sulfatase (microsomal), isozyme S), FST (follistatin), KRT1 (keratin 1), EIF6 (eukaryotic translation initiation factor 6), JUP (junction plakoglobin), HDAC4 (histone deacetylase 4), NEDD4 (neural precursor cell expressed, developmentally down-regulated 4), KRT14 (keratin 14), GLI2 (GLI family zinc finger 2), MYH11 (myosin, heavy chain 11, smooth muscle), MAPKAPK5 (mitogen-activated protein kinase-activated protein kinase 5), MAD1 L1 (MAD1 mitotic arrest deficient-like 1 (yeast)), TNFAIP3 (tumor necrosis factor, alpha-induced protein 3), WEE1 (WEE1 homolog (S. pombe)), BTRC (beta-transducin repeat containing), NKX3-1 (NK3 homeobox 1), GPC3 (glypican 3), CREB3 (cAMP responsive element binding protein 3), PLCB3 (phospholipase C, beta 3 (phosphatidylinositol-specific)), DMPK (dystrophia myotonica-protein kinase), BLNK (B-cell linker), PPIA (peptidylprolyl isomerase A

(cyclophilin A)), DAB2 (disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila)), KLF4 (Kruppel-like factor 4 (gut)), RUNX3 (runt-related transcription factor 3), FLG (filaggrin), IVL (involucrin), CCT5 (chaperonin containing TCP1, subunit 5 (epsilon)), LRPAP1 (low density lipoprotein receptor-related protein associated protein 1), IGF2R (insulin-like growth factor 2 receptor), PER1 (period homolog 1 (Drosophila)), BIK (BCL2-interacting killer (apoptosis-inducing)), PSMC4 (proteasome (prosome, macropain) 26S subunit, ATPase, 4), USF2 (upstream transcription factor 2, c-fos interacting), GAS1 (growth arrest-specific 1), LAMP2 (lysosomal-associated membrane protein 2), PSMD10 (proteasome (prosome, macropain) 26S subunit, non-ATPase, 10), IL24 (interleukin 24), GADD45G (growth arrest and DNA-damage-inducible, gamma), ARHGAP1 (Rho GTPase activating protein 1), CLDN1 (claudin 1), ANXA7 (annexin A7), CHN1 (chimerin (chimaerin) 1), TXNIP (thioredoxin interacting protein), PEG3 (paternally expressed 3), EIF3A (eukaryotic translation initiation factor 3, subunit A), CASC5 (cancer susceptibility candidate 5), (transcription factor 4), CSNK2A2 (casein kinase 2, alpha prime polypeptide), CSNK2B (casein kinase 2, beta polypeptide), CRY1 (cryptochrome 1 (photolyase-like)), CRY2 (cryptochrome 2 (photolyase-like)), EIF4G2 (eukaryotic translation initiation factor 4 gamma, 2), LOXL2 (lysyl oxidase-like 2), (proteasome (prosome, macropain) 26S subunit, non-ATPase, 13), ANP32A
(acidic (leucine-rich) nuclear phosphoprotein 32 family, member A), COL4A3 (collagen, type IV, alpha 3 (Goodpasture antigen)), SCGB1A1 (secretoglobin, family 1A, member 1 (uteroglobin)), BNIP3L (BCL2/adenovirus E1 B 19kDa interacting protein 3-like), MCC (mutated in colorectal cancers), EFNB3 (ephrin-B3), RBBP8 (retinoblastoma binding protein 8), PALB2 (partner and localizer of BRCA2), HBP1 (HMG-box transcription factor 1), MRPL28 (mitochondrial ribosomal protein L28), KDM5A (lysine (K)-specific demethylase 5A), QSOX1 (quiescin Q6 sulfhydryl oxidase 1), ZFR (zinc finger RNA binding protein), MN1 (meningioma (disrupted in balanced translocation) 1), SMYD4 (SET and MYND
domain containing 4), USP7 (ubiquitin specific peptidase 7 (herpes virus-associated)), STK4 (serine/threonine kinase 4), THY1 (Thy-1 cell surface antigen), PTPRG (protein tyrosine phosphatase, receptor type, G), E2F6 (E2F
transcription factor 6), STX11 (syntaxin 11), CDC42BPA (CDC42 binding protein kinase alpha (DMPK-like)), MYOCD (myocardin), DAP (death-associated protein), LOXL1 (lysyl oxidase-like 1), RNF139 (ring finger protein 139), (HIV-1 Tat interactive protein 2, 30kDa), AIM1 (absent in melanoma 1), BCCIP
(BRCA2 and CDKNIA interacting protein), LOXL4 (lysyl oxidase-like 4), WWC1 (WW and C2 domain containing 1), LOXL3 (lysyl oxidase-like 3), CENPN
(centromere protein N), TNS4 (tensin 4), SIK1 (salt-inducible kinase 1), PCGF6 (polycomb group ring finger 6), PHLDA3 (pleckstrin homology-like domain, family A, member 3), IL32 (interleukin 32), LATS1 (LATS, large tumor suppressor, homolog 1 (Drosophila)), COMMD7 (COMM domain containing 7), CDHR2 (cadherin-related family member 2), LELP1 (late cornified envelope-like proline-rich 1), NCRNA00188 (non-protein coding RNA 188), and ENSG00000131023.
[0185] Exemplary non-limiting examples of tumor suppression proteins include ATM (ataxia telangiectasia mutated), ATR (ataxia telangiectasia and Rad3 related), EGFR (epidermal growth factor receptor), ERBB2 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 2), ERBB3 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 3), ERBB4 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 4), Notch 1, Notch2, Notch 3, Notch 4, ATK1 (v-akt murine thymoma viral oncogene homolog 1), ATK2 (v-akt murine thymoma viral oncogene homolog 2), ATK3 (v-akt murine thymoma viral oncogene homolog 3), HIF1a (hypoxia-inducible factor 1a), HIF3a (hypoxia-inducible factor 1 a), Met (met pronto-oncogene), HRG (histidine-rich glycoprotein), Bc12 , PPAR(alpha) (peroxisome proliferator-activated receptor alpha), Ppar(gamma) (peroxisome proliferator-activated receptor gamma), WT1 (Wilmus Tumor 1), FGF1 R(fibroblast growth factor 1 receptor) , FGF2R
(fibroblast growth factor 1 receptor), FGF3R (fibroblast growth factor 3 receptor), FGF4R (fibroblast growth factor 4 receptor), FGF5R (fibroblast growth factor 5 receptor), CDKN2a (cyclin-dependent kinase inhibitor 2A), APC (adenomatous polyposis coli), Rbl (retinoblastoma 1), MEN1 (multiple endocrine neoplasial), VHL (von-Hippel-Lindau tumor suppressor), BRCA1 (breast cancer 1), BRCA2 (breast cancer 2), AR (androgen receptor), TSG1 01 (tumor susceptibility gene 101), Igf1(insulin-like growth factor 1), Igf2 (insulin-like growth factor 2), Igf 1 R
(insulin-like growth factor 1 receptor), Igf 2R(insulin-like growth factor 2 receptor) Bax (BCL-2 associated X protein), CASP 1 (Caspase 1), CASP 2 (Caspase 2), CASP 3 (Caspase 3), CASP 4(Caspase 4), CASP 6 (Caspase 6), CASP
7(Caspase 7), CASP 8 (Caspase 8), CASP 9 (Caspase 9), CASP 12 (Caspase 12), Kras (v-Ki-ras2 Kirsten rate sarcoma viral oncogene homolog), PTEN
(phosphate and tensin homolog), BCRP (breast cancer receptor protein), p53, and combinations thereof.
[0186] In certain embodiments, an animal created by a method of the invention may be used to study the effects of mutations on the animal and on tumor suppression using measures commonly used in the study of tumor suppression. In one embodiment, a genetically modified animal comprising an inactivated chromosomal sequence involved with tumor suppression may be used to determine susceptibility to developing tumors. The method comprises exposing the genetically modified animal comprising an inactivated tumor suppressor sequence and a wild-type animal to a carcinogenic agent, and then monitoring the development of tumors. The animal comprising the inactivated tumor suppressor sequence may have an increased risk for tumor formation.
Moreover, an animal homozygous for the inactivated tumor suppressor sequence may have increased risk relative to an animal heterozygous for the same inactivated sequence, which in turn may have increased risk relative to a wild-type animal. A similar method may be used to screen for spontaneous tumors, wherein the animals described above are not exposed to a carcinogenic agent.
[0187] In another embodiment, an animal comprising an inactivated chromosomal sequence associated with tumor suppression may be used to evaluate the carcinogenic potential of a test agent. The method comprises contacting the genetically modified animal comprising an inactivated tumor suppressor sequence and a wild-type animal to the test agent, and then monitoring the development of tumors. If the animal comprising an inactivated tumor suppressor sequence has an increased incidence of tumors relative to the wild-type animal, the test agent may be carcinogenic.

J. secretase associated disorders [0188] Secretases make up a diverse set of proteins that affect susceptibility for numerous disorders, the presence of a disorder, the severity of a disorder, or any combination thereof. Secretases are enzymes that clip off smaller pieces of another transmembrane protein. Secretases are implicated in many disorders including, for example, Alzheimer's discase. In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with secretase associated disorders has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0189] In each of the above embodiments, one or more chromosomal sequences associated with a secretase associated disorder may be edited. A secretase associated disorder-associated protein or control sequence may typically be selected based on an experimental association of the secretase-related proteins with the development of a secretase disorder. For example, the production rate or circulating concentration of a protein associated with a secretase disorder may be elevated or depressed in a population with a secretase disorder relative to a population without a secretase disorder.
Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art.
[0190] By way of non-limiting example, proteins associated with a secretase disorder include PSENEN (presenilin enhancer 2 homolog (C.
elegans)), CTSB (cathepsin B), PSEN1 (presenilin 1), APP (amyloid beta (A4) precursor protein), APH1 B (anterior pharynx defective 1 homolog B (C.
elegans)), PSEN2 (presenilin 2 (Alzheimer disease 4)), BACE1 (beta-site APP-cleaving enzyme 1), ITM2B (integral membrane protein 2B), CTSD (cathepsin D), NOTCH1 (Notch homolog 1, translocation-associated (Drosophila)), TNF
(tumor necrosis factor (TNF superfamily, member 2)), INS (insulin), DYT10 (dystonia 10), ADAM17 (ADAM metallopeptidase domain 17), APOE
(apolipoprotein E), ACE (angiotensin I converting enzyme (peptidyl-dipeptidase A) 1), STN (statin), TP53 (tumor protein p53), IL6 (interleukin 6 (interferon, beta 2)), NGFR (nerve growth factor receptor (TNFR superfamily, member 16)), IL1 B
(interleukin 1, beta), ACHE (acetylcholinesterase (Yt blood group)), CTNNB1 (catenin (cadherin-associated protein), beta 1, 88kDa), IGF1 (insulin-like growth factor 1 (somatomedin C)), IFNG (interferon, gamma), NRG1 (neuregulin 1), CASP3 (caspase 3, apoptosis-related cysteine peptidase), MAPK1 (mitogen-activated protein kinase 1), CDH1 (cadherin 1, type 1, E-cadherin (epithelial)), APBB1 (amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65)), HMGCR (3-hydroxy-3-methylglutaryl-Coenzyme A reductase), CREB1 (cAMP responsive element binding protein 1), PTGS2 (prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)), HES1 (hairy and enhancer of split 1, (Drosophila)), CAT (catalase), TGFB1 (transforming growth factor, beta 1), ENO2 (enolase 2 (gamma, neuronal)), ERBB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)), TRAPPC10 (trafficking protein particle complex 10), MAOB (monoamine oxidase B), NGF (nerve growth factor (beta polypeptide)), MMP12 (matrix metallopeptidase 12 (macrophage elastase)), JAG1 (jagged 1 (Alagille syndrome)), CD40LG (CD40 ligand), PPARG (peroxisome proliferator-activated receptor gamma), FGF2 (fibroblast growth factor 2 (basic)), IL3 (interleukin 3 (colony-stimulating factor, multiple)), LRP1 (low density lipoprotein receptor-related protein 1), NOTCH4 (Notch homolog 4 (Drosophila)), MAPK8 (mitogen-activated protein kinase 8), PREP (prolyl endopeptidase), NOTCH3 (Notch homolog 3 (Drosophila)), PRNP (prion protein), CTSG (cathepsin G), EGF
(epidermal growth factor (beta-urogastrone)), REN (renin), CD44 (CD44 molecule (Indian blood group)), SELP (selectin P (granule membrane protein 140kDa, antigen CD62)), GHR (growth hormone receptor), ADCYAP1 (adenylate cyclase activating polypeptide 1 (pituitary)), INSR (insulin receptor), GFAP
(glial fibrillary acidic protein), MMP3 (matrix metallopeptidase 3 (stromelysin 1, progelatinase)), MAPK10 (mitogen-activated protein kinase 10), SP1 (Spl transcription factor), MYC (v-myc myelocytomatosis viral oncogene homolog (avian)), CTSE (cathepsin E), PPARA (peroxisome proliferator-activated receptor alpha), JUN (jun oncogene), TIMP1 (TIMP metallopeptidase inhibitor 1), IL5 (interleukin 5 (colony-stimulating factor, eosinophil)), IL1A (interleukin 1, alpha), MMP9 (matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)), HTR4 (5-hydroxytryptamine (serotonin) receptor 4), HSPG2 (heparan sulfate proteoglycan 2), KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog), CYCS (cytochrome c, somatic), SMG1 (SMG1 homolog, phosphatidylinositol 3-kinase-related kinase (C. elegans)), IL1 R1 (interleukin 1 receptor, type I), PROK1 (prokineticin 1), MAPK3 (mitogen-activated protein kinase 3), NTRK1 (neurotrophic tyrosine kinase, receptor, type 1), IL13 (interleukin 13), MME (membrane metallo-endopeptidase), TKT (transketolase), CXCR2 (chemokine (C-X-C motif) receptor 2), IGF1 R (insulin-like growth factor receptor), RARA (retinoic acid receptor, alpha), CREBBP (CREB binding protein), PTGS1 (prostaglandin-endoperoxide synthase 1 (prostaglandin G/H
synthase and cyclooxygenase)), GALT (galactose-1 -phosphate uridylyltransferase), CHRM1 (cholinergic receptor, muscarinic 1), ATXN1 (ataxin 1), PAWR (PRKC, apoptosis, WT1, regulator), NOTCH2 (Notch homolog 2 (Drosophila)), M6PR (mannose-6-phosphate receptor (cation dependent)), CYP46A1 (cytochrome P450, family 46, subfamily A, polypeptide 1), CSNK1 D
(casein kinase 1, delta), MAPK14 (mitogen-activated protein kinase 14), PRG2 (proteoglycan 2, bone marrow (natural killer cell activator, eosinophil granule major basic protein)), PRKCA (protein kinase C, alpha), L1 CAM (L1 cell adhesion molecule), CD40 (CD40 molecule, TNF receptor superfamily member 5), NR1 12 (nuclear receptor subfamily 1, group I, member 2), JAG2 (jagged 2), CTNND1 (catenin (cadherin-associated protein), delta 1), CDH2 (cadherin 2, type 1, N-cadherin (neuronal)), CMA1 (chymase 1, mast cell), SORT1 (sortilin 1), DLK1 (delta-like 1 homolog (Drosophila)), THEM4 (thioesterase superfamily member 4), JUP (junction plakoglobin), CD46 (CD46 molecule, complement regulatory protein), CCL1 1 (chemokine (C-C motif) ligand 11), CAV3 (caveolin 3), RNASE3 (ribonuclease, RNase A family, 3 (eosinophil cationic protein)), HSPA8 (heat shock 70kDa protein 8), CASP9 (caspase 9, apoptosis-related cysteine peptidase), CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4), CCR3 (chemokine (C-C motif) receptor 3), TFAP2A (transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha)), SCP2 (sterol carrier protein 2), CDK4 (cyclin-dependent kinase 4), HIF1A (hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)), TCF7L2 (transcription factor 7-like 2 (T-cell specific, HMG-box)), IL1 R2 (interleukin 1 receptor, type II), B3GALTL (beta 1,3-galactosyltransferase-like), MDM2 (Mdm2 p53 binding protein homolog (mouse)), RELA (v-rel reticuloendotheliosis viral oncogene homolog A (avian)), CASP7 (caspase 7, apoptosis-related cysteine peptidase), IDE (insulin-degrading enzyme), FABP4 (fatty acid binding protein 4, adipocyte), CASK (calcium/calmodulin-dependent serine protein kinase (MAGUK family)), ADCYAP1 R1 (adenylate cyclase activating polypeptide 1 (pituitary) receptor type I), ATF4 (activating transcription factor 4 (tax-responsive enhancer element B67)), PDGFA (platelet-derived growth factor alpha polypeptide), C21 orf33 (chromosome 21 open reading frame 33), SCG5 (secretogranin V (7B2 protein)), RNF1 23 (ring finger protein 123), NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1), ERBB2 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)), CAV1 (caveolin 1, caveolae protein, 22kDa), MMP7 (matrix metallopeptidase 7 (matrilysin, uterine)), TGFA (transforming growth factor, alpha), RXRA (retinoid X receptor, alpha), STX1A (syntaxin 1A (brain)), PSMC4 (proteasome (prosome, macropain) 26S subunit, ATPase, 4), P2RY2 (purinergic receptor P2Y, G-protein coupled, 2), TNFRSF21 (tumor necrosis factor receptor superfamily, member 21), DLG1 (discs, large homolog 1 (Drosophila)), NUMBL

(numb homolog (Drosophila)-like), SPN (sialophorin), PLSCR1 (phospholipid scramblase 1), UBQLN2 (ubiquilin 2), UBQLN1 (ubiquilin 1), PCSK7 (proprotein convertase subtilisin/kexin type 7), SPON1 (spondin 1, extracellular matrix protein), SILV (silver homolog (mouse)), QPCT (glutaminyl-peptide cyclotransferase), HES5 (hairy and enhancer of split 5 (Drosophila)), GCC1 (GRIP and coiled-coil domain containing 1), and any combination thereof.
[0191] Preferred proteins associated with a secretase disorder include APH-1A (anterior pharynx-defective 1, alpha), APH-1 B (anterior pharynx-defective 1, beta), PSEN-1 (presenilin-1), NCSTN (nicastrin), PEN-2 (presenilin enhancer 2), and any combination thereof.
[0192] In certain embodiments, an animal created by a method of the invention may be used to study the effects of mutations on the animal and development and/or progression of a secretase associated disorder using measures commonly used in the study of secretase disorders.
[0193] The incidence or indication of a secretase disorder may occur spontaneously in the genetically modified animal. Alternatively, the incidence or indication of the secretase disorder may be promoted by exposure to a disruptive agent. Non-limiting examples of disruptive agents include a protein associated with a secretase disorder such as any of those described above, a drug, a toxin, a chemical, an activated retrovirus, and an environmental stress. Non-limiting examples of environmental stresses include forced swimming, cold swimming, platform shaker stimuli, loud noises, and immobilization stress.

K. amyotrophic lateral sclerosis [0194] Certain nucleic acid sequences, and the proteins encoded by them, are associated with motor neuron disorders. These sequences make up a diverse set of sequences that affect susceptibility for developing a motor neuron disorder, the presence of the motor neuron disorder, the severity of the motor neuron disorder or any combination thereof. In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with a specific motor neuron disorder, amyotrophic lateral sclerosis (ALS), has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0195] In each of the above embodiments, one or more chromosomal sequences associated with ALS may be edited. A chromosomal sequence associated with ALS may typically be selected based on an experimental association of an ALS-related sequence to ALS. An ALS-related nucleic acid sequence may encode an ALS-related protein or may be an ALS-related control sequence. For example, the production rate or circulating concentration of a protein associated with ALS may be elevated or depressed in a population with ALS relative to a population without ALS. Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art.
[0196] By way of non-limiting example, proteins associated with ALS include but are not limited to SOD1 (superoxide dismutase 1), ALS2 (amyotrophic lateral sclerosis 2), FUS (fused in sarcoma), TARDBP (TAR DNA
binding protein), VAGFA (vascular endothelial growth factor A), VAGFB
(vascular endothelial growth factor B), and VAGFC (vascular endothelial growth factor C), and any combination thereof.
[0197] In certain embodiments, an animal created by a method of the invention may be used to study the effects of mutations on the animal and development and/or progression of ALS using measures commonly used in the study of ALS.

L. prion diseases [0198] Prion disorders appear to be diseases of protein conformation, which results in abnormal protein aggregation. In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with a prion disease has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0199] In each of the above embodiments, one or more chromosomal sequences encoding a protein or control sequence associated with prion disorders may be edited. A prion disorder-related nucleic acid sequence may typically be selected based on an experimental association of the prion disorder-related nucleic acid sequence to a prion disorder. A prion disorder-related nucleic acid sequence may encode a prion disorder-related protein or isoform thereof, or may be a prion disorder-related control sequence. For example, the production rate or circulating concentration of a prion disorder-related protein or isoform may be elevated or depressed in a population having a prion disorder relative to a population lacking the prion disorder.
Differences in protein or certain isoform levels may be assessed using proteomic techniques including but not limited to Western blot, immunohistochemical staining, enzyme linked immunosorbent assay (ELISA), and mass spectrometry. Alternatively, the prion disorder-related proteins may be identified by obtaining gene expression profiles of the genes encoding the proteins using genomic techniques including but not limited to DNA microarray analysis, serial analysis of gene expression (SAGE), and quantitative real-time polymerase chain reaction (Q-PCR).
[0200] Non-limiting examples of prion disorder-related proteins include PrPc and its isoforms, PrPsc and its isoforms, HECTD2 (e3-ubipuitin ligase protein), ST11 (stress inducible protein 1), DPL (residue Doppel protein, encoded by Prnd), APOA1 (Apolipoprotein Al), BCL-2 (B-cell lymphoma 2), HSP60 (Heat shock 60kDa protein), BAX- inhibiting peptide (Bcl-2-associated X
protein inhibitor), NRF2 (nuclear respiratory factor 2), NCAMs (neural cell-adhesion molecules), heparin, laminin and laminin receptor.
[0201] Further, non-limiting examples of genes that may be related to neurodegenerative conditions in prion disorders include A2M (Alpha-2-Macroglobulin), AATF (Apoptosis antagonizing transcription factor), ACPP (Acid phosphatase prostate), ACTA2 (Actin alpha 2 smooth muscle aorta), ADAM22 (ADAM metallopeptidase domain), ADORA3 (Adenosine A3 receptor), ADRA1 D
(Alpha-1 D adrenergic receptor for Alpha-1 D adrenoreceptor), AHSG (Alpha-2-HS-glycoprotein), AIF1 (Allograft inflammatory factor 1), ALAS2 (Delta-aminolevulinate synthase 2), AMBP (Alpha-1-microglobulin/bikunin precursor), ANK3 (Ankryn 3), ANXA3 (Annexin A3), APCS (Amyloid P component serum), APOA1 (Apolipoprotein Al), APOA12 (Apolipoprotein A2), APOB (Apolipoprotein B), APOC1 (Apolipoprotein Cl), APOE (Apolipoprotein E), APOH (Apolipoprotein H), APP (Amyloid precursor protein), ARC (Activity-regulated cytoskeleton-associated protein), ARF6 (ADP-ribosylation factor 6), ARHGAP5 (Rho GTPase activating protein 5), ASCL1 (Achaete-scute homolog 1), B2M (Beta-2 microglobulin), B4GALNTI (Beta-1,4-N-acetyl-galactosaminyl transferase 1), BAX (Bcl-2-associated X protein), BCAT (Branched chain amino-acid transaminase 1 cytosolic), BCKDHA (Branched chain keto acid dehydrogenase E1 alpha), BCKDK (Branched chain alpha-ketoacid dehydrogenase kinase), BCL2 (B-cell lymphoma 2), BCL2L1 (BCL2-like 1), BDNF (Brain-derived neurotrophic factor), BHLHE40 (Class E basic helix-loop-helix protein 40), BHLHE41 (Class E basic helix-loop-helix protein 41), BMP2 (Bone morphogenetic protein 2A), BMP3 (Bone morphogenetic protein 3), BMP5 (Bone morphogenetic protein 5), BRD1 (Bromodomain containing 1), BTC
(Betacellulin), BTNL8 (Butyrophilin-like protein 8), CALB1 (Calbindin 1), (Calmodulin 1), CAMK1 (Calcium/calmodulin-dependent protein kinase type I), CAMK4 (Calcium/calmodulin-dependent protein kinase type IV), CAMKIIB
(Calcium/calmodulin-dependent protein kinase type IIB), CAMKIIG
(Calcium/calmodulin-dependent protein kinase type IIG), CASP11 (Caspase-10), CASP8 (Caspase 8 apoptosis-related cysteine peptidase), CBLN1 (cerebellin 1 precursor), CCL2 (Chemokine (C-C motif) ligand 2), CCL22 (Chemokine (C-C
motif) ligand 22), CCL3 (Chemokine (C-C motif) ligand 3), CCL8 (Chemokine (C-C motif) ligand 8), CCNG1 (Cyclin-G1), CCNT2 (Cyclin T2), CCR4 (C-C
chemokine receptor type 4 (CD194)), CD58 (CD58), CD59 (Protectin), CD5L
(CD5 antigen-like), CD93 (CD93), CDKN2AIP (CDKN2A interacting protein), CDKN2B (Cyclin-dependent kinase inhibitor 2B), CDX1 (Homeobox protein CDX-1), CEA (Carcinoembryonic antigen), CEBPA (CCAAT/enhancer-binding protein alpha), CEBPB (CCAAT/enhancer binding protein C/EBP beta), CEBPB
(CCAAT/enhancer-binding protein beta), CEBPD (CCAAT/enhancer-binding protein delta), CEBPG (CCAAT/enhancer-binding protein gamma), CENPB
(Centromere protein B), CGA (Glycoprotein hormone alpha chain), CGGBP1 (CGG triplet repeat-binding protein 1), CHGA (Chromogranin A), CHGB
(Secretoneurin), CHN2 (Beta-chimaerin), CHRD (Chordin), CHRM1 (Cholinergic receptor muscarinic 1), CITED2 (Cbp/p300-interacting transactivator 2), CLEC4E
(C-type lectin domain family 4 member E), CMTM2 (CKLF-like MARVEL
transmembrane domain-containing protein 2), CNTN1 (Contactin 1), CNTNAP1 (Contactin-associated protein-like 1), CR1 (Erythrocyte complement receptor 1), CREM (cAMP-responsive element modulator), CRH (Corticotropin-releasing hormone), CRHR1 (Corticotropin releasing hormone receptor 1), CRKRS (Cell division cycle 2-related protein kinase 7), CSDA (DNA-binding protein A), CSF3 (Granulocyte colony stimulating factor 3), CSF3R (Granulocyte colony-stimulating factor 3 receptor), CSP (Chemosensory protein), CSPG4 (Chondroitin sulfate proteoglycan 4), CTCF (CCCTC-binding factor zinc finger protein), CTGF
(Connective tissue growth factor), CXCL1 2 (Chemokine C-X-C motif ligand 12), DAD1 (Defender against cell death 1), DAXX (Death associated protein 6), DBN1 (Drebrin 1), DBP (D site of albumin promoter-albumin D-box binding protein), DDR1 (Discoidin domain receptor family member 1), DDX14 (DEAD/DEAN box helicase), DEFA3 (Defensin alpha 3 neutrophil-specific), DVL3 (Dishevelled dsh homolog 3), EDN1 (Endothelin 1), EDNRA (Endothelin receptor type A), EGF
(Epidermal growth factor), EGFR (Epidermal growth factor receptor), EGR1 (Early growth response protein 1), EGR2 (Early growth response protein 2), EGR3 (Early growth response protein 3), EIF2AK2 (Eukaryotic translation initiation factor 2-alpha kinase 2), ELANE (Elastase neutrophil expressed), (ELK1 member of ETS oncogene family), ELK3 (ELK3 ETS-domain protein (SRF
accessory protein 2)), EML2 (Echinoderm microtubule associated protein like 2), EPHA4 (EPH receptor A4), ERBB2 (V-erb-b2 erythroblastic leukemia viral oncogene homolog 2), ERBB3 (Receptor tyrosine-protein kinase erbB-3), ESR2 (Estrogen receptor 2), ESR2 (Estrogen receptor 2), ETS1 (V-ets erythroblastosis virus E26 oncogene homolog 1), ETV6 (Ets variant 6), FASLG (Fas ligand TNF
superfamily member 6), FCAR (Fc fragment of IgA receptor), FCER1 G (Fc fragment of IgE high affinity I receptor for gamma polypeptide), FCGR2A (Fc fragment of IgG low affinity Ila receptor - CD32), FCGR3B (Fc fragment of IgG
low affinity Illb receptor - CD16b), FCGRT (Fc fragment of IgG receptor transporter alpha), FGA (Basic fibrinogen), FGF1 (Acidic fibroblast growth factor 1), FGF14 (Fibroblast growth factor 14), FGF16 (fibroblast growth factor 16), FGF18 (Fibroblast growth factor 18), FGF2 (Basic fibroblast growth factor 2), FIBP (Acidic fibroblast growth factor intracellular binding protein), FIGF (C-fos induced growth factor), FMR1 (Fragile X mental retardation 1), FOSB (FBJ
murine osteosarcoma viral oncogene homolog B), FOXO1 (Forkhead box 01), FSHB (Follicle stimulating hormone beta polypeptide), FTH1 (Ferritin heavy polypeptide 1), FTL (Ferritin light polypeptide), G1 P3 (Interferon alpha-inducible protein 6), G6S (N-acetylglucosamine-6-sulfatase), GABRA2 (Gamma-aminobutyric acid A receptor alpha 2), GABRA3 (Gamma-aminobutyric acid A
receptor alpha 3), GABRA4 (Gamma-aminobutyric acid A receptor alpha 4), GABRB1 (Gamma-aminobutyric acid A receptor beta 1), GABRG1 (Gamma-aminobutyric acid A receptor gamma 1), GADD45A (Growth arrest and DNA-damage-inducible alpha), GCLC (Glutamate-cysteine ligase catalytic subunit), GDF15 (Growth differentiation factor 15), GDF9 (Growth differentiation factor 9), GFRA1 (GDNF family receptor alpha 1), GIT1 (G protein-coupled receptor kinase interactor 1), GNA13 (Guanine nucleotide-binding protein/G protein alpha 13), GNAQ (Guanine nucleotide binding protein/G protein q polypeptide), GPR12 (G
protein-coupled receptor 12), GPR18 (G protein-coupled receptor 18), GPR22 (G
protein-coupled receptor 22), GPR26 (G protein-coupled receptor 26), GPR27 (G
protein-coupled receptor 27), GPR77 (G protein-coupled receptor 77), GPR85 (G
protein-coupled receptor 85), GRB2 (Growth factor receptor-bound protein 2), GRLF1 (Glucocorticoid receptor DNA binding factor 1), GST (Glutathione S-transferase), GTF2B (General transcription factor IIB), GZMB (Granzyme B), HAND1 (Heart and neural crest derivatives expressed 1), HAVCR1 (Hepatitis A
virus cellular receptor 1), HES1 (Hairy and enhancer of split 1), HES5 (Hairy and enhancer of split 5), HLA-DQA1 (Major histocompatibility complex class II DQ
alpha), HOXA2 (Homeobox A2), HOXA4 (Homeobox A4), HP (Haptoglobin), HPGDS (Prostaglandin-D synthase), HSPA8 (Heat shock 70kDa protein 8), HTR1A (5-hydroxytryptamine receptor 1A), HTR2A (5-hydroxytryptamine receptor 2A), HTR3A (5-hydroxytryptamine receptor 3A), ICAM1 (Intercellular adhesion molecule 1 (CD54)), IFIT2 (Interferon-induced protein with tetratricopeptide repeats 2), IFNAR2 (Interferon alpha/beta/omega receptor 2), IGF1 (Insulin-like growth factor 1), IGF2 (Insulin-like growth factor 2), (Insulin-like growth factor binding protein 2, 36kDa), IGFBP7 (Insulin-like growth factor binding protein 7), IL10 (Interleukin 10), IL1 ORA (Interleukin 10 receptor alpha), IL11 (Interleukin 11), IL11 RA (Interleukin 11 receptor alpha), IL11 RB
(Interleukin 11 receptor beta), IL13 (Interleukin 13), IL15 (Interleukin 15), (Interleukin 17A), IL17RB (interleukin 17 receptor B), IL18 (Interleukin 18), ILI8RAP (Interleukin 18 receptor accessory protein), IL1 R2 (Interleukin 1 receptor type II), IL1 RN (Interleukin 1 receptor antagonist), IL2RA
(Interleukin 2 receptor alpha), IL4R (Interleukin 4 receptor), IL6 (Interleukin 6), IL6R
(Interleukin 6 receptor), IL7 (Interleukin 7), IL8 (Interleukin 8), IL8RA (Interleukin 8 receptor alpha), IL8RB (Interleukin 8 receptor beta), ILK (Integrin-linked kinase), (Inositol polyphosphate-4-phosphatase type I, 107kDa), INPP4B (Inositol polyphosphate-4-phosphatase type I beta), INS (Insulin), IRF2 (Interferon regulatory factor 2), IRF3 (Interferon regulatory factor 3), IRF9 (Interferon regulatory factor 9), IRS1 (Insulin receptor substrate 1), ITGA4 (integrin alpha 4), ITGA6 (Integrin alpha-6), ITGAE (Integrin alpha E), ITGAV (Integrin alpha-V), JAG1 (Jagged 1), JAK1 (Janus kinase 1), JDP2 (Jun dimerization protein 2), JUN (Jun oncogene), JUNB (Jun B proto-oncogene), KCNJ15 (Potassium inwardly-rectifying channel subfamily J member 15), KIF5B (Kinesin family member 5B), KLRC4 (Killer cell lectin-like receptor subfamily C member 4), KRT8 (Keratin 8), LAMP2 (Lysosomal-associated membrane protein 2), LEP
(Leptin), LHB (Luteinizing hormone beta polypeptide), LRRN3 (Leucine rich repeat neuronal 3), MAL (Mal T-cell differentiation protein), MAN1A1 (Mannosidase alpha class 1A member 1), MAOB (Monoamine oxidase B), MAP3K1 (Mitogen-activated protein kinase kinase kinase 1), MAPK1 (Mitogen-activated protein kinase 1), MAPK3 (Mitogen-activated protein kinase 3), MAPRE2 (Microtubule-associated protein RP/EB family member 2), MARCKS
(Myristoylated alanine-rich protein kinase C substrate), MAS1 (MAS1 oncogene), MASL1 (MAS1 oncogene-like), MBP (Myelin basic protein), MCL1 (Myeloid cell leukemia sequence 1), MDMX (MDM2-like p53-binding protein), MECP2 (Methyl CpG binding protein 2), MFGE8 (Milk fat globule-EGF factor 8 protein), MIF
(Macrophage migration inhibitory factor), MMP2 (Matrix metal lopepticlase 2), MOBP (Myelin-associated oligodendrocyte basic protein), MUC16 (Cancer antigen 125), MX2 (Myxovirus (influenza virus) resistance 2), MYBBP1A (MYB
binding protein 1 a), NBN (Nibrin), NCAM1 (Neural cell adhesion molecule 1), NCF4 (Neutrophil cytosolic factor 4 40kDa), NCOA1 (Nuclear receptor coactivator 1), NCOA2 (Nuclear receptor coactivator 2), NEDD9 (Neural precursor cell expressed developmentally down-regulated 9), NEUR
(Neuraminidase), NFATC1 (Nuclear factor of activated T-cells cytoplasmic calcineurin-dependent 1), NFE2L2 (Nuclear factor erythroid-derived 2-like 2), NFIC (Nuclear factor I/C), NFKBIA (Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha), NGFR (Nerve growth factor receptor), NIACR2 (niacin receptor 2), NLGN3 (Neuroligin 3), NPFFR2 (neuropeptide FF
receptor 2), NPY (Neuropeptide Y), NR3C2 (Nuclear receptor subfamily 3 group C member 2), NRAS (Neuroblastoma RAS viral (v-ras) oncogene homolog), NRCAM (Neuronal cell adhesion molecule), NRG1 (Neuregulin 1), NRTN
(Neurturin), NRXN1 (Neurexin 1), NSMAF (Neutral sphingomyelinase activation associated factor), NTF3 (Neurotrophin 3), NTF5 (Neurotrophin 4/5), ODC1 (Ornithine decarboxylase 1), OR10A1 (Olfactory receptor 1 OA1), OR1A1 (Olfactory receptor family 1 subfamily A member 1), OR1 N1 (Olfactory receptor family 1 subfamily N member 1), OR3A2 (Olfactory receptor family 3 subfamily A
member 2), OR7A1 7 (Olfactory receptor family 7 subfamily A member 17), ORM1 (Orosomucoid 1), OXTR (Oxytocin receptor), P2RY13 (Purinergic receptor P2Y G-protein coupled 13), P2Y12 (Purinergic receptor P2Y G-protein coupled 12), P70S6K (P70S6 kinase), PAK1 (P21 /Cdc42/Rac1-activated kinase 1), PAR1 (Prader-Willi/Angelman region-1), PBEF1 (Pre-B-cell colony enhancing factor 1), PCAF (P300/CBP-associated factor), PDE4A (cAMP-specific 3',5'-cyclic phosphodiesterase 4A), PDE4B (Phosphodiesterase 4B cAMP-specific), PDE4B (Phosphodiesterase 4B cAMP-specific), PDE4D (Phosphodiesterase 4D
cAMP-specific), PDGFA (Platelet-derived growth factor alpha polypeptide), PDGFB (Platelet-derived growth factor beta polypeptide), PDGFC (Platelet derived growth factor C), PDGFRB (Beta-type platelet-derived growth factor receptor), PDPN (Podoplanin), PENK (Enkephalin), PER1 (Period homolog 1), PLA2 (Phospholipase A2), PLAU (Plasminogen activator urokinase), PLXNCI
(Plexin Cl), PMVK (Phosphomevalonate kinase), PNOC (Prepronociceptin), POLH (Polymerase (DNA directed) eta), POMC (Proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/
beta-melanocyte stimulating hormone/ beta-endorphin)), POU2AF1 (POU
domain class 2 associating factor 1), PRKAA1 (5'-AMP-activated protein kinase catalytic subunit alpha-1), PRL (Prolactin), PSCDBP (Cytohesin 1 interacting protein), PSPN (Persephin), PTAFR (Platelet-activating factor receptor), PTGS2 (Prostaglandin-endoperoxide synthase 2), PTN (Pleiotrophin), PTPN11 (Protein tyrosine phosphatase non-receptor type 11), PYY (Peptide YY), RAB11 B
(RAB11 B member RAS oncogene family), RAB6A (RAB6A member RAS
oncogene family), RAD17 (RAD17 homolog), RAF1 (RAF proto-oncogene serine/threonine-protein kinase), RANBP2 (RAN binding protein 2), RAP1A
(RAP1A member of RAS oncogene family), RB1 (Retinoblastoma 1), RBL2 (Retinoblastoma-like 2 (p130)), RCVRN (Recoverin), REM2 (RAS/RAD/GEM-like GTP binding 2), RFRP (RFamide-related peptide), RPS6KA3 (Ribosomal protein S6 kinase 90kDa polypeptide 3), RTN4 (Reticulon 4), RUNX1 (Runt-related transcription factor 1), S100A4 (S100 calcium binding protein A4), S1 PR1 (Sphingosine-1 -phosphate receptor 1), SCG2 (Secretogranin II), SCYE1 (Small inducible cytokine subfamily E member 1), SELENBP1 (Selenium binding protein 1), SGK (Serum/glucocorticoid regulated kinase), SKD1 (Suppressor of K+
transport growth defect 1), SLC14A1 (Solute carrier family 14 (urea transporter) member 1 (Kidd blood group)), SLC25A37 (Solute carrier family 25 member 37), SMAD2 (SMAD family member 2), SMAD5 (SMAD family member 5), SNAP23 (Synaptosomal-associated protein 23kDa), SNOB (Synuclein beta), SNF1 LK
(SNP-like kinase), SORT1 (Sortilin 1), SSB (Sjogren syndrome antigen B), STAT1 (Signal transducer and activator of transcription 1, 91 kDa), STAT5A
(Signal transducer and activator of transcription 5A), STAT5B (Signal transducer and activator of transcription 5B), STX16 (Syntaxin 16), TAC1 (Tachykinin precursor 1), TBX1 (T-box 1), TEF (Thyrotrophic embryonic factor), TF
(Transferrin), TGFA (Transforming growth factor alpha), TGFB1 (Transforming growth factor beta 1), TGFB2 (Transforming growth factor beta 2), TGFB3 (Transforming growth factor beta 3), TGFBR1 (Transforming growth factor beta receptor I), TGM2 (Transglutaminase 2), THPO (Thrombopoietin), TIMP1 (TIMP
metallopeptidase inhibitor 1), TIMP3 (TIMP metallopeptidase inhibitor 3), TMEM129 (Transmembrane protein 129), TNFRC6 (TNFR/NGFR cysteine-rich region), TNFRSF10A (Tumor necrosis factor receptor superfamily member 1 Oa), TNFRSF10C (Tumor necrosis factor receptor superfamily member 1 Oc decoy without an intracellular domain), TNFRSF1A (Tumor necrosis factor receptor superfamily member 1A), TOB2 (Transducer of ERBB2 2), TOP1 (Topoisomerase (DNA) I), TOPOII (Topoisomerase 2), TRAK2 (Trafficking protein kinesin binding 2), TRH (Thyrotropin-releasing hormone), TSH (Thyroid-stimulating hormone alpha), TUBAIA (Tubulin alpha 1a), TXK (TXK tyrosine kinase), TYK2 (Tyrosine kinase 2), UCP1 (Uncoupling protein 1), UCP2 (Uncoupling protein 2), ULIP (Unc-33-like phosphoprotein), UTRN (Utrophin), VEGF (Vascular endothelial growth factor), VGF (VGF nerve growth factor inducible), VIP (Vasoactive intestinal peptide), VNN1 (Vanin 1), VTN
(Vitronectin), WNT2 (Wingless-type MMTV integration site family member 2), XRCC6 (X-ray repair cross-complementing 6), ZEB2 (Zinc finger E-box binding homeobox 2), and ZNF461 (Zinc finger protein 461).
[0202] Exemplary prion disorder-related proteins, include PrPc and isoforms thereof, PrPsc and isoforms thereof, HECTD2 (e3-ubipuitin ligase protein), STI1 (stress inducible protein 1), DPL (residue Doppel protein, encoded by Prnd), APOA1 (Apolipoprotein Al), BCL-2 (B-cell lymphoma 2), HSP60 (Heat shock 60kDa protein), BAX- inhibiting peptide (Bcl-2-associated X protein inhibitor), NRF2 (nuclear respiratory factor 2), NCAMs (neural cell-adhesion molecules), heparin, laminin and laminin receptor and any combination thereof.
[0203] In certain embodiments, an animal created by a method of the invention may be used to study the effects of mutations on the animal and development and/or progression of a prion disorder using measures commonly used in the study of prion disorders.

M. immunodeficiency [0204] In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with immunodeficiency has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0205] In each of the above embodiments, one or more chromosomal sequences associated with immunodeficiency may be edited. An immunodeficiency protein or control sequence is a protein or control sequence for which an alteration in activity is linked to an immunodeficiency, which may be the primary or a secondary symptom of an animal disease or condition, preferably a mammalian, e.g., a human, disease or condition. An immunodeficiency sequence may typically be selected based on an experimental association of the immunodeficiency sequence to an immunodeficiency disease or condition, especially a mammalian, e.g., a human, disease or condition. For example, the expression of an immunodeficiency protein in a particular tissue may be elevated or depressed in a population having an immunodeficiency disease or condition relative to a population lacking the disease or condition.
Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art.
[0206] Non-limiting examples of human immunodeficiency genes include A2M [alpha-2-macroglobulin]; AANAT [arylalkylamine N-acetyltransferase]; ABCA1 [ATP-binding cassette, sub-family A (ABC1), member 1 ]; ABCA2 [ATP-binding cassette, sub-family A (ABC1), member 2]; ABCA3 [ATP-binding cassette, sub-family A (ABC1), member 3]; ABCA4 [ATP-binding cassette, sub-family A (ABC1), member 4]; ABCB1 [ATP-binding cassette, sub-family B (MDR/TAP), member 1]; ABCC1 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 1]; ABCC2 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 2]; ABCC3 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 3]; ABCC4 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 4]; ABCC8 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 8]; ABCD2 [ATP-binding cassette, sub-family D (ALD), member 2]; ABCD3 [ATP-binding cassette, sub-family D (ALD), member 3];
ABCG1 [ATP-binding cassette, sub-family G (WHITE), member 1]; ABCG2 [ATP-binding cassette, sub-family G (WHITE), member 2]; ABCG5 [ATP-binding cassette, sub-family G (WHITE), member 5]; ABCG8 [ATP-binding cassette, sub-family G (WHITE), member 8]; ABHD2 [abhydrolase domain containing 2]; ABL1 [c-abl oncogene 1, receptor tyrosine kinase]; ABO [ABO blood group (transferase A, alpha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3-galactosyltransferase)]; ABP1 [amiloride binding protein 1 (amine oxidase (copper-containing))]; ACAA1 [acetyl-Coenzyme A acyltransferase 1]; ACACA
[acetyl-Coenzyme A carboxylase alpha]; ACAN [aggrecan]; ACAT1 [acetyl-Coenzyme A acetyltransferase 1 ]; ACAT2 [acetyl-Coenzyme A acetyltransferase 2]; ACCN5 [amiloride-sensitive cation channel 5, intestinal]; ACE [angiotensin I
converting enzyme (peptidyl-dipeptidase A) 1]; ACE2 [angiotensin I converting enzyme (peptidyl-dipeptidase A) 2]; ACHE [acetylcholinesterase (Yt blood group)]; ACLY [ATP citrate lyase]; ACOT9 [acyl-CoA thioesterase 9]; ACOX1 [acyl-Coenzyme A oxidase 1, palmitoyl]; ACP1 [acid phosphatase 1, soluble];
ACP2 [acid phosphatase 2, lysosomal]; ACP5 [acid phosphatase 5, tartrate resistant]; ACPP [acid phosphatase, prostate]; ACSL3 [acyl-CoA synthetase long-chain family member 3]; ACSM3 [acyl-CoA synthetase medium-chain family member 3]; ACTA1 [actin, alpha 1, skeletal muscle]; ACTA2 [actin, alpha 2, smooth muscle, aorta]; ACTB [actin, beta]; ACTC1 [actin, alpha, cardiac muscle 1]; ACTG1 [actin, gamma 1]; ACTN1 [actinin, alpha 1]; ACTN2 [actinin, alpha 2];
ACTN4 [actinin, alpha 4]; ACTR2 [ARP2 actin-related protein 2 homolog (yeast)];
ACVR1 [activin A receptor, type I]; ACVR1 B [activin A receptor, type IB];
ACVRL1 [activin A receptor type 11-1 ike 1 ]; ACY1 [aminoacylase 1 ]; ADA
[adenosine deaminase]; ADAM10 [ADAM metallopeptidase domain 10]; ADAM12 [ADAM metallopeptidase domain 12]; ADAM17 [ADAM metallopeptidase domain 17]; ADAM23 [ADAM metallopeptidase domain 23]; ADAM33 [ADAM
metallopeptidase domain 33]; ADAM8 [ADAM metallopeptidase domain 8];
ADAMS [ADAM metallopeptidase domain 9 (meltrin gamma)]; ADAMTS1 [ADAM
metallopeptidase with thrombospondin type 1 motif, 1]; ADAMTS12 [ADAM
metallopeptidase with thrombospondin type 1 motif, 12]; ADAMTS13 [ADAM
metallopeptidase with thrombospondin type 1 motif, 13]; ADAMTS15 [ADAM
metallopeptidase with thrombospondin type 1 motif, 15]; ADAMTSL1 [ADAMTS-like 1]; ADAMTSL4 [ADAMTS-like 4]; ADAR [adenosine deaminase, RNA-specific]; ADCY1 [adenylate cyclase 1 (brain)]; ADCY10 [adenylate cyclase 10 (soluble)]; ADCY3 [adenylate cyclase 3]; ADCY9 [adenylate cyclase 9];
ADCYAP1 [adenylate cyclase activating polypeptide 1 (pituitary)]; ADCYAP1 R1 [adenylate cyclase activating polypeptide 1 (pituitary) receptor type I]; ADD1 [adducin 1 (alpha)]; ADH5 [alcohol dehydrogenase 5 (class III), chi polypeptide];
ADIPOQ [adiponectin, C1Q and collagen domain containing]; ADIPOR1 [adiponectin receptor 1]; ADK [adenosine kinase]; ADM [adrenomedullin];
ADORA1 [adenosine Al receptor]; ADORA2A [adenosine A2a receptor];

ADORA2B [adenosine A2b receptor]; ADORA3 [adenosine A3 receptor];
ADRA1 B [adrenergic, alpha-1 B-, receptor]; ADRA2A [adrenergic, alpha-2A-, receptor]; ADRA2B [adrenergic, alpha-2B-, receptor]; ADRB1 [adrenergic, beta-1-, receptor]; ADRB2 [adrenergic, beta-2-, receptor, surface]; ADSL
[adenylosuccinate lyase]; ADSS [adenylosuccinate synthase]; AEBP1 [AE
binding protein 1]; AFP [alpha-fetoprotein]; AGER [advanced glycosylation end product-specific receptor]; AGMAT [agmatine ureohydrolase (agmatinase)];
AGPS [alkylglycerone phosphate synthase]; AGRN [agrin]; AGRP [agouti related protein homolog (mouse)]; AGT [angiotensinogen (serpin peptidase inhibitor, Glade A, member 8)]; AGTR1 [angiotensin II receptor, type 1]; AGTR2 [angiotensin II receptor, type 2]; AHOY [adenosylhomocysteinase]; AHI1 [Abelson helper integration site 1]; AHR [aryl hydrocarbon receptor]; AHSP
[alpha hemoglobin stabilizing protein]; AICDA [activation-induced cytidine deaminase]; AIDA [axin interactor, dorsalization associated]; AIMP1 [aminoacyl tRNA synthetase complex-interacting multifunctional protein 1]; AIRE
[autoimmune regulator]; AK1 [adenylate kinase 1]; AK2 [adenylate kinase 2];
AKR1Al [aldo-keto reductase family 1, member Al (aldehyde reductase)];
AKR1 131 [aldo-keto reductase family 1, member 131 (aldose reductase)]; AKR1 [aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II)]; AKT1 [v-akt murine thymoma viral oncogene homolog 1]; AKT2 [v-akt murine thymoma viral oncogene homolog 2]; AKT3 [v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma)]; ALB [albumin];
ALCAM [activated leukocyte cell adhesion molecule]; ALDHIAI [aldehyde dehydrogenase 1 family, member A1]; ALDH2 [aldehyde dehydrogenase 2 family (mitochondrial)]; ALDH3A1 [aldehyde dehydrogenase 3 family, memberA1 ];
ALDH7A1 [aldehyde dehydrogenase 7 family, member Al ]; ALDH9A1 [aldehyde dehydrogenase 9 family, member A1]; ALG1 [asparagine-linked glycosylation 1, beta- l,4-mannosyltransferase homolog (S. cerevisiae)]; ALG12 [asparagine-linked glycosylation 12, alpha-1,6-mannosyltransferase homolog (S.
cerevisiae)];
ALK [anaplastic lymphoma receptor tyrosine kinase]; ALOX12 [arachidonate 12-lipoxygenase]; ALOX15 [arachidonate 15-lipoxygenase]; ALOX15B [arachidonate 15-lipoxygenase, type B]; ALOX5 [arachidonate 5-lipoxygenase]; ALOX5AP
[arachidonate 5-lipoxygenase-activating protein]; ALPI [alkaline phosphatase, intestinal]; ALPL [alkaline phosphatase, liver/bone/kidney]; ALPP [alkaline phosphatase, placental (Regan isozyme)]; AMACR [alpha-methylacyl-CoA
racemase]; AMBP [alpha-1-microglobulin/bikunin precursor]; AMPD3 [adenosine monophosphate deaminase 3]; ANG [angiogenin, ribonuclease, RNase A family, 5]; ANGPT1 [angiopoietin 1]; ANGPT2 [angiopoietin 2]; ANK1 [ankyrin 1, erythrocytic]; ANKH [ankylosis, progressive homolog (mouse)]; ANKRD1 [ankyrin repeat domain 1 (cardiac muscle)]; ANPEP [alanyl (membrane) aminopeptidase];
ANTXR2 [anthrax toxin receptor 2]; ANXA1 [annexin Al ]; ANXA2 [annexin A2];
ANXA5 [annexin A5]; ANXA6 [annexin A6]; AOAH [acyloxyacyl hydrolase (neutrophil)]; AOC2 [amine oxidase, copper containing 2 (retina-specific)];

[adaptor-related protein complex 2, beta 1 subunit]; AP3B1 [adaptor-related protein complex 3, beta 1 subunit]; APC [adenomatous polyposis coli]; APCS
[amyloid P component, serum]; APEX1 [APEX nuclease (multifunctional DNA
repair enzyme) 1]; APLNR [apelin receptor]; APOA1 [apolipoprotein A-I]; APOA2 [apolipoprotein A-II]; APOA4 [apolipoprotein A-IV]; APOB [apolipoprotein B
(including Ag(x) antigen)]; APOBEC1 [apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1]; APOBEC3G [apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G]; APOC3 [apolipoprotein C-III]; APOD
[apolipoprotein D]; APOE [apolipoprotein E]; APOH [apolipoprotein H (beta-2-glycoprotein I)]; APP [amyloid beta (A4) precursor protein]; APRT [adenine phosphoribosyltransferase]; APTX [aprataxin]; AQP1 [aquaporin 1 (Colton blood group)]; AQP2 [aquaporin 2 (collecting duct)]; AQP3 [aquaporin 3 (Gill blood group)]; AQP4 [aquaporin 4]; AQP5 [aquaporin 5]; AQP7 [aquaporin 7]; AQP8 [aquaporin 8]; AR [androgen receptor]; AREG [amphiregulin]; ARF6 [ADP-ribosylation factor 6]; ARG1 [arginase, liver]; ARG2 [arginase, type II];

[Rho GTPase activating protein 6]; ARHGEF2 [Rho/Rac guanine nucleotide exchange factor (GEF) 2]; ARHGEF6 [Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6]; ARL13B [ADP-ribosylation factor-like 13B]; ARNT [aryl hydrocarbon receptor nuclear translocator]; ARNTL [aryl hydrocarbon receptor nuclear translocator-like]; ARRB1 [arrestin, beta 1]; ARRB2 [arrestin, beta 2];
ARSA [arylsulfatase A]; ARSB [arylsulfatase B]; ARSH [arylsulfatase family, member H]; ART1 [ADP-ribosyltransferase 1]; ASAH1 [N-acylsphingosine amidohydrolase (acid ceramidase) 1]; ASAP1 [ArfGAP with SH3 domain, ankyrin repeat and PH domain 1]; ASGR2 [asialoglycoprotein receptor 2]; ASL
[argininosuccinate lyase]; ASNS [asparagine synthetase]; ASPA [aspartoacylase (Canavan disease)]; ASPG [asparaginase homolog (S. cerevisiae)]; ASPH
[aspartate beta-hydroxylase]; ASRGL1 [asparaginase like 1]; ASS1 [argininosuccinate synthase 1]; ATF1 [activating transcription factor 1]; ATF2 [activating transcription factor 2]; ATF3 [activating transcription factor 3];

[activating transcription factor 4 (tax-responsive enhancer element B67)];
ATG16L1 [ATG16 autophagy related 16-like 1 (S. cerevisiae)]; ATM [ataxia telangiectasia mutated]; ATMIN [ATM interactor]; ATN1 [atrophin 1]; ATOH1 [atonal homolog 1 (Drosophila)]; ATP2A2 [ATPase, Ca++ transporting, cardiac muscle, slow twitch 2]; ATP2A3 [ATPase, Ca++ transporting, ubiquitous];
ATP2C1 [ATPase, Ca++ transporting, type 2C, member 1]; ATP5E [ATP
synthase, H+ transporting, mitochondrial F1 complex, epsilon subunit]; ATP7B
[ATPase, Cu++ transporting, beta polypeptide]; ATP8B1 [ATPase, class I, type 8B, member 1]; ATPAF2 [ATP synthase mitochondrial F1 complex assembly factor 2]; ATR [ataxia telangiectasia and Rad3 related]; ATRIP [ATR
interacting protein]; ATRN [attractin]; AURKA [aurora kinase A]; AURKB [aurora kinase B];
AURKC [aurora kinase C]; AVP [arginine vasopressin]; AVPR2 [arginine vasopressin receptor 2]; AXL [AXL receptor tyrosine kinase]; AZGP1 [alpha-2-glycoprotein 1, zinc-binding]; B2M [beta-2-microglobulin]; B3GALTL [beta 1,3-galactosyltransferase-like]; B3GAT1 [beta- 1,3-g I ucu ronyltransferase 1 (glucuronosyltransferase P)]; B4GALNT1 [beta-l,4-N-acetyl-galactosaminyl transferase 1 ]; B4GALT1 [UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 1]; BACE1 [beta-site APP-cleaving enzyme 1]; BACE2 [beta-site APP-cleaving enzyme 2]; BACH1 [BTB and CNC homology 1, basic leucine zipper transcription factor 1]; BAD [BCL2-associated agonist of cell death];
BAIAP2 [BAI1-associated protein 2]; BAK1 [BCL2-antagonist/killer 1]; BARX2 [BARX homeobox 2]; BAT1 [HLA-B associated transcript 1]; BAT2 [HLA-B
associated transcript 2]; BAX [BCL2-associated X protein]; BBC3 [BCL2 binding component 3]; BCAR1 [breast cancer anti-estrogen resistance 1 ]; BCAT1 [branched chain aminotransferase 1, cytosolic]; BCAT2 [branched chain aminotransferase 2, mitochondrial]; BCHE [butyrylcholinesterase]; BCL10 [B-cell CLL/lymphoma 10]; BCL11 B [B-cell CLL/lymphoma 11 B (zinc finger protein)];
BCL2 [B-cell CLL/lymphoma 2]; BCL2A1 [BCL2-related protein Al]; BCL2L1 [BCL2-like 1]; BCL2L1 1 [BCL2-like 11 (apoptosis facilitator)]; BCL3 [B-cell CLL/lymphoma 3]; BCL6 [B-cell CLL/lymphoma 6]; BCR [breakpoint cluster region]; BDKRB1 [bradykinin receptor B1]; BDKRB2 [bradykinin receptor B2];
BDNF [brain-derived neurotrophic factor]; BECN1 [beclin 1, autophagy related];
BEST1 [bestrophin 1]; BFAR [bifunctional apoptosis regulator]; BGLAP [bone gamma-carboxyglutamate (gla) protein]; BHMT [betaine-homocysteine methyltransferase]; BID [BH3 interacting domain death agonist]; BIK [BCL2-interacting killer (apoptosis-inducing)]; BIRC2 [baculoviral IAP repeat-containing 2]; BIRC3 [baculoviral IAP repeat-containing 3]; BIRC5 [baculoviral IAP repeat-containing 5]; BLK [B lymphoid tyrosine kinase]; BLM [Bloom syndrome, RecQ
helicase-like]; BLNK [B-cell linker]; BLVRB [biliverdin reductase B (flavin reductase (NADPH))]; BMI1 [BMI1 polycomb ring finger oncogene]; BMP1 [bone morphogenetic protein 1]; BMP2 [bone morphogenetic protein 2]; BMP4 [bone morphogenetic protein 4]; BMP6 [bone morphogenetic protein 6]; BMP7 [bone morphogenetic protein 7]; BMPR1A [bone morphogenetic protein receptor, type IA]; BMPR1 B [bone morphogenetic protein receptor, type IB]; BMPR2 [bone morphogenetic protein receptor, type II (serine/threonine kinase)]; BPI
[bactericidal/permeability-increasing protein]; BRCA1 [breast cancer 1, early onset]; BRCA2 [breast cancer 2, early onset]; BRCC3 [BRCA1/BRCA2-containing complex, subunit 3]; BRD8 [bromodomain containing 8]; BRIP1 [BRCA1 interacting protein C-terminal helicase 1]; BSG [basigin (Ok blood group)]; BSN [bassoon (presynaptic cytomatrix protein)]; BSX [brain-specific homeobox]; BTD [biotinidase]; BTK [Bruton agammaglobulinemia tyrosine kinase]; BTLA [B and T lymphocyte associated]; BTNL2 [butyrophilin-like 2 (MHC
class II associated)]; BTRC [beta-transducin repeat containing]; C10orf67 [chromosome 10 open reading frame 67]; C11orf30 [chromosome 11 open reading frame 30]; C11orf58 [chromosome 11 open reading frame 58]; C13orf23 [chromosome 13 open reading frame 23]; C13orf31 [chromosome 13 open reading frame 31]; C15orf2 [chromosome 15 open reading frame 2]; C16orf75 [chromosome 16 open reading frame 75]; C19orf10 [chromosome 19 open reading frame 10]; C1 QA [complement component 1, q subcomponent, A chain];
C1 QB [complement component 1, q subcomponent, B chain]; C1 QC
[complement component 1, q subcomponent, C chain]; C1 QTNF5 [C1 q and tumor necrosis factor related protein 5]; C1 R [complement component 1, r subcomponent]; C1S [complement component 1, s subcomponent]; C2 [complement component 2]; C20orf29 [chromosome 20 open reading frame 29];
C21orf33 [chromosome 21 open reading frame 33]; C3 [complement component 3]; C3AR1 [complement component 3a receptor 1]; C3orf27 [chromosome 3 open reading frame 27]; C4A [complement component 4A (Rodgers blood group)]; C4B [complement component 4B (Chido blood group)]; C4BPA
[complement component 4 binding protein, alpha]; C4BPB [complement component 4 binding protein, beta]; C5 [complement component 5]; C5AR1 [complement component 5a receptor 1]; C5orf56 [chromosome 5 open reading frame 56]; C5orf62 [chromosome 5 open reading frame 62]; C6 [complement component 6]; C6orf142 [chromosome 6 open reading frame 142]; C6orf25 [chromosome 6 open reading frame 25]; C7 [complement component 7]; C7orf72 [chromosome 7 open reading frame 72]; C8A [complement component 8, alpha polypeptide]; C8B [complement component 8, beta polypeptide]; C8G
[complement component 8, gamma polypeptide]; C8orf38 [chromosome 8 open reading frame 38]; C9 [complement component 9]; CA2 [carbonic anhydrase II];

CA6 [carbonic anhydrase VI]; CA8 [carbonic anhydrase VIII]; CA9 [carbonic anhydrase IX]; CABIN1 [calcineurin binding protein 1]; CACNA1C [calcium channel, voltage-dependent, L type, alpha 1 C subunit]; CACNA1 S [calcium channel, voltage-dependent, L type, alpha 1 S subunit]; CAD [carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase];
CALB1 [calbindin 1, 28kDa]; CALB2 [calbindin 2]; CALCA [calcitonin-related polypeptide alpha]; CALCRL [calcitonin receptor-like]; CALD1 [caldesmon 1];
CALM1 [calmodulin 1 (phosphorylase kinase, delta)]; CALM2 [calmodulin 2 (phosphorylase kinase, delta)]; CALM3 [calmodulin 3 (phosphorylase kinase, delta)]; CALR [calreticulin]; CAMK2G [calcium/calmodulin-dependent protein kinase II gamma]; CAMP [cathelicidin antimicrobial peptide]; CANT1 [calcium activated nucleotidase 1]; CANX [calnexin]; CAPN1 [calpain 1, (mu/I) large subunit]; CARD10 [caspase recruitment domain family, member 10]; CARD16 [caspase recruitment domain family, member 16]; CARD8 [caspase recruitment domain family, member 8]; CARDS [caspase recruitment domain family, member 9]; CASP1 [caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)]; CASP10 [caspase 10, apoptosis-related cysteine peptidase];
CASP2 [caspase 2, apoptosis-related cysteine peptidase]; CASP3 [caspase 3, apoptosis-related cysteine peptidase]; CASP5 [caspase 5, apoptosis-related cysteine peptidase]; CASP6 [caspase 6, apoptosis-related cysteine peptidase];
CASP7 [caspase 7, apoptosis-related cysteine peptidase]; CASP8 [caspase 8, apoptosis-related cysteine peptidase]; CASP8AP2 [caspase 8 associated protein 2]; CASP9 [caspase 9, apoptosis-related cysteine peptidase]; CASR [calcium-sensing receptor]; CAST [calpastatin]; CAT [catalase]; CAV1 [caveolin 1, caveolae protein, 22kDa]; CAV2 [caveolin 2]; CBL [Cas-Br-M (murine) ecotropic retroviral transforming sequence]; CBS [cystathionine-beta-synthase]; CBX5 [chromobox homolog 5 (HP1 alpha homolog, Drosophila)]; CC2D2A [coiled-coil and C2 domain containing 2A]; CCBP2 [chemokine binding protein 2];
CCDC144A [coiled-coil domain containing 144A]; CCDC144B [coiled-coil domain containing 144B]; CCDC68 [coiled-coil domain containing 68]; CCK

[cholecystokinin]; CCL1 [chemokine (C-C motif) ligand 1]; CCL11 [chemokine (C-C motif) ligand 11]; CCL13 [chemokine (C-C motif) ligand 13]; CCL14 [chemokine (C-C motif) ligand 14]; CCL17 [chemokine (C-C motif) ligand 17];
CCL18 [chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated)];
CCL19 [chemokine (C-C motif) ligand 19]; CCL2 [chemokine (C-C motif) ligand 2]; CCL20 [chemokine (C-C motif) ligand 20]; CCL21 [chemokine (C-C motif) ligand 21]; CCL22 [chemokine (C-C motif) ligand 22]; CCL24 [chemokine (C-C
motif) ligand 24]; CCL25 [chemokine (C-C motif) ligand 25]; CCL26 [chemokine (C-C motif) ligand 26]; CCL27 [chemokine (C-C motif) ligand 27]; CCL28 [chemokine (C-C motif) ligand 28]; CCL3 [chemokine (C-C motif) ligand 3]; CCL4 [chemokine (C-C motif) ligand 4]; CCL4L1 [chemokine (C-C motif) ligand 4-like 1]; CCL5 [chemokine (C-C motif) ligand 5]; CCL7 [chemokine (C-C motif) ligand 7]; CCL8 [chemokine (C-C motif) ligand 8]; CCNA1 [cyclin Al]; CCNA2 [cyclin A2]; CCNB1 [cyclin B1]; CCNB2 [cyclin B2]; CCNC [cyclin C]; CCND1 [cyclin D1]; CCND2 [cyclin D2]; CCND3 [cyclin D3]; CCNE1 [cyclin El]; CCNG1 [cyclin G1]; CCNH [cyclin H]; CCNT1 [cyclin T1]; CCNT2 [cyclin T2]; CCNY [cyclin Y];
CCR1 [chemokine (C-C motif) receptor 1]; CCR2 [chemokine (C-C motif) receptor 2]; CCR3 [chemokine (C-C motif) receptor 3]; CCR4 [chemokine (C-C
motif) receptor 4]; CCR5 [chemokine (C-C motif) receptor 5]; CCR6 [chemokine (C-C motif) receptor 6]; CCR7 [chemokine (C-C motif) receptor 7]; CCR8 [chemokine (C-C motif) receptor 8]; CCR9 [chemokine (C-C motif) receptor 9];
CCRL1 [chemokine (C-C motif) receptor-like 1]; CD14 [CD14 molecule]; CD151 [CD151 molecule (Raph blood group)]; CD160 [CD160 molecule]; CD163 [CD163 molecule]; CD180 [CD180 molecule]; CD19 [CD19 molecule]; CD1A
[CD1 a molecule]; CD1 B [CD1 b molecule]; CD1 C [CD1 c molecule]; CD1 D [CD1 d molecule]; CD2 [CD2 molecule]; CD200 [CD200 molecule]; CD207 [CD207 molecule, langerin]; CD209 [CD209 molecule]; CD22 [CD22 molecule]; CD226 [CD226 molecule]; CD24 [CD24 molecule]; CD244 [CD244 molecule, natural killer cell receptor 2B4]; CD247 [CD247 molecule]; CD27 [CD27 molecule];
CD274 [CD274 molecule]; CD28 [CD28 molecule]; CD2AP [CD2-associated protein]; CD300LF [CD300 molecule-like family member f]; CD34 [CD34 molecule]; CD36 [CD36 molecule (thrombospondin receptor)]; CD37 [CD37 molecule]; CD38 [CD38 molecule]; CD3E [CD3e molecule, epsilon (CD3-TCR
complex)]; CD4 [CD4 molecule]; CD40 [CD40 molecule, TNF receptor superfamily member 5]; CD40LG [CD40 ligand]; CD44 [CD44 molecule (Indian blood group)]; CD46 [CD46 molecule, complement regulatory protein]; CD47 [CD47 molecule]; CD48 [CD48 molecule]; CD5 [CD5 molecule]; CD52 [CD52 molecule]; CD53 [CD53 molecule]; CD55 [CD55 molecule, decay accelerating factor for complement (Cromer blood group)]; CD58 [CD58 molecule]; CD59 [CD59 molecule, complement regulatory protein]; CD63 [CD63 molecule]; CD68 [CD68 molecule]; CD69 [CD69 molecule]; CD7 [CD7 molecule]; CD70 [CD70 molecule]; CD72 [CD72 molecule]; CD74 [CD74 molecule, major histocompatibility complex, class II invariant chain]; CD79A [CD79a molecule, immunoglobulin-associated alpha]; CD79B [CD79b molecule, immunoglobulin-associated beta]; CD80 [CD80 molecule]; CD81 [CD81 molecule]; CD82 [CD82 molecule]; CD83 [CD83 molecule]; CD86 [CD86 molecule]; CD8A [CD8a molecule]; CD9 [CD9 molecule]; CD93 [CD93 molecule]; CD97 [CD97 molecule];
CDC20 [cell division cycle 20 homolog (S. cerevisiae)]; CDC25A [cell division cycle 25 homolog A (S. pombe)]; CDC25B [cell division cycle 25 homolog B (S.
pombe)]; CDC25C [cell division cycle 25 homolog C (S. pombe)]; CDC42 [cell division cycle 42 (GTP binding protein, 25kDa)]; CDC45 [CDC45 cell division cycle 45 homolog (S. cerevisiae)]; CDC5L [CDC5 cell division cycle 5-like (S.
pombe)]; CDC6 [cell division cycle 6 homolog (S. cerevisiae)]; CDC7 [cell division cycle 7 homolog (S. cerevisiae)]; CDH1 [cadherin 1, type 1, E-cadherin (epithelial)]; CDH2 [cadherin 2, type 1, N-cadherin (neuronal)]; CDH26 [cadherin 26]; CDH3 [cadherin 3, type 1, P-cadherin (placental)]; CDH5 [cadherin 5, type (vascular endothelium)]; CDIPT [CDP-diacylglycerol--inositol 3-phosphatidyltransferase (phosphatidylinositol synthase)]; CDK1 [cyclin-dependent kinase 1]; CDK2 [cyclin-dependent kinase 2]; CDK4 [cyclin-dependent kinase 4]; CDK5 [cyclin-dependent kinase 5]; CDK5R1 [cyclin-dependent kinase 5, regulatory subunit 1 (p35)]; CDK7 [cyclin-dependent kinase 7]; CDK9 [cyclin-dependent kinase 9]; CDKAL1 [CDK5 regulatory subunit associated protein 1-like 1]; CDKN1A [cyclin-dependent kinase inhibitor 1A (p21, Cip1)]; CDKN1B [cyclin-dependent kinase inhibitor 1B (p27, Kip1)]; CDKN1C [cyclin-dependent kinase inhibitor 1C (p57, Kip2)]; CDKN2A [cyclin-dependent kinase inhibitor 2A
(melanoma, p16, inhibits CDK4)]; CDKN2B [cyclin-dependent kinase inhibitor 2B
(p15, inhibits CDK4)]; CDKN3 [cyclin-dependent kinase inhibitor 3]; CDR2 [cerebellar degeneration-related protein 2, 62kDa]; CDT1 [chromatin licensing and DNA replication factor 1]; CDX2 [caudal type homeobox 2]; CEACAM1 [carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)]; CEACAM3 [carcinoembryonic antigen-related cell adhesion molecule 3]; CEACAM5 [carcinoembryonic antigen-related cell adhesion molecule 5]; CEACAM6 [carcinoembryonic antigen-related cell adhesion molecule 6 (non-specific cross reacting antigen)]; CEACAM7 [carcinoembryonic antigen-related cell adhesion molecule 7]; CEBPB [CCAAT/enhancer binding protein (C/EBP), beta]; CEL [carboxyl ester lipase (bile salt-stimulated lipase)];
CENPJ [centromere protein J]; CENPV [centromere protein V]; CEP290 [centrosomal protein 290kDa]; CERK [ceramide kinase]; CETP [cholesteryl ester transfer protein, plasma]; CFB [complement factor B]; CFD [complement factor D
(adipsin)]; CFDP1 [craniofacial development protein 1]; CFH [complement factor H]; CFHR1 [complement factor H-related 1]; CFHR3 [complement factor H-related 3]; CFI [complement factor I]; CFL1 [cofilin 1 (non-muscle)]; CFL2 [cofilin 2 (muscle)]; CFLAR [CASP8 and FADD-like apoptosis regulator]; CFP
[complement factor properdin]; CFTR [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)]; CGA
[glycoprotein hormones, alpha polypeptide]; CGB [chorionic gonadotropin, beta polypeptide]; CGBS [chorionic gonadotropin, beta polypeptide 5]; CHAD
[chondroadherin]; CHAFIA [chromatin assembly factor 1, subunit A (p150)];
CHAF1 B [chromatin assembly factor 1, subunit B (p60)]; CHAT [choline acetyltransferase]; CHD2 [chromodomain helicase DNA binding protein 2]; CHD7 [chromodomain helicase DNA binding protein 7]; CHEK1 [CHK1 checkpoint homolog (S. pombe)]; CHEK2 [CHK2 checkpoint homolog (S. pombe)]; CHGA
[chromogranin A (parathyroid secretory protein 1)]; CHGB [chromogranin B
(secretogranin 1)]; CHI3L1 [chitinase 3-like 1 (cartilage glycoprotein-39)];
CHIA
[chitinase, acidic]; CHIT1 [chitinase 1 (chitotriosidase)]; CHKA [choline kinase alpha]; CHML [choroideremia-like (Rab escort protein 2)]; CHRD [chordin];
CHRDL1 [chordin-like 1]; CHRM1 [cholinergic receptor, muscarinic 1]; CHRM2 [cholinergic receptor, muscarinic 2]; CHRM3 [cholinergic receptor, muscarinic 3];
CHRNA3 [cholinergic receptor, nicotinic, alpha 3]; CHRNA4 [cholinergic receptor, nicotinic, alpha 4]; CHRNA7 [cholinergic receptor, nicotinic, alpha 7]; CHUK
[conserved helix-loop-helix ubiquitous kinase]; CIB1 [calcium and integrin binding 1 (calmyrin)]; CIITA [class II, major histocompatibility complex, transactivator];
CILP [cartilage intermediate layer protein, nucleotide pyrophosphohydrolase];
CISH [cytokine inducible SH2-containing protein]; CKB [creatine kinase, brain];
CKLF [chemokine-like factor]; CKM [creatine kinase, muscle]; CLC [Charcot-Leyden crystal protein]; CLCA1 [chloride channel accessory 1]; CLCN1 [chloride channel 1, skeletal muscle]; CLCN3 [chloride channel 3]; CLDN1 [claudin 1];
CLDN11 [claudin 11]; CLDN14 [claudin 14]; CLDN16 [claudin 16]; CLDN19 [claudin 19]; CLDN2 [claudin 2]; CLDN3 [claudin 3]; CLDN4 [claudin 4]; CLDN5 [claudin 5]; CLDN7 [claudin 7]; CLDN8 [claudin 8]; CLEC12A [C-type lectin domain family 12, member A]; CLEC16A [C-type lectin domain family 16, member A]; CLEC4A [C-type lectin domain family 4, member A]; CLEC4D [C-type lectin domain family 4, member D]; CLEC4M [C-type lectin domain family 4, member M]; CLEC7A [C-type lectin domain family 7, member A]; CLIP2 [CAP-GLY domain containing linker protein 2]; CLK2 [CDC-like kinase 2]; CLSPN
[claspin homolog (Xenopus laevis)]; CLSTN2 [calsyntenin 2]; CLTCL1 [clathrin, heavy chain-like 1]; CLU [clusterin]; CMA1 [chymase 1, mast cell]; CMKLR1 [chemokine-like receptor 1]; CNBP [CCHC-type zinc finger, nucleic acid binding protein]; CNDP2 [CNDP dipeptidase 2 (metallopeptidase M20 family)]; CNN1 [calponin 1, basic, smooth muscle]; CNP [2',3'-cyclic nucleotide 3' phosphodiesterase]; CNR1 [cannabinoid receptor 1 (brain)]; CNR2 [cannabinoid receptor 2 (macrophage)]; CNTF [ciliary neurotrophic factor]; CNTN2 [contactin (axonal)]; COG1 [component of oligomeric golgi complex 1]; COG2 [component of oligomeric golgi complex 2]; COIL [coilin]; COL11A1 [collagen, type XI, alpha 1]; COL11A2 [collagen, type XI, alpha 2]; COL17A1 [collagen, type XVII, alpha 1]; COL18A1 [collagen, type XVI I I, alpha 1]; COL1A1 [collagen, type I, alpha 1];
COL1A2 [collagen, type I, alpha 2]; COL2A1 [collagen, type II, alpha 1];

[collagen, type III, alpha 1]; COL4A1 [collagen, type IV, alpha 1]; COL4A3 [collagen, type IV, alpha 3 (Goodpasture antigen)]; COL4A4 [collagen, type IV, alpha 4]; COL4A5 [collagen, type IV, alpha 5]; COL4A6 [collagen, type IV, alpha 6]; COL5A1 [collagen, type V, alpha 1 ]; COL5A2 [collagen, type V, alpha 2];
COL6A1 [collagen, type VI, alpha 1 ]; COL6A2 [collagen, type VI, alpha 2];
COL6A3 [collagen, type VI, alpha 3]; COL7A1 [collagen, type VII, alpha 1];
COL8A2 [collagen, type VIII, alpha 2]; COL9A1 [collagen, type IX, alpha 1];
COMT [catechol-O-methyltransferase]; COQ3 [coenzyme Q3 homolog, methyltransferase (S. cerevisiae)]; COQ7 [coenzyme Q7 homolog, ubiquinone (yeast)]; CORO1A [coronin, actin binding protein, 1A]; COX10 [COX10 homolog, cytochrome c oxidase assembly protein, heme A: farnesyltransferase (yeast)];
COX15 [COX15 homolog, cytochrome c oxidase assembly protein (yeast)];
COXSA [cytochrome c oxidase subunit Va]; COXBA [cytochrome c oxidase subunit VIIIA (ubiquitous)]; CP [ceruloplasmin (ferroxidase)]; CPA1 [carboxypeptidase Al (pancreatic)]; CPB2 [carboxypeptidase B2 (plasma)];
CPN1 [carboxypeptidase N, polypeptide 1]; CPOX [coproporphyrinogen oxidase];
CPS1 [carbamoyl-phosphate synthetase 1, mitochondrial]; CPT2 [carnitine palmitoyltransferase 2]; CR1 [complement component (3b/4b) receptor 1 (Knops blood group)]; CR2 [complement component (3d/Epstein Barr virus) receptor 2];
CRAT [carnitine O-acetyltransferase]; CRB1 [crumbs homolog 1 (Drosophila)];
CREB1 [cAMP responsive element binding protein 1]; CREBBP [CREB binding protein]; CREM [cAMP responsive element modulator]; CRH [corticotropin releasing hormone]; CRHR1 [corticotropin releasing hormone receptor 1];

CRHR2 [corticotropin releasing hormone receptor 2]; CRK [v-crk sarcoma virus CT10 oncogene homolog (avian)]; CRKL [v-crk sarcoma virus CT10 oncogene homolog (avian)-like]; CRLF2 [cytokine receptor-like factor 2]; CRLF3 [cytokine receptor-like factor 3]; CROT [carnitine 0-octanoyltransferase]; CRP [C-reactive protein, pentraxin-related]; CRX [cone-rod homeobox]; CRY2 [cryptochrome 2 (photolyase-like)]; CRYAA [crystallin, alpha A]; CRYAB [crystallin, alpha B];
CS
[citrate synthase]; CSF1 [colony stimulating factor 1 (macrophage)]; CSF1 R
[colony stimulating factor 1 receptor]; CSF2 [colony stimulating factor 2 (granulocyte-macrophage)]; CSF2RB [colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage)]; CSF3 [colony stimulating factor 3 (granulocyte)]; CSF3R [colony stimulating factor 3 receptor (granulocyte)];
CSK
[c-src tyrosine kinase]; CSMD3 [CUB and Sushi multiple domains 3]; CSN1S1 [casein alpha s1]; CSN2 [casein beta]; CSNK1A1 [casein kinase 1, alpha 1];
CSNK2A1 [casein kinase 2, alpha 1 polypeptide]; CSNK2B [casein kinase 2, beta polypeptide]; CSPG4 [chondroitin sulfate proteoglycan 4]; CST3 [cystatin C];
CST8 [cystatin 8 (cystatin-related epididymal specific)]; CSTA [cystatin A
(stefin A)]; CSTB [cystatin B (stefin B)]; CTAGE1 [cutaneous T-cell lymphoma-associated antigen 1]; CTF1 [cardiotrophin 1]; CTGF [connective tissue growth factor]; CTH [cystathionase (cystathionine gamma-lyase)]; CTLA4 [cytotoxic T-lymphocyte-associated protein 4]; CTNNA1 [catenin (cad herin-associated protein), alpha 1, 102kDa]; CTNNA3 [catenin (cadherin-associated protein), alpha 3]; CTNNAL1 [catenin (cadherin-associated protein), alpha-like 1];
CTNNB1 [catenin (cadherin-associated protein), beta 1, 88kDa]; CTNND1 [catenin (cadherin-associated protein), delta 1]; CTNS [cystinosis, nephropathic];
CTRL [chymotrypsin-like]; CTSB [cathepsin B]; CTSC [cathepsin C]; CTSD
[cathepsin D]; CTSE [cathepsin E]; CTSG [cathepsin G]; CTSH [cathepsin H];
CTSK [cathepsin K]; CTSL1 [cathepsin L1]; CTTN [cortactin]; CUL1 [cullin 1];
CUL2 [cullin 2]; CUL4A [cullin 4A]; CUL5 [cullin 5]; CX3CL1 [chemokine (C-X3-C
motif) ligand 1]; CX3CR1 [chemokine (C-X3-C motif) receptor 1]; CXADR
[coxsackie virus and adenovirus receptor]; CXCL1 [chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha)]; CXCL10 [chemokine (C-X-C motif) ligand 10]; CXCL11 [chemokine (C-X-C motif) ligand 11]; CXCL12 [chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)]; CXCL13 [chemokine (C-X-C motif) ligand 13]; CXCL2 [chemokine (C-X-C motif) ligand 2];
CXCL5 [chemokine (C-X-C motif) ligand 5]; CXCL6 [chemokine (C-X-C motif) ligand 6 (granulocyte chemotactic protein 2)]; CXCL9 [chemokine (C-X-C motif) ligand 9]; CXCR1 [chemokine (C-X-C motif) receptor 1]; CXCR2 [chemokine (C-X-C motif) receptor 2]; CXCR3 [chemokine (C-X-C motif) receptor 3]; CXCR4 [chemokine (C-X-C motif) receptor 4]; CXCR5 [chemokine (C-X-C motif) receptor 5]; CXCR6 [chemokine (C-X-C motif) receptor 6]; CXCR7 [chemokine (C-X-C
motif) receptor 7]; CXorf40A [chromosome X open reading frame 40A]; CYB5A
[cytochrome b5 type A (microsomal)]; CYB5R3 [cytochrome b5 reductase 3];
CYBA [cytochrome b-245, alpha polypeptide]; CYBB [cytochrome b-245, beta polypeptide]; CYC1 [cytochrome c-1]; CYCS [cytochrome c, somatic]; CYFIP2 [cytoplasmic FMR1 interacting protein 2]; CYP11A1 [cytochrome P450, family 11, subfamily A, polypeptide 1 ]; CYP11 B1 [cytochrome P450, family 11, subfamily B, polypeptide 1]; CYP1 1 B2 [cytochrome P450, family 11, subfamily B, polypeptide 2]; CYP17A1 [cytochrome P450, family 17, subfamily A, polypeptide 1];
CYP19A1 [cytochrome P450, family 19, subfamily A, polypeptide 1]; CYP1A1 [cytochrome P450, family 1, subfamily A, polypeptide 1]; CYP1A2 [cytochrome P450, family 1, subfamily A, polypeptide 2]; CYP1 B1 [cytochrome P450, family 1, subfamily B, polypeptide 1]; CYP21A2 [cytochrome P450, family 21, subfamily A, polypeptide 2]; CYP24A1 [cytochrome P450, family 24, subfamily A, polypeptide 1]; CYP27A1 [cytochrome P450, family 27, subfamily A, polypeptide 1];
CYP27B1 [cytochrome P450, family 27, subfamily B, polypeptide 1]; CYP2A6 [cytochrome P450, family 2, subfamily A, polypeptide 6]; CYP2B6 [cytochrome P450, family 2, subfamily B, polypeptide 6]; CYP2C19 [cytochrome P450, family 2, subfamily C, polypeptide 19]; CYP2C8 [cytochrome P450, family 2, subfamily C, polypeptide 8]; CYP2C9 [cytochrome P450, family 2, subfamily C, polypeptide 9]; CYP2D6 [cytochrome P450, family 2, subfamily D, polypeptide 6]; CYP2E1 [cytochrome P450, family 2, subfamily E, polypeptide 1]; CYP2J2 [cytochrome P450, family 2, subfamily J, polypeptide 2]; CYP2R1 [cytochrome P450, family 2, subfamily R, polypeptide 1]; CYP3A4 [cytochrome P450, family 3, subfamily A, polypeptide 4]; CYP3A5 [cytochrome P450, family 3, subfamily A, polypeptide 5];
CYP4F3 [cytochrome P450, family 4, subfamily F, polypeptide 3]; CYP51A1 [cytochrome P450, family 51, subfamily A, polypeptide 1]; CYP7A1 [cytochrome P450, family 7, subfamily A, polypeptide 1]; CYR61 [cysteine-rich, angiogenic inducer, 61]; CYSLTR1 [cysteinyl leukotriene receptor 1]; CYSLTR2 [cysteinyl leukotriene receptor 2]; DAO [D-amino-acid oxidase]; DAOA [D-amino acid oxidase activator]; DAP3 [death associated protein 3]; DAPK1 [death-associated protein kinase 1]; DARC [Duffy blood group, chemokine receptor]; DAZ1 [deleted in azoospermia 1]; DBH [dopamine beta-hydroxylase (dopamine beta-monooxygenase)]; DCK [deoxycytidine kinase]; DCLRE1 C [DNA cross-link repair 1 C (PSO2 homolog, S. cerevisiae)]; DCN [decorin]; DCT [dopachrome tautomerase (dopachrome delta-isomerase, tyrosine-related protein 2)]; DCTN2 [dynactin 2 (p50)]; DDB1 [damage-specific DNA binding protein 1, 127kDa];
DDB2 [damage-specific DNA binding protein 2, 48kDa]; DDC [dopa decarboxylase (aromatic L-amino acid decarboxylase)]; DDIT3 [DNA-damage-inducible transcript 3]; DDR1 [discoidin domain receptor tyrosine kinase 1];

[DEAD (Asp-Glu-Ala-Asp) box polypeptide 1]; DDX41 [DEAD (Asp-Glu-Ala-Asp) box polypeptide 41]; DDX42 [DEAD (Asp-Glu-Ala-Asp) box polypeptide 42];
DDX58 [DEAD (Asp-Glu-Ala-Asp) box polypeptide 58]; DEFA1 [defensin, alpha 1]; DEFAS [defensin, alpha 5, Paneth cell-specific]; DEFA6 [defensin, alpha 6, Paneth cell-specific]; DEFB1 [defensin, beta 1]; DEFB103B [defensin, beta 103B]; DEFB104A [defensin, beta 104A]; DEFB4A [defensin, beta 4A]; DEK
[DEK oncogene]; DENND1 B [DENN/MADD domain containing 1 B]; DES
[desmin]; DGAT1 [diacylglycerol 0-acyltransferase homolog 1 (mouse)];
DGCR14 [DiGeorge syndrome critical region gene 14]; DGCR2 [DiGeorge syndrome critical region gene 2]; DGCR6 [DiGeorge syndrome critical region gene 6]; DGCR6L [DiGeorge syndrome critical region gene 6-like]; DGCR8 [DiGeorge syndrome critical region gene 8]; DGUOK [deoxyguanosine kinase];
DHFR [dihydrofolate reductase]; DHODH [dihydroorotate dehydrogenase]; DHPS
[deoxyhypusine synthase]; DHRS7B [dehydrogenase/reductase (SDR family) member 7B]; DHRS9 [dehydrogenase/reductase (SDR family) member 9];
DIAPH1 [diaphanous homolog 1 (Drosophila)]; DICER1 [dicer 1, ribonuclease type III]; D102 [deiodinase, iodothyronine, type II]; DKC1 [dyskeratosis congenita 1, dyskerin]; DKK1 [dickkopf homolog 1 (Xenopus laevis)]; DLAT
[dihydrolipoamide S-acetyltransferase]; DLG2 [discs, large homolog 2 (Drosophila)]; DLG5 [discs, large homolog 5 (Drosophila)]; DMBT1 [deleted in malignant brain tumors 1]; DMC1 [DMC1 dosage suppressor of mckl homolog, meiosis-specific homologous recombination (yeast)]; DMD [dystrophin]; DMP1 [dentin matrix acidic phosphoprotein 1]; DMPK [dystrophia myotonica-protein kinase]; DMRT1 [doublesex and mab-3 related transcription factor 1]; DMXL2 [Dmx-like 2]; DNA2 [DNA replication helicase 2 homolog (yeast)]; DNAH1 [dynein, axonemal, heavy chain 1]; DNAH12 [dynein, axonemal, heavy chain 12];
DNAI1 [dynein, axonemal, intermediate chain 1]; DNAI2 [dynein, axonemal, intermediate chain 2]; DNASE1 [deoxyribonuclease I]; DNM2 [dynamin 2]; DNM3 [dynamin 3]; DNMT1 [DNA (cytosine-5-)-methyltransferase 1]; DNMT3B [DNA
(cytosine-5-)-methyltransferase 3 beta]; DNTT [deoxynucleotidyltransferase, terminal]; DOCK1 [dedicator of cytokinesis 1]; DOCK3 [dedicator of cytokinesis 3]; DOCK8 [dedicator of cytokinesis 8]; DOK1 [docking protein 1, 62kDa (downstream of tyrosine kinase 1)]; DOLK [dolichol kinase]; DPAGT1 [dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1 (GIcNAc-1-P transferase)]; DPEP1 [dipeptidase 1 (renal)]; DPH1 [DPH1 homolog (S. cerevisiae)]; DPM1 [dolichyl-phosphate mannosyltransferase polypeptide 1, catalytic subunit]; DPP1 0 [dipeptidyl-peptidase 10]; DPP4 [dipeptidyl-peptidase 4]; DPYD [dihydropyrimidine dehydrogenase]; DRD2 [dopamine receptor D2]; DRD3 [dopamine receptor D3]; DRD4 [dopamine receptor D4]; DSC2 [desmocollin 2]; DSG1 [desmoglein 1]; DSG2 [desmoglein 2]; DSG3 [desmoglein 3 (pemphigus vulgaris antigen)]; DSP [desmoplakin];

DTNA [dystrobrevin, alpha]; DTYMK [deoxythymidylate kinase (thymidylate kinase)]; DUOX1 [dual oxidase 1]; DUOX2 [dual oxidase 2]; DUSP1 [dual specificity phosphatase 1]; DUSP14 [dual specificity phosphatase 14]; DUSP2 [dual specificity phosphatase 2]; DUSP5 [dual specificity phosphatase 5]; DUT
[deoxyuridine triphosphatase]; DVL1 [dishevelled, dsh homolog 1 (Drosophila)];
DYNC2H1 [dynein, cytoplasmic 2, heavy chain 1]; DYNLL1 [dynein, light chain, LC8-type 1]; DYRK1A [dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A]; DYSF [dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive)]; E2F1 [E2F transcription factor 1]; EBF2 [early B-cell factor 2];

[Epstein-Barr virus induced 3]; ECE1 [endothelin converting enzyme 1]; ECM1 [extracellular matrix protein 1]; EDA [ectodysplasin A]; EDAR [ectodysplasin A
receptor]; EDN1 [endothelin 1]; EDNRA [endothelin receptor type A]; EDNRB
[endothelin receptor type B]; EEF1A1 [eukaryotic translation elongation factor alpha 1]; EEF1A2 [eukaryotic translation elongation factor 1 alpha 2]; EFEMP2 [EGF-containing fibulin-like extracellular matrix protein 2]; EFNA1 [ephrin-A1];
EFNB2 [ephrin-B2]; EFS [embryonal Fyn-associated substrate]; EGF [epidermal growth factor (beta-urogastrone)]; EGFR [epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)]; EGR1 [early growth response 1]; EGR2 [early growth response 2]; EHF [ets homologous factor]; EHMT2 [euchromatic histone-lysine N-methyltransferase 2]; EIF2AK2 [eukaryotic translation initiation factor 2-alpha kinase 2]; EIF2S1 [eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa ]; EIF2S2 [eukaryotic translation initiation factor 2, subunit 2 beta, 38kDa]; EIF3A [eukaryotic translation initiation factor 3, subunit A]; EIF4B [eukaryotic translation initiation factor 4B]; EIF4E [eukaryotic translation initiation factor 4E]; EIF4EBP1 [eukaryotic translation initiation factor 4E binding protein 1]; EIF4G1 [eukaryotic translation initiation factor 4 gamma, 1]; EIF6 [eukaryotic translation initiation factor 6]; ELAC2 [elaC homolog 2 (E. coli)]; ELANE [elastase, neutrophil expressed]; ELAVL1 [ELAV (embryonic lethal, abnormal vision, Drosophila)-like 1 (Hu antigen R)]; ELF3 [E74-like factor 3 (ets domain transcription factor, epithelial-specific )]; ELF5 [E74-like factor 5 (ets domain transcription factor)];
ELN [elastin]; ELOVL4 [elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 4]; EMD [emerin]; EMILIN1 [elastin microfibril interfacer 1]; EMR2 [egf-like module containing, mucin-like, hormone receptor-like 2];

[engrailed homeobox 2]; ENG [endoglin]; ENO1 [enolase 1, (alpha)]; ENO2 [enolase 2 (gamma, neuronal)]; ENO3 [enolase 3 (beta, muscle)]; ENPP2 [ectonucleotide pyrophosphatase/phosphodiesterase 2]; ENPP3 [ectonucleotide pyrophosphatase/phosphodiesterase 3]; ENTPD1 [ectonucleoside triphosphate diphosphohydrolase 1]; EP300 [E1A binding protein p300]; EPAS1 [endothelial PAS domain protein 1]; EPB42 [erythrocyte membrane protein band 4.2];
EPCAM [epithelial cell adhesion molecule]; EPHA1 [EPH receptor Al ]; EPHA2 [EPH receptor A2]; EPHB2 [EPH receptor B2]; EPHB4 [EPH receptor B4];
EPHB6 [EPH receptor B6]; EPHX1 [epoxide hydrolase 1, microsomal (xenobiotic)]; EPHX2 [epoxide hydrolase 2, cytoplasmic]; EPO [erythropoietin];
EPOR [erythropoietin receptor]; EPRS [glutamyl-prolyl-tRNA synthetase]; EPX
[eosinophil peroxidase]; ERBB2 [v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)]; ERBB2IP
[erbb2 interacting protein]; ERBB3 [v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian)]; ERBB4 [v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)]; ERCC1 [excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence)]; ERCC2 [excision repair cross-complementing rodent repair deficiency, complementation group 2]; ERCC3 [excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)]; ERCC4 [excision repair cross-complementing rodent repair deficiency, complementation group 4]; ERCC5 [excision repair cross-complementing rodent repair deficiency, complementation group 5]; ERCC6 [excision repair cross-complementing rodent repair deficiency, complementation group 6]; ERCC6L [excision repair cross-complementing rodent repair deficiency, complementation group 6-like]; ERCC8 [excision repair cross-complementing rodent repair deficiency, complementation group 8]; ERO1 LB
[ERO1-like beta (S. cerevisiae)]; ERVK6 [endogenous retroviral sequence K, 6];
ERVWE1 [endogenous retroviral family W, env(C7), member 1]; ESD [esterase D/formylglutathione hydrolase]; ESR1 [estrogen receptor 1]; ESR2 [estrogen receptor 2 (ER beta)]; ESRRA [estrogen-related receptor alpha]; ESRRB
[estrogen-related receptor beta]; ETS1 [v-ets erythroblastosis virus E26 oncogene homolog 1 (avian)]; ETS2 [v-ets erythroblastosis virus E26 oncogene homolog 2 (avian)]; EWSR1 [Ewing sarcoma breakpoint region 1]; EXO1 [exonuclease 1]; EYA1 [eyes absent homolog 1 (Drosophila)]; EZH2 [enhancer of zeste homolog 2 (Drosophila)]; EZR [ezrin]; F10 [coagulation factor X]; F11 [coagulation factor XI]; F12 [coagulation factor XII (Hageman factor)]; F13A1 [coagulation factor XIII, Al polypeptide]; F1 3B [coagulation factor XIII, B
polypeptide]; F2 [coagulation factor II (thrombin)]; F2R [coagulation factor II
(thrombin) receptor]; F2RL1 [coagulation factor II (thrombin) receptor-like 1];
F2RL3 [coagulation factor II (thrombin) receptor-like 3]; F3 [coagulation factor III
(thromboplastin, tissue factor)]; F5 [coagulation factor V (proaccelerin, labile factor)]; F7 [coagulation factor VII (serum prothrombin conversion accelerator)];
F8 [coagulation factor VIII, procoagulant component]; F9 [coagulation factor IX];
FABP1 [fatty acid binding protein 1, liver]; FABP2 [fatty acid binding protein 2, intestinal]; FABP4 [fatty acid binding protein 4, adipocyte]; FADD [Fas (TNFRSF6)-associated via death domain]; FADS1 [fatty acid desaturase 1];
FADS2 [fatty acid desaturase 2]; FAF1 [Fas (TNFRSF6) associated factor 1];
FAH [fumarylacetoacetate hydrolase (fumarylacetoacetase)]; FAM189B [family with sequence similarity 189, member B]; FAM92B [family with sequence similarity 92, member B]; FANCA [Fanconi anemia, complementation group A];
FANCB [Fanconi anemia, complementation group B]; FANCC [Fanconi anemia, complementation group C]; FANCD2 [Fanconi anemia, complementation group D2]; FANCE [Fanconi anemia, complementation group E]; FANCF [Fanconi anemia, complementation group F]; FANCG [Fanconi anemia, complementation group G]; FANCI [Fanconi anemia, complementation group I]; FANCL [Fanconi anemia, complementation group L]; FANCM [Fanconi anemia, complementation group M]; FANK1 [fibronectin type III and ankyrin repeat domains 1]; FAS [Fas (TNF receptor superfamily, member 6)]; FASLG [Fas ligand (TNF superfamily, member 6)]; FASN [fatty acid synthase]; FASTK [Fas-activated serine/threonine kinase]; FBLN5 [fibulin 5]; FBN1 [fibrillin 1]; FBP1 [fructose-1,6-bisphosphatase 1]; FBXO32 [F-box protein 32]; FBXW7 [F-box and WD repeat domain containing 7]; FCAR [Fc fragment of IgA, receptor for]; FCERIA [Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide]; FCER1 G [Fc fragment of IgE, high affinity I, receptor for; gamma polypeptide]; FCER2 [Fc fragment of IgE, low affinity II, receptor for (CD23)]; FCGRIA [Fc fragment of IgG, high affinity Ia, receptor (CD64)]; FCGR2A [Fc fragment of IgG, low affinity Ila, receptor (CD32)];
FCGR2B [Fc fragment of IgG, low affinity Ilb, receptor (CD32)]; FCGR3A [Fc fragment of IgG, low affinity Ilia, receptor (CD16a)]; FCGR3B [Fc fragment of IgG, low affinity Illb, receptor (CD16b)]; FCN2 [ficolin (collagen/fibrinogen domain containing lectin) 2 (hucolin)]; FCN3 [ficolin (collagen/fibrinogen domain containing) 3 (Hakata antigen)]; FCRL3 [Fc receptor-like 3]; FCRL6 [Fc receptor-like 6]; FDFT1 [farnesyl-diphosphate farnesyltransferase 1]; FDPS [farnesyl diphosphate synthase (farnesyl pyrophosphate synthetase, dimethylallyltranstransferase, geranyltranstransferase)]; FDX1 [ferredoxin 1];
FEN1 [flap structure-specific endonuclease 1]; FERMTI [fermitin family homolog 1 (Drosophila)]; FERMT3 [fermitin family homolog 3 (Drosophila)]; FES [feline sarcoma oncogene]; FFAR2 [free fatty acid receptor 2]; FGA [fibrinogen alpha chain]; FGB [fibrinogen beta chain]; FGF1 [fibroblast growth factor 1 (acidic)];
FGF2 [fibroblast growth factor 2 (basic)]; FGF5 [fibroblast growth factor 5];

[fibroblast growth factor 7 (keratinocyte growth factor)]; FGF8 [fibroblast growth factor 8 (androgen-induced)]; FGFBP2 [fibroblast growth factor binding protein 2];
FGFR1 [fibroblast growth factor receptor 1]; FGFR1 OP [FGFR1 oncogene partner]; FGFR2 [fibroblast growth factor receptor 2]; FGFR3 [fibroblast growth factor receptor 3]; FGFR4 [fibroblast growth factor receptor 4]; FGG
[fibrinogen gamma chain]; FGR [Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog]; FHIT [fragile histidine triad gene]; FHL1 [four and a half LIM
domains 1]; FHL2 [four and a half LIM domains 2]; FIBP [fibroblast growth factor (acidic) intracellular binding protein]; FIGF [c-fos induced growth factor (vascular endothelial growth factor D)]; FKBP1A [FK506 binding protein 1A, 12kDa];
FKBP4 [FK506 binding protein 4, 59kDa]; FKBP5 [FK506 binding protein 5];
FLCN [folliculin]; FLG [filaggrin]; FLG2 [filaggrin family member 2]; FLNA
[filamin A, alpha]; FLNB [filamin B, beta]; FLT1 [fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)]; FLT3 [fms-related tyrosine kinase 3]; FLT3LG [fms-related tyrosine kinase 3 ligand];

[fms-related tyrosine kinase 4]; FMN1 [formin 1]; FMOD [fibromodulin]; FMR1 [fragile X mental retardation 1]; FN1 [fibronectin 1]; FOLH1 [folate hydrolase (prostate-specific membrane antigen) 1]; FOLR1 [folate receptor 1 (adult)];
FOS
[FBJ murine osteosarcoma viral oncogene homolog]; FOXL2 [forkhead box L2];
FOXN1 [forkhead box N1]; FOXN2 [forkhead box N2]; FOXO3 [forkhead box 03]; FOXP3 [forkhead box P3]; FPGS [folylpolyglutamate synthase]; FPR1 [formyl peptide receptor 1]; FPR2 [formyl peptide receptor 2]; FRAS1 [Fraser syndrome 1]; FREM2 [FRAS1 related extracellular matrix protein 2]; FSCN1 [fascin homolog 1, actin-bundling protein (Strongylocentrotus purpuratus)];
FSHB
[follicle stimulating hormone, beta polypeptide]; FSHR [follicle stimulating hormone receptor]; FST [follistatin]; FTCD [formiminotransferase cyclodeaminase]; FTH1 [ferritin, heavy polypeptide 1]; FTL [ferritin, light polypeptide]; FURIN [furin (paired basic amino acid cleaving enzyme)]; FUT1 [fucosyltransferase 1 (galactoside 2-alpha-L-fucosyltransferase, H blood group)];
FUT2 [fucosyltransferase 2 (secretor status included)]; FUT3 [fucosyltransferase 3 (galactoside 3(4)-L-fucosyltransferase, Lewis blood group)]; FUT4 [fucosyltransferase 4 (alpha (1,3) fucosyltransferase, myeloid-specific)];

[fucosyltransferase 7 (alpha (1,3) fucosyltransferase)]; FUT8 [fucosyltransferase 8 (alpha (1,6) fucosyltransferase)]; FXN [frataxin]; FYN [FYN oncogene related to SRC, FGR, YES]; FZD4 [frizzled homolog 4 (Drosophila)]; G6PC3 [glucose 6 phosphatase, catalytic, 3]; G6PD [glucose-6-phosphate dehydrogenase]; GAA

[glucosidase, alpha; acid]; GAB2 [GRB2-associated binding protein 2]; GABBR1 [gamma-aminobutyric acid (GABA) B receptor, 1]; GABRB3 [gamma-aminobutyric acid (GABA) A receptor, beta 3]; GABRE [gamma-aminobutyric acid (GABA) A receptor, epsilon]; GAD1 [glutamate decarboxylase 1 (brain, 67kDa)]; GAD2 [glutamate decarboxylase 2 (pancreatic islets and brain, 65kDa)];
GADD45A [growth arrest and DNA-damage-inducible, alpha]; GAL [galanin prepropeptide]; GALC [galactosylceramidase]; GALK1 [galactokinase 1]; GALR1 [galanin receptor 1]; GAP43 [growth associated protein 43]; GAPDH
[glyceraldehyde-3-phosphate dehydrogenase]; GART
[phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase]; GAST [gastrin]; GATA1 [GATA binding protein 1 (globin transcription factor 1)]; GATA2 [GATA binding protein 2]; GATA3 [GATA binding protein 3]; GATA4 [GATA binding protein 4];
GATA6 [GATA binding protein 6]; GBA [glucosidase, beta, acid]; GBA3 [glucosidase, beta, acid 3 (cytosolic)]; GBE1 [glucan (1 [4-alpha-), branching enzyme 1]; GC [group-specific component (vitamin D binding protein)]; GCG
[glucagon]; GCH1 [GTP cyclohydrolase 1]; GCKR [glucokinase (hexokinase 4) regulator]; GCLC [glutamate-cysteine ligase, catalytic subunit]; GCLM
[glutamate-cysteine ligase, modifier subunit]; GCNT2 [glucosaminyl (N-acetyl) transferase 2, I-branching enzyme (I blood group)]; GDAP1 [ganglioside-induced differentiation-associated protein 1]; GDF15 [growth differentiation factor 15];
GDNF [glial cell derived neurotrophic factor]; GFAP [glial fibrillary acidic protein];
GGH [gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase)]; GGT1 [gamma-glutamyltransferase 1]; GGT2 [gamma-glutamyltransferase 2]; GH1 [growth hormone 1]; GHR [growth hormone receptor]; GHRH [growth hormone releasing hormone]; GHRL [ghrelin/obestatin prepropeptide]; GHSR [growth hormone secretagogue receptor]; GIF [gastric intrinsic factor (vitamin B synthesis)]; GIP [gastric inhibitory polypeptide];

[gap junction protein, alpha 1, 43kDa]; GJA4 [gap junction protein, alpha 4, 37kDa]; GJB2 [gap junction protein, beta 2, 26kDa]; GLA [galactosidase, alpha];

GLB1 [galactosidase, beta 1]; GLI2 [GLI family zinc finger 2]; GLMN [glomulin, FKBP associated protein]; GLRX [glutaredoxin (thioltransferase)]; GLS
[glutaminase]; GLT25D1 [glycosyltransferase 25 domain containing 1]; GLUL
[glutamate-ammonia ligase (glutamine synthetase)]; GLYAT [glycine-N-acyltransferase]; GM2A [GM2 ganglioside activator]; GMDS [GDP-mannose 4 [6-dehydratase]; GNA12 [guanine nucleotide binding protein (G protein) alpha 12];
GNA13 [guanine nucleotide binding protein (G protein), alpha 13]; GNAI1 [guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1]; GNAO1 [guanine nucleotide binding protein (G protein), alpha activating activity polypeptide 0]; GNAQ [guanine nucleotide binding protein (G
protein), q polypeptide]; GNAS [GNAS complex locus]; GNAZ [guanine nucleotide binding protein (G protein), alpha z polypeptide]; GNB1 [guanine nucleotide binding protein (G protein), beta polypeptide 1]; GNB1L [guanine nucleotide binding protein (G protein), beta polypeptide 1-like]; GNB2L1 [guanine nucleotide binding protein (G protein), beta polypeptide 2-like 1]; GNB3 [guanine nucleotide binding protein (G protein), beta polypeptide 3]; GNE [glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase]; GNG2 [guanine nucleotide binding protein (G protein), gamma 2]; GNLY [granulysin]; GNPAT
[glyceronephosphate 0-acyltransferase]; GNPDA2 [glucosamine-6-phosphate deaminase 2]; GNRH1 [gonadotropin-releasing hormone 1 (luteinizing-releasing hormone)]; GNRHR [gonadotropin-releasing hormone receptor]; GOLGA8B
[golgin A8 family, member B]; GOLGB1 [golgin B1]; GOT1 [glutamic-oxaloacetic transaminase 1, soluble (aspartate aminotransferase 1)]; GOT2 [glutamic-oxaloacetic transaminase 2, mitochondrial (aspartate aminotransferase 2)];
GP1 BA [glycoprotein lb (platelet), alpha polypeptide]; GP2 [glycoprotein 2 (zymogen granule membrane)]; GP6 [glycoprotein VI (platelet)]; GPBAR1 [G
protein-coupled bile acid receptor 1]; GPC5 [glypican 5]; GPI [glucose phosphate isomerase]; GPLD1 [glycosylphosphatidylinositol specific phospholipase D1];
GPN1 [GPN-loop GTPase 1]; GPR1 [G protein-coupled receptor 1]; GPR12 [G
protein-coupled receptor 12]; GPR123 [G protein-coupled receptor 123]; GPR143 [G protein-coupled receptor 143]; GPR15 [G protein-coupled receptor 15];
GPR182 [G protein-coupled receptor 182]; GPR44 [G protein-coupled receptor 44]; GPR77 [G protein-coupled receptor 77]; GPRASP1 [G protein-coupled receptor associated sorting protein 1 ]; GPRC6A [G protein-coupled receptor, family C, group 6, member A]; GPT [glutamic-pyruvate transaminase (alanine aminotransferase)]; GPX1 [glutathione peroxidase 1]; GPX2 [glutathione peroxidase 2 (gastrointestinal)]; GPX3 [glutathione peroxidase 3 (plasma)];
GRAP2 [GRB2-related adaptor protein 2]; GRB2 [growth factor receptor-bound protein 2]; GRIA2 [glutamate receptor, ionotropic, AMPA 2]; GRIN1 [glutamate receptor, ionotropic, N-methyl D-aspartate 1]; GRIN2A [glutamate receptor, ionotropic, N-methyl D-aspartate 2A]; GRIN2B [glutamate receptor, ionotropic, N-methyl D-aspartate 2B]; GRIN2C [glutamate receptor, ionotropic, N-methyl D-aspartate 2C]; GRIN2D [glutamate receptor, ionotropic, N-methyl D-aspartate 2D]; GRIN3A [glutamate receptor, ionotropic, N-methyl-D-aspartate 3A]; GRIN3B
[glutamate receptor, ionotropic, N-methyl-D-aspartate 3B]; GRK5 [G protein-coupled receptor kinase 5]; GRLF1 [glucocorticoid receptor DNA binding factor 1]; GRM1 [glutamate receptor, metabotropic 1]; GRP [gastrin-releasing peptide];
GRPR [gastrin-releasing peptide receptor]; GSC [goosecoid homeobox]; GSC2 [goosecoid homeobox 2]; GSDMB [gasdermin B]; GSK3B [glycogen synthase kinase 3 beta]; GSN [gelsolin]; GSR [glutathione reductase]; GSS [glutathione synthetase]; GSTA1 [glutathione S-transferase alpha 1]; GSTA2 [glutathione S-transferase alpha 2]; GSTM1 [glutathione S-transferase mu 1]; GSTM3 [glutathione S-transferase mu 3 (brain)]; GSTO2 [glutathione S-transferase omega 2]; GSTP1 [glutathione S-transferase pi 1]; GSTT1 [glutathione S-transferase theta 1]; GTF2A1 [general transcription factor I IA, 1, 19/37kDa];
GTF2F1 [general transcription factor IF, polypeptide 1, 74kDa]; GTF2H2 [general transcription factor IIH, polypeptide 2, 44kDa]; GTF2H4 [general transcription factor IIH, polypeptide 4, 52kDa]; GTF2H5 [general transcription factor IIH, polypeptide 5]; GTF2I [general transcription factor Ili]; GTF3A
[general transcription factor IIIA]; GUCA2A [guanylate cyclase activator 2A
(guanylin)];

GUCA2B [guanylate cyclase activator 2B (uroguanylin)]; GUCY2C [guanylate cyclase 2C (heat stable enterotoxin receptor)]; GUK1 [guanylate kinase 1];
GULP1 [GULP, engulfment adaptor PTB domain containing 1]; GUSB
[glucuronidase, beta]; GYPA [glycophorin A (MNS blood group)]; GYPB
[glycophorin B (MNS blood group)]; GYPC [glycophorin C (Gerbich blood group)];
GYPE [glycophorin E (MNS blood group)]; GYS1 [glycogen synthase 1 (muscle)];
GZMA [granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)]; GZMB [granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1)]; GZMK [granzyme K (granzyme 3; tryptase II)];
H1 FO [H1 histone family, member 0]; H2AFX [H2A histone family, member X];
HABP2 [hyaluronan binding protein 2]; HACL1 [2-hydroxyacyl-CoA lyase 1];
HADHA [hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A
thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), alpha subunit];
HAL
[histidine ammonia-lyase]; HAMP [hepcidin antimicrobial peptide]; HAPLNI
[hyaluronan and proteoglycan link protein 1]; HAVCR1 [hepatitis A virus cellular receptor 1 ]; HAVCR2 [hepatitis A virus cellular receptor 2]; HAX1 [HCLS1 associated protein X-1]; HBA1 [hemoglobin, alpha 1]; HBA2 [hemoglobin, alpha 2]; HBB [hemoglobin, beta]; HBE1 [hemoglobin, epsilon 1]; HBEGF [heparin-binding EGF-like growth factor]; HBG2 [hemoglobin, gamma G]; HCCS
[holocytochrome c synthase (cytochrome c heme-lyase)]; HCK [hemopoietic cell kinase]; HCRT [hypocretin (orexin) neuropeptide precursor]; HCRTR1 [hypocretin (orexin) receptor 1]; HCRTR2 [hypocretin (orexin) receptor 2];
HOST
[hematopoietic cell signal transducer]; HDAC1 [histone deacetylase 1]; HDAC2 [histone deacetylase 2]; HDAC6 [histone deacetylase 6]; HDAC9 [histone deacetylase 9]; HDC [histidine decarboxylase]; HERC2 [hect domain and RLD 2];
HES1 [hairy and enhancer of split 1, (Drosophila)]; HES6 [hairy and enhancer of split 6 (Drosophila)]; HESX1 [HESX homeobox 1]; HEXA [hexosaminidase A
(alpha polypeptide)]; HEXB [hexosaminidase B (beta polypeptide)]; HFE
[hemochromatosis]; HGF [hepatocyte growth factor (hepapoietin A; scatter factor)]; HGS [hepatocyte growth factor-regulated tyrosine kinase substrate];

HGSNAT [heparan-alpha-glucosaminide N-acetyltransferase]; HIF1A [hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)];
HINFP [histone H4 transcription factor]; HINT1 [histidine triad nucleotide binding protein 1]; HIPK2 [homeodomain interacting protein kinase 2]; HIRA [HIR
histone cell cycle regulation defective homolog A (S. cerevisiae)]; HIST1 H1 B
[histone cluster 1, H1b]; HIST1H3E [histone cluster 1, H3e]; HIST2H2AC [histone cluster 2, H2ac]; HIST2H3C [histone cluster 2, H3c]; HIST4H4 [histone cluster 4, H4];
HJURP [Holliday junction recognition protein]; HK2 [hexokinase 2]; HLA-A
[major histocompatibility complex, class I, A]; HLA-B [major histocompatibility complex, class I, B]; HLA-C [major histocompatibility complex, class I, C]; HLA-DMA
[major histocompatibility complex, class II, DM alpha]; HLA-DMB [major histocompatibility complex, class II, DM beta]; HLA-DOA [major histocompatibility complex, class II, DO alpha]; HLA-DOB [major histocompatibility complex, class II, DO beta]; HLA-DPA1 [major histocompatibility complex, class II, DP alpha 1];
HLA-DPB1 [major histocompatibility complex, class II, DP beta 1]; HLA-DQA1 [major histocompatibility complex, class II, DQ alpha 1]; HLA-DQA2 [major histocompatibility complex, class II, DQ alpha 2]; HLA-DQB1 [major histocompatibility complex, class II, DQ beta 1]; HLA-DRA [major histocompatibility complex, class II, DR alpha]; HLA-DRB1 [major histocompatibility complex, class II, DR beta 1]; HLA-DRB3 [major histocompatibility complex, class II, DR beta 3]; HLA-DRB4 [major histocompatibility complex, class II, DR beta 4]; HLA-DRB5 [major histocompatibility complex, class II, DR beta 5]; HLA-E [major histocompatibility complex, class I, E]; HLA-F [major histocompatibility complex, class I, F];
HLA-G
[major histocompatibility complex, class I, G]; HLCS [holocarboxylase synthetase (biotin-(proprionyl-Coenzyme A-carboxylase (ATP-hydrolysing)) ligase)]; HLTF
[helicase-like transcription factor]; HLX [H2.0-like homeobox]; HMBS
[hydroxymethylbilane synthase]; HMGA1 [high mobility group AT-hook 1];
HMGB1 [high-mobility group box 1]; HMGCR [3-hydroxy-3-methylglutaryl-Coenzyme A reductase]; HMOX1 [heme oxygenase (decycling) 1]; HMOX2 [heme oxygenase (decycling) 2]; HNF1A [HNF1 homeobox A]; HNF4A
[hepatocyte nuclear factor 4, alpha]; HNMT [histamine N-m ethyltransferase];
HNRNPA1 [heterogeneous nuclear ribonucleoprotein Al]; HNRNPA2B1 [heterogeneous nuclear ribonucleoprotein A2/B1]; HNRNPH2 [heterogeneous nuclear ribonucleoprotein H2 (H')]; HNRNPUL1 [heterogeneous nuclear ribonucleoprotein U-like 1]; HOXA13 [homeobox Al 3]; HOXA4 [homeobox A4];
HOXA9 [homeobox A9]; HOXB4 [homeobox B4]; HP [haptoglobin]; HPGDS
[hematopoietic prostaglandin D synthase]; HPR [haptoglobin-related protein];
HPRT1 [hypoxanthine phosphoribosyltransferase 1]; HPS1 [Hermansky-Pudlak syndrome 1]; HPS3 [Hermansky-Pudlak syndrome 3]; HPS4 [Hermansky-Pudlak syndrome 4]; HPSE [heparanase]; HPX [hemopexin]; HRAS [v-Ha-ras Harvey rat sarcoma viral oncogene homolog]; HRG [histidine-rich glycoprotein]; HRH1 [histamine receptor H1]; HRH2 [histamine receptor H2]; HRH3 [histamine receptor H3]; HRH4 [histamine receptor H4]; HSD11 B1 [hydroxysteroid (11-beta) dehydrogenase 1]; HSD11 B2 [hydroxysteroid (11-beta) dehydrogenase 2];
HSD17B1 [hydroxysteroid (17-beta) dehydrogenase 1 ]; HSD17B4 [hydroxysteroid (17-beta) dehydrogenase 4]; HSF1 [heat shock transcription factor 1]; HSP90AA1 [heat shock protein 90kDa alpha (cytosolic), class A
member 1]; HSP90AB1 [heat shock protein 90kDa alpha (cytosolic), class B
member 1]; HSP90B1 [heat shock protein 90kDa beta (Grp94), member 1];
HSPA14 [heat shock 70kDa protein 14]; HSPA1 A [heat shock 70kDa protein 1 A];
HSPA1 B [heat shock 70kDa protein 1 B]; HSPA2 [heat shock 70kDa protein 2];
HSPA4 [heat shock 70kDa protein 4]; HSPA5 [heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa)]; HSPA8 [heat shock 70kDa protein 8];
HSPB1 [heat shock 27kDa protein 1]; HSPB2 [heat shock 27kDa protein 2];
HSPD1 [heat shock 60kDa protein 1 (chaperonin)]; HSPE1 [heat shock 1 OkDa protein 1 (chaperonin 10)]; HSPG2 [heparan sulfate proteoglycan 2]; HTN3 [histatin 3]; HTR1A [5-hydroxytryptamine (serotonin) receptor 1A]; HTR2A [5-hydroxytryptamine (serotonin) receptor 2A]; HTR3A [5-hydroxytryptamine (serotonin) receptor 3A]; HTRA1 [HtrA serine peptidase 1]; HTT [huntingtin];

HUS1 [HUS1 checkpoint homolog (S. pombe)]; HUWE1 [HECT, UBA and WWE
domain containing 1]; HYAL1 [hyaluronoglucosaminidase 1]; HYLS1 [hydrolethalus syndrome 1]; IAPP [islet amyloid polypeptide]; IBSP [integrin-binding sialoprotein]; ICAM1 [intercellular adhesion molecule 1]; ICAM2 [intercellular adhesion molecule 2]; ICAM3 [intercellular adhesion molecule 3];
ICAM4 [intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)];
ICOS [inducible T-cell co-stimulator]; ICOSLG [inducible T-cell co-stimulator ligand]; ID1 [inhibitor of DNA binding 1, dominant negative helix-loop-helix protein]; ID2 [inhibitor of DNA binding 2, dominant negative helix-loop-helix protein]; IDO1 [indoleamine 2 [3-dioxygenase 1]; IDS [iduronate 2-sulfatase];
IDUA [iduronidase, alpha-L-]; IF127 [interferon, alpha-inducible protein 27];

[interferon, gamma-inducible protein 30]; IFITM1 [interferon induced transmembrane protein 1 (9-27)]; IFNA1 [interferon, alpha 1]; IFNA2 [interferon, alpha 2]; IFNAR1 [interferon (alpha, beta and omega) receptor 1]; IFNAR2 [interferon (alpha, beta and omega) receptor 2]; IFNB1 [interferon, beta 1, fibroblast]; IFNG [interferon, gamma]; IFNGR1 [interferon gamma receptor 1];
IFNGR2 [interferon gamma receptor 2 (interferon gamma transducer 1)]; IGF1 [insulin-like growth factor 1 (somatomedin C)]; IGF1 R [insulin-like growth factor 1 receptor]; IGF2 [insulin-like growth factor 2 (somatomedin A)]; IGF2R [insulin-like growth factor 2 receptor]; IGFBP1 [insulin-like growth factor binding protein 1];
IGFBP2 [insulin-like growth factor binding protein 2, 36kDa]; IGFBP3 [insulin-like growth factor binding protein 3]; IGFBP4 [insulin-like growth factor binding protein 4]; IGFBP5 [insulin-like growth factor binding protein 5]; IGHA1 [immunoglobulin heavy constant alpha 1]; IGHE [immunoglobulin heavy constant epsilon]; IGHG1 [immunoglobulin heavy constant gamma 1 (G1 m marker)]; IGHG3 [immunoglobulin heavy constant gamma 3 (G3m marker)]; IGHG4 [immunoglobulin heavy constant gamma 4 (G4m marker)]; IGHM
[immunoglobulin heavy constant mu]; IGHMBP2 [immunoglobulin mu binding protein 2]; IGKC [immunoglobulin kappa constant]; IGKV2D-29 [immunoglobulin kappa variable 2D-29]; IGLL1 [immunoglobulin lambda-like polypeptide 1]; IGSF1 [immunoglobulin superfamily, member 1]; IKBKAP [inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein];
IKBKB [inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta]; IKBKE [inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon]; IKBKG [inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma]; IKZF1 [IKAROS family zinc finger 1 (Ikaros)]; IKZF2 [IKAROS family zinc finger 2 (Helios)]; U0 [interleukin 10]; IL10RA
[interleukin receptor, alpha]; IL1ORB [interleukin 10 receptor, beta]; IL11 [interleukin 11];
IL12A [interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35)]; IL12B [interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40) ];

[interleukin 12 receptor, beta 1]; IL12RB2 [interleukin 12 receptor, beta 2];

[interleukin 13]; IL13RA1 [interleukin 13 receptor, alpha 1]; IL13RA2 [interleukin 13 receptor, alpha 2]; IL15 [interleukin 15]; IL15RA [interleukin 15 receptor, alpha]; U6 [interleukin 16 (lymphocyte chemoattractant factor)]; IL17A
[interleukin 17A]; IL17F [interleukin 17F]; IL17RA [interleukin 17 receptor A];
IL17RB [interleukin 17 receptor B]; IL17RC [interleukin 17 receptor C]; U8 [interleukin 18 (interferon-gamma-inducing factor)]; IL18BP [interleukin 18 binding protein]; IL18R1 [interleukin 18 receptor 1]; IL18RAP [interleukin 18 receptor accessory protein]; IL19 [interleukin 19]; ILIA [interleukin 1, alpha]; IL1 B
[interleukin 1, beta]; IL1 F9 [interleukin 1 family, member 9]; IL1 R1 [interleukin 1 receptor, type I]; IL1 RAP [interleukin 1 receptor accessory protein]; IL1 RL1 [interleukin 1 receptor-like 1 ]; IL1 RN [interleukin 1 receptor antagonist];

[interleukin 2]; IL20 [interleukin 20]; IL21 [interleukin 21]; IL21R
[interleukin 21 receptor]; IL22 [interleukin 22]; IL23A [interleukin 23, alpha subunit p19];

[interleukin 23 receptor]; IL24 [interleukin 24]; IL25 [interleukin 25]; IL26 [interleukin 26]; IL27 [interleukin 27]; IL27RA [interleukin 27 receptor, alpha]; IL29 [interleukin 29 (interferon, lambda 1)]; IL2RA [interleukin 2 receptor, alpha];
IL2RB [interleukin 2 receptor, beta]; IL2RG [interleukin 2 receptor, gamma (severe combined immunodeficiency)]; IL3 [interleukin 3 (colony-stimulating factor, multiple)]; IL31 [interleukin 31]; IL32 [interleukin 32]; IL33 [interleukin 33];
IL3RA [interleukin 3 receptor, alpha (low affinity)]; IL4 [interleukin 4];

[interleukin 4 receptor]; IL5 [interleukin 5 (colony-stimulating factor, eosinophil)];
IL5RA [interleukin 5 receptor, alpha]; IL6 [interleukin 6 (interferon, beta 2)]; IL6R
[interleukin 6 receptor]; IL6ST [interleukin 6 signal transducer (gp130, oncostatin M receptor)]; IL7 [interleukin 7]; IL7R [interleukin 7 receptor]; IL8 [interleukin 8];
IL9 [interleukin 9]; IL9R [interleukin 9 receptor]; ILK [integrin-linked kinase]; IMP5 [intramembrane protease 5]; INCENP [inner centromere protein antigens 135/155kDa]; ING1 [inhibitor of growth family, member 1]; INHA [inhibin, alpha];
INHBA [inhibin, beta A]; INPP4A [inositol polyphosphate-4-phosphatase, type I, 107kDa]; INPP5D [inositol polyphosphate-5-phosphatase, 145kDa]; INPP5E
[inositol polyphosphate-5-phosphatase, 72 kDa]; INPPL1 [inositol polyphosphate phosphatase-like 1]; INS [insulin]; INSL3 [insulin-like 3 (Leydig cell)]; INSR
[insulin receptor]; IP013 [importin 13]; IP07 [importin 7]; IQGAP1 [IQ motif containing GTPase activating protein 1]; IRAK1 [interleukin-1 receptor-associated kinase 1]; IRAK3 [interleukin-1 receptor-associated kinase 3]; IRAK4 [interleukin-1 receptor-associated kinase 4]; IRF1 [interferon regulatory factor 1]; IRF2 [interferon regulatory factor 2]; IRF3 [interferon regulatory factor 3]; IRF4 [interferon regulatory factor 4]; IRF5 [interferon regulatory factor 5]; IRF7 [interferon regulatory factor 7]; IRF8 [interferon regulatory factor 8]; IRGM
[immunity-related GTPase family, M]; IRS1 [insulin receptor substrate 1]; IRS2 [insulin receptor substrate 2]; IRS4 [insulin receptor substrate 4]; ISG15 [ISG15 ubiquitin-like modifier]; ITCH [itchy E3 ubiquitin protein ligase homolog (mouse)];
ITFG1 [integrin alpha FG-GAP repeat containing 1]; ITGA1 [integrin, alpha 1];
ITGA2 [integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor)]; ITGA2B
[integrin, alpha 2b (platelet glycoprotein IIb of IIb/Ills complex, antigen CD41)];
ITGA3 [integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor)];
ITGA4 [integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)];
ITGA5 [integrin, alpha 5 (fibronectin receptor, alpha polypeptide)]; ITGA6 [integrin, alpha 6]; ITGA8 [integrin, alpha 8]; ITGAE [integrin, alpha E
(antigen CD103, human mucosal lymphocyte antigen 1; alpha polypeptide)]; ITGAL
[integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)]; ITGAM [integrin, alpha M (complement component 3 receptor 3 subunit)]; ITGAV [integrin, alpha V (vitronectin receptor, alpha polypeptide, antigen CD51)]; ITGAX [integrin, alpha X (complement component 3 receptor 4 subunit)]; ITGB1 [integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12)]; ITGB2 [integrin, beta 2 (complement component 3 receptor 3 and 4 subunit)]; ITGB3 [integrin, beta 3 (platelet glycoprotein Ilia, antigen CD61)]; ITGB3BP [integrin beta 3 binding protein (beta3-endonexin)]; ITGB4 [integrin, beta 4]; ITGB6 [integrin, beta 6];
ITGB7 [integrin, beta 7]; ITIH4 [inter-alpha (globulin) inhibitor H4 (plasma Kallikrein-sensitive glycoprotein)]; ITK [IL2-inducible T-cell kinase]; ITLN1 [intelectin 1 (galactofuranose binding)]; ITLN2 [intelectin 2]; ITPA [inosine triphosphatase (nucleoside triphosphate pyrophosphatase)]; ITPR1 [inositol 1,4,5-triphosphate receptor, type 1]; ITPR3 [inositol 1,4,5-triphosphate receptor, type 3]; IVD [isovaleryl Coenzyme A dehydrogenase]; IVL [involucrin]; IVNS1ABP
[influenza virus NS1A binding protein]; JAG1 [jagged 1 (Alagille syndrome)];
JAK1 [Janus kinase 1]; JAK2 [Janus kinase 2]; JAK3 [Janus kinase 3]; JAKMIP1 [Janus kinase and microtubule interacting protein 1]; JMJD6 [jumonji domain containing 6]; JPH4 [junctophilin 4]; JRKL [jerky homolog-like (mouse)]; JUN
[Jun oncogene]; JUND [Jun D proto-oncogene]; JUP [junction plakoglobin]; KARS
[lysyl-tRNA synthetase]; KAT5 [K(lysine) acetyltransferase 5]; KCNA2 [potassium voltage-gated channel, shaker-related subfamily, member 2]; KCNA5 [potassium voltage-gated channel, shaker-related subfamily, member 5]; KCND1 [potassium voltage-gated channel, Shal-related subfamily, member 1]; KCNH2 [potassium voltage-gated channel, subfamily H (eag-related), member 2]; KCNIP4 [Kv channel interacting protein 4]; KCNMA1 [potassium large conductance calcium-activated channel, subfamily M, alpha member 1]; KCNMB1 [potassium large conductance calcium-activated channel, subfamily M, beta member 1]; KCNN3 [potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3]; KCNS3 [potassium voltage-gated channel, delayed-rectifier, subfamily S, member 3]; KDR [kinase insert domain receptor (a type III
receptor tyrosine kinase)]; KHDRBS1 [KH domain containing, RNA binding, signal transduction associated 1]; KHDRBS3 [KH domain containing, RNA binding, signal transduction associated 3]; KIAA0101 [KIAA0101]; KIP 6B [kinesin family member 16B]; KIF20B [kinesin family member 20B]; KIF21 B [kinesin family member 21 B]; KIF22 [kinesin family member 22]; KIF2B [kinesin family member 2B]; KIF2C [kinesin family member 2C]; KIR2DL1 [killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 1]; KIR2DL2 [killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 2]; KIR2DL3 [killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 3];
KIR2DL5A [killer cell immunoglobulin-like receptor, two domains, long cytoplasmic tail, 5A]; KIR2DS1 [killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 1]; KIR2DS2 [killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 2]; KIR2DS5 [killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 5]; KIR3DL1 [killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 1];
KIR3DS1 [killer cell immunoglobulin-like receptor, three domains, short cytoplasmic tail, 1]; KISS1 [KiSS-1 metastasis-suppressor]; KISS1R [KISS1 receptor]; KIT [v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog];
KITLG [KIT ligand]; KLF2 [Kruppel-like factor 2 (lung)]; KLF4 [Kruppel-like factor 4 (gut)]; KLK1 [kallikrein 1]; KLK11 [kallikrein-related peptidase 11]; KLK3 [kallikrein-related peptidase 3]; KLKB1 [kallikrein B, plasma (Fletcher factor) 1 ];
KLRB1 [killer cell lectin-like receptor subfamily B, member 1]; KLRC1 [killer cell lectin-like receptor subfamily C, member 1]; KLRD1 [killer cell lectin-like receptor subfamily D, member 1]; KLRK1 [killer cell lectin-like receptor subfamily K, member 1]; KNG1 [kininogen 1]; KPNA1 [karyopherin alpha 1 (importin alpha 5)];
KPNA2 [karyopherin alpha 2 (RAG cohort 1, importin alpha 1)]; KPNB1 [karyopherin (importin) beta 1]; KRAS [v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog]; KRT1 [keratin 1 ]; KRT10 [keratin 10]; KRT13 [keratin 13];

KRT14 [keratin 14]; KRT16 [keratin 16]; KRT18 [keratin 18]; KRT19 [keratin 19];
KRT20 [keratin 20]; KRT5 [keratin 5]; KRT7 [keratin 7]; KRT8 [keratin 8]; KRT9 [keratin 9]; KRTAP19-3 [keratin associated protein 19-3]; KRTAP2-1,keratin associated protein 2-1]; L1 CAM [L1 cell adhesion molecule]; LACTB [lactamase, beta]; LAG3 [lymphocyte-activation gene 3]; LALBA [lactalbumin, alpha-]; LAMA1 [laminin, alpha 1]; LAMA2 [laminin, alpha 2]; LAMA3 [laminin, alpha 3]; LAMA4 [laminin, alpha 4]; LAMB1 [laminin, beta 1]; LAMB2 [laminin, beta 2 (laminin S)];
LAMB3 [laminin, beta 3]; LAMC1 [laminin, gamma 1 (formerly LAMB2)]; LAMC2 [laminin, gamma 2]; LAMP1 [lysosomal-associated membrane protein 1]; LAMP2 [lysosomal-associated membrane protein 2]; LAMP3 [lysosomal-associated membrane protein 3]; LAP3 [leucine aminopeptidase 3]; LAPTM4A [lysosomal protein transmembrane 4 alpha]; LAT [linker for activation of T cells]; LBP
[Iipopolysaccharid e binding protein]; LBR [lamin B receptor]; LBXCOR1 [Lbxcor1 homolog (mouse)]; LCAT [lecithin-cholesterol acyltransferase]; LCK [lymphocyte-specific protein tyrosine kinase]; LCN1 [lipocalin 1 (tear prealbumin)]; LCN2 [lipocalin 2]; LCP1 [lymphocyte cytosolic protein 1 (L-plastin)]; LCT
[lactase];
LDLR [low density lipoprotein receptor]; LDLRAP1 [low density lipoprotein receptor adaptor protein 1]; LECT2 [leukocyte cell-derived chemotaxin 2];

[late cornified envelope-like proline-rich 1]; LEMD3 [LEM domain containing 3];
LEP [leptin]; LEPR [leptin receptor]; LGALS1 [lectin, galactoside-binding, soluble, 1]; LGALS3 [lectin, galactoside-binding, soluble, 3]; LGALS3BP [lectin, galactoside-binding, soluble, 3 binding protein]; LGALS4 [lectin, galactoside-binding, soluble, 4]; LGALS9 [lectin, galactoside-binding, soluble, 9];

[lectin, galactoside-binding, soluble, 9B]; LGR4 [leucine-rich repeat-containing G
protein-coupled receptor 4]; LHCGR [luteinizing hormone/choriogonadotropin receptor]; LIF [leukemia inhibitory factor (cholinergic differentiation factor)]; LIFR
[leukemia inhibitory factor receptor alpha]; LIG1 [ligase I, DNA, ATP-dependent];
LIG3 [ligase III, DNA, ATP-dependent]; LIG4 [ligase IV, DNA, ATP-dependent];
LILRA3 [leukocyte immunoglobulin-like receptor, subfamily A (without TM
domain), member 3]; LILRB4 [leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 4]; LIMS1 [LIM and senescent cell antigen-like domains 1]; LIPA [lipase A, lysosomal acid, cholesterol esterase];
LIPC [lipase, hepatic]; LIPE [lipase, hormone-sensitive]; LIPG [lipase, endothelial]; LMAN1 [lectin, mannose-binding, 1]; LMLN [leishmanolysin-like (metallopeptidase M8 family)]; LMNA [lamin A/C]; LMNB1 [lamin B1]; LMNB2 [lamin B2]; LOC646627 [phospholipase inhibitor]; LOX [lysyl oxidase]; LOXHD1 [lipoxygenase homology domains 1]; LOXL1 [lysyl oxidase-like 1]; LPA
[lipoprotein, Lp(a)]; LPAR3 [lysophosphatidic acid receptor 3]; LPCAT2 [lysophosphatidylcholine acyltransferase 2]; LPL [lipoprotein lipase]; LPO
[lactoperoxidase]; LPP [LIM domain containing preferred translocation partner in lipoma]; LRBA [LPS-responsive vesicle trafficking, beach and anchor containing];
LRP1 [low density lipoprotein receptor-related protein 1]; LRP6 [low density lipoprotein receptor-related protein 6]; LRPAP1 [low density lipoprotein receptor-related protein associated protein 1]; LRRC32 [leucine rich repeat containing 32];
LRRC37B [leucine rich repeat containing 37B]; LRRC8A [leucine rich repeat containing 8 family, member A]; LRRK2 [leucine-rich repeat kinase 2]; LRTOMT
[leucine rich transmembrane and 0-methyltransferase domain containing]; LSM1 [LSM1 homolog, U6 small nuclear RNA associated (S. cerevisiae)]; LSM2 [LSM2 homolog, U6 small nuclear RNA associated (S. cerevisiae)]; LSP1 [lymphocyte-specific protein 1 ]; LTA [lymphotoxin alpha (TNF superfamily, member 1)];
LTA4H [leukotriene A4 hydrolase]; LTB [lymphotoxin beta (TNF superfamily, member 3)]; LTB4R [leukotriene B4 receptor]; LTB4R2 [leukotriene B4 receptor 2]; LTBR [lymphotoxin beta receptor (TNFR superfamily, member 3)]; LTC4S
[leukotriene C4 synthase]; LTF [lactotransferrin]; LY86 [lymphocyte antigen 86];
LY9 [lymphocyte antigen 9]; LYN [v-yes-1 Yamaguchi sarcoma viral related oncogene homolog]; LYRM4 [LYR motif containing 4]; LYST [lysosomal trafficking regulator]; LYZ [lysozyme (renal amyloidosis)]; LYZL6 [lysozyme-like 6]; LZTR1 [leucine-zipper-like transcription regulator 1]; M6PR [mannose-6-phosphate receptor (cation dependent)]; MADCAMI [mucosal vascular addressin cell adhesion molecule 1 ]; MAF [v-maf musculoaponeurotic fibrosarcoma oncogene homolog (avian)]; MAG [myelin associated glycoprotein]; MAN2A1 [mannosidase, alpha, class 2A, member 1]; MAN2B1 [mannosidase, alpha, class 2B, member 1]; MANBA [mannosidase, beta A, lysosomal]; MANF
[mesencephalic astrocyte-derived neurotrophic factor]; MAOB [monoamine oxidase B]; MAP2 [microtubule-associated protein 2]; MAP2K1 [mitogen-activated protein kinase kinase 1]; MAP2K2 [mitogen-activated protein kinase kinase 2]; MAP2K3 [mitogen-activated protein kinase kinase 3]; MAP2K4 [mitogen-activated protein kinase kinase 4]; MAP3K1 [mitogen-activated protein kinase kinase kinase 1 ]; MAP3K11 [mitogen-activated protein kinase kinase kinase 11]; MAP3K14 [mitogen-activated protein kinase kinase kinase 14];
MAP3K5 [mitogen-activated protein kinase kinase kinase 5]; MAP3K7 [mitogen-activated protein kinase kinase kinase 7]; MAP3K9 [mitogen-activated protein kinase kinase kinase 9]; MAPK1 [mitogen-activated protein kinase 1]; MAPK10 [mitogen-activated protein kinase 10]; MAPK1 1 [mitogen-activated protein kinase 11]; MAPK12 [mitogen-activated protein kinase 12]; MAPK13 [mitogen-activated protein kinase 13]; MAPK14 [mitogen-activated protein kinase 14]; MAPK3 [mitogen-activated protein kinase 3]; MAPK8 [mitogen-activated protein kinase 8]; MAPK9 [mitogen-activated protein kinase 9]; MAPKAP1 [mitogen-activated protein kinase associated protein 1]; MAPKAPK2 [mitogen-activated protein kinase-activated protein kinase 2]; MAPKAPK5 [mitogen-activated protein kinase-activated protein kinase 5]; MAPT [microtubule-associated protein tau];
MARCKS [myristoylated alanine-rich protein kinase C substrate]; MASP2 [mannan-binding lectin serine peptidase 2]; MATN1 [matrilin 1, cartilage matrix protein]; MAVS [mitochondrial antiviral signaling protein]; MB [myoglobin];

[methyl-CpG binding domain protein 2]; MBL2 [mannose-binding lectin (protein C) 2, soluble (opsonic defect)]; MBP [myelin basic protein]; MBTPS2 [membrane-bound transcription factor peptidase, site 2]; MC2R [melanocortin 2 receptor (adrenocorticotropic hormone)]; MC3R [melanocortin 3 receptor]; MC4R
[melanocortin 4 receptor]; MCCC2 [m ethylcrotonoyl-Coenzyme A carboxylase 2 (beta)]; MCHR1 [melanin-concentrating hormone receptor 1]; MCL1 [myeloid cell leukemia sequence 1 (BCL2-related)]; MCM2 [minichromosome maintenance complex component 2]; MCM4 [minichromosome maintenance complex component 4]; MCOLN1 [mucolipin 1]; MCPH1 [microcephalin 1]; MDC1 [mediator of DNA-damage checkpoint 1]; MDH2 [malate dehydrogenase 2, NAD
(mitochondrial)]; MDM2 [Mdm2 p53 binding protein homolog (mouse)]; ME2 [malic enzyme 2, NAD(+)-dependent, mitochondrial]; MECOM [MDS1 and EVI1 complex locus]; MED1 [mediator complex subunit 1]; MED12 [mediator complex subunit 12]; MED1 5 [mediator complex subunit 15]; MED28 [mediator complex subunit 28]; MEFV [Mediterranean fever]; MEN1 [multiple endocrine neoplasia I];
MEPE [matrix extracellular phosphoglycoprotein]; MERTK [c-mer proto-oncogene tyrosine kinase]; MESP2 [mesoderm posterior 2 homolog (mouse)];
MET [met proto-oncogene (hepatocyte growth factor receptor)]; MGAM [maltase-glucoamylase (alpha-glucosidase)]; MGAT1 [mannosyl (alpha-1,3-)-glycoprotein beta- 1,2-N-acetylglucosaminyltransferase]; MGAT2 [mannosyl (alpha-1,6+
glycoprotein beta-1,2-N-acetylglucosaminyltransferase]; MGLL [monoglyceride lipase]; MGMT [O-6-methylguanine-DNA methyltransferase]; MGST2 [microsomal glutathione S-transferase 2]; MICA [MHC class I polypeptide-related sequence A]; MICB [MHC class I polypeptide-related sequence B]; MIF
[macrophage migration inhibitory factor (glycosylation-inhibiting factor)];

[antigen identified by monoclonal antibody Ki-67]; MKS1 [Meckel syndrome, type 1]; MLH1 [mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)]; MLL
[myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila)];
MLLT4 [myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4]; MLN [motilin]; MLXIPL [MLX interacting protein-like]; MMAA [methylmalonic aciduria (cobalamin deficiency) cb1A type]; MMAB
[methylmalonic aciduria (cobalamin deficiency) cb1B type]; MMACHC
[methylmalonic aciduria (cobalamin deficiency) cblC type, with homocystinuria];
MME [membrane metallo-endopeptidase]; MMP1 [matrix metallopeptidase 1 (interstitial collagenase)]; MMP10 [matrix metallopeptidase 10 (stromelysin 2)];
MMP12 [matrix metallopeptidase 12 (macrophage elastase)]; MMP13 [matrix metallopeptidase 13 (collagenase 3)]; MMP14 [matrix metallopeptidase 14 (membrane-inserted)]; MMP15 [matrix metallopeptidase 15 (membrane-inserted)]; MMP17 [matrix metallopeptidase 17 (membrane-inserted)]; MMP2 [matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV
collagenase)]; MMP20 [matrix metallopeptidase 20]; MMP21 [matrix metallopeptidase 21]; MMP28 [matrix metallopeptidase 28]; MMP3 [matrix metallopeptidase 3 (stromelysin 1, progelatinase)]; MMP7 [matrix metallopeptidase 7 (matrilysin, uterine)]; MMP8 [matrix metallopeptidase 8 (neutrophil collagenase)]; MMP9 [matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)]; MMRN1 [multimerin 1]; MNAT1 [menage a trois homolog 1, cyclin H assembly factor (Xenopus laevis)]; MOG
[myelin oligodendrocyte glycoprotein]; MOGS [mannosyl-oligosaccharide glucosidase]; MPG [N-methylpurine-DNA glycosylase]; MPL [myeloproliferative leukemia virus oncogene]; MPO [myeloperoxidase]; MPZ [myelin protein zero];
MR1 [major histocompatibility complex, class I-related]; MRC1 [mannose receptor, C type 1]; MRC2 [mannose receptor, C type 2]; MRE1 1A [MRE1 1 meiotic recombination 11 homolog A (S. cerevisiae)]; MRGPRX1 [MAS-related GPR, member Xl]; MRPL28 [mitochondrial ribosomal protein L28]; MRPL40 [mitochondrial ribosomal protein L40]; MRPS16 [mitochondrial ribosomal protein S16]; MRPS22 [mitochondrial ribosomal protein S22]; MS4A1 [membrane-spanning 4-domains, subfamily A, member 1]; MS4A2 [membrane-spanning 4-domains, subfamily A, member 2 (Fc fragment of IgE, high affinity I, receptor for;
beta polypeptide)]; MS4A3 [membrane-spanning 4-domains, subfamily A, member 3 (hematopoietic cell-specific)]; MSH2 [mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)]; MSH5 [mutS homolog 5 (E. coli)]; MSH6 [mutS
homolog 6 (E. coli)]; MSLN [mesothelin]; MSN [moesin]; MSR1 [macrophage scavenger receptor 1]; MST1 [macrophage stimulating 1 (hepatocyte growth factor-like)]; MST1 R [macrophage stimulating 1 receptor (c-met-related tyrosine kinase)]; MSTN [myostatin]; MSX2 [msh homeobox 2]; MT2A [metallothionein 2A]; MTCH2 [mitochondrial carrier homolog 2 (C. elegans)]; MT-C02 [mitochondrially encoded cytochrome c oxidase II]; MTCP1 [mature T-cell proliferation 1]; MT-CYB [mitochondrially encoded cytochrome b]; MTHFD1 [m ethyl enetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase];
MTHFR [5 [10-methyl enetetrahydrofolate reductase (NADPH) ]; MTMR14 [myotubularin related protein 14]; MTMR2 [myotubularin related protein 2]; MT-ND1 [mitochondrially encoded NADH dehydrogenase 1]; MT-ND2 [mitochondrially encoded NADH dehydrogenase 2]; MTOR [mechanistic target of rapamycin (serine/threonine kinase)]; MTR [5-methyltetrahydrofolate-homocysteine methyltransferase]; MTRR [5-methyltetrahydrofolate-homocysteine methyltransferase reductase]; MTTP [microsomal triglyceride transfer protein];
MTX1 [metaxin 1]; MUC1 [mucin 1, cell surface associated]; MUC12 [mucin 12, cell surface associated]; MUC16 [mucin 16, cell surface associated]; MUC19 [mucin 19, oligomeric]; MUC2 [mucin 2, oligomeric mucus/gel-forming]; MUC3A
[mucin 3A, cell surface associated]; MUC3B [mucin 3B, cell surface associated];
MUC4 [mucin 4, cell surface associated]; MUC5AC [mucin SAC, oligomeric mucus/gel-forming]; MUCSB [mucin 5B, oligomeric mucus/gel-forming]; MUC6 [mucin 6, oligomeric mucus/gel-forming]; MUC7 [mucin 7, secreted]; MUS81 [MUS81 endonuclease homolog (S. cerevisiae)]; MUSK [muscle, skeletal, receptor tyrosine kinase]; MUT [methylmalonyl Coenzyme A mutase]; MVK
[mevalonate kinase]; MVP [major vault protein]; MX1 [myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse)]; MYB [v-myb myeloblastosis viral oncogene homolog (avian)]; MYBPH [myosin binding protein H]; MYC [v-myc myelocytomatosis viral oncogene homolog (avian)]; MYCN [v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)];
MYD88 [myeloid differentiation primary response gene (88)]; MYH1 [myosin, heavy chain 1, skeletal muscle, adult]; MYH10 [myosin, heavy chain 10, non-muscle]; MYH11 [myosin, heavy chain 11, smooth muscle]; MYH14 [myosin, heavy chain 14, non-muscle]; MYH2 [myosin, heavy chain 2, skeletal muscle, adult]; MYH3 [myosin, heavy chain 3, skeletal muscle, embryonic]; MYH6 [myosin, heavy chain 6, cardiac muscle, alpha]; MYH7 [myosin, heavy chain 7, cardiac muscle, beta]; MYH8 [myosin, heavy chain 8, skeletal muscle, perinatal];
MYH9 [myosin, heavy chain 9, non-muscle]; MYL2 [myosin, light chain 2, regulatory, cardiac, slow]; MYL3 [myosin, light chain 3, alkali; ventricular, skeletal, slow]; MYL7 [myosin, light chain 7, regulatory]; MYL9 [myosin, light chain 9, regulatory]; MYLK [myosin light chain kinase ]; MYO15A [myosin XVA];
MYO1A [myosin IA]; MYO1 F [myosin IF]; MYO3A [myosin IIIA]; MYO5A [myosin VA (heavy chain 12, myoxin)]; MYO6 [myosin VI]; MYO7A [myosin VIIA]; MYO9B
[myosin IXB]; MYOC [myocilin, trabecular meshwork inducible glucocorticoid response]; MYOD1 [myogenic differentiation 1]; MYOM2 [myomesin (M-protein) 2, 165kDa]; MYST1 [MYST histone acetyltransferase 1]; MYST2 [MYST histone acetyltransferase 2]; MYST3 [MYST histone acetyltransferase (monocytic leukemia) 3]; MYST4 [MYST histone acetyltransferase (monocytic leukemia) 4];
NAGA [N-acetylgalactosaminidase, alpha-]; NAGLU [N-acetylglucosaminidase, alpha-]; NAMPT [nicotinamide phosphoribosyltransferase]; NANOG [Nanog homeobox]; NANOS1 [nanos homolog 1 (Drosophila)]; NAPA [N-ethylmaleimide-sensitive factor attachment protein, alpha]; NAT1 [N-acetyltransferase 1 (arylamine N-acetyltransferase)]; NAT2 [N-acetyltransferase 2 (arylamine N-acetyltransferase)]; NAT9 [N-acetyltransferase 9 (GCN5-related, putative)];
NBEA [neurobeachin]; NBN [nibrin]; NCAM1 [neural cell adhesion molecule 1];
NCF1 [neutrophil cytosolic factor 1]; NCF2 [neutrophil cytosolic factor 2];

[neutrophil cytosolic factor 4, 40kDa]; NCK1 [NCK adaptor protein 1]; NCL
[nucleolin]; NCOA1 [nuclear receptor coactivator 1]; NCOA2 [nuclear receptor coactivator 2]; NCOR1 [nuclear receptor co-repressor 1 ]; NCR3 [natural cytotoxicity triggering receptor 3]; NDUFA13 [NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 13]; NDUFAB1 [NADH dehydrogenase (ubiquinone) 1, alpha/beta subcomplex, 1, 8kDa]; NDUFAF2 [NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, assembly factor 2]; NEDD4 [neural precursor cell expressed, developmentally down-regulated 4]; NEFL [neurofilament, light polypeptide]; NEFM [neurofilament, medium polypeptide]; NEGR1 [neuronal growth regulator 1]; NEK6 [NIMA (never in mitosis gene a)-related kinase 6];
NELF [nasal embryonic LHRH factor]; NELL1 [NEL-like 1 (chicken)]; NES
[nestin]; NEW [sialidase 1 (lysosomal sialidase)]; NEUROD1 [neurogenic differentiation 1]; NF1 [neurofibromin 1]; NF2 [neurofibromin 2 (merlin)];

[nuclear factor of activated T-cells 5, tonicity-responsive]; NFATC1 [nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1]; NFATC2 [nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2]; NFATC4 [nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4];
NFE2L2 [nuclear factor (erythroid-derived 2)-like 2]; NFKB1 [nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 ]; NFKB2 [nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)]; NFKBIA
[nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha];
NFKBIB [nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta]; NFKBIL1 [nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 1]; NFU1 [NFU1 iron-sulfur cluster scaffold homolog (S. cerevisiae)]; NGF [nerve growth factor (beta polypeptide)]; NGFR
[nerve growth factor receptor (TNFR superfamily, member 16)]; NHEJ1 [nonhomologous end-joining factor 1]; NID1 [nidogen 1]; NKAP [NFkB activating protein]; NKX2-1,NK2 homeobox 1]; NKX2-3 [NK2 transcription factor related, locus 3 (Drosophila)]; NLRP3 [NLR family, pyrin domain containing 3]; NMB
[neuromedin B]; NME1 [non-metastatic cells 1, protein (NM23A) expressed in];
NME2 [non-metastatic cells 2, protein (NM23B) expressed in]; NMU [neuromedin U]; NNAT [neuronatin]; NOD1 [nucleotide-binding oligomerization domain containing 1]; NOD2 [nucleotide-binding oligomerization domain containing 2];
NONO [non-POU domain containing, octamer-binding]; NOS1 [nitric oxide synthase 1 (neuronal)]; NOS2 [nitric oxide synthase 2, inducible]; NOS3 [nitric oxide synthase 3 (endothelial cell)]; NOTCH1 [Notch homolog 1, translocation-associated (Drosophila)]; NOTCH2 [Notch homolog 2 (Drosophila)]; NOTCH3 [Notch homolog 3 (Drosophila)]; NOTCH4 [Notch homolog 4 (Drosophila)]; NOX1 [NADPH oxidase 1]; NOX3 [NADPH oxidase 3]; NOX4 [NADPH oxidase 4];

NOX5 [NADPH oxidase, EF-hand calcium binding domain 5]; NPAT [nuclear protein, ataxia-telangiectasia locus]; NPC1 [Niemann-Pick disease, type Cl];
NPC1 L1 [NPC1 (Niemann-Pick disease, type C1, gene)-like 1]; NPC2 [Niemann-Pick disease, type C2]; NPHP1 [nephronophthisis 1 (juvenile)]; NPHS1 [nephrosis 1, congenital, Finnish type (nephrin)]; NPHS2 [nephrosis 2, idiopathic, steroid-resistant (podocin)]; NPLOC4 [nuclear protein localization 4 homolog (S.
cerevisiae)]; NPM1 [nucleophosmin (nucleolar phosphoprotein B23, numatrin)];
NPPA [natriuretic peptide precursor A]; NPPB [natriuretic peptide precursor B];
NPPC [natriuretic peptide precursor C]; NPR1 [natriuretic peptide receptor A/guanylate cyclase A (atrionatriuretic peptide receptor A)]; NPR3 [natriuretic peptide receptor C/guanylate cyclase C (atrionatriuretic peptide receptor C)];
NPS [neuropeptide S]; NPSR1 [neuropeptide S receptor 1]; NPY [neuropeptide Y]; NPY2R [neuropeptide Y receptor Y2]; NQO1 [NAD(P)H dehydrogenase, quinone 1]; NROB1 [nuclear receptor subfamily 0, group B, member 1]; NR1 H2 [nuclear receptor subfamily 1, group H, member 2]; NR1 H3 [nuclear receptor subfamily 1, group H, member 3]; NR1 H4 [nuclear receptor subfamily 1, group H, member 4]; NR112 [nuclear receptor subfamily 1, group I, member 2]; NR113 [nuclear receptor subfamily 1, group I, member 3]; NR2F2 [nuclear receptor subfamily 2, group F, member 2]; NR3C1 [nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor)]; NR3C2 [nuclear receptor subfamily 3, group C, member 2]; NR4A1 [nuclear receptor subfamily 4, group A, member 1];
NR4A3 [nuclear receptor subfamily 4, group A, member 3]; NR5A1 [nuclear receptor subfamily 5, group A, member 1]; NRF1 [nuclear respiratory factor 1];
NRG1 [neuregulin 1]; NRIP1 [nuclear receptor interacting protein 1]; NRIP2 [nuclear receptor interacting protein 2]; NRP1 [neuropilin 1]; NSD1 [nuclear receptor binding SET domain protein 1]; NSDHL [NAD(P) dependent steroid dehydrogenase-like]; NSF [N-ethylmaleimide-sensitive factor]; NT5E [5'-nucleotidase, ecto (CD73)]; NTAN1 [N-terminal asparagine amidase]; NTF3 [neurotrophin 3]; NTF4 [neurotrophin 4]; NTN1 [netrin 1]; NTRK1 [neurotrophic tyrosine kinase, receptor, type 1]; NTRK2 [neurotrophic tyrosine kinase, receptor, type 2]; NTRK3 [neurotrophic tyrosine kinase, receptor, type 3]; NTS
[neurotensin]; NUCB2 [nucleobindin 2]; NUDT1 [nudix (nucleoside diphosphate linked moiety X)-type motif 1]; NUDT2 [nudix (nucleoside diphosphate linked moiety X)-type motif 2]; NUDT6 [nudix (nucleoside diphosphate linked moiety X)-type motif 6]; NUFIP2 [nuclear fragile X mental retardation protein interacting protein 2]; NUP98 [nucleoporin 98kDa]; NXF1 [nuclear RNA export factor 1];
OCA2 [oculocutaneous albinism II]; OCLN [occludin]; ODC1 [ornithine decarboxylase 1]; OFD1 [oral-facial-digital syndrome 1]; OGDH [oxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide)]; OGG1 [8-oxoguanine DNA
glycosylase]; OGT [0-linked N-acetylglucosamine (GIcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase)]; OLR1 [oxidized low density lipoprotein (lectin-like) receptor 1]; OMP [olfactory marker protein]; ONECUT2 [one cut homeobox 2]; OPN3 [opsin 3]; OPRK1 [opioid receptor, kappa 1]; OPRM1 [opioid receptor, mu 1]; OPTN [optineurin]; OR2B11 [olfactory receptor, family 2, subfamily B, member 11]; ORMDL3 [ORM1-like 3 (S. cerevisiae)]; OSBP [oxysterol binding protein]; OSGIN2 [oxidative stress induced growth inhibitor family member 2]; OSM [oncostatin M]; OTC [ornithine carbamoyltransferase]; OTOP2 [otopetrin 2]; OTOP3 [otopetrin 3]; OTUD1 [OTU
domain containing 1]; OXA1 L [oxidase (cytochrome c) assembly 1-like]; OXER1 [oxoeicosanoid (OXE) receptor 1]; OXT [oxytocin, prepropeptide]; OXTR
[oxytocin receptor]; P2RX7 [purinergic receptor P2X, ligand-gated ion channel, 7]; P2RY1 [purinergic receptor P2Y, G-protein coupled, 1]; P2RY12 [purinergic receptor P2Y, G-protein coupled, 12]; P2RY14 [purinergic receptor P2Y, G-protein coupled, 14]; P2RY2 [purinergic receptor P2Y, G-protein coupled, 2];
P4HA2 [prolyl 4-hydroxylase, alpha polypeptide II]; P4HB [prolyl 4-hydroxylase, beta polypeptide]; P4HTM [prolyl 4-hydroxylase, transmembrane (endoplasmic reticulum)]; PABPC1 [poly(A) binding protein, cytoplasmic 1]; PACSIN3 [protein kinase C and casein kinase substrate in neurons 3]; PAEP [progestagen-associated endometrial protein]; PAFAH1B1 [platelet-activating factor acetylhydrolase 1 b, regulatory subunit 1 (45kDa)]; PAH [phenylalanine hydroxylase]; PAK1 [p21 protein (Cdc42/Rac)-activated kinase 1]; PAK2 [p21 protein (Cdc42/Rac)-activated kinase 2]; PAK3 [p21 protein (Cdc42/Rac)-activated kinase 3]; PAM [peptidylglycine alpha-amidating monooxygenase];
PAPPA [pregnancy-associated plasma protein A, pappalysin 1]; PARG [poly (ADP-ribose) glycohydrolase]; PARK2 [Parkinson disease (autosomal recessive, juvenile) 2, parkin]; PARP1 [poly (ADP-ribose) polymerase 1]; PAWR [PRKC, apoptosis, WT1, regulator]; PAX2 [paired box 2]; PAX3 [paired box 3]; PAX5 [paired box 5]; PAX6 [paired box 6]; PAXIP1 [PAX interacting (with transcription-activation domain) protein 1]; PC [pyruvate carboxylase]; PCCA [propionyl Coenzyme A carboxylase, alpha polypeptide]; PCCB [propionyl Coenzyme A
carboxylase, beta polypeptide]; PCDH1 [protocadherin 1]; PCK1 [phosphoenolpyruvate carboxykinase 1 (soluble)]; PCM1 [pericentriolar material 1]; PCNA [proliferating cell nuclear antigen ]; PCNT [pericentrin]; PCSK1 [proprotein convertase subtilisin/kexin type 1]; PCSK6 [proprotein convertase subtilisin/kexin type 6]; PCSK7 [proprotein convertase subtilisin/kexin type 7];
PCYT1A [phosphate cytidylyltransferase 1, choline, alpha]; PCYT2 [phosphate cytidylyltransferase 2, ethanolamine]; PDCD1 [programmed cell death 1];
PDCD1 LG2 [programmed cell death 1 ligand 2]; PDCD6 [programmed cell death 6]; PDE3B [phosphodiesterase 3B, cGMP-inhibited]; PDE4A [phosphodiesterase 4A, cAMP-specific (phosphodiesterase E2 dunce homolog, Drosophila)]; PDE4B
[phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)]; PDE4D [phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila)]; PDE7A [phosphodiesterase 7A]; PDGFA
[platelet-derived growth factor alpha polypeptide]; PDGFB [platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog)];
PDGFRA [platelet-derived growth factor receptor, alpha polypeptide]; PDGFRB
[platelet-derived growth factor receptor, beta polypeptide]; PDIA2 [protein disulfide isomerase family A, member 2]; PDIA3 [protein disulfide isomerase family A, member 3]; PDK1 [pyruvate dehydrogenase kinase, isozyme 1 ];
PDLIM1 [PDZ and LIM domain 1]; PDLIM5 [PDZ and LIM domain 5]; PDLIM7 [PDZ and LIM domain 7 (enigma)]; PDP1 [pyruvate dehyrogenase phosphatase catalytic subunit 1]; PDX1 [pancreatic and duodenal homeobox 1]; PDXK
[pyridoxal (pyridoxine, vitamin B6) kinase]; PDYN [prodynorphin]; PECAM1 [platelet/endothelial cell adhesion molecule]; PEMT [phosphatidylethanolamine N-methyltransferase]; PENK [proenkephalin]; PEPD [peptidase D]; PER1 [period homolog 1 (Drosophila)]; PEX1 [peroxisomal biogenesis factor 1]; PEX10 [peroxisomal biogenesis factor 10]; PEX12 [peroxisomal biogenesis factor 12];
PEX13 [peroxisomal biogenesis factor 13]; PEX14 [peroxisomal biogenesis factor 14]; PEX16 [peroxisomal biogenesis factor 16]; PEX19 [peroxisomal biogenesis factor 19]; PEX2 [peroxisomal biogenesis factor 2]; PEX26 [peroxisomal biogenesis factor 26]; PEX3 [peroxisomal biogenesis factor 3];
PEX5 [peroxisomal biogenesis factor 5]; PEX6 [peroxisomal biogenesis factor 6];
PEX7 [peroxisomal biogenesis factor 7]; PF4 [platelet factor 4]; PFAS
[phosphoribosylformylglycinamidine synthase]; PFDN4 [prefoldin subunit 4];
PFN1 [profilin 1]; PGC [progastricsin (pepsinogen C)]; PGD [phosphogluconate dehydrogenase]; PGF [placental growth factor]; PGK1 [phosphoglycerate kinase 1]; PGM1 [phosphoglucomutase 1]; PGR [progesterone receptor]; PHB
[prohibitin]; PHEX [phosphate regulating endopeptidase homolog, X-linked];
PHF11 [PHD finger protein 11]; PHOX2B [paired-like homeobox 2b]; PHTF1 [putative homeodomain transcription factor 1]; PHYH [phytanoyl-CoA 2-hydroxylase]; PHYHIP [phytanoyl-CoA 2-hydroxylase interacting protein]; P13 [peptidase inhibitor 3, skin-derived]; PIGA [phosphatidylinositol glycan anchor biosynthesis, class A]; PIGR [polymeric immunoglobulin receptor]; PIK3C2A
[phosphoinositide-3-kinase, class 2, alpha polypeptide]; PIK3C2B
[phosphoinositide-3-kinase, class 2, beta polypeptide]; PIK3C2G
[phosphoinositide-3-kinase, class 2, gamma polypeptide]; PIK3C3 [phosphoinositide-3-kinase, class 3]; PIK3CA [phosphoinositide-3-kinase, catalytic, alpha polypeptide]; PIK3CB [phosphoinositide-3-kinase, catalytic, beta polypeptide]; PIK3CD [phosphoinositide-3-kinase, catalytic, delta polypeptide];
PIK3CG [phosphoinositide-3-kinase, catalytic, gamma polypeptide]; PIK3R1 [phosphoinositide-3-kinase, regulatory subunit 1 (alpha)]; PIK3R2 [phosphoinositide-3-kinase, regulatory subunit 2 (beta)]; PIK3R3 [phosphoinositide-3-kinase, regulatory subunit 3 (gamma)]; PIKFYVE
[phosphoinositide kinase, FYVE finger containing]; PIN1 [peptidylprolyl cis/trans isomerase, NIMA-interacting 1]; PINK1 [PTEN induced putative kinase 1]; PIP
[prolactin-induced protein]; PIP5KL1 [phosphatidylinositol-4-phosphate 5-kinase-like 1]; PITPNM1 [phosphatidylinositol transfer protein, membrane-associated 1];
PITRM1 [pitrilysin metallopeptidase 1]; PITX2 [paired-like homeodomain 2];
PKD2 [polycystic kidney disease 2 (autosomal dominant)]; PKLR [pyruvate kinase, liver and RBC]; PKM2 [pyruvate kinase, muscle]; PKN1 [protein kinase Ni]; PL-5283 [PL-5283 protein]; PLA2G1B [phospholipase A2, group IB
(pancreas)]; PLA2G2A [phospholipase A2, group IIA (platelets, synovial fluid)];
PLA2G2D [phospholipase A2, group IID]; PLA2G4A [phospholipase A2, group IVA (cytosolic, calcium-dependent)]; PLA2G6 [phospholipase A2, group VI
(cytosolic, calcium-independent)]; PLA2G7 [phospholipase A2, group VII
(platelet-activating factor acetylhydrolase, plasma)]; PLA2R1 [phospholipase receptor 1, 180kDa]; PLAT [plasminogen activator, tissue]; PLAU [plasminogen activator, urokinase]; PLAUR [plasminogen activator, urokinase receptor];

[phospholipase C, beta 1 (phosphoinositide-specific)]; PLCB2 [phospholipase C, beta 2]; PLCB4 [phospholipase C, beta 4]; PLCD1 [phospholipase C, delta 1];
PLCG1 [phospholipase C, gamma 1]; PLCG2 [phospholipase C, gamma 2 (phosphatidylinositol-specific)]; PLD1 [phospholipase D1, phosphatidylcholine-specific]; PLEC [plectin]; PLEK [pleckstrin]; PLG [plasminogen]; PLIN1 [perilipin 1]; PLK1 [polo-like kinase 1 (Drosophila)]; PLK2 [polo-like kinase 2 (Drosophila)];
PLK3 [polo-like kinase 3 (Drosophila)]; PLP1 [proteolipid protein 1]; PLTP
[phospholipid transfer protein]; PMAIP1 [phorbol-1 2-myristate-1 3-acetate-induced protein 1]; PMCH [pro-melanin-concentrating hormone]; PML
[promyelocytic leukemia]; PMP22 [peripheral myelin protein 22]; PMS2 [PMS2 postmeiotic segregation increased 2 (S. cerevisiae)]; PNLIP [pancreatic lipase];
PNMA3 [paraneoplastic antigen MA3]; PNMT [phenylethanolamine N-methyltransferase]; PNP [purine nucleoside phosphorylase]; POLB [polymerase (DNA directed), beta]; POLD3 [polymerase (DNA-directed), delta 3, accessory subunit]; POLD4 [polymerase (DNA-directed), delta 4]; POLH [polymerase (DNA
directed), eta]; POLL [polymerase (DNA directed), lambda]; POLR2A
[polymerase (RNA) II (DNA directed) polypeptide A, 220kDa]; POLR2B
[polymerase (RNA) II (DNA directed) polypeptide B, 140kDa]; POLR2C
[polymerase (RNA) II (DNA directed) polypeptide C, 33kDa]; POLR2D
[polymerase (RNA) II (DNA directed) polypeptide D]; POLR2E [polymerase (RNA) II (DNA directed) polypeptide E, 25kDa]; POLR2F [polymerase (RNA) II
(DNA directed) polypeptide F]; POLR2G [polymerase (RNA) II (DNA directed) polypeptide G]; POLR2H [polymerase (RNA) II (DNA directed) polypeptide H];
POLR2I [polymerase (RNA) II (DNA directed) polypeptide I, 14.5kDa]; POLR2J
[polymerase (RNA) II (DNA directed) polypeptide J, 13.3kDa]; POLR2K
[polymerase (RNA) II (DNA directed) polypeptide K, 7.OkDa]; POLR2L
[polymerase (RNA) II (DNA directed) polypeptide L, 7.6kDa]; POMC
[proopiomelanocortin]; POMT1 [protein-O-mannosyltransferase 1]; PON1 [paraoxonase 1]; PON2 [paraoxonase 2]; PON3 [paraoxonase 3]; POSTN
[periostin, osteoblast specific factor]; POT1 [POT1 protection of telomeres 1 homolog (S. pombe)]; POU2AF1 [POU class 2 associating factor 1]; POU2F1 [POU class 2 homeobox 1]; POU2F2 [POU class 2 homeobox 2]; POU5F1 [POU
class 5 homeobox 1]; PPA1 [pyrophosphatase (inorganic) 1]; PPARA
[peroxisome proliferator-activated receptor alpha]; PPARD [peroxisome proliferator-activated receptor delta]; PPARG [peroxisome proliferator-activated receptor gamma]; PPARGC1A [peroxisome proliferator-activated receptor gamma, coactivator 1 alpha]; PPAT [phosphoribosyl pyrophosphate amidotransferase]; PPBP [pro-platelet basic protein (chemokine (C-X-C motif) ligand 7)]; PPFIA1 [protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 1]; PPIA [peptidylprolyl isomerase A
(cyclophilin A)]; PPIB [peptidylprolyl isomerase B (cyclophilin B)]; PPIG
[peptidylprolyl isomerase G (cyclophilin G)]; PPOX [protoporphyrinogen oxidase];

PPP1 CB [protein phosphatase 1, catalytic subunit, beta isozyme]; PPP1 R1 2A
[protein phosphatase 1, regulatory (inhibitor) subunit 12A]; PPP1R2 [protein phosphatase 1, regulatory (inhibitor) subunit 2]; PPP2R1 B [protein phosphatase 2, regulatory subunit A, beta]; PPP2R2B [protein phosphatase 2, regulatory subunit B, beta]; PPP2R4 [protein phosphatase 2A activator, regulatory subunit 4]; PPP6C [protein phosphatase 6, catalytic subunit]; PPT1 [palmitoyl-protein thioesterase 1]; PPY [pancreatic polypeptide]; PRDM1 [PR domain containing 1, with ZNF domain]; PRDM2 [PR domain containing 2, with ZNF domain]; PRDX2 [peroxiredoxin 2]; PRDX3 [peroxiredoxin 3]; PRDX5 [peroxiredoxin 5]; PRF1 [perforin 1 (pore forming protein)]; PRG2 [proteoglycan 2, bone marrow (natural killer cell activator, eosinophil granule major basic protein)]; PRG4 [proteoglycan 4]; PRIM1 [primase, DNA, polypeptide 1 (49kDa)]; PRKAA1 [protein kinase, AMP-activated, alpha 1 catalytic subunit]; PRKAA2 [protein kinase, AMP-activated, alpha 2 catalytic subunit]; PRKAB1 [protein kinase, AMP-activated, beta 1 non-catalytic subunit]; PRKACA [protein kinase, cAMP-dependent, catalytic, alpha]; PRKACB [protein kinase, cAMP-dependent, catalytic, beta];
PRKACG [protein kinase, cAMP-dependent, catalytic, gamma]; PRKAR1A
[protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)]; PRKAR2A [protein kinase, cAMP-dependent, regulatory, type II, alpha]; PRKAR2B [protein kinase, cAMP-dependent, regulatory, type II, beta];
PRKCA [protein kinase C, alpha]; PRKCB [protein kinase C, beta]; PRKCD
[protein kinase C, delta]; PRKCE [protein kinase C, epsilon]; PRKCG [protein kinase C, gamma]; PRKCH [protein kinase C, eta]; PRKCI [protein kinase C, iota]; PRKCQ [protein kinase C, theta]; PRKCZ [protein kinase C, zeta]; PRKD1 [protein kinase D1]; PRKD3 [protein kinase D3]; PRKDC [protein kinase, DNA-activated, catalytic polypeptide; also known as DNAPK]; PRKG1 [protein kinase, cGMP-dependent, type I]; PRKRIR [protein-kinase, interferon-inducible double stranded RNA dependent inhibitor, repressor of (P58 repressor)]; PRL
[prolactin];
PRLR [prolactin receptor]; PRNP [prion protein]; PROC [protein C (inactivator of coagulation factors Va and Villa)]; PRODH [proline dehydrogenase (oxidase) 1];

PROK1 [prokineticin 1]; PROK2 [prokineticin 2]; PROM1 [prominin 1]; PROS1 [protein S (alpha)]; PRPH [peripherin]; PRSS1 [protease, serine, 1 (trypsin 1)];
PRSS2 [protease, serine, 2 (trypsin 2)]; PRSS21 [protease, serine, 21 (testisin)];
PRSS3 [protease, serine, 3]; PRTN3 [proteinase 3]; PSAP [prosaposin]; PSEN1 [presenilin 1]; PSEN2 [presenilin 2 (Alzheimer disease 4)]; PSMA1 [proteasome (prosome, macropain) subunit, alpha type, 1]; PSMA2 [proteasome (prosome, macropain) subunit, alpha type, 2]; PSMA3 [proteasome (prosome, macropain) subunit, alpha type, 3]; PSMA5 [proteasome (prosome, macropain) subunit, alpha type, 5]; PSMA6 [proteasome (prosome, macropain) subunit, alpha type, 6]; PSMA7 [proteasome (prosome, macropain) subunit, alpha type, 7]; PSMB10 [proteasome (prosome, macropain) subunit, beta type, 10]; PSMB2 [proteasome (prosome, macropain) subunit, beta type, 2]; PSMB4 [proteasome (prosome, macropain) subunit, beta type, 4]; PSMB5 [proteasome (prosome, macropain) subunit, beta type, 5]; PSMB6 [proteasome (prosome, macropain) subunit, beta type, 6]; PSMB8 [proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7)]; PSMB9 [proteasome (prosome, macropain) subunit, beta type, 9 (large multifunctional peptidase 2)]; PSMC3 [proteasome (prosome, macropain) 26S subunit, ATPase, 3]; PSMC4 [proteasome (prosome, macropain) 26S subunit, ATPase, 4]; PSMC6 [proteasome (prosome, macropain) 26S subunit, ATPase, 6]; PSMD4 [proteasome (prosome, macropain) 26S
subunit, non-ATPase, 4]; PSMD9 [proteasome (prosome, macropain) 26S
subunit, non-ATPase, 9]; PSME1 [proteasome (prosome, macropain) activator subunit 1 (PA28 alpha)]; PSME3 [proteasome (prosome, macropain) activator subunit 3 (PA28 gamma; Ki)]; PSMG2 [proteasome (prosome, macropain) assembly chaperone 2]; PSORS1C1 [psoriasis susceptibility 1 candidate 1];
PSTPIP1 [proline-serine-threonine phosphatase interacting protein 1]; PTAFR
[platelet-activating factor receptor]; PTBP1 [polypyrimidine tract binding protein 1]; PTCH1 [patched homolog 1 (Drosophila)]; PTEN [phosphatase and tensin homolog]; PTGDR [prostaglandin D2 receptor (DP)]; PTGDS [prostaglandin D2 synthase 21 kDa (brain)]; PTGER1 [prostaglandin E receptor 1 (subtype EP1), 42kDa]; PTGER2 [prostaglandin E receptor 2 (subtype EP2), 53kDa]; PTGER3 [prostaglandin E receptor 3 (subtype EP3)]; PTGER4 [prostaglandin E receptor 4 (subtype EP4)]; PTGES [prostaglandin E synthase]; PTGFR [prostaglandin F
receptor (FP)]; PTGIR [prostaglandin 12 (prostacyclin) receptor (IP)]; PTGS1 [prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase)]; PTGS2 [prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)]; PTH [parathyroid hormone];
PTHLH [parathyroid hormone-like hormone]; PTK2 [PTK2 protein tyrosine kinase 2]; PTK2B [PTK2B protein tyrosine kinase 2 beta]; PTK7 [PTK7 protein tyrosine kinase 7]; PTMS [parathymosin]; PTN [pleiotrophin]; PTPN1 [protein tyrosine phosphatase, non-receptor type 1]; PTPN11 [protein tyrosine phosphatase, non-receptor type 11]; PTPN12 [protein tyrosine phosphatase, non-receptor type 12];
PTPN2 [protein tyrosine phosphatase, non-receptor type 2]; PTPN22 [protein tyrosine phosphatase, non-receptor type 22 (lymphoid)]; PTPN6 [protein tyrosine phosphatase, non-receptor type 6]; PTPRC [protein tyrosine phosphatase, receptor type, C]; PTPRD [protein tyrosine phosphatase, receptor type, D];
PTPRE [protein tyrosine phosphatase, receptor type, E]; PTPRJ [protein tyrosine phosphatase, receptor type, J]; PTPRN [protein tyrosine phosphatase, receptor type, N]; PTPRT [protein tyrosine phosphatase, receptor type, T]; PTPRU
[protein tyrosine phosphatase, receptor type, U]; PTRF [polymerase I and transcript release factor]; PTS [6-pyruvoyltetrahydropterin synthase]; PTTG1 [pituitary tumor-transforming 1]; PTX3 [pentraxin 3, long]; PUS10 [pseudouridylate synthase 10]; PXK [PX domain containing serine/threonine kinase]; PXN [paxillin]; PYCR1 [pyrroline-5-carboxylate reductase 1]; PYCR2 [pyrroline-5-carboxylate reductase family, member 2]; PYGB [phosphorylase, glycogen; brain]; PYGM [phosphorylase, glycogen, muscle]; PYY [peptide YY];
PZP [pregnancy-zone protein]; QDPR [quinoid dihydropteridine reductase];
RAB1 1A [RAB11A, member RAS oncogene family]; RAB1 1 FIP1 [RAB1 1 family interacting protein 1 (class I)]; RAB27A [RAB27A, member RAS oncogene family]; RAB37 [RAB37, member RAS oncogene family]; RAB39 [RAB39, member RAS oncogene family]; RAB7A [RAB7A, member RAS oncogene family]; RAB9A [RAB9A, member RAS oncogene family]; RAC1 [ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)];

[ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2)]; RAD17 [RAD17 homolog (S. pombe)]; RAD50 [RAD50 homolog (S.
cerevisiae)]; RAD51 [RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae)];
RAD51 C [RAD51 homolog C (S. cerevisiae)]; RAD51 L1 [RAD51-like 1 (S.
cerevisiae)]; RAD51L3 [RAD51 -like 3 (S. cerevisiae)]; RAD54L [RAD54-like (S.
cerevisiae)]; RAD9A [RAD9 homolog A (S. pombe)]; RAF1 [v-raf-1 murine leukemia viral oncogene homolog 1]; RAG1 [recombination activating gene 1];
RAG2 [recombination activating gene 2]; RAN [RAN, member RAS oncogene family]; RANBP1 [RAN binding protein 1]; RAP1A [RAP1A, member of RAS
oncogene family]; RAPGEF4 [Rap guanine nucleotide exchange factor (GEF) 4];
RARA [retinoic acid receptor, alpha]; RARB [retinoic acid receptor, beta];
RARG
[retinoic acid receptor, gamma]; RARRES2 [retinoic acid receptor responder (tazarotene induced) 2]; RARS [arginyl-tRNA synthetase]; RASA1 [RAS p21 protein activator (GTPase activating protein) 1]; RASGRP1 [RAS guanyl releasing protein 1 (calcium and DAG-regulated)]; RASGRP2 [RAS guanyl releasing protein 2 (calcium and DAG-regulated)]; RASGRP4 [RAS guanyl releasing protein 4]; RASSF1 [Ras association (RaIGDS/AF-6) domain family member 1]; RB1 [retinoblastoma 1]; RBBP4 [retinoblastoma binding protein 4];
RBBP8 [retinoblastoma binding protein 8]; RBL1 [retinoblastoma-like 1 (p107)];
RBL2 [retinoblastoma-like 2 (p130)]; RBP4 [retinol binding protein 4, plasma];
RBX1 [ring-box 1 ]; RCBTB1 [regulator of chromosome condensation (RCC1) and BTB (POZ) domain containing protein 1]; RCN1 [reticulocalbin 1, EF-hand calcium binding domain]; RCN2 [reticulocalbin 2, EF-hand calcium binding domain]; RDX [radixin]; RECK [reversion-inducing-cysteine-rich protein with kazal motifs]; RECQL [RecQ protein-like (DNA helicase Q1-like)]; RECQL4 [RecQ protein-like 4]; RECQL5 [RecQ protein-like 5]; REG1A [regenerating islet-derived 1 alpha]; REG3A [regenerating islet-derived 3 alpha]; REG4 [regenerating islet-derived family, member 4]; REL [v-rel reticuloendotheliosis viral oncogene homolog (avian)]; RELA [v-rel reticuloendotheliosis viral oncogene homolog A (avian)]; RELB [v-rel reticuloendotheliosis viral oncogene homolog B]; REN [renin]; RET [ret proto-oncogene]; RETN [resistin]; RETNLB
[resistin like beta]; RFC1 [replication factor C (activator 1) 1, 145kDa];

[replication factor C (activator 1) 2, 40kDa]; RFC3 [replication factor C
(activator 1) 3, 38kDa]; RFX1 [regulatory factor X, 1 (influences HLA class II
expression)];
RFX5 [regulatory factor X, 5 (influences HLA class II expression)]; RFXANK
[regulatory factor X-associated ankyrin-containing protein]; RFXAP [regulatory factor X-associated protein]; RGS1 8 [regulator of G-protein signaling 18];
RHAG
[Rh-associated glycoprotein]; RHD [Rh blood group, D antigen]; RHO
[rhodopsin]; RHOA [ras homolog gene family, member A]; RHOD [ras homolog gene family, member D]; RIF1 [RAP1 interacting factor homolog (yeast)]; RIPK1 [receptor (TNFRSF)-interacting serine-threonine kinase 1]; RIPK2 [receptor-interacting serine-threonine kinase 2]; RLBP1 [retinaldehyde binding protein 1];
RLN1 [relaxin 1]; RLN2 [relaxin 2]; RMI1 [RMI1, RecQ mediated genome instability 1, homolog (S. cerevisiae)]; RNASE1 [ribonuclease, RNase A family, (pancreatic)]; RNASE2 [ribonuclease, RNase A family, 2 (liver, eosinophil-derived neurotoxin)]; RNASE3 [ribonuclease, RNase A family, 3 (eosinophil cationic protein)]; RNASEH1 [ribonuclease H1]; RNASEH2A [ribonuclease H2, subunit A]; RNASEL [ribonuclease L (2' [5'-oligoisoadenylate synthetase-dependent)]; RNASEN [ribonuclease type III, nuclear]; RNF123 [ring finger protein 123]; RNF13 [ring finger protein 13]; RNF135 [ring finger protein 135];
RNF138 [ring finger protein 138]; RNF4 [ring finger protein 4]; RNH1 [ribonuclease/angiogenin inhibitor 1]; RNPC3 [RNA-binding region (RNP1, RRM) containing 3]; RNPEP [arginyl aminopeptidase (aminopeptidase B)]; ROCK1 [Rho-associated, coiled-coil containing protein kinase 1]; ROM1 [retinal outer segment membrane protein 1]; ROR2 [receptor tyrosine kinase-like orphan receptor 2]; RORA [RAR-related orphan receptor A]; RPA1 [replication protein Al, 70kDa]; RPA2 [replication protein A2, 32kDa]; RPGRIP1L [RPGRIP1 -like];

RPLP1 [ribosomal protein, large, P1]; RPS19 [ribosomal protein S19]; RPS6KA3 [ribosomal protein S6 kinase, 90kDa, polypeptide 3]; RPS6KB1 [ribosomal protein S6 kinase, 70kDa, polypeptide 1]; RPSA [ribosomal protein SA]; RRBP1 [ribosome binding protein 1 homolog 180kDa (dog)]; RRM1 [ribonucleotide reductase M1]; RRM2B [ribonucleotide reductase M2 B (TP53 inducible)];
RUNX1 [runt-related transcription factor 1]; RUNX3 [runt-related transcription factor 3]; RXRA [retinoid X receptor, alpha]; RXRB [retinoid X receptor, beta];
RYR1 [ryanodine receptor 1 (skeletal)]; RYR3 [ryanodine receptor 3]; S100A1 [S100 calcium binding protein Al]; S100A12 [S100 calcium binding protein A12];
S100A4 [S100 calcium binding protein A4]; S100A7 [S100 calcium binding protein A7]; S100A8 [S100 calcium binding protein A8]; S100A9 [S100 calcium binding protein A9]; S100B [S100 calcium binding protein B]; S100G [S100 calcium binding protein G]; S1 PR1 [sphingosine-l -phosphate receptor 1 ];

[serum amyloid Al]; SAA4 [serum amyloid A4, constitutive]; SAFB [scaffold attachment factor B]; SAG [S-antigen; retina and pineal gland (arrestin)];

[sarcoma antigen 1]; SARDH [sarcosine dehydrogenase]; SART3 [squamous cell carcinoma antigen recognized by T cells 3]; SBDS [Shwachman-Bodian-Diamond syndrome]; SBNO2 [strawberry notch homolog 2 (Drosophila)];
SCAMP3 [secretory carrier membrane protein 3]; SOAP [SREBF chaperone];
SCARB1 [scavenger receptor class B, member 1]; SCD [stearoyl-CoA
desaturase (delta-9-desaturase)]; SCG2 [secretogranin II]; SCG3 [secretogranin III]; SCG5 [secretogranin V (7B2 protein)]; SCGB1A1 [secretoglobin, family 1A, member 1 (uteroglobin) ]; SCGB3A2 [secretoglobin, family 3A, member 2];
SCN4A [sodium channel, voltage-gated, type IV, alpha subunit]; SCNN1A
[sodium channel, nonvoltage-gated 1 alpha]; SCNN1G [sodium channel, nonvoltage-gated 1, gamma]; SCO1 [SCO cytochrome oxidase deficient homolog 1 (yeast)]; SC02 [SCO cytochrome oxidase deficient homolog 2 (yeast)]; SCP2 [sterol carrier protein 2]; SCT [secretin]; SDC1 [syndecan 1];
SDC2 [syndecan 2]; SDC4 [syndecan 4]; SDHB [succinate dehydrogenase complex, subunit B, iron sulfur (Ip)]; SDHD [succinate dehydrogenase complex, subunit D, integral membrane protein]; SEC14L2 [SEC14-like 2 (S. cerevisiae)];
SEC16A [SEC16 homolog A (S. cerevisiae)]; SEC23B [Sec23 homolog B (S.
cerevisiae)]; SELE [selectin E]; SELL [selectin L]; SELP [selectin P (granule membrane protein 140kDa, antigen CD62)]; SELPLG [selectin P ligand]; SEPT5 [septin 5]; SEPP1 [selenoprotein P, plasma, 1]; SEPSECS [Sep (0-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase]; SERBP1 [SERPINE1 mRNA binding protein 1]; SERPINA1 [serpin peptidase inhibitor, Glade A (alpha-1 antiproteinase, antitrypsin), member 1]; SERPINA2 [serpin peptidase inhibitor, Glade A (alpha-1 antiproteinase, antitrypsin), member 2];
SERPINA3 [serpin peptidase inhibitor, Glade A (alpha-1 antiproteinase, antitrypsin), member 3]; SERPINA5 [serpin peptidase inhibitor, Glade A (alpha-antiproteinase, antitrypsin), member 5]; SERPINA6 [serpin peptidase inhibitor, Glade A (alpha-1 antiproteinase, antitrypsin), member 6]; SERPINA7 [serpin peptidase inhibitor, Glade A (alpha-1 antiproteinase, antitrypsin), member 7];
SERPINBI [serpin peptidase inhibitor, Glade B (ovalbumin), member 1];
SERPINB2 [serpin peptidase inhibitor, Glade B (ovalbumin), member 2];
SERPINB3 [serpin peptidase inhibitor, Glade B (ovalbumin), member 3];
SERPINB4 [serpin peptidase inhibitor, Glade B (ovalbumin), member 4];
SERPINB5 [serpin peptidase inhibitor, Glade B (ovalbumin), member 5];
SERPINB6 [serpin peptidase inhibitor, Glade B (ovalbumin), member 6];
SERPINB9 [serpin peptidase inhibitor, Glade B (ovalbumin), member 9];
SERPINCI [serpin peptidase inhibitor, Glade C (antithrombin), member 1];
SERPINDI [serpin peptidase inhibitor, Glade D (heparin cofactor), member 1];
SERPINEI [serpin peptidase inhibitor, Glade E (nexin, plasminogen activator inhibitor type 1), member 1 ]; SERPINE2 [serpin peptidase inhibitor, Glade E
(nexin, plasminogen activator inhibitor type 1), member 2]; SERPINF2 [serpin peptidase inhibitor, Glade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 2]; SERPINGI [serpin peptidase inhibitor, Glade G (Cl inhibitor), member 1]; SERPINHI [serpin peptidase inhibitor, Glade H (heat shock protein 47), member 1, (collagen binding protein 1)]; SET [SET nuclear oncogene];

SETDB2 [SET domain, bifurcated 2]; SETX [senataxin]; SFPQ [splicing factor proline/glutamine-rich (polypyrimidine tract binding protein associated)];

[secreted frizzled-related protein 1]; SFRP2 [secreted frizzled-related protein 2];
SFRP5 [secreted frizzled-related protein 5]; SFTPA1 [surfactant protein Al];
SFTPB [surfactant protein B]; SFTPC [surfactant protein C]; SFTPD [surfactant protein D]; SGCA [sarcoglycan, alpha (50kDa dystrophin-associated glycoprotein)]; SGCB [sarcoglycan, beta (43kDa dystrophin-associated glycoprotein)]; SGK1 [serum/glucocorticoid regulated kinase 1]; SGSH [N-sulfoglucosamine sulfohydrolase]; SGTA [small glutamine-rich tetratricopeptide repeat (TPR)-containing, alpha]; SH2B1 [SH2B adaptor protein 1]; SH2B3 [SH2B
adaptor protein 3]; SH2D1A [SH2 domain containing 1A]; SH2D4B [SH2 domain containing 4B]; SH3KBP1 [SH3-domain kinase binding protein 1]; SHBG [sex hormone-binding globulin]; SHC1 [SHC (Src homology 2 domain containing) transforming protein 1]; SHH [sonic hedgehog homolog (Drosophila)]; SHMT2 [serine hydroxymethyltransferase 2 (mitochondrial)]; SI [sucrase-isomaltase (alpha-glucosidase)]; SIGIRR [single immunoglobulin and toll-interleukin 1 receptor (TIR) domain]; SIP1 [survival of motor neuron protein interacting protein 1]; SIPA1 [signal-induced proliferation-associated 1]; SIRPA [signal-regulatory protein alpha]; SIRPB2 [signal-regulatory protein beta 2]; SIRT1 [sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae)]; SKIV2L
[superkiller viralicidic activity 2-like (S. cerevisiae)]; SKP2 [S-phase kinase-associated protein 2 (p45)]; SLAMFI [signaling lymphocytic activation molecule family member 1]; SLAMF6 [SLAM family member 6]; SLC11A1 [solute carrier family 11 (proton-coupled divalent metal ion transporters), member 1]; SLC11A2 [solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2]; SLC1 2A1 [solute carrier family 12 (sodium/potassium/chloride transporters), member 1]; SLC12A2 [solute carrier family 12 (sodium/potassium/chloride transporters), member 2]; SLC14A1 [solute carrier family 14 (urea transporter), member 1 (Kidd blood group)]; SLC15A1 [solute carrier family 15 (oligopeptide transporter), member 1 ]; SLC16A1 [solute carrier family 16, member 1 (monocarboxylic acid transporter 1)]; SLC17A5 [solute carrier family 17 (anion/sugar transporter), member 5]; SLC1 7A6 [solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 6]; SLC17A7 [solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 7]; SLC19A1 [solute carrier family 19 (folate transporter), member 1];
SLC1A1 [solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1]; SLC1A2 [solute carrier family 1 (glial high affinity glutamate transporter), member 2]; SLC1A4 [solute carrier family 1 (glutamate/neutral amino acid transporter), member 4]; SLC22A1 2 [solute carrier family 22 (organic anion/urate transporter), member 12]; SLC22A2 [solute carrier family 22 (organic cation transporter), member 2]; SLC22A23 [solute carrier family 22, member 23]; SLC22A3 [solute carrier family 22 (extraneuronal monoamine transporter), member 3]; SLC22A4 [solute carrier family 22 (organic cation/ergothioneine transporter), member 4]; SLC22A5 [solute carrier family (organic cation/carnitine transporter), member 5]; SLC22A6 [solute carrier family 22 (organic anion transporter), member 6]; SLC24A2 [solute carrier family 24 (sodium/potassium/calcium exchanger), member 2]; SLC25A1 [solute carrier family 25 (mitochondrial carrier; citrate transporter), member 1]; SLC25A20 [solute carrier family 25 (carnitine/acylcarnitine translocase), member 20];
SLC25A3 [solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 3]; SLC25A32 [solute carrier family 25, member 32]; SLC25A33 [solute carrier family 25, member 33]; SLC25A4 [solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4]; SLC26A4 [solute carrier family 26, member 4]; SLC27A4 [solute carrier family 27 (fatty acid transporter), member 4]; SLC28A1 [solute carrier family 28 (sodium-coupled nucleoside transporter), member 1]; SLC2A1 [solute carrier family 2 (facilitated glucose transporter), member 1]; SLC2A13 [solute carrier family 2 (facilitated glucose transporter), member 13]; SLC2A3 [solute carrier family 2 (facilitated glucose transporter), member 3]; SLC2A4 [solute carrier family 2 (facilitated glucose transporter), member 4]; SLC30A1 [solute carrier family 30 (zinc transporter), member 1]; SLC30A8 [solute carrier family 30 (zinc transporter), member 8];
SLC31A1 [solute carrier family 31 (copper transporters), member 1]; SLC35A1 [solute carrier family 35 (CMP-sialic acid transporter), member Al]; SLC35A2 [solute carrier family 35 (UDP-galactose transporter), member A2]; SLC35C1 [solute carrier family 35, member C1 ]; SLC35F2 [solute carrier family 35, member F2]; SLC39A3 [solute carrier family 39 (zinc transporter), member 3];
SLC3A2 [solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2]; SLC46A1 [solute carrier family 46 (folate transporter), member 1]; SLC5A5 [solute carrier family 5 (sodium iodide symporter), member 5]; SLC6A1 1 [solute carrier family 6 (neurotransmitter transporter, GABA), member 11]; SLC6A14 [solute carrier family 6 (amino acid transporter), member 14]; SLC6A19 [solute carrier family 6 (neutral amino acid transporter), member 19]; SLC6A3 [solute carrier family 6 (neurotransmitter transporter, dopamine), member 3]; SLC6A4 [solute carrier family 6 (neurotransmitter transporter, serotonin), member 4]; SLC6A8 [solute carrier family 6 (neurotransmitter transporter, creatine), member 8]; SLC7A1 [solute carrier family 7 (cationic amino acid transporter, y+ system), member 1 ]; SLC7A2 [solute carrier family 7 (cationic amino acid transporter, y+ system), member 2]; SLC7A4 [solute carrier family 7 (cationic amino acid transporter, y+ system), member 4]; SLC7A5 [solute carrier family 7 (cationic amino acid transporter, y+ system), member 5];

[solute carrier family 8 (sodium/calcium exchanger), member 1]; SLC9A1 [solute carrier family 9 (sodium/hydrogen exchanger), member 1]; SLC9A3R1 [solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1]; SLCO1A2 [solute carrier organic anion transporter family, member 1A2]; SLCO1 B1 [solute carrier organic anion transporter family, member 1 B1 ]; SLCO1 B3 [solute carrier organic anion transporter family, member 1 B3]; SLPI [secretory leukocyte peptidase inhibitor]; SMAD1 [SMAD family member 1]; SMAD2 [SMAD family member 2]; SMAD3 [SMAD family member 3]; SMAD4 [SMAD family member 4];
SMAD7 [SMAD family member 7]; SMARCA4 [SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4];

SMARCAL1 [SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a-like 1]; SMARCB1 [SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1]; SMC1A
[structural maintenance of chromosomes 1A]; SMC3 [structural maintenance of chromosomes 3]; SMG1 [SMG1 homolog, phosphatidylinositol 3-kinase-related kinase (C. elegans)]; SMN1 [survival of motor neuron 1, telomeric]; SMPD1 [sphingomyelin phosphodiesterase 1, acid lysosomal]; SMPD2 [sphingomyelin phosphodiesterase 2, neutral membrane (neutral sphingomyelinase)]; SMTN
[smoothelin]; SNAI2 [snail homolog 2 (Drosophila)]; SNAP25 [synaptosomal-associated protein, 25kDa]; SNCA [synuclein, alpha (non A4 component of amyloid precursor)]; SNCG [synuclein, gamma (breast cancer-specific protein 1)]; SNURF [SNRPN upstream reading frame]; SNW1 [SNW domain containing 1]; SNX9 [sorting nexin 9]; SOAT1 [sterol 0-acyltransferase 1]; SOCS1 [suppressor of cytokine signaling 1]; SOCS2 [suppressor of cytokine signaling 2];
SOCS3 [suppressor of cytokine signaling 3]; SOD1 [superoxide dismutase 1, soluble]; SOD2 [superoxide dismutase 2, mitochondrial]; SORBS3 [sorbin and SH3 domain containing 3]; SORD [sorbitol dehydrogenase]; SOX2 [SRY (sex determining region Y)-box 2]; SP1 [Spl transcription factor]; SP1 10 [SP1 10 nuclear body protein]; SP3 [Sp3 transcription factor]; SPA17 [sperm autoantigenic protein 17]; SPARC [secreted protein, acidic, cysteine-rich (osteonectin)]; SPHK1 [sphingosine kinase 1]; SPI1 [spleen focus forming virus (SFFV) proviral integration oncogene spit]; SPINK1 [serine peptidase inhibitor, Kazal type 1]; SPINK13 [serine peptidase inhibitor, Kazal type 13 (putative)];
SPINK5 [serine peptidase inhibitor, Kazal type 5]; SPN [sialophorin]; SPON1 [spondin 1, extracellular matrix protein]; SPP1 [secreted phosphoprotein 1];
SPRED1 [sprouty-related, EVH1 domain containing 1]; SPRR2A [small proline-rich protein 2A]; SPRR2B [small proline-rich protein 2B]; SPTB [spectrin, beta, erythrocytic]; SRC [v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian)]; SRD5A1 [steroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 1)]; SREBF1 [sterol regulatory element binding transcription factor 1]; SREBF2 [sterol regulatory element binding transcription factor 2]; SRF [serum response factor (c-fos serum response element-binding transcription factor)]; SRGN [serglycin]; SRP9 [signal recognition particle 9kDa]; SRPX [sushi-repeat-containing protein, X-linked];
SRR
[serine racemase]; SRY [sex determining region Y]; SSB [Sjogren syndrome antigen B (autoantigen La)]; SST [somatostatin]; SSTR2 [somatostatin receptor 2]; SSTR4 [somatostatin receptor 4]; ST8SIA4 [ST8 alpha-N-acetyl-neuraminide alpha--2,8-sialyltransferase 4]; STAR [steroidogenic acute regulatory protein];
STAT1 [signal transducer and activator of transcription 1, 91 kDa]; STAT2 [signal transducer and activator of transcription 2, 113kDa]; STAT3 [signal transducer and activator of transcription 3 (acute-phase response factor)]; STAT4 [signal transducer and activator of transcription 4]; STAT5A [signal transducer and activator of transcription 5A]; STAT5B [signal transducer and activator of transcription 5B]; STAT6 [signal transducer and activator of transcription 6, interleukin-4 induced]; STELLAR [germ and embryonic stem cell enriched protein STELLA]; STIM1 [stromal interaction molecule 1]; STIP1 [stress-induced-phosphoprotein 1]; STK1 1 [serine/threonine kinase 11]; STMN2 [stathmin-like 2];
STRAP [serine/threonine kinase receptor associated protein]; STRC
[stereocilin];
STS [steroid sulfatase (microsomal), isozyme S]; STX6 [syntaxin 6]; STX8 [syntaxin 8]; SULT1A1 [sulfotransferase family, cytosolic, 1A, phenol-preferring, member 1]; SULT1A3 [sulfotransferase family, cytosolic, 1A, phenol-preferring, member 3]; SUMF1 [sulfatase modifying factor 1]; SUMO1 [SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae)]; SUMO3 [SMT3 suppressor of mif two 3 homolog 3 (S. cerevisiae)]; SUOX [sulfite oxidase]; SUV39H1 [suppressor of variegation 3-9 homolog 1 (Drosophila)]; SWAP70 [SWAP switching B-cell complex 70kDa subunit]; SYCP3 [synaptonemal complex protein 3]; SYK [spleen tyrosine kinase]; SYNM [synemin, intermediate filament protein]; SYNPO
[synaptopodin]; SYNPO2 [synaptopodin 2]; SYP [synaptophysin]; SYT3 [synaptotagmin III]; SYTL1 [synaptotagmin-like 1]; T [T, brachyury homolog (mouse)]; TAC1 [tachykinin, precursor 1]; TAC4 [tachykinin 4 (hemokinin)];

TACR1 [tachykinin receptor 1]; TACR2 [tachykinin receptor 2]; TACR3 [tachykinin receptor 3]; TAGLN [transgelin]; TALI [T-cell acute lymphocytic leukemia 1]; TAOK3 [TAO kinase 3]; TAP1 [transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)]; TAP2 [transporter 2, ATP-binding cassette, sub-family B (MDR/TAP)]; TARDBP [TAR DNA binding protein]; TARP [TCR gamma alternate reading frame protein]; TAT [tyrosine aminotransferase]; TBK1 [TANK-binding kinase 1]; TBP [TATA box binding protein]; TBX1 [T-box 1]; TBX2 [T-box 2]; TBX21 [T-box 21]; TBX3 [T-box 3]; TBX5 [T-box 5]; TBXA2R [thromboxane A2 receptor]; TBXAS1 [thromboxane A synthase 1 (platelet)]; TCEA1 [transcription elongation factor A (SII), 1 ]; TCEAL1 [transcription elongation factor A (SII)-like 1]; TCF4 [transcription factor 4]; TCF7L2 [transcription factor 7-like 2 (T-cell specific, HMG-box)]; TCL1A [T-cell leukemia/lymphoma 1A]; TCL1 B [T-cell leukemia/lymphoma 1 B]; TCN1 [transcobalamin I (vitamin B12 binding protein, R binder family)]; TCN2 [transcobalamin II; macrocytic anemia]; TDP1 [tyrosyl-DNA phosphodiesterase 1]; TEC [tec protein tyrosine kinase]; TECTA
[tectorin alpha]; TEK [TEK tyrosine kinase, endothelial]; TERF1 [telomeric repeat binding factor (NIMA-interacting) 1]; TERF2 [telomeric repeat binding factor 2];
TERT [telomerase reverse transcriptase]; TES [testis derived transcript (3 LIM
domains)]; TF [transferrin]; TFAM [transcription factor A, mitochondrial];

[transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha)];
TFF2 [trefoil factor 2]; TFF3 [trefoil factor 3 (intestinal)]; TFPI [tissue factor pathway inhibitor (lipoprotein-associated coagulation inhibitor)]; TFPT [TCF3 (E2A) fusion partner (in childhood Leukemia)]; TFR2 [transferrin receptor 2];
TFRC [transferrin receptor (p90, CD71)]; TG [thyroglobulin]; TGFA
[transforming growth factor, alpha]; TGFB1 [transforming growth factor, beta 1]; TGFB2 [transforming growth factor, beta 2]; TGFB3 [transforming growth factor, beta 3];
TGFBR1 [transforming growth factor, beta receptor 1]; TGFBR2 [transforming growth factor, beta receptor II (70/8OkDa)]; TGIF1 [TGFB-induced factor homeobox 1]; TGM1 [transglutaminase 1 (K polypeptide epidermal type I, protein-glutamine-gamma-glutamyltransferase)]; TGM2 [transglutaminase 2 (C

polypeptide, protein-glutamine-gamma-glutamyltransferase)]; TGM3 [transglutaminase 3 (E polypeptide, protein-glutamine-gamma-glutamyltransferase)]; TH [tyrosine hydroxylase]; THAP1 [THAP domain containing, apoptosis associated protein 1]; THBD [thrombomodulin]; THBS1 [thrombospondin 1]; THBS3 [thrombospondin 3]; THPO [thrombopoietin]; THY1 [Thy-1 cell surface antigen]; TIA1 [TIA1 cytotoxic granule-associated RNA
binding protein]; TIE1 [tyrosine kinase with immunoglobulin-like and EGF-like domains 1]; TIMD4 [T-cell immunoglobulin and mucin domain containing 4];
TIMELESS [timeless homolog (Drosophila)]; TIMP1 [TIMP metallopeptidase inhibitor 1]; TIMP2 [TIMP metallopeptidase inhibitor 2]; TIMP3 [TIMP
metallopeptidase inhibitor 3]; TIRAP [toll-interleukin 1 receptor (TIR) domain containing adaptor protein]; TJP1 [tight junction protein 1 (zona occludens 1)];
TK1 [thymidine kinase 1, soluble]; TK2 [thymidine kinase 2, mitochondrial];
TKT
[transketolase]; TLE4 [transducin-like enhancer of split 4 (E(spl) homolog, Drosophila)]; TLR1 [toll-like receptor 1]; TLR10 [toll-like receptor 10]; TLR2 [toll-like receptor 2]; TLR3 [toll-like receptor 3]; TLR4 [toll-like receptor 4];
TLR5 [toll-like receptor 5]; TLR6 [toll-like receptor 6]; TLR7 [toll-like receptor 7];
TLR8 [toll-like receptor 8]; TLR9 [toll-like receptor 9]; TLX1 [T-cell leukemia homeobox 1];
TM7SF4 [transmembrane 7 superfamily member 4]; TMED3 [transmembrane emp24 protein transport domain containing 3]; TMEFF2 [transmembrane protein with EGF-like and two follistatin-like domains 2]; TMEM132E [transmembrane protein 132E]; TMEM18 [transmembrane protein 18]; TMEM19 [transmembrane protein 19]; TMEM216 [transmembrane protein 216]; TMEM27 [transmembrane protein 27]; TMEM67 [transmembrane protein 67]; TMPO [thymopoietin];
TMPRSS15 [transmembrane protease, serine 15]; TMSB4X [thymosin beta 4, X-linked]; TNC [tenascin C]; TNF [tumor necrosis factor (TNF superfamily, member 2)]; TNFAIP1 [tumor necrosis factor, alpha-induced protein 1 (endothelial)];
TNFAIP3 [tumor necrosis factor, alpha-induced protein 3]; TNFAIP6 [tumor necrosis factor, alpha-induced protein 6]; TNFRSF1 OA [tumor necrosis factor receptor superfamily, member 1 Oa]; TNFRSF1 OB [tumor necrosis factor receptor superfamily, member 10b]; TNFRSF10C [tumor necrosis factor receptor superfamily, member 10c, decoy without an intracellular domain]; TNFRSF1OD
[tumor necrosis factor receptor superfamily, member 10d, decoy with truncated death domain]; TNFRSF1 1A [tumor necrosis factor receptor superfamily, member 11 a, NFKB activator]; TNFRSF1 1 B [tumor necrosis factor receptor superfamily, member 11 b]; TNFRSF1 3B [tumor necrosis factor receptor superfamily, member 13B]; TNFRSF13C [tumor necrosis factor receptor superfamily, member 13C]; TNFRSF14 [tumor necrosis factor receptor superfamily, member 14 (herpesvirus entry mediator)]; TNFRSF17 [tumor necrosis factor receptor superfamily, member 17]; TNFRSF1 8 [tumor necrosis factor receptor superfamily, member 18]; TNFRSF1A [tumor necrosis factor receptor superfamily, member 1A]; TNFRSF1 B [tumor necrosis factor receptor superfamily, member 1 B]; TNFRSF21 [tumor necrosis factor receptor superfamily, member 21]; TNFRSF25 [tumor necrosis factor receptor superfamily, member 25]; TNFRSF4 [tumor necrosis factor receptor superfamily, member 4]; TNFRSF6B [tumor necrosis factor receptor superfamily, member 6b, decoy]; TNFRSF8 [tumor necrosis factor receptor superfamily, member 8];
TNFRSF9 [tumor necrosis factor receptor superfamily, member 9]; TNFSF10 [tumor necrosis factor (ligand) superfamily, member 10]; TNFSF1 1 [tumor necrosis factor (ligand) superfamily, member 11]; TNFSF12 [tumor necrosis factor (ligand) superfamily, member 12]; TNFSF13 [tumor necrosis factor (ligand) superfamily, member 13]; TNFSF13B [tumor necrosis factor (ligand) superfamily, member 13b]; TNFSF14 [tumor necrosis factor (ligand) superfamily, member 14];
TNFSF15 [tumor necrosis factor (ligand) superfamily, member 15]; TNFSF18 [tumor necrosis factor (ligand) superfamily, member 18]; TNFSF4 [tumor necrosis factor (ligand) superfamily, member 4]; TNFSF8 [tumor necrosis factor (ligand) superfamily, member 8]; TNFSF9 [tumor necrosis factor (ligand) superfamily, member 9]; TNKS [tankyrase, TRF1 -interacting ankyrin-related ADP-ribose polymerase]; TNNC1 [troponin C type 1 (slow)]; TNNI2 [troponin I type 2 (skeletal, fast)]; TNNI3 [troponin I type 3 (cardiac)]; TNNT3 [troponin T type (skeletal, fast)]; TNP01 [transportin 1]; TNS1 [tensin 1]; TNXB [tenascin XB];
TOM1 L2 [target of mybl -like 2 (chicken)]; TOP1 [topoisomerase (DNA) I];
TOP1 MT [topoisomerase (DNA) I, mitochondrial]; TOP2A [topoisomerase (DNA) II alpha 170kDa]; TOP2B [topoisomerase (DNA) II beta 180kDa]; TOP3A
[topoisomerase (DNA) III alpha]; TOPBP1 [topoisomerase (DNA) II binding protein 1]; TP53 [tumor protein p53]; TP53BP1 [tumor protein p53 binding protein 1]; TP53RK [TP53 regulating kinase]; TP63 [tumor protein p63]; TP73 [tumor protein p73]; TPD52 [tumor protein D52]; TPH1 [tryptophan hydroxylase 1]; TPI1 [triosephosphate isomerase 1]; TPM1 [tropomyosin 1 (alpha)]; TPM2 [tropomyosin 2 (beta)]; TPMT [thiopurine S-methyltransferase]; TPO [thyroid peroxidase]; TPP1 [tripeptidyl peptidase I]; TPP2 [tripeptidyl peptidase II];
TPPP
[tubulin polymerization promoting protein]; TPPP3 [tubulin polymerization-promoting protein family member 3]; TPSAB1 [tryptase alpha/beta 1]; TPSB2 [tryptase beta 2 (gene/pseudogene)]; TPSD1 [tryptase delta 1]; TPSG1 [tryptase gamma 1]; TPT1 [tumor protein, translationally-controlled 1]; TRADD
[TNFRSFIA-associated via death domain]; TRAF1 [TNF receptor-associated factor 1]; TRAF2 [TNF receptor-associated factor 2]; TRAF3IP2 [TRAF3 interacting protein 2]; TRAF6 [TNF receptor-associated factor 6]; TRAP [TRAF
interacting protein]; TRAPPC10 [trafficking protein particle complex 10]; TRDN
[triadin]; TREX1 [three prime repair exonuclease 1]; TRH [thyrotropin-releasing hormone]; TRIB1 [tribbles homolog 1 (Drosophila)]; TRIM21 [tripartite motif-containing 21]; TRIM22 [tripartite motif-containing 22]; TRIM26 [tripartite motif-containing 26]; TRIM28 [tripartite motif-containing 28]; TRIM29 [tripartite motif-containing 29]; TRIM68 [tripartite motif-containing 68]; TRPA1 [transient receptor potential cation channel, subfamily A, member 1]; TRPC1 [transient receptor potential cation channel, subfamily C, member 1]; TRPC3 [transient receptor potential cation channel, subfamily C, member 3]; TRPC6 [transient receptor potential cation channel, subfamily C, member 6]; TRPM1 [transient receptor potential cation channel, subfamily M, member 1]; TRPM8 [transient receptor potential cation channel, subfamily M, member 8]; TRPS1 [trichorhinophalangeal syndrome I]; TRPV1 [transient receptor potential cation channel, subfamily V, member 1]; TRPV4 [transient receptor potential cation channel, subfamily V, member 4]; TRPV5 [transient receptor potential cation channel, subfamily V, member 5]; TRPV6 [transient receptor potential cation channel, subfamily V, member 6]; TRRAP [transformation/transcription domain-associated protein];
TSC1 [tuberous sclerosis 1]; TSC2 [tuberous sclerosis 2]; TSC22D3 [TSC22 domain family, member 3]; TSG101 [tumor susceptibility gene 101]; TSHR
[thyroid stimulating hormone receptor]; TSLP [thymic stromal lymphopoietin];
TSPAN7 [tetraspanin 7]; TSPO [translocator protein (18kDa)]; TSSK2 [testis-specific serine kinase 2]; TSTA3 [tissue specific transplantation antigen P35B];
TTF2 [transcription termination factor, RNA polymerase II]; TTN [titin]; TTPA
[tocopherol (alpha) transfer protein]; TTR [transthyretin]; TUBA1 B [tubulin, alpha 1b]; TUBA4A [tubulin, alpha 4a]; TUBB [tubulin, beta]; TUBB1 [tubulin, beta 1];
TUBG1 [tubulin, gamma 1]; TWIST1 [twist homolog 1 (Drosophila)]; TWSG1 [twisted gastrulation homolog 1 (Drosophila)]; TXK [TXK tyrosine kinase]; TXN
[thioredoxin]; TXN2 [thioredoxin 2]; TXNDC5 [thioredoxin domain containing 5 (endoplasmic reticulum)]; TXNDC9 [thioredoxin domain containing 9]; TXNIP
[thioredoxin interacting protein]; TXNRD1 [thioredoxin reductase 1]; TXNRD2 [thioredoxin reductase 2]; TYK2 [tyrosine kinase 2]; TYMP [thymidine phosphorylase]; TYMS [thymidylate synthetase]; TYR [tyrosinase (oculocutaneous albinism IA)]; TYRO3 [TYRO3 protein tyrosine kinase];
TYROBP [TYRO protein tyrosine kinase binding protein]; TYRP1 [tyrosinase-related protein 1]; UBB [ubiquitin B]; UBC [ubiquitin C]; UBE2C [ubiquitin-conjugating enzyme E2C]; UBE2N [ubiquitin-conjugating enzyme E2N (UBC13 homolog, yeast)]; UBE2U [ubiquitin-conjugating enzyme E2U (putative)]; UBE3A
[ubiquitin protein ligase E3A]; UBE4A [ubiquitination factor E4A (UFD2 homolog, yeast)]; UCHL1 [ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)];
UCN [urocortin]; UCN2 [urocortin 2]; UCP1 [uncoupling protein 1 (mitochondrial, proton carrier)]; UCP2 [uncoupling protein 2 (mitochondrial, proton carrier)];
UCP3 [uncoupling protein 3 (mitochondrial, proton carrier)]; UFD1 L [ubiquitin fusion degradation 1 like (yeast)]; UGCG [UDP-glucose ceramide glucosyltransferase]; UGP2 [UDP-glucose pyrophosphorylase 2]; UGT1A1 [UDP
glucuronosyltransferase 1 family, polypeptide Al]; UGT1A6 [UDP
glucuronosyltransferase 1 family, polypeptide A6]; UGT1A7 [UDP
glucuronosyltransferase 1 family, polypeptide A7]; UGT8 [UDP
glycosyltransferase 8]; UIMC1 [ubiquitin interaction motif containing 1];

[UL16 binding protein 1]; ULK2 [unc-51-like kinase 2 (C. elegans)]; UMOD
[uromodulin]; UMPS [uridine monophosphate synthetase]; UNC13D [unc-13 homolog D (C. elegans)]; UNC93B1 [unc-93 homolog 131 (C. elegans)]; UNG
[uracil-DNA glycosylase]; UQCRFS1 [ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1]; UROD [uroporphyrinogen decarboxylase]; USF1 [upstream transcription factor 1]; USF2 [upstream transcription factor 2, c-fos interacting]; USP18 [ubiquitin specific peptidase 18]; USP34 [ubiquitin specific peptidase 34]; UTRN [utrophin]; UTS2 [urotensin 2]; VAMP8 [vesicle-associated membrane protein 8 (endobrevin)]; VAPA [VAMP (vesicle-associated membrane protein)-associated protein A, 33kDa]; VASP [vasodilator-stimulated phosphoprotein]; VAV1 [vav 1 guanine nucleotide exchange factor]; VAV3 [vav 3 guanine nucleotide exchange factor]; VCAM1 [vascular cell adhesion molecule 1]; VCAN [versican]; VCL [vinculin]; VDAC1 [voltage-dependent anion channel 1]; VDR [vitamin D (1 [25- dihydroxyvitamin D3) receptor]; VEGFA [vascular endothelial growth factor A]; VEGFC [vascular endothelial growth factor C];
VHL
[von Hippel-Lindau tumor suppressor]; VIL1 [villin 1]; VIM [vimentin]; VIP
[vasoactive intestinal peptide]; VIPR1 [vasoactive intestinal peptide receptor 1];
VIPR2 [vasoactive intestinal peptide receptor 2]; VLDLR [very low density lipoprotein receptor]; VMAC [vimentin-type intermediate filament associated coiled-coil protein]; VPREB1 [pre-B lymphocyte 1]; VPS39 [vacuolar protein sorting 39 homolog (S. cerevisiae)]; VTN [vitronectin]; VWF [von Willebrand factor]; WARS [tryptophanyl-tRNA synthetase]; WAS [Wiskott-Ald rich syndrome (eczema-thrombocytopenia)]; WASF1 [WAS protein family, member 1]; WASF2 [WAS protein family, member 2]; WASL [Wiskott-Aldrich syndrome-like]; WDFY3 [WD repeat and FYVE domain containing 3]; WDR36 [WD repeat domain 36];
WEE1 [WEE1 homolog (S. pombe)]; WIF1 [WNT inhibitory factor 1]; WIPF1 [WAS/WASL interacting protein family, member 1]; WNK1 [WNK lysine deficient protein kinase 1]; WNT5A [wingless-type MMTV integration site family, member 5A]; WRN [Werner syndrome, RecQ helicase-like]; WT1 [Wilms tumor 1]; XBP1 [X-box binding protein 1]; XCL1 [chemokine (C motif) ligand 1]; XDH [xanthine dehydrogenase]; XIAP [X-linked inhibitor of apoptosis]; XPA [xeroderma pigmentosum, complementation group A]; XPC [xeroderma pigmentosum, complementation group C]; XPO5 [exportin 5]; XRCC1 [X-ray repair complementing defective repair in Chinese hamster cells 1]; XRCC2 [X-ray repair complementing defective repair in Chinese hamster cells 2]; XRCC3 [X-ray repair complementing defective repair in Chinese hamster cells 3]; XRCC4 [X-ray repair complementing defective repair in Chinese hamster cells 4]; XRCC5 [X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)]; XRCC6 [X-ray repair complementing defective repair in Chinese hamster cells 6]; YAP1 [Yes-associated protein 1]; YARS [tyrosyl-tRNA
synthetase]; YBX1 [Y box binding protein 1]; YES1 [v-yes-1 Yamaguchi sarcoma viral oncogene homolog 1]; YPEL1 [yippee-like 1 (Drosophila)]; YPEL2 [yippee-like 2 (Drosophila)]; YWHAB [tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta polypeptide]; YWHAQ [tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide]; YWHAZ [tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide]; YY1 [YY1 transcription factor]; ZAP70 [zeta-chain (TCR) associated protein kinase 70kDa]; ZBED1 [zinc finger, BED-type containing 1]; ZC3H12A [zinc finger CCCH-type containing 12A]; ZC3H12D [zinc finger CCCH-type containing 12D]; ZFR [zinc finger RNA binding protein];
ZNF148 [zinc finger protein 148]; ZNF267 [zinc finger protein 267]; ZNF287 [zinc finger protein 287]; ZNF300 [zinc finger protein 300]; ZNF365 [zinc finger protein 365]; ZNF521 [zinc finger protein 521]; ZNF74 [zinc finger protein 74]; and ZPBP2 [zona pellucida binding protein 2].

[0207] In certain embodiments, an animal created by a method of the invention may be used to study the effects of mutations on the animal and development and/or progression of an immunodeficiency using measures commonly used in the study of immunodeficiencies.
[0208] It should be understood that the genetically modified animals, e.g., knock-out and transgenic animals created by a method of the invention may include genes altered singly or in combination, including alteration to any one or more of Rag 1, Rag2, FoxN1, and DNAPK. Accordingly, for example, animals including a single, double or triple gene knock-out are contemplated. Any of these may be used in various methods in which alteration of one or more immunodeficiency genes may be useful. For example, genetically modified animals as described herein may be used in studies of hematopoietic cells, such as in the identification of progenitor cells including lymphoid progenitors and pluripotential stem cells; in the identification of new cytokines which play a role in the growth and differentiation of hematopoietic cells; in the analysis of the effect of known cytokines; and in the analysis of drugs effects on hematopoietic cells. Such animals can also be used in studies on pathogenetic mechanisms in disease caused by viral infections such as but not limited to influenza, West Nile virus, herpesviruses, picornaviruses, neurotropic coronavirus, Varicella-zoster (chicken pox), respiratory syncytial virus, cowpox, hepatitis B, rabies, and Dengue virus, and lymphotropic viruses including human immunodeficiency virus (HIV), human T lymphotropic virus (HTLV-1), and Epstein Barr virus (EBV), and also a virus that specifically infects rats but models the effects of a human-specific virus on its host, for example the rat-adapted influenza virus (see, e.g., H. Lebrec and G.R. Burleson (1994) Toxicology. Jul 1;91(2):179-88).
[0209] In other embodiments, a genetically modified animal created by a method of the invention may also be useful in studies of defense mechanisms against microorganisms that cause disease in immunocompromised patients, wherein the microorganism may be cytomegalovirus, Pneumocystic carinii or Candida species. Genetically modified animals, such as for example knock-out rats can be subjects for pre-clinical evaluation of a specific "gene therapy". For example, genes may be introduced into hematopoietic progenitor cells, preferably into pluripotential stem cells with self-renewal capacity from patients with inherited genetic defects, or into pluripotential stem cells with self-renewal capacity from rat models of inherited genetic defects, and the cells re-introduced into the genetically modified rats for the purpose of determining therapeutic usefulness of the modified cells. Genetically modified animals may also be useful for studying the biological mechanisms underlying immunodeficiency diseases and conditions caused by or linked to a mutation in an immunodeficiency gene such as Rag 1, Rag2, FoxN1, or DNAPK.
[0210] Furthermore, a genetically modified animal created by a method of the invention may be used to develop a diagnostic assay for an immunodeficiency disorder including but not limited to a leukemia, in which the animal, either untreated or previously treated with a therapeutic agent, is assessed for the presence of one or more biomarkers relative to a non-affected control animal. Such a genetically modified animal may be used in a method of screening a candidate therapy or therapeutic compound for treating an immunodeficiency disorder such as a leukemia, using a genetically modified animal in which one or more immunodeficiency genes including but not limited to Rag 1, Rag2, FoxN1, or DNAPK are knocked out, and the animal, either untreated or previously treated with another therapeutic agent which may be a drug, microbe, transplanted cells, or other agent, is then treated with the candidate therapy or candidate therapeutic agent, a biological sample is obtained from the animal, and the biological sample evaluated relative to a sample from a non-affected wild-type control sample, or a sample from a genetically modified animal not subjected to the candidate therapy or therapeutic agent.
[0211] In still further embodiments, a method for modeling an autoimmune disease may involve the adoptive transfer of B cells reacting to an antigen for an autoimmune disease, or T cells activated for an autoimmune disease. The appropriate non-human mammal with the antigen target of the autoimmune disease can be immunized as follows.
[0212] Immune cells may be prepared from the immunized animal and may be then transplanted to a genetically modified animal as described herein such as a Rag 1, Rag2, FoxN1, or DNAPK knock-out rat, or a rat with any combination of these genes knocked out. The development of autoimmune phenotypes in the recipient knock-out animal may then evaluated as compared to either a non-transplanted knock-out animal, or as compared to a knock-out animal transplanted with non-pathologic immune cells that lack auto-reactivity, or as compared to a wild type animal transplanted with immune cells as described above.
[0213] In some embodiments, a method for creating a combined immunodeficiency syndrome model may include providing a genetically modified animal such as a rat wherein Rag 1, Rag2, FoxN1, or DNAPK are knocked out as described herein, and the knock-out animal may be further rendered deficient for natural killer (NK) cells by any one of several possible methods. Non-limiting examples of methods of rendering the knock-out animal deficient for NK include i) disruption of the Lyst gene; or ii) treatment of FoxN1 mutant animals with a compound that inhibits NK cell activity including but not limited to NSAIDs (non-steroidal anti-inflammatory drugs), statins, allosteric LFA-1 inhibitors, vinblastine, paclitaxel, docetaxel, cladribine, chlorambucil, bortezomib, or MG-132.

N. trinucleotide repeat disorders [0214] Trinucleotide repeat expansion disorders are divided into two categories determined by the type of repeat. The most common repeat is the triplet CAG, which, when present in the coding region of a gene, codes for the amino acid glutamine (Q). Therefore, these disorders are referred to as the polyglutamine (polyQ) disorders and may include Huntington Disease (HD);
Spinobulbar Muscular Atrophy (SBMA); Spinocerebellar Ataxias (SCA types 1, 2, 3, 6, 7, and 17); and Dentatorubro-PalIidol uysian Atrophy (DRPLA). Other trinucleotide repeat expansion disorders either do not involve the CAG
triplet, or the CAG triplet is not in the coding region of the gene and are referred to as the non-polyglutamine disorders. Non-polyglutamine disorders may include Fragile X Syndrome (FRAXA); Fragile XE Mental Retardation (FRAXE); Friedreich Ataxia (FRDA); Myotonic Dystrophy (DM); and Spinocerebellar Ataxias (SCA
types 8, and 12).
[0215] In one embodiment, a method of the invention may be used to create a genetically modified animal or cell in which at least one chromosomal sequence associated with a trinucleotide repeat disorder has been edited.
Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0216] In each of the above embodiments, one or more chromosomal sequences associated with a trinucleotide repeat disorder may be edited. A trinucleotide repeat disorder associated protein or control sequence may typically be selected based on an experimental association of the protein or sequence to a trinucleotide repeat expansion disorder. Trinucleotide repeat expansion proteins may include proteins associated with susceptibility for developing a trinucleotide repeat expansion disorder, the presence of a trinucleotide repeat expansion disorder, the severity of a trinucleotide repeat expansion disorder or any combination thereof. For example, the production rate or circulating concentration of a protein associated with a trinucleotide repeat expansion disorder may be elevated or depressed in a population having a trinucleotide repeat expansion disorder relative to a population lacking the trinucleotide repeat expansion disorder. Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art.
[0217] Non-limiting examples of proteins associated with trinucleotide repeat expansion disorders include AR (androgen receptor), FMR1 (fragile X mental retardation 1), HTT (huntingtin), DMPK (dystrophia myotonica-protein kinase), FXN (frataxin), ATXN2 (ataxin 2), ATN1 (atrophin 1), FEN1 (flap structure-specific endonuclease 1), TNRC6A (trinucleotide repeat containing 6A), PABPN1 (poly(A) binding protein, nuclear 1), JPH3 (junctophilin 3), MED15 (mediator complex subunit 15), ATXN1 (ataxin 1), ATXN3 (ataxin 3), TBP (TATA
box binding protein), CACNA1A (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit), ATXN8OS (ATXN8 opposite strand (non-protein coding)), PPP2R2B (protein phosphatase 2, regulatory subunit B, beta), ATXN7 (ataxin 7), TNRC6B (trinucleotide repeat containing 6B), TNRC6C (trinucleotide repeat containing 6C), CELF3 (CUGBP, Elav-like family member 3), MAB21 L1 (mab-21-like 1 (C. elegans)), MSH2 (mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)), TMEM185A (transmembrane protein 185A), SIX5 (SIX homeobox 5), CNPY3 (canopy 3 homolog (zebrafish)), FRAXE (fragile site, folic acid type, rare, fra(X)(q28) E), GNB2 (guanine nucleotide binding protein (G protein), beta polypeptide 2), RPL14 (ribosomal protein L14), ATXN8 (ataxin 8), INSR (insulin receptor), TTR (transthyretin), EP400 (E1A binding protein p400), GIGYF2 (GRB1 0 interacting GYF protein 2), OGG1 (8-oxoguanine DNA glycosylase), STC1 (stanniocalcin 1), CNDP1 (carnosine dipeptidase 1 (metallopeptidase M20 family)), C1 Oorf2 (chromosome 10 open reading frame 2), MAML3 mastermind-like 3 (Drosophila), DKC1 (dyskeratosis congenita 1, dyskerin), PAXIP1 (PAX
interacting (with transcription-activation domain) protein 1), CASK
(calcium/calmodulin-dependent serine protein kinase (MAGUK family)), MAPT
(microtubule-associated protein tau), SP1 (Spl transcription factor), POLG
(polymerase (DNA directed), gamma), AFF2 (AF4/FMR2 family, member 2), THBS1 (thrombospondin 1), TP53 (tumor protein p53), ESR1 (estrogen receptor 1), CGGBP1 (CGG triplet repeat binding protein 1), ABT1 (activator of basal transcription 1), KLK3 (kallikrein-related peptidase 3), PRNP (prion protein), JUN
(Jun oncogene), KCNN3 (potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3), BAX (BCL2-associated X protein), FRAXA (fragile site, folic acid type, rare, fra(X)(q27.3) A (macroorchidism, mental retardation)), KBTBD10 (kelch repeat and BTB (POZ) domain containing 10), MBNL1 (muscleblind-like (Drosophila)), RAD51 (RAD51 homolog (RecA
homolog, E. coli) (S. cerevisiae)), NCOA3 (nuclear receptor coactivator 3), ERDA1 (expanded repeat domain, CAG/CTG 1), TSC1 (tuberous sclerosis 1), COMP (cartilage oligomeric matrix protein), GCLC (glutamate-cysteine ligase, catalytic subunit), RRAD (Ras-related associated with diabetes), MSH3 (mutS
homolog 3 (E. coli)), DRD2 (dopamine receptor D2), CD44 (CD44 molecule (Indian blood group)), CTCF (CCCTC-binding factor (zinc finger protein)), CCND1 (cyclin D1), CLSPN (claspin homolog (Xenopus laevis)), MEF2A
(myocyte enhancer factor 2A), PTPRU (protein tyrosine phosphatase, receptor type, U), GAPDH (glyceraldehyde-3-phosphate dehydrogenase), TRIM22 (tripartite motif-containing 22), WT1 (Wilms tumor 1), AHR (aryl hydrocarbon receptor), GPX1 (glutathione peroxidase 1), TPMT (thiopurine S-methyltransferase), NDP (Norrie disease (pseudoglioma)), ARX (aristaless related homeobox), MUS81 (MUS81 endonuclease homolog (S. cerevisiae)), TYR (tyrosinase (oculocutaneous albinism IA)), EGR1 (early growth response 1), UNG (uracil-DNA glycosylase), NUMBL (numb homolog (Drosophila)-like), FABP2 (fatty acid binding protein 2, intestinal), EN2 (engrailed homeobox 2), CRYGC (crystallin, gamma C), SRP14 (signal recognition particle 14kDa (homologous Alu RNA binding protein)), CRYGB (crystallin, gamma B), PDCD1 (programmed cell death 1), HOXA1 (homeobox Al), ATXN2L (ataxin 2-like), PMS2 (PMS2 postmeiotic segregation increased 2 (S. cerevisiae)), GLA
(galactosidase, alpha), CBL (Cas-Br-M (murine) ecotropic retroviral transforming sequence), FTH1 (ferritin, heavy polypeptide 1), IL12RB2 (interleukin 12 receptor, beta 2), OTX2 (orthodenticle homeobox 2), HOXA5 (homeobox A5), POLG2 (polymerase (DNA directed), gamma 2, accessory subunit), DLX2 (distal-less homeobox 2), SIRPA (signal-regulatory protein alpha), OTX1 (orthodenticle homeobox 1), AHRR (aryl-hydrocarbon receptor repressor), MANF
(mesencephalic astrocyte-derived neurotrophic factor), TMEM158 (transmembrane protein 158 (gene/pseudogene)), and ENSG00000078687.
[0218] Exemplary proteins associated with trinucleotide repeat expansion disorders include HTT (Huntingtin), AR (androgen receptor), FXN
(frataxin), Atxn3 (ataxin), Atxnl (ataxin), Atxn2 (ataxin), Atxn7 (ataxin), Atxn10 (ataxin), DMPK (dystrophia myotonica-protein kinase), Atn1 (atrophin 1), CBP
(creb binding protein), VLDLR (very low density lipoprotein receptor), and any combination thereof.
[0219] In certain embodiments, an animal created by a method of the invention may be used to study the effects of mutations on the animal and the development and/or progression of a trinucleotide repeat disorder using measures commonly used in the study of a trinucleotide repeat disorder.

0. neurotransmission disorders [0220] Non-limiting examples of a neurotransmission disorder include amylotropic lateral sclerosis (ALS), spinocerebellar ataxias (SCA) including SCA2, Alzheimer's; autism, mental retardation, Rett's syndrome, fragile X syndrome, depression, schizophrenia, bi-polar disorders, disorders of learning, memory or behavior, anxiety, brain injury, seizure disorders, Huntington's disease (chorea), mania, neuroleptic malignant syndrome, pain, Parkinsonism, Parkinson's disease, tardive dyskinesia, myasthenia gravis, episodic ataxias, hyperkalemic periodic paralysis, hypokalemic periodic paralysis, Lambert-Eaton syndrome, paramyotonia congenita, Rasmussen's encephalitis, startle disease (hyperexplexia, stiff baby syndrome), and the effects of poisoning such as botulism, mushroom poisoning, organophosphates, snake venom such as from Bungarus multicinctus (Taiwanese banded krait). In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with a neurotransmission disorder has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
[0221] In each of the above embodiments, one or more chromosomal sequences associated with a neurotransmission disorder may be edited. A neurotransmission disorder associated protein or control sequence may typically be selected based on an experimental association of the protein to a neurotransmission disorder. Neurotransmission disorder-related proteins include proteins associated with the susceptibility for developing a neurotransmission disorder, the presence of a neurotransmission disorder, the severity of a neurotransmission disorder or any combination thereof. For example, the production rate or circulating concentration of a neurotransmission disorder-related protein may be elevated or depressed in a population having a neurotransmission disorder relative to a population lacking the neurotransmission disorder. Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art.
[0222] Non-limiting examples of neurotransmission disorder-related proteins include SST (somatostatin), NOS1 (nitric oxide synthase 1 (neuronal)), ADRA2A (adrenergic, alpha-2A-, receptor), ADRA2C (adrenergic, alpha-2C-, receptor), TACR1 (tachykinin receptor 1), HTR2C (5-hydroxytryptamine (serotonin) receptor 2C), SLC1A2 (solute carrier family 1 (glial high affinity glutamate transporter), member 2), GRM5 (glutamate receptor, metabotropic 5), GRM2 (glutamate receptor, metabotropic 2), GABRG3 (gamma-aminobutyric acid (GABA) A receptor, gamma 3), CACNA1 B (calcium channel, voltage-dependent, N type, alpha 1 B subunit), NOS2 (nitric oxide synthase 2, inducible), SLC6A5 (solute carrier family 6 (neurotransmitter transporter, glycine), member 5), GABRG1 (gamma-aminobutyric acid (GABA) A receptor, gamma 1), NOS3 (nitric oxide synthase 3 (endothelial cell)), GRM3 (glutamate receptor, metabotropic 3), HTR6 (5-hydroxytryptamine (serotonin) receptor 6), SLC1A3 (solute carrier family 1 (glial high affinity glutamate transporter), member 3), GRM7 (glutamate receptor, metabotropic 7), HRH1 (histamine receptor H1), SLC1A1 (solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1), GRM4 (glutamate receptor, metabotropic 4), GLUD2 (glutamate dehydrogenase 2), ADRA2B (adrenergic, alpha-2B-, receptor), SLC1A6 (solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6), GRM6 (glutamate receptor, metabotropic 6), SLC1A7 (solute carrier family 1 (glutamate transporter), member 7), SLC6A1 1 (solute carrier family 6 (neurotransmitter transporter, GABA), member 11), CACNA1A

(calcium channel, voltage-dependent, P/Q type, alpha 1A subunit), CACNA1 G
(calcium channel, voltage-dependent, T type, alpha 1 G subunit), GRM1 (glutamate receptor, metabotropic 1), CACNA1 H (calcium channel, voltage-dependent, T type, alpha 1 H subunit), GRM8 (glutamate receptor, metabotropic 8), CHRNA3 (cholinergic receptor, nicotinic, alpha 3), P2RY2 (purinergic receptor P2Y, G-protein coupled, 2), TRPV6 (transient receptor potential cation channel, subfamily V, member 6), CACNA1 E (calcium channel, voltage-dependent, R
type, alpha 1 E subunit), ACCN1 (amiloride-sensitive cation channel 1, neuronal), CACNA1 I (calcium channel, voltage-dependent, T type, alpha 11 subunit), GABARAP (GABA (A) receptor-associated protein), P2RY1 (purinergic receptor P2Y, G-protein coupled, 1), P2RY6 (pyrimidinergic receptor P2Y, G-protein coupled, 6), RPH3A (rabphilin 3A homolog (mouse)), HDC (histidine decarboxylase), P2RY14 (purinergic receptor P2Y, G-protein coupled, 14), P2RY4 (pyrimidinergic receptor P2Y, G-protein coupled, 4), P2RY10 (purinergic receptor P2Y, G-protein coupled, 10), SLC28A3 (solute carrier family 28 (sodium-coupled nucleoside transporter), member 3), NOSTRIN (nitric oxide synthase trafficker), P2RY13 (purinergic receptor P2Y, G-protein coupled, 13), P2RY8 (purinergic receptor P2Y, G-protein coupled, 8), P2RY1 1 (purinergic receptor P2Y, G-protein coupled, 11), SLC6A3 (solute carrier family 6 (neurotransmitter transporter, dopamine), member 3), HTR3A (5-hydroxytryptamine (serotonin) receptor 3A), DRD2 (dopamine receptor D2), HTR2A (5-hydroxytryptamine (serotonin) receptor 2A), TH (tyrosine hydroxylase), CNR1 (cannabinoid receptor 1 (brain)), VIP (vasoactive intestinal peptide), NPY (neuropeptide Y), GAL (galanin prepropeptide), TAC1 (tachykinin, precursor 1), SYP (synaptophysin), SLC6A4 (solute carrier family 6 (neurotransmitter transporter, serotonin), member 4), DBH (dopamine beta-hydroxylase (dopamine beta-monooxygenase)), DRD3 (dopamine receptor D3), NR3C1 (nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor)), HTR1 B (5-hydroxytryptamine (serotonin) receptor 1 B), GABBR1 (gamma-aminobutyric acid (GABA) B receptor, 1), CALCA (calcitonin-related polypeptide alpha), CRH (corticotropin releasing hormone), HTR1A (5-hydroxytryptamine (serotonin) receptor 1A), TACR2 (tachykinin receptor 2), COMT (catechol-O-methyltransferase), GRIN2B (glutamate receptor, ionotropic, N-methyl D-aspartate 2B), GRIN2A (glutamate receptor, ionotropic, N-methyl D-aspartate 2A), PRL (prolactin), ACHE (acetylcholinesterase (Yt blood group)), ADRB2 (adrenergic, beta-2-, receptor, surface), ACE (angiotensin I converting enzyme (peptidyl-dipeptidase A) 1), SNAP25 (synaptosomal-associated protein, 25kDa), GABRA5 (gamma-aminobutyric acid (GABA) A receptor, alpha 5), MECP2 (methyl CpG binding protein 2 (Rett syndrome)), BCHE
(butyrylcholinesterase), ADRB1 (adrenergic, beta-1 -,receptor), GABRAI
(gamma-aminobutyric acid (GABA) A receptor, alpha 1), GCH1 (GTP
cyclohydrolase 1), DDC (dopa decarboxylase (aromatic L-amino acid decarboxylase)), MAOB (monoamine oxidase B), DRD5 (dopamine receptor D5), GABRE (gamma-aminobutyric acid (GABA) A receptor, epsilon), SLC6A2 (solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2), GABRR2 (gamma-aminobutyric acid (GABA) receptor, rho 2), SV2A (synaptic vesicle glycoprotein 2A), GABRRI (gamma-aminobutyric acid (GABA) receptor, rho 1), GHRH (growth hormone releasing hormone), CCK (cholecystokinin), PDYN (prodynorphin), SLC6A9 (solute carrier family 6 (neurotransmitter transporter, glycine), member 9), KCND1 (potassium voltage-gated channel, Shal-related subfamily, member 1), SRR (serine racemase), DYT10 (dystonia 10), MAPT (microtubule-associated protein tau), APP (amyloid beta (A4) precursor protein), CTSB (cathepsin B), ADA (adenosine deaminase), AKT1 (v-akt murine thymoma viral oncogene homolog 1), GRIN1 (glutamate receptor, ionotropic, N-methyl D-aspartate 1), BDNF (brain-derived neurotrophic factor), HMOX1 (heme oxygenase (decycling) 1), OPRM1 (opioid receptor, mu 1), GRIN2C (glutamate receptor, ionotropic, N-methyl D-aspartate 2C), GRIA1 (glutamate receptor, ionotropic, AMPA 1), GABRA6 (gamma-aminobutyric acid (GABA) A receptor, alpha 6), FOS (FBJ murine osteosarcoma viral oncogene homolog), GABRG2 (gamma-aminobutyric acid (GABA) A receptor, gamma 2), GABRB3 (gamma-aminobutyric acid (GABA) A receptor, beta 3), OPRK1 (opioid receptor, kappa 1), GABRB2 (gamma-aminobutyric acid (GABA) A receptor, beta 2), GABRD (gamma-aminobutyric acid (GABA) A receptor, delta), ALDH5A1 (aldehyde dehydrogenase 5 family, member Al), GAD1 (glutamate decarboxylase 1 (brain, 67kDa)), NSF (N-ethylmaleimide-sensitive factor), GRIN2D (glutamate receptor, ionotropic, N-methyl D-aspartate 2D), ADORA1 (adenosine Al receptor), GABRA2 (gamma-aminobutyric acid (GABA) A
receptor, alpha 2), GLRA1 (glycine receptor, alpha 1), CHRM3 (cholinergic receptor, muscarinic 3), CHAT (choline acetyltransferase), KNG1 (kininogen 1), HMOX2 (heme oxygenase (decycling) 2), DRD4 (dopamine receptor D4), MAOA
(monoamine oxidase A), CHRM2 (cholinergic receptor, muscarinic 2), ADORA2A
(adenosine A2a receptor), STXBP1 (syntaxin binding protein 1), GABRA3 (gamma-aminobutyric acid (GABA) A receptor, alpha 3), TPH1 (tryptophan hydroxylase 1), HCRTR1 (hypocretin (orexin) receptor 1), HCRTR2 (hypocretin (orexin) receptor 2), CHRM1 (cholinergic receptor, muscarinic 1), FOLH1 (folate hydrolase (prostate-specific membrane antigen) 1), AANAT (arylalkylamine N-acetyltransferase), INS (insulin), NR3C2 (nuclear receptor subfamily 3, group C, member 2), FAAH (fatty acid amide hydrolase), GALR2 (galanin receptor 2), ADCYAP1 (adenylate cyclase activating polypeptide 1 (pituitary)), PPP1 R1 B
(protein phosphatase 1, regulatory (inhibitor) subunit 1 B), HOMER1 (homer homolog 1 (Drosophila)), ADCY10 (adenylate cyclase 10 (soluble)), PSEN2 (presenilin 2 (Alzheimer disease 4)), UBE3A (ubiquitin protein ligase E3A), (superoxide dismutase 1, soluble), LYN (v-yes-1 Yamaguchi sarcoma viral related oncogene homolog), TSC2 (tuberous sclerosis 2), PRKCA (protein kinase C, alpha), PPARG (peroxisome proliferator-activated receptor gamma), ESR1 (estrogen receptor 1), NTRK1 (neurotrophic tyrosine kinase, receptor, type 1), EGFR (epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)), S100B (S100 calcium binding protein B), NTRK3 (neurotrophic tyrosine kinase, receptor, type 3), PLCG2 (phospholipase C, gamma 2 (phosphatidylinositol-specific)), NTRK2 (neurotrophic tyrosine kinase, receptor, type 2), DNMT1 (DNA (cytosine-5-)-m ethyltransferase 1), EGF
(epidermal growth factor (beta-urogastrone)), GRIA3 (glutamate receptor, ionotrophic, AMPA 3), NCAM1 (neural cell adhesion molecule 1), CDKN1A
(cyclin-dependent kinase inhibitor 1A (p21, Cip1)), BCL2L1 (BCL2-like 1), TP53 (tumor protein p53), CASP9 (caspase 9, apoptosis-related cysteine peptidase), CCKBR (cholecystokinin B receptor), PARK2 (Parkinson's disease (autosomal recessive, juvenile) 2, parkin), ADRA1 B (adrenergic, alpha-1 B-, receptor), CASP3 (caspase 3, apoptosis-related cysteine peptidase), PRNP (prion protein), CRHR1 (corticotropin releasing hormone receptor 1), L1 CAM (L1 cell adhesion molecule), NGFR (nerve growth factor receptor (TNFR superfamily, member 16)), CREB1 (cAMP responsive element binding protein 1), PLCG1 (phospholipase C, gamma 1), CAV1 (caveolin 1, caveolae protein, 22kDa), ABCC8 (ATP-binding cassette, sub-family C (CFTR/MRP), member 8), ACTN2 (actinin, alpha 2), GRIA2 (glutamate receptor, ionotropic, AMPA 2), HPRT1 (hypoxanthine phosphoribosyltransferase 1), SYN1 (synapsin I), CSNK2A1 (casein kinase 2, alpha 1 polypeptide), GRIK1 (glutamate receptor, ionotropic, kainate 1), ABCB1 (ATP-binding cassette, sub-family B (MDR/TAP), member 1), AVPR2 (arginine vasopressin receptor 2), HTR4 (5-hydroxytryptamine (serotonin) receptor 4), C3 (complement component 3), AGT (angiotensinogen (serpin peptidase inhibitor, Glade A, member 8)), AGTR1 (angiotensin II
receptor, type 1), CDK5 (cyclin-dependent kinase 5), LRP1 (low density lipoprotein receptor-related protein 1), ARRB2 (arrestin, beta 2), PLD2 (phospholipase D2), OPRD1 (opioid receptor, delta 1), GNB3 (guanine nucleotide binding protein (G
protein), beta polypeptide 3), PIK3CG (phosphoinositide-3-kinase, catalytic, gamma polypeptide), APAF1 (apoptotic peptidase activating factor 1), SSTR2 (somatostatin receptor 2), IL2 (interleukin 2), ADORA3 (adenosine A3 receptor), ADRA1A (adrenergic, alpha-1A-, receptor), HTR7 (5-hydroxytryptamine (serotonin) receptor 7 (adenylate cyclase-coupled)), ADRBK2 (adrenergic, beta, receptor kinase 2), ALOX5 (arachidonate 5-lipoxygenase), NPR1 (natriuretic peptide receptor A/guanylate cyclase A (atrionatriuretic peptide receptor A)), AVPR1A (arginine vasopressin receptor 1A), CHRNB1 (cholinergic receptor, nicotinic, beta 1 (muscle)), SET (SET nuclear oncogene), PAH (phenylalanine hydroxylase), POMC (proopiomelanocortin), LEPR (leptin receptor), SDC2 (syndecan 2), VIPR1 (vasoactive intestinal peptide receptor 1), DBI (diazepam binding inhibitor (GABA receptor modulator, acyl-Coenzyme A binding protein)), NPY1 R (neuropeptide Y receptor Y1), NPR2 (natriuretic peptide receptor B/guanylate cyclase B (atrionatriuretic peptide receptor B)), CNR2 (cannabinoid receptor 2 (macrophage)), LEP (leptin), CCKAR (cholecystokinin A receptor), GLRB (glycine receptor, beta), KCNQ2 (potassium voltage-gated channel, KQT-like subfamily, member 2), CHRNA2 (cholinergic receptor, nicotinic, alpha 2 (neuronal)), BDKRB2 (bradykinin receptor B2), CHRNA1 (cholinergic receptor, nicotinic, alpha 1 (muscle)), CHRND (cholinergic receptor, nicotinic, delta), CHRNA7 (cholinergic receptor, nicotinic, alpha 7), PLD1 (phospholipase D1, phosphatidylcholine-specific), NRXN1 (neurexin 1), NRP1 (neuropilin 1), DLG3 (discs, large homolog 3 (Drosophila)), GNAQ (guanine nucleotide binding protein (G protein), q polypeptide), DRD1 (dopamine receptor D1), PRKG1 (protein kinase, cGMP-dependent, type I), CNTNAP2 (contactin associated protein-like 2), EDN3 (endothelin 3), ABAT (4-aminobutyrate aminotransferase), TDO2 (tryptophan 2,3-dioxygenase), NEUROD1 (neurogenic differentiation 1), CHRNE
(cholinergic receptor, nicotinic, epsilon), CHRNB2 (cholinergic receptor, nicotinic, beta 2 (neuronal)), CHRNB3 (cholinergic receptor, nicotinic, beta 3), HTR1 D
(5-hydroxytryptamine (serotonin) receptor 1 D), ADRA1 D (adrenergic, alpha-1 D-, receptor), HTR2B (5-hydroxytryptamine (serotonin) receptor 2B), GRIK3 (glutamate receptor, ionotropic, kainate 3), NPY2R (neuropeptide Y receptor Y2), GRIK5 (glutamate receptor, ionotropic, kainate 5), GRIA4 (glutamate receptor, ionotrophic, AMPA 4), EDN1 (endothelin 1), PRLR (prolactin receptor), GABRB1 (gamma-aminobutyric acid (GABA) A receptor, beta 1), GARS (glycyl-tRNA
synthetase), GRIK2 (glutamate receptor, ionotropic, kainate 2), ALOX12 (arachidonate 12-lipoxygenase), GAD2 (glutamate decarboxylase 2 (pancreatic islets and brain, 65kDa)), LHCGR (luteinizing hormone/choriogonadotropin receptor), SHMT1 (serine hydroxymethyltransferase 1 (soluble)), PDXK
(pyridoxal (pyridoxine, vitamin B6) kinase), LIF (leukemia inhibitory factor (cholinergic differentiation factor)), PLCD1 (phospholipase C, delta 1), NTF3 (neurotrophin 3), NFE2L2 (nuclear factor (erythroid-derived 2)-like 2), PLCB4 (phospholipase C, beta 4), GNRHR (gonadotropin-releasing hormone receptor), NLGN1 (neuroligin 1), PPP2R4 (protein phosphatase 2A activator, regulatory subunit 4), SSTR3 (somatostatin receptor 3), CRHR2 (corticotropin releasing hormone receptor 2), NGF (nerve growth factor (beta polypeptide)), NRCAM
(neuronal cell adhesion molecule), NRXN3 (neurexin 3), GNRH1 (gonadotropin-releasing hormone 1 (luteinizing-releasing hormone)), TRHR (thyrotropin-releasing hormone receptor), ARRB1 (arrestin, beta 1), INPP1 (inositol polyphosphate-1-phosphatase), PTN (pleiotrophin), PSMD10 (proteasome (prosome, macropain) 26S subunit, non-ATPase, 10), DLG1 (discs, large homolog 1 (Drosophila)), PSMB8 (proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional peptidase 7)), CYCS (cytochrome c, somatic), ADORA2B (adenosine A2b receptor), ADRB3 (adrenergic, beta-3-, receptor), CHGA (chromogranin A (parathyroid secretory protein 1)), ADM
(adrenomedullin), GABRP (gamma-aminobutyric acid (GABA) A receptor, pi), GLRA2 (glycine receptor, alpha 2), PRKG2 (protein kinase, cGMP-dependent, type II), GLS (glutaminase), TACR3 (tachykinin receptor 3), ALDH7A1 (aldehyde dehydrogenase 7 family, member Al), GABBR2 (gamma-aminobutyric acid (GABA) B receptor, 2), GDNF (glial cell derived neurotrophic factor), CNTFR
(ciliary neurotrophic factor receptor), CNTN2 (contactin 2 (axonal)), TOR1A
(torsin family 1, member A (torsin A)), CNTN1 (contactin 1), CAMK1 (calcium/calmodulin-dependent protein kinase I), NPPB (natriuretic peptide precursor B), OXTR (oxytocin receptor), OSM (oncostatin M), VIPR2 (vasoactive intestinal peptide receptor 2), CHRNB4 (cholinergic receptor, nicotinic, beta 4), CHRNA5 (cholinergic receptor, nicotinic, alpha 5), AVP (arginine vasopressin), RELN (reelin), GRLF1 (glucocorticoid receptor DNA binding factor 1), NPR3 (natriuretic peptide receptor C/guanylate cyclase C (atrionatriuretic peptide receptor C)), GRIK4 (glutamate receptor, ionotropic, kainate 4), KISS1 (KiSS-1 metastasis-suppressor), HTR5A (5-hydroxytryptamine (serotonin) receptor 5A), ADCYAP1 R1 (adenylate cyclase activating polypeptide 1 (pituitary) receptor type I), GABRA4 (gamma-aminobutyric acid (GABA) A receptor, alpha 4), GLRA3 (glycine receptor, alpha 3), INHBA (inhibin, beta A), DLG2 (discs, large homolog 2 (Drosophila)), PPYR1 (pancreatic polypeptide receptor 1), SSTR4 (somatostatin receptor 4), NPPA (natriuretic peptide precursor A), SNAP23 (synaptosomal-associated protein, 23kDa), AKAP9 (A kinase (PRKA) anchor protein (yotiao) 9), NRXN2 (neurexin 2), FHL2 (four and a half LIM domains 2), TJP1 (tight junction protein 1 (zona occludens 1)), NRG1 (neuregulin 1), CAMK4 (calcium/calmodulin-dependent protein kinase IV), CAV3 (caveolin 3), VAMP2 (vesicle-associated membrane protein 2 (synaptobrevin 2)), GALR1 (galanin receptor 1), GHRHR (growth hormone releasing hormone receptor), HTR1 E (5-hydroxytryptamine (serotonin) receptor 1 E), PENK (proenkephalin), HTT
(huntingtin), HOXA1 (homeobox Al), NPY5R (neuropeptide Y receptor Y5), UNC1 19 (unc-119 homolog (C. elegans)), TAT (tyrosine aminotransferase), CNTF (ciliary neurotrophic factor), SHMT2 (serine hydroxymethyltransferase 2 (mitochondrial)), ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1), GRIP1 (glutamate receptor interacting protein 1), GRP (gastrin-releasing peptide), NCAM2 (neural cell adhesion molecule 2), SSTR1 (somatostatin receptor 1), CLTB (clathrin, light chain (Lcb)), DAO (D-amino-acid oxidase), QDPR (quinoid dihydropteridine reductase), PYY (peptide YY), PNMT
(phenylethanolamine N-methyltransferase), NTSR1 (neurotensin receptor 1 (high affinity)), NTS (neurotensin), HCRT (hypocretin (orexin) neuropeptide precursor), SNAP29 (synaptosomal-associated protein, 29kDa), SNAP91 (synaptosomal-associated protein, 91 kDa homolog (mouse)), MADD (MAP-kinase activating death domain), IDO1 (indoleamine 2,3-dioxygenase 1), TPH2 (tryptophan hydroxylase 2), TAC3 (tachykinin 3), GRIN3A (glutamate receptor, ionotropic, N-methyl -D-aspartate 3A), REN (renin), GALR3 (galanin receptor 3), MAGI2 (membrane associated guanylate kinase, WW and PDZ domain containing 2), KCNJ9 (potassium inwardly-rectifying channel, subfamily J, member 9), BDKRB1 (bradykinin receptor B1), CHRNA6 (cholinergic receptor, nicotinic, alpha 6), CHRM5 (cholinergic receptor, muscarinic 5), CHRNG (cholinergic receptor, nicotinic, gamma), SLC6A1 (solute carrier family 6 (neurotransmitter transporter, GABA), member 1), ENTPD2 (ectonucleoside triphosphate diphosphohydrolase 2), CALCB (calcitonin-related polypeptide beta), SHBG (sex hormone-binding globulin), SERPINA6 (serpin peptidase inhibitor, Glade A (alpha-1 antiproteinase, antitrypsin), member 6), NRG2 (neuregulin 2), PNOC (prepronociceptin), NAPA
(N-ethylmaleimide-sensitive factor attachment protein, alpha), PICK1 (protein interacting with PRKCA 1), PLCD4 (phospholipase C, delta 4), GCDH (glutaryl-Coenzyme A dehydrogenase), NLGN2 (neuroligin 2), NBEA (neurobeachin), ATP1 OA (ATPase, class V, type 1 OA), RAPGEF4 (Rap guanine nucleotide exchange factor (GEF) 4), UCN (urocortin), PCSK6 (proprotein convertase subtilisin/kexin type 6), HTR1 F (5-hydroxytryptamine (serotonin) receptor 1 F), SGCB (sarcoglycan, beta (43kDa dystrophin-associated glycoprotein)), GABRQ
(gamma-aminobutyric acid (GABA) receptor, theta), GHRL (ghrelin/obestatin prepropeptide), NCALD (neurocalcin delta), NEUROD2 (neurogenic differentiation 2), DPEP1 (dipeptidase 1 (renal)), SLC1A4 (solute carrier family 1 (glutamate/neutral amino acid transporter), member 4), DNM3 (dynamin 3), SLC6A12 (solute carrier family 6 (neurotransmitter transporter, betaine/GABA), member 12), SLC6A6 (solute carrier family 6 (neurotransmitter transporter, taurine), member 6), YME1 L1 (YME1-like 1 (S. cerevisiae)), VSNL1 (visinin-like 1), SLC17A7 (solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 7), HOMER2 (homer homolog 2 (Drosophila)), SYT7 (synaptotagmin VII), TFIP11 (tuftelin interacting protein 11), GMFB (glia maturation factor, beta), PREB (prolactin regulatory element binding), NTSR2 (neurotensin receptor 2), NTF4 (neurotrophin 4), PPP1 R9B (protein phosphatase 1, regulatory (inhibitor) subunit 9B), DISC1 (disrupted in schizophrenia 1), (neuregulin 3), OXT (oxytocin, prepropeptide), TRH (thyrotropin-releasing hormone), NISCH (nischarin), CRHBP (corticotropin releasing hormone binding protein), SLC6A1 3 (solute carrier family 6 (neurotransmitter transporter, GABA), member 13), NPPC (natriuretic peptide precursor C), CNTN3 (contactin 3 (plasmacytoma associated)), KAT5 (K (lysine) acetyltransferase 5), CNTN6 (contactin 6), KIAA0101 (KIAA0101), PANX1 (pannexin 1), CTSL1 (cathepsin L1), EARS2 (glutamyl-tRNA synthetase 2, mitochondrial (putative)), CRIPT
(cysteine-rich PDZ-binding protein), CORT (cortistatin), DLGAP4 (discs, large (Drosophila) homolog-associated protein 4), ASTN2 (astrotactin 2), HTR3B (5-hydroxytryptamine (serotonin) receptor 3B), PMCH (pro-melanin-concentrating hormone), TSPO (translocator protein (18kDa)), GDF2 (growth differentiation factor 2), CNTNAP1 (contactin associated protein 1), GNRH2 (gonadotropin-releasing hormone 2), AUTS2 (autism susceptibility candidate 2), SV2C
(synaptic vesicle glycoprotein 2C), CARTPT (CART prepropeptide), NSUN4 (NOP2/Sun domain family, member 4), CNTN5 (contactin 5), NEUROD4 (neurogenic differentiation 4), NEUROG1 (neurogenin 1), SLTM (SAFB-like, transcription modulator), GNRHR2 (gonadotropin-releasing hormone (type 2) receptor 2), ASTN1 (astrotactin 1), SLC22A18 (solute carrier family 22, member 18), SLC17A6 (solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 6), GABRR3 (gamma-aminobutyric acid (GABA) receptor, rho 3), DAOA (D-amino acid oxidase activator), ENSG00000123384, nd NOS2P1 (nitric oxide synthase 2 pseudogene 1).
[0223] Exemplary neurotransmission-related proteins include 5-HTT
(5-hydroxyltryptamine transporter), SLC6A4 (Solute carrier family 6, member 4), COMT (Catechol-O-methyltransferase), DRD1A (Dopamine receptor D1A), SLC6A3 (Solute carrier family 6, member 3), DAO1 (D-amino-acid oxidase), DTNBP1 (Dystrobrevin binding protein 1), and any combination thereof.
[0224] In certain embodiments, an animal created by a method of the invention may be used to study the effects of mutations on the animal and on the development and/or progression of a neurotransmission disorder using measures commoningly used in the study of a neurotransmission disorder.

ii. pharmacological models [0225] A method of the invention may be used to create an animal or cell that may be used as a pharmacological model. Such a pharmacological model may be a model for pharmacokinetics or a model for pharmacodynamics.
For instance, in one embodiment, a method of the invention may be used to create an animal or cell that comprises a chromosomal edit in one or more nucleic acid sequences associated with the metabolism of a pharmaceutically active compound. Such an animal or cell may be used to study the effect of the nucleic acid sequence on the pharmaceutical compound.
[0226] Alternatively, a method of the invention may be used to create an animal or cell that comprises a chromosomal edit in a disease associated sequence. Such an animal or cell may be used for assessing the effect(s) of a therapeutic agent in the development or progression of the disease.
For example, the effect(s) of a therapeutic agent may be measured in a "humanized" animal, such that the information gained therefrom may be used to predict the effect of the agent in a human. In general, the method comprises contacting a genetically modified animal comprising at least one edited chromosomal sequence encoding a protein associated with the disease with the therapeutic agent, and comparing results of a selected parameter to results obtained from contacting a wild-type animal with the same agent. Non-limiting examples of suitable diseases include those listed in section II(a)i.
[0227] Also provided are methods to assess the effect(s) of an agent in an isolated cell comprising at least one edited chromosomal sequence encoding a protein associated with a disease, as well as methods of using lysates of such cells (or cells derived from a genetically modified animal disclosed herein) to assess the effect(s) of an agent. For example, the role of a particular protein associated with a disease in the metabolism of a particular agent may be determined using such methods. Similarly, substrate specificity and pharmacokinetic parameters may be readily determined using such methods. Those of skill in the art are familiar with suitable tests and/or procedures.
[0228] In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with toxicology has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above. Any chromosomal sequence or protein involved in absorption, distribution, metabolism, and excretion (ADME) and toxicology may be utilized for purposes of the present invention. The ADME and toxicology-related proteins are typically selected based on an experimental association of the protein to an ADME and toxicology-related disorder. For example, the production rate or circulating concentration of an ADME and toxicology-related protein may be elevated or depressed in a population having an ADME and toxicology disorder relative to a population lacking the ADME and toxicology disorder. Differences in protein levels may be assessed using proteomic or genomic analysis techniques known in the art.
[0229] Exemplary non-limiting examples of the chromosomal sequence or protein involved in ADME and toxicology may be chosen from Oct 1, Oct 2, Hfe2, Ppar(alpha) MDR1 a (ABC Transporter ABCB1 a), MDR1 b (ABCB1b), BCRP (ABCC1), MRP1 (ABCG2), MRP2 (ABCC2, cMOAT), and combinations thereof [0230] A further aspect of the present disclosure encompasses a method for assessing the effect(s) of an agent. Suitable agents include without limit pharmaceutically active ingredients, drugs, food additives, pesticides, herbicides, toxins, industrial chemicals, household chemicals, and other environmental chemicals. For example, the effect(s) of an agent may be measured in a "humanized" genetically modified animal, such that the information gained therefrom may be used to predict the effect of the agent in a human. In general, the method comprises contacting a genetically modified animal comprising at least one inactivated chromosomal sequence involved in ADME

and toxicology and at least one chromosomally integrated sequence encoding an orthologous human protein involved in ADME and toxicology with the agent, and comparing results of a selected parameter to results obtained from contacting a wild-type animal with the same agent. Selected parameters include but are not limited to (a) rate of elimination of the agent or its metabolite(s); (b) circulatory levels of the agent or its metabolite(s); (c)bioavailability of the agent or its metabolite(s); (d) rate of metabolism of the agent or its metabolite(s); (e) rate of clearance of the agent or its metabolite(s); (f) toxicity of the agent or its metabolite(s); (g) efficacy of the agent or its metabolite(s); (h) disposition of the agent or its metabolite(s); and (i) extrahepatic contribution to metabolic rate and clearance of the agent or its metabolite(s).
[0231] Also provided are methods to assess the effect(s) of an agent in an isolated cell comprising at least one edited chromosomal sequence involved in ADME and toxicology, as well as methods of using lysates of such cells (or cells derived from a genetically modified animal disclosed herein) to assess the effect(s) of an agent. For example, the role of a particular protein involved in ADME and toxicology in the metabolism of a particular agent may be determined using such methods. Similarly, substrate specificity and pharmacokinetic parameters may be readily determined using such methods.
Those of skill in the art are familiar with suitable tests and/or procedures.
[0232] Among the proteins of interest that are involved in drug ADME and toxicology are the ABC transporters, also known as efflux transport proteins. Thus, for example, the genetically modified animals as described herein containing an edited chromosomal sequences encoding an ABC
transporter can be useful for screening biologically active agents including drugs and for investigating their distribution, efficacy, metabolism and/or toxicity. These screening methods are of particular use for assessing with improved predictability the behavior of a drug in a genetically modified animal as described herein, e.g. in a genetically modified rat, as a model for humans.
Accordingly, the present disclosure also features a method of assessing the ADME profile of a drug in a genetically modified animal, as part of a drug screening or evaluation process. A candidate therapeutic agent, i.e, a candidate drug can be administered to a genetically modified animal that harbors a targeted gene knock-out and/or an expressed transgene, which was achieved through use of ZFNs. The knock-out or knock-in gene is associated with at least one aspect of the drug ADME profile or toxicology, and/or metabolism, and may be derived from a mouse, rat, or human genome.
[0233] For example, a method of screening for the target of a test compound can make use of a genetically modified animal in which any one or more of an ABC transporter such as Mdrl a, Mdrl b, PXR, BCRP, MRP1, or MRP2 are knocked out, thus inhibiting or eliminating transmembrane transport mediated by the knocked out protein(s). Such an animal can be exposed to a test compound suspected of inhibiting transporter activity of the knocked-out protein(s). Inhibition of transport by the compound in the genetically modified animal can be determined using any of a number of routine laboratory tests and techniques, and the inhibition of transport may be compared to that observed in a wild-type animal treated with the same test compound. A difference in the effect of the test compound in the two animals can be indicative of the target of the test compound. Further, inhibition of one or more ABC transporter proteins such as Mdrl a, Mdrl b, PXR, BCRP, MRP1, or MRP2, may improve certain ADME
characteristics of a candidate therapeutic agent. For example, the absorption or efficacy of a candidate therapeutic compound may be improved by knock-ing out expression of one or more ABC transporter proteins such as Mdrl a, Mdrl b, PXR, BCRP, MRP1, or MRP2, in a particular tissue. It will thus be understood that genetically modified animals and cells as described herein, for example genetically modified animals and cells including a genetic modification of one or more ABC transporter proteins, can be used advantageously in many methods that evaluate the ADME and toxicology characteristics of a candidate therapeutic compound, to identify targets of a test compound, or to identify ways in which the ADME characteristics and toxicology of a candidate compound may be improved.

[0234] The overwhelming need to accurately predict how drugs and environmental chemicals may affect large populations can be readily appreciated. The genetically modified animals, embryos, cells and cell lines described herein can be used to analyze how various compounds may interact with biological systems. Genetically modified cells and cell lines can be used, for example, to control many of the known complexities in biological systems to improve the predictive ability of cell-based assay systems, such as those used to evaluate new molecular entities and possible drug-drug interactions. More specifically, it is recognized that biological systems typically include multiple components that respond to exposure to new, potentially harmful compounds.
[0235] The "ADMET system" has been described as including five components. The first component are those biological systems that when disrupted signal the drug metabolism system to turn on, and may include stress response and DNA repair pathways. Once the drug metabolism system is activated "xenosensors" surveil for exogenous molecules that need removal.
Detection of an exogenous molecule by the xenosensors then activates a cascade of gene inductions that up-regulate the enzymes responsible for metabolizing exogenous molecules into forms for easier removal. The enzymes of the third ADMET component include Phase I enzymes that include at least three classes of oxidases, of which the best known class is the cytochrome s class. Cytochrome 450 enzymes typically add reactive hydroxyl moieties to potential toxins to inactivate and render the toxins more polar (soluble). The fourth component of the ADMET system includes at least seven classes of enzymes that further alter the products of Phase I enzymatic modification.
Typically, these enzymes are conjugating enzymes that add hydrophilic moieties to make the now oxidized xenobiotics even more water soluble ADMET, and readily collected and excreted through urine or bile. The last component is the transporter system involving transporter proteins, such as the ABC
transporters, that function as molecular pumps to facilitate the movement of the xenobiotics from one tissue to another. The transporter proteins are responsible for moving drugs into a cell, out of a cell, or through a cell.
[0236] Each component of the ADMET system has its own set of substrate structural specificities, which must be taken into account by any assay.
Making predictability an even larger challenge is that, for critical members of each of the five component classes, a constellation of genetic polymorphisms exists in the population and these can dramatically affect activity towards specific xenobiotic chemical structures. The growing field of pharmacogenomics addresses the challenges created by such genetic variation. In addition, gender differences in how the different components of the xenobiotic system respond are also known to play a role in variations in drug metabolism.
[0237] Thus, genetically modified animals, cells and particularly cell lines as described herein will be useful as the basis for cell-based assays with improved predictive ability with respect to a drug's clinical outcome or a chemical's toxicological problems. Panels of cell lines are expressly contemplated for such a purpose. For example, cell-based assays can be created that are representative of the target tissue where metabolism or toxicity of a drug compound is likely to occur. Presently, standard assays are usually run in transformed cell lines that are derived from the target tissue and have some concordant functional properties. To create even better cell-based assays that are even more representative of the natural state, genetically modified and differentiated pluripotent cells could be used to replace the immortalized cell components. In other words, genetically modified cell lines can be used in more highly predictive cell-based assays suitable for high-throughput, high-content compound screening.
[0238] Accordingly, the present disclosure contemplates ZFN-mediated genetic modifications of genes relevant to each part of the xenobiotic metabolism machinery. Such modifications include knock-outs, knock-ins of reporter tags, the introduction of specific mutations known to affect activity, or combinations of these. For example, the genetically modified cells and cell lines can be used to create tissue-specific, gender-specific, and/or population-reflective transporter panels; cell-based xenosenor assay panels that are tissue-specific and functionally reflective of the population; and induction assays that measure the genetic activation of different drug metabolism components and overt toxicological responses such as genotoxicity, cardiotoxicity, and apoptosis.
[0239] According to the present disclosure, tissue-specific lines can be established that have been modified to isolate specific transporter activities and predict the reaction of populations to individual chemical entities. For example, ZFNs can be used to create transporter gene knock-outs in enterocyte cell lines, such as to introduce important, common polymorphisms into enterocyte cell lines, and in cell lines representative of liver, blood-brain-barrier (brain micro-vasculature endothelial cells), kidney and any relevant tissue-specific cell lines. Panels of cell lines can include enterocytes (Caco2 or BBe1) with knock-outs of individual transporter proteins (e.g. MDR-1, MRP1, 2, 3, 4, 6, BCRP), knock-out combinations to isolate effects of individual transporters (e.g.
BCRP and MRP2, MDR-1 and MRP2, MRP-3 and MRP1), and a transporter null line (i.e. all 7 transporters knocked out). Panels of enterocytes may include knock-outs of OATP-2B1, PEPT-1, and OCT-N2. Panels of enterocytes may be created which include prevalent polymorphisms in the major transporter genes that affect drug transport and are of concern to pharmaceutical researchers.
[0240] The three xenosensors in humans (PXR, AhR and CAR) are known to have overlapping specificities in response to xenobiotics. Knowing which xenosensors are activated and to what extent by any particular chemical compound is also an important consideration for understanding drug responses, and drug-drug interactions. Creating panels of cells that report induction by the xenosensors can delineate the specificities. Further modifying the cells to address functionally important polymorphisms in the xenosensors would permit population predictions. ZFNs can be used to create knock-out cell lines analogous to transporter knockout cell lines as described above, and to create reporter cell lines that express different fluorescent proteins upon induction of different xenosensors. For example, cell lines can be created in which green FP
is expressed if PXR is induced, red FP if CAR activity is induced, blue FP if AhR
is induced. All lines may be constructed in the relevant tissue-type cell lines, i.e.
intestine, liver, kidney, brain, and heart. Panels of cells can be created that represent the tissues most involved with drug toxicity and metabolism, and in which each xenosensor (CAR, PXR, AhR) is knocked out. Cell lines can also be produced that produce fluorescent proteins upon the activation of each of the three xenosensors.
[0241] Also contemplated are induction assays of ADME
biotransformation and toxicological response genes. While the activities of each of the many Phase I and Phase II enzymes can be done today in simple biochemical assays, available assays cannot measure, in high-throughput fashion, the induction of any particular enzyme by an exogenously added xenobiotic. ZFNs can be used to create genetically modified cell lines as described herein that can provide the basis for assays that can measure the up/down regulation of key Phase I and Phase II enzymes, along with genes involved in a toxicological response. For example, ZFNs can be used to build lines that have a reporter gene (e.g. encoding fluorescent protein or luciferase) inserted proximal to the promoter of the gene being measured. These gene targets can be any of the critical Phase I, Phase II, transporter, genotox, or apoptosis/necrosis pathway components. Tissue-specific panels of cells can also be created, which report on the activation of genes encoding either the Phase I
or Phase II enzymes, the transporters, or toxicity response pathways (e.g., genotoxicity or apoptosis).

N. developmental models [0242] A method of the invention may be used to create an animal or cell that may be used as a developmental model. Such a model may be used to study embryogenesis, organ development, organ system development, or the like. For instance, in one embodiment, a method of the invention may be used to create an animal or cell that comprises a chromosomal edit in one or more nucleic acid sequences associated with the development of an organ or organ system. Non-limiting examples of organs include the brain, eyes, nose, ears, throat, mouth (including teeth, tongue, lips, gums), spinal cord, bones, heart, blood vessels, lungs, liver, pancreas, gall bladder, spleen, esophagus, stomach, small intestines, large intestines, appendix, rectum, bladder, organs of the reproductive system, organs of the immune system (including thyroid, lymph nodes, lymph vessels), and organs of the endocrine system. Non-limiting examples of organ systems include the nervous system, the circulatory system, the digestive system, the respiratory system, the skeletal system, the lymphatic system, the reproductive system, the muscular system, the integumentary system, the excretory system, and the endocrine system.
[0243] In one embodiment, a method of the invention may be used to create an animal or cell in which at least one chromosomal sequence associated with neurodevelopment has been edited. Suitable chromosomal edits may include, but are not limited to, the type of edits detailed in section I(f) above.
A chromosomal sequence associated with neurodevelopment may be a protein coding sequence or a control sequence. In certain embodiments, a neurodevelopmental sequence may be associated with a neurodevelopmental disorder, with biochemical pathways associated with a neurodevelopmental disorder, or associated with a disorder such as phenylketonuria that is closely associated with neurodevelopmental disorders.
[0244] Non-limiting examples of neurodevelopmental-associated sequences include A2BP1 [ataxin 2-binding protein 1], AADAT [aminoadipate aminotransferase], AANAT [arylalkylamine N-acetyltransferase], ABAT [4-aminobutyrate aminotransferase], ABCA1 [ATP-binding cassette, sub-family A
(ABC1), member 1 ], ABCA13 [ATP-binding cassette, sub-family A (ABC1), member 13], ABCA2 [ATP-binding cassette, sub-family A (ABC1), member 2], ABCB1 [ATP-binding cassette, sub-family B (MDR/TAP), member 1], ABCB11 [ATP-binding cassette, sub-family B (MDR/TAP), member 11], ABCB4 [ATP-binding cassette, sub-family B (MDR/TAP), member 4], ABCB6 [ATP-binding cassette, sub-family B (MDR/TAP), member 6], ABCB7 [ATP-binding cassette, sub-family B (MDR/TAP), member 7], ABCC1 [ATP-binding cassette, sub-family C (CFTR/MRP), member 1], ABCC2 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 2], ABCC3 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 3], ABCC4 [ATP-binding cassette, sub-family C
(CFTR/MRP), member 4], ABCD1 [ATP-binding cassette, sub-family D (ALD), member 1], ABCD3 [ATP-binding cassette, sub-family D (ALD), member 3], ABCG1 [ATP-binding cassette, sub-family G (WHITE), member 1], ABCG2 [ATP-binding cassette, sub-family G (WHITE), member 2], ABCG4 [ATP-binding cassette, sub-family G (WHITE), member 4], ABHD1 1 [abhydrolase domain containing 11], ABI1 [abl-interactor 1], ABL1 [c-abl oncogene 1, receptor tyrosine kinase], ABL2 [v-abl Abelson murine leukemia viral oncogene homolog 2 (arg, Abelson-related gene)], ABLIM1 [actin binding LIM protein 1], ABLIM2 [actin binding LIM protein family, member 2], ABLIM3 [actin binding LIM protein family, member 3], ABO [ABO blood group (transferase A, alpha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3-galactosyltransferase)], ACAA1 [acetyl-Coenzyme A acyltransferase 1 ], ACACA
[acetyl-Coenzyme A carboxylase alpha], ACACB [acetyl-Coenzyme A
carboxylase beta], ACADL [acyl-Coenzyme A dehydrogenase, long chain], ACADM [acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain], ACADS
[acyl-Coenzyme A dehydrogenase, C-2 to C-3 short chain], ACADSB [acyl-Coenzyme A dehydrogenase, short/branched chain], ACAN [aggrecan], ACAT2 [acetyl-Coenzyme A acetyltransferase 2], ACCN1 [amiloride-sensitive cation channel 1, neuronal], ACE [angiotensin I converting enzyme (peptidyl-dipeptidase A) 1], ACE2 [angiotensin I converting enzyme (peptidyl-dipeptidase A) 2], ACHE [acetylcholinesterase (Yt blood group)], ACLY [ATP citrate lyase], ACO1 [aconitase 1, soluble], ACTA1 [actin, alpha 1, skeletal muscle], ACTB
[actin, beta], ACTC1 [actin, alpha, cardiac muscle 1], ACTG1 [actin, gamma 1], ACTL6A [actin-like 6A], ACTL6B [actin-like 6B], ACTN1 [actinin, alpha 1], ACTR1A [ARP1 actin-related protein 1 homolog A, centractin alpha (yeast)], ACTR2 [ARP2 actin-related protein 2 homolog (yeast)], ACTR3 [ARP3 actin-related protein 3 homolog (yeast)], ACTR3B [ARP3 actin-related protein 3 homolog B (yeast)], ACVR1 [activin A receptor, type I], ACVR2A [activin A
receptor, type IIA], ADA [adenosine deaminase], ADAM10 [ADAM
metallopeptidase domain 10], ADAM1 1 [ADAM metallopeptidase domain 11], ADAM12 [ADAM metallopeptidase domain 12], ADAM15 [ADAM
metallopeptidase domain 15], ADAM17 [ADAM metallopeptidase domain 17], ADAM18 [ADAM metallopeptidase domain 18], ADAM19 [ADAM
metallopeptidase domain 19 (meltrin beta)], ADAM2 [ADAM metallopeptidase domain 2], ADAM20 [ADAM metallopeptidase domain 20], ADAM21 [ADAM
metallopeptidase domain 21], ADAM22 [ADAM metallopeptidase domain 22], ADAM23 [ADAM metallopeptidase domain 23], ADAM28 [ADAM
metallopeptidase domain 28], ADAM29 [ADAM metallopeptidase domain 29], ADAM30 [ADAM metallopeptidase domain 30], ADAM8 [ADAM metallopeptidase domain 8], ADAMS [ADAM metallopeptidase domain 9 (meltrin gamma)], ADAMTS1 [ADAM metallopeptidase with thrombospondin type 1 motif, 1], ADAMTS13 [ADAM metallopeptidase with thrombospondin type 1 motif, 13], ADAMTS4 [ADAM metallopeptidase with thrombospondin type 1 motif, 4], ADAMTS5 [ADAM metallopeptidase with thrombospondin type 1 motif, 5], ADAP2 [ArfGAP with dual PH domains 2], ADAR [adenosine deaminase, RNA-specific], ADARB1 [adenosine deaminase, RNA-specific, B1 (RED1 homolog rat)], ADCY1 [adenylate cyclase 1 (brain)], ADCY10 [adenylate cyclase 10 (soluble)], ADCYAP1 [adenylate cyclase activating polypeptide 1 (pituitary)], ADD1 [adducin 1 (alpha)], ADD2 [adducin 2 (beta)], ADH1A [alcohol dehydrogenase 1A (class I), alpha polypeptide], ADIPOQ [adiponectin, C1Q and collagen domain containing], ADK [adenosine kinase], ADM [adrenomedullin], ADNP [activity-dependent neuroprotector homeobox], ADORA1 [adenosine Al receptor], ADORA2A [adenosine A2a receptor], ADORA2B [adenosine A2b receptor], ADORA3 [adenosine A3 receptor], ADRA1 B [adrenergic, alpha-1 B-, receptor], ADRA2A [adrenergic, alpha-2A-, receptor], ADRA2B [adrenergic, alpha-2B-, receptor], ADRA2C [adrenergic, alpha-2C-, receptor], ADRB1 [adrenergic, beta-l-, receptor], ADRB2 [adrenergic, beta-2-, receptor, surface], ADRB3 [adrenergic, beta-3-, receptor], ADRBK2 [adrenergic, beta, receptor kinase 2], ADSL [adenylosuccinate lyase], AFF2 [AF4/FMR2 family, member 2], AFM [afamin], AFP [alpha-fetoprotein], AGAP1 [ArfGAP with GTPase domain, ankyrin repeat and PH domain 1], AGER [advanced glycosylation end product-specific receptor], AGFG1 [ArfGAP with FG repeats 1], AGPS [alkylglycerone phosphate synthase], AGRN [agrin], AGRP [agouti related protein homolog (mouse)], AGT [angiotensinogen (serpin peptidase inhibitor, Glade A, member 8)], AGTR1 [angiotensin II receptor, type 1], AGTR2 [angiotensin II receptor, type 2], AHOY [adenosylhomocysteinase], AHI1 [Abelson helper integration site 1], AHR [aryl hydrocarbon receptor], AHSG [alpha-2-HS-glycoprotein], AICDA
[activation-induced cytidine deaminase], AIFM1 [apoptosis-inducing factor, mitochondrion-associated, 1], AIRE [autoimmune regulator], AKAP1 2 [A kinase (PRKA) anchor protein 12], AKAP9 [A kinase (PRKA) anchor protein (yotiao) 9], AKR1A1 [aldo-keto reductase family 1, member Al (aldehyde reductase)], AKR1 131 [aldo-keto reductase family 1, member 131 (aldose reductase)], AKR1 [aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II)], AKT1 [v-akt murine thymoma viral oncogene homolog 1], AKT2 [v-akt murine thymoma viral oncogene homolog 2], AKT3 [v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma)], ALAD
[aminolevulinate, delta-, dehydratase], ALB [albumin], ALB [albumin], ALCAM
[activated leukocyte cell adhesion molecule], ALDHIAI [aldehyde dehydrogenase 1 family, member Al ], ALDH3A1 [aldehyde dehydrogenase 3 family, memberA1], ALDH5A1 [aldehyde dehydrogenase 5 family, member A1], ALDH7A1 [aldehyde dehydrogenase 7 family, member Al ], ALDH9A1 [aldehyde dehydrogenase 9 family, member Al ], ALDOA [aldolase A, fructose-bisphosphate], ALDOB [aldolase B, fructose-bisphosphate], ALDOC [aldolase C, fructose-bisphosphate], ALK [anaplastic lymphoma receptor tyrosine kinase], ALOX12 [arachidonate 12-lipoxygenase], ALOX5 [arachidonate 5-lipoxygenase], ALOX5AP [arachidonate 5-lipoxygenase-activating protein ], ALPI [alkaline phosphatase, intestinal], ALPL [alkaline phosphatase, liver/bone/kidney], ALPP
[alkaline phosphatase, placental (Regan isozyme)], ALS2 [amyotrophic lateral sclerosis 2 (juvenile)], AMACR [alpha-methylacyl-CoA racemase], AMBP [alpha-1-microglobulin/bikunin precursor], AMPH [amphiphysin], ANG [angiogenin, ribonuclease, RNase A family, 5], ANGPT1 [angiopoietin 1], ANGPT2 [angiopoietin 2], ANGPTL3 [angiopoietin-like 3], ANK1 [ankyrin 1, erythrocytic], ANK3 [ankyrin 3, node of Ranvier (ankyrin G)], ANKRD1 [ankyrin repeat domain 1 (cardiac muscle)], ANP32E [acidic (leucine-rich) nuclear phosphoprotein 32 family, member E], ANPEP [alanyl (membrane) aminopeptidase], ANXA1 [annexin Al ], ANXA2 [annexin A2], ANXA5 [annexin A5], AP1 S1 [adaptor-related protein complex 1, sigma 1 subunit], AP1S2 [adaptor-related protein complex 1, sigma 2 subunit], AP2A1 [adaptor-related protein complex 2, alpha 1 subunit], AP2B1 [adaptor-related protein complex 2, beta 1 subunit], APAF1 [apoptotic peptidase activating factor 1], APBA1 [amyloid beta (A4) precursor protein-binding, family A, member 1], APBA2 [amyloid beta (A4) precursor protein-binding, family A, member 2], APBB1 [amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65)], APBB2 [amyloid beta (A4) precursor protein-binding, family B, member 2], APC [adenomatous polyposis coli], APCS
[amyloid P component, serum], APEX1 [APEX nuclease (multifunctional DNA
repair enzyme) 1], APH1 B [anterior pharynx defective 1 homolog B (C.
elegans)], APLP1 [amyloid beta (A4) precursor-like protein 1], APOA1 [apolipoprotein A-I], APOA5 [apolipoprotein A-V], APOB [apolipoprotein B (including Ag(x) antigen)], APOC2 [apolipoprotein C-II], APOD [apolipoprotein D], APOE [apolipoprotein E], APOM [apolipoprotein M], APP [amyloid beta (A4) precursor protein], APPL1 [adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1], APRT [adenine phosphoribosyltransferase], APTX [aprataxin], AQP1 [aquaporin 1 (Colton blood group)], AQP2 [aquaporin 2 (collecting duct)], AQP3 [aquaporin 3 (Gill blood group)], AQP4 [aquaporin 4], AR [androgen receptor], ARC [activity-regulated cytoskeleton-associated protein], AREG
[amphiregulin], ARFGEF2 [ADP-ribosylation factor guanine nucleotide-exchange factor 2 (brefeldin A-inhibited)], ARG1 [arginase, liver], ARHGAP1 [Rho GTPase activating protein 1], ARHGAP32 [Rho GTPase activating protein 32], ARHGAP4 [Rho GTPase activating protein 4], ARHGAP5 [Rho GTPase activating protein 5], ARHGDIA [Rho GDP dissociation inhibitor (GDI) alpha], ARHGEF1 [Rho guanine nucleotide exchange factor (GEF) 1], ARHGEF10 [Rho guanine nucleotide exchange factor (GEF) 10], ARHGEF11 [Rho guanine nucleotide exchange factor (GEF) 11 ], ARHGEF1 2 [Rho guanine nucleotide exchange factor (GEF) 12], ARHGEF15 [Rho guanine nucleotide exchange factor (GEF) 15], ARHGEF16 [Rho guanine nucleotide exchange factor (GEF) 16], ARHGEF2 [Rho/Rac guanine nucleotide exchange factor (GEF) 2], ARHGEF3 [Rho guanine nucleotide exchange factor (GEF) 3], ARHGEF4 [Rho guanine nucleotide exchange factor (GEF) 4], ARHGEF5 [Rho guanine nucleotide exchange factor (GEF) 5], ARHGEF6 [Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6], ARHGEF7 [Rho guanine nucleotide exchange factor (GEF) 7], ARHGEF9 [Cdc42 guanine nucleotide exchange factor (GEF) 9], ARID1A [AT rich interactive domain 1A (SWI-like)], ARID1 B [AT rich interactive domain 1 B
(SWI1-like)], ARL13B [ADP-ribosylation factor-like 13B], ARPC1A [actin related protein 2/3 complex, subunit 1A, 41 kDa], ARPC1 B [actin related protein 2/3 complex, subunit 1 B, 41 kDa], ARPC2 [actin related protein 2/3 complex, subunit 2, 34kDa], ARPC3 [actin related protein 2/3 complex, subunit 3, 21 kDa], ARPC4 [actin related protein 2/3 complex, subunit 4, 20kDa], ARPC5 [actin related protein complex, subunit 5, 16kDa], ARPC5L [actin related protein 2/3 complex, subunit 5-like], ARPP19 [cAMP-regulated phosphoprotein, 19kDa], ARR3 [arrestin 3, retinal (X-arrestin)], ARRB2 [arrestin, beta 2], ARSA [arylsulfatase A], ARTN
[artemin], ARX [aristaless related homeobox], ASCL1 [achaete-scute complex homolog 1 (Drosophila)], ASMT [acetylserotonin 0-methyltransferase], ASPA
[aspartoacylase (Canavan disease)], ASPG [asparaginase homolog (S.
cerevisiae)], ASPH [aspartate beta-hydroxylase], ASPM [asp (abnormal spindle) homolog, microcephaly associated (Drosophila)], ASRGL1 [asparaginase like 1], ASS1 [argininosuccinate synthase 1], ASTN1 [astrotactin 1], ATAD5 [ATPase family, AAA domain containing 5], ATF2 [activating transcription factor 2], [activating transcription factor 4 (tax-responsive enhancer element B67)], [activating transcription factor 6], ATM [ataxia telangiectasia mutated], [atonal homolog 1 (Drosophila)], ATOX1 [ATX1 antioxidant protein 1 homolog (yeast)], ATP10A [ATPase, class V, type 10A], ATP2A2 [ATPase, Ca++
transporting, cardiac muscle, slow twitch 2], ATP2B2 [ATPase, Ca++
transporting, plasma membrane 2], ATP2B4 [ATPase, Ca++ transporting, plasma membrane 4], ATP5O [ATP synthase, H+ transporting, mitochondrial F1 complex, 0 subunit], ATP6AP1 [ATPase, H+ transporting, lysosomal accessory protein 1], ATP6VOC [ATPase, H+ transporting, lysosomal 16kDa, VO subunit c], ATP7A [ATPase, Cu++ transporting, alpha polypeptide], ATP8A1 [ATPase, aminophospholipid transporter (APLT), class I, type 8A, member 1], ATR [ataxia telangiectasia and Rad3 related], ATRN [attractin], ATRX [alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S.
cerevisiae)], ATXN1 [ataxin 1], ATXN2 [ataxin 2], ATXN3 [ataxin 3], AURKA
[aurora kinase A], AUTS2 [autism susceptibility candidate 2], AVP [arginine vasopressin], AVPR1A [arginine vasopressin receptor 1A], AXIN2 [axin 2], AXL
[AXL receptor tyrosine kinase], AZU1 [azurocidin 1], B2M [beta-2-microglobulin], B3GNT2 [UDP-GIcNAc:betaGal beta-1 [3-N-acetylglucosaminyltransferase 2], B9D1 [B9 protein domain 1 ], BACE1 [beta-site APP-cleaving enzyme 1 ], BACE2 [beta-site APP-cleaving enzyme 2], BACH1 [BTB and CNC homology 1, basic leucine zipper transcription factor 1 ], BAD [BCL2-associated agonist of cell death], BAGE2 [B melanoma antigen family, member 2], BAIAP2 [BAI1-associated protein 2], BAIAP2L1 [BAI1-associated protein 2-like 1], BAK1 [BCL2-antagonist/killer 1], BARD1 [BRCA1 associated RING domain 1], BARHLI [BarH-like homeobox 1], BARHL2 [BarH-like homeobox 2], BASP1 [brain abundant, membrane attached signal protein 1], BAX [BCL2-associated X protein], BAZ1A
[bromodomain adjacent to zinc finger domain, 1A], BAZ1 B [bromodomain adjacent to zinc finger domain, 1 B], BBS9 [Bardet-Biedl syndrome 9], BCAR1 [breast cancer anti-estrogen resistance 1], BCHE [butyrylcholinesterase], [B-cell CLL/lymphoma 10], BCL2 [B-cell CLL/lymphoma 2], BCL2A1 [BCL2-related protein Al], BCL2L1 [BCL2-like 1], BCL2L1 1 [BCL2-like 11 (apoptosis facilitator)], BCL3 [B-cell CLL/lymphoma 3], BCL6 [B-cell CLL/lymphoma 6], BCL7A [B-cell CLL/lymphoma 7A], BCL7B [B-cell CLL/lymphoma 7B], BCL7C [B-cell CLL/lymphoma 7C], BCR [breakpoint cluster region], BDKRB1 [bradykinin receptor B1], BDNF [brain-derived neurotrophic factor], BECN1 [beclin 1, autophagy related], BEST1 [bestrophin 1], BEX1 [brain expressed, X-linked 1], BEX2 [brain expressed X-linked 2], BGLAP [bone gamma-carboxyglutamate (gla) protein], BGN [biglycan], BID [BH3 interacting domain death agonist], [bridging integrator 1], BIRC2 [baculoviral IAP repeat-containing 2], BIRC3 [baculoviral IAP repeat-containing 3], BIRC5 [baculoviral IAP repeat-containing 5], BIRC7 [baculoviral IAP repeat-containing 7], BLK [B lymphoid tyrosine kinase], BLVRB [biliverdin reductase B (flavin reductase (NADPH))], BMI1 [BMI1 polycomb ring finger oncogene], BMP1 [bone morphogenetic protein 1], BMP10 [bone morphogenetic protein 10], BMP15 [bone morphogenetic protein 15], BMP2 [bone morphogenetic protein 2], BMP3 [bone morphogenetic protein 3], BMP4 [bone morphogenetic protein 4], BMP5 [bone morphogenetic protein 5], BMP6 [bone morphogenetic protein 6], BMP7 [bone morphogenetic protein 7], BMP8A [bone morphogenetic protein 8a], BMP8B [bone morphogenetic protein 8b], BMPR1A [bone morphogenetic protein receptor, type IA], BMPR1 B [bone morphogenetic protein receptor, type IB], BMPR2 [bone morphogenetic protein receptor, type II (serine/threonine kinase)], BOC [Boc homolog (mouse)], BOK
[BCL2-related ovarian killer], BPI [bactericidal/permeability-increasing protein], BRAF [v-raf murine sarcoma viral oncogene homolog 131], BRCA1 [breast cancer 1, early onset], BRCA2 [breast cancer 2, early onset], BRWD1 [bromodomain and WD repeat domain containing 1], BSND [Bartter syndrome, infantile, with sensorineural deafness (Barttin)], BST2 [bone marrow stromal cell antigen 2], BTBD10 [BTB (POZ) domain containing 10], BTC [betacellulin], BTD

[biotinidase], BTG3 [BTG family, member 3], BTK [Bruton agammaglobulinemia tyrosine kinase], BTN1A1 [butyrophilin, subfamily 1, member Al], BUB1B
[budding uninhibited by benzimidazoles 1 homolog beta (yeast)], C15orf2 [chromosome 15 open reading frame 2], C16orf75 [chromosome 16 open reading frame 75], C17orf42 [chromosome 17 open reading frame 42], C1orf187 [chromosome 1 open reading frame 187], C1 R [complement component 1, r subcomponent], C1 S [complement component 1, s subcomponent], C21 orf2 [chromosome 21 open reading frame 2], C21orf33 [chromosome 21 open reading frame 33], C21orf45 [chromosome 21 open reading frame 45], C21orf62 [chromosome 21 open reading frame 62], C21orf74 [chromosome 21 open reading frame 74], C3 [complement component 3], C3orf58 [chromosome 3 open reading frame 58], C4A [complement component 4A (Rodgers blood group)], C4B [complement component 4B (Chido blood group)], C5AR1 [complement component 5a receptor 1], C6orf106 [chromosome 6 open reading frame 106], C6orf25 [chromosome 6 open reading frame 25], CA1 [carbonic anhydrase I], CA2 [carbonic anhydrase II], CA3 [carbonic anhydrase III, muscle specific], [carbonic anhydrase VI], CA9 [carbonic anhydrase IX], CABIN1 [calcineurin binding protein 1], CABLES1 [CdkS and AN enzyme substrate 1], CACNA1 B
[calcium channel, voltage-dependent, N type, alpha 1B subunit], CACNA1C
[calcium channel, voltage-dependent, L type, alpha 1 C subunit], CACNA1 G
[calcium channel, voltage-dependent, T type, alpha 1 G subunit], CACNA1 H
[calcium channel, voltage-dependent, T type, alpha 1 H subunit], CACNA2D1 [calcium channel, voltage-dependent, alpha 2/delta subunit 1], CADM1 [cell adhesion molecule 1], CADPS2 [Ca++-dependent secretion activator 2], CALB2 [calbindin 2], CALCA [calcitonin-related polypeptide alpha], CALCR [calcitonin receptor], CALM3 [calmodulin 3 (phosphorylase kinase, delta)], CALR
[calreticulin], CAMK1 [calcium/calmodulin-dependent protein kinase I], CAMK2A
[calcium/calmodulin-dependent protein kinase II alpha], CAMK2B
[calcium/calmodulin-dependent protein kinase II beta], CAMK2G
[calcium/calmodulin-dependent protein kinase II gamma], CAMK4 [calcium/calmodulin-dependent protein kinase IV], CAMKK2 [calcium/calmodulin-dependent protein kinase kinase 2, beta], CAMP [cathelicidin antimicrobial peptide], CANT1 [calcium activated nucleotidase 1], CANX [calnexin], CAPN1 [calpain 1, (mu/1) large subunit], CAPN2 [calpain 2, (m/II) large subunit], [calpain 5], CAPZA1 [capping protein (actin filament) muscle Z-line, alpha 1], CARD16 [caspase recruitment domain family, member 16], CARM1 [coactivator-associated arginine methyltransferase 1], CARTPT [CART prepropeptide], CASK
[calcium/calmodulin-dependent serine protein kinase (MAGUK family)], CASP1 [caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)], CASP10 [caspase 10, apoptosis-related cysteine peptidase], CASP2 [caspase 2, apoptosis-related cysteine peptidase], CASP3 [caspase 3, apoptosis-related cysteine peptidase], CASP6 [caspase 6, apoptosis-related cysteine peptidase], CASP7 [caspase 7, apoptosis-related cysteine peptidase], CASP8 [caspase 8, apoptosis-related cysteine peptidase], CASP8AP2 [caspase 8 associated protein 2], CASP9 [caspase 9, apoptosis-related cysteine peptidase], CASR [calcium-sensing receptor], CAST [calpastatin], CAT
[catalase], CAV1 [caveolin 1, caveolae protein, 22kDa], CAV2 [caveolin 2], [caveolin 3], CBL [Cas-Br-M (murine) ecotropic retroviral transforming sequence], CBLB [Cas-Br-M (murine) ecotropic retroviral transforming sequence b], CBR1 [carbonyl reductase 1], CBR3 [carbonyl reductase 3], CBS [cystathionine-beta-synthase], CBX1 [chromobox homolog 1 (HP1 beta homolog Drosophila )], CBX5 [chromobox homolog 5 (HP1 alpha homolog, Drosophila)], CC2D2A [coiled-coil and C2 domain containing 2A], CCBE1 [collagen and calcium binding EGF
domains 1], CCBL1 [cysteine conjugate-beta lyase, cytoplasmic], CCDC50 [coiled-coil domain containing 50], CCK [cholecystokinin], CCKAR
[cholecystokinin A receptor], CCL1 [chemokine (C-C motif) ligand 1], CCL1 1 [chemokine (C-C motif) ligand 11], CCL13 [chemokine (C-C motif) ligand 13], CCL17 [chemokine (C-C motif) ligand 17], CCL19 [chemokine (C-C motif) ligand 19], CCL2 [chemokine (C-C motif) ligand 2], CCL20 [chemokine (C-C motif) ligand 20], CCL21 [chemokine (C-C motif) ligand 21], CCL22 [chemokine (C-C

motif) ligand 22], CCL26 [chemokine (C-C motif) ligand 26], CCL27 [chemokine (C-C motif) ligand 27], CCL3 [chemokine (C-C motif) ligand 3], CCL4 [chemokine (C-C motif) ligand 4], CCL5 [chemokine (C-C motif) ligand 5], CCL7 [chemokine (C-C motif) ligand 7], CCL8 [chemokine (C-C motif) ligand 8], CCNA1 [cyclin Al], CCNA2 [cyclin A2], CCNB1 [cyclin B1], CCND1 [cyclin D1], CCND2 [cyclin D2], CCND3 [cyclin D3], CCNG1 [cyclin G1], CCNH [cyclin H], CCNT1 [cyclin T1], CCR1 [chemokine (C-C motif) receptor 1], CCR3 [chemokine (C-C motif) receptor 3], CCR4 [chemokine (C-C motif) receptor 4], CCR5 [chemokine (C-C
motif) receptor 5], CCR6 [chemokine (C-C motif) receptor 6], CCR7 [chemokine (C-C motif) receptor 7], COTS [chaperonin containing TCP1, subunit 5 (epsilon)], CD14 [CD14 molecule], CD19 [CD19 molecule], CD1 A [CD1 a molecule], CD1 B
[CD1 b molecule], CD1D [CD1 d molecule], CD2 [CD2 molecule], CD209 [CD209 molecule], CD22 [CD22 molecule], CD244 [CD244 molecule, natural killer cell receptor 2B4], CD247 [CD247 molecule], CD27 [CD27 molecule], CD274 [CD274 molecule], CD28 [CD28 molecule], CD2AP [CD2-associated protein], CD33 [CD33 molecule], CD34 [CD34 molecule], CD36 [CD36 molecule (thrombospondin receptor)], CD3E [CD3e molecule, epsilon (CD3-TCR
complex)], CD3G [CD3g molecule, gamma (CD3-TCR complex)], CD4 [CD4 molecule], CD40 [CD40 molecule, TNF receptor superfamily member 5], CD40LG [CD40 ligand], CD44 [CD44 molecule (Indian blood group)], CD46 [CD46 molecule, complement regulatory protein], CD47 [CD47 molecule], CD5 [CD5 molecule], CD55 [CD55 molecule, decay accelerating factor for complement (Cromer blood group)], CD58 [CD58 molecule], CD59 [CD59 molecule, complement regulatory protein], CD63 [CD63 molecule], CD69 [CD69 molecule], CD7 [CD7 molecule], CD72 [CD72 molecule], CD74 [CD74 molecule, major histocompatibility complex, class II invariant chain], CD79A [CD79a molecule, immunoglobulin-associated alpha], CD79B [CD79b molecule, immunoglobulin-associated beta], CD80 [CD80 molecule], CD81 [CD81 molecule], CD86 [CD86 molecule], CD8A [CD8a molecule], CD9 [CD9 molecule], CD99 [CD99 molecule], CDA [cytidine deaminase], CDC25A [cell division cycle 25 homolog A (S. pombe)], CDC25C [cell division cycle 25 homolog C (S.
pombe)], CDC37 [cell division cycle 37 homolog (S. cerevisiae)], CDC42 [cell division cycle 42 (GTP binding protein, 25kDa)], CDC5L [CDC5 cell division cycle 5-like (S. pombe)], CDH1 [cadherin 1, type 1, E-cadherin (epithelial)], CDH10 [cadherin 10, type 2 (T2-cadherin)], CDH12 [cadherin 12, type 2 (N-cadherin 2)], CDH15 [cadherin 15, type 1, M-cadherin (myotubule)], CDH2 [cadherin 2, type 1, N-cadherin (neuronal)], CDH4 [cadherin 4, type 1, R-cadherin (retinal)], CDH5 [cadherin 5, type 2 (vascular endothelium)], CDH9 [cadherin 9, type 2 (T1-cadherin)], CDIPT [CDP-diacylglycerol--inositol 3-phosphatidyltransferase (phosphatidylinositol synthase)], CDK1 [cyclin-dependent kinase 1], CDK14 [cyclin-dependent kinase 14], CDK2 [cyclin-dependent kinase 2], CDK4 [cyclin-dependent kinase 4], CDK5 [cyclin-dependent kinase 5], CDK5R1 [cyclin-dependent kinase 5, regulatory subunit 1 (p35)], CDK5RAP2 [CDK5 regulatory subunit associated protein 2], CDK6 [cyclin-dependent kinase 6], CDK7 [cyclin-dependent kinase 7], CDK9 [cyclin-dependent kinase 9], CDKL5 [cyclin-dependent kinase-like 5], CDKN1A [cyclin-dependent kinase inhibitor 1A (p21, Cip1)], CDKN1B [cyclin-dependent kinase inhibitor 1B (p27, Kip1)], CDKN1C
[cyclin-dependent kinase inhibitor 1C (p57, Kip2)], CDKN2A [cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)], CDKN2B [cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)], CDKN2C [cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)], CDKN2D [cyclin-dependent kinase inhibitor (p19, inhibits CDK4)], CDNF [cerebral dopamine neurotrophic factor], CDO1 [cysteine dioxygenase, type I], CDR2 [cerebellar degeneration-related protein 2, 62kDa], CDT1 [chromatin licensing and DNA replication factor 1], CDX1 [caudal type homeobox 1], CDX2 [caudal type homeobox 2], CEACAM1 [carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)], CEACAM3 [carcinoembryonic antigen-related cell adhesion molecule 3], CEACAMS [carcinoembryonic antigen-related cell adhesion molecule 5], CEACAM7 [carcinoembryonic antigen-related cell adhesion molecule 7], CEBPB [CCAAT/enhancer binding protein (C/EBP), beta], CEBPD

[CCAAT/enhancer binding protein (C/EBP), delta], CECR2 [cat eye syndrome chromosome region, candidate 2], CEL [carboxyl ester lipase (bile salt-stimulated lipase)], CENPC1 [centromere protein C 1], CENPJ [centromere protein J], CEP290 [centrosomal protein 290kDa], CER1 [cerberus 1, cysteine knot superfamily, homolog (Xenopus laevis)], CETP [cholesteryl ester transfer protein, plasma], CFC1 [cripto, FRL-1, cryptic family 1], CFH [complement factor H], CFHR1 [complement factor H-related 1], CFHR3 [complement factor H-related 3], CFHR4 [complement factor H-related 4], CFI [complement factor I], CFL1 [cofilin 1 (non-muscle)], CFL2 [cofilin 2 (muscle)], CFLAR [CASP8 and FADD-like apoptosis regulator], CFTR [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)], CGA [glycoprotein hormones, alpha polypeptide], CGB [chorionic gonadotropin, beta polypeptide], CGB5 [chorionic gonadotropin, beta polypeptide 5], CGGBP1 [CGG triplet repeat binding protein 1], CHAFIA [chromatin assembly factor 1, subunit A (p150)], CHAF1 B [chromatin assembly factor 1, subunit B (p60)], CHAT [choline acetyltransferase], CHEK1 [CHK1 checkpoint homolog (S. pombe)], CHEK2 [CHK2 checkpoint homolog (S. pombe)], CHGA [chromogranin A (parathyroid secretory protein 1)], CHKA [choline kinase alpha], CHL1 [cell adhesion molecule with homology to L1 CAM (close homolog of L1)], CHN1 [chimerin (chimaerin) 1 ], CHP [calcium binding protein P22], CHP2 [calcineurin B homologous protein 2], CHRD [chordin], CHRM1 [cholinergic receptor, muscarinic 1], CHRM2 [cholinergic receptor, muscarinic 2], CHRM3 [cholinergic receptor, muscarinic 3], CHRM5 [cholinergic receptor, muscarinic 5], CHRNA3 [cholinergic receptor, nicotinic, alpha 3], CHRNA4 [cholinergic receptor, nicotinic, alpha 4], CHRNA7 [cholinergic receptor, nicotinic, alpha 7], CHRNB2 [cholinergic receptor, nicotinic, beta 2 (neuronal)], CHST1 [carbohydrate (keratan sulfate Gal-6) sulfotransferase 1], CHST10 [carbohydrate sulfotransferase 10], CHST3 [carbohydrate (chondroitin 6) sulfotransferase 3], CHUK [conserved helix-loop-helix ubiquitous kinase], CHURC1 [churchill domain containing 1], CIB1 [calcium and integrin binding 1 (calmyrin)], CIITA [class II, major histocompatibility complex, transactivator], CIRBP [cold inducible RNA binding protein], CISD1 [CDGSH iron sulfur domain 1], CISH [cytokine inducible SH2-containing protein], CIT
[citron (rho-interacting, serine/threonine kinase 21)], CLASP2 [cytoplasmic linker associated protein 2], CLCF1 [cardiotrophin-like cytokine factor 1], CLCN2 [chloride channel 2], CLDN1 [claudin 1], CLDN14 [claudin 14], CLDN16 [claudin 16], CLDN3 [claudin 3], CLDN4 [claudin 4], CLDN5 [claudin 5], CLDN8 [claudin 8], CLEC1 2A [C-type lectin domain family 12, member A], CLEC1 6A [C-type lectin domain family 16, member A], CLEC5A [C-type lectin domain family 5, member A], CLEC7A [C-type lectin domain family 7, member A], CLIP2 [CAP-GLY domain containing linker protein 2], CLSTN1 [calsyntenin 1], CLTC
[clathrin, heavy chain (Hc)], CLU [clusterin], CMIP [c-Maf-inducing protein], CNBP [CCHC-type zinc finger, nucleic acid binding protein], CNGA3 [cyclic nucleotide gated channel alpha 3], CNGB3 [cyclic nucleotide gated channel beta 3], CNN1 [calponin 1, basic, smooth muscle], CNN2 [calponin 2], CNN3 [calponin 3, acidic], CNOT8 [CCR4-NOT transcription complex, subunit 8], CNP [2' [3'-cyclic nucleotide 3' phosphodiesterase], CNR1 [cannabinoid receptor 1 (brain)], CNR2 [cannabinoid receptor 2 (macrophage)], CNTF [ciliary neurotrophic factor], CNTFR [ciliary neurotrophic factor receptor], CNTFR [ciliary neurotrophic factor receptor], CNTFR [ciliary neurotrophic factor receptor], CNTLN [centlein, centrosomal protein], CNTN1 [contactin 1], CNTN2 [contactin 2 (axonal)], CNTN4 [contactin 4], CNTNAP1 [contactin associated protein 1], CNTNAP2 [contactin associated protein-like 2], COBL [cordon-bleu homolog (mouse)], COG2 [component of oligomeric golgi complex 2], COL18A1 [collagen, type XVIII, alpha 1], COL1A1 [collagen, type I, alpha 1], COL1 A2 [collagen, type I, alpha 2], COL2A1 [collagen, type II, alpha 1], COL3A1 [collagen, type III, alpha 1], COL4A3 [collagen, type IV, alpha 3 (Goodpasture antigen)], COL4A3BP
[collagen, type IV, alpha 3 (Goodpasture antigen) binding protein], COL5A1 [collagen, type V, alpha 1 ], COL5A2 [collagen, type V, alpha 2], COL6A1 [collagen, type VI, alpha 1], COL6A2 [collagen, type VI, alpha 2], COL6A3 [collagen, type VI, alpha 3], COMT [catechol-O-methyltransferase], COPG2 [coatomer protein complex, subunit gamma 2], COPS4 [COP9 constitutive photomorphogenic homolog subunit 4 (Arabidopsis)], CORO1A [coronin, actin binding protein, 1A], COXSA [cytochrome c oxidase subunit Va], COX7B
[cytochrome c oxidase subunit VIIb], CP [ceruloplasmin (ferroxidase)], CPA1 [carboxypeptidase Al (pancreatic)], CPA2 [carboxypeptidase A2 (pancreatic)], CPA5 [carboxypeptidase A5], CPB2 [carboxypeptidase B2 (plasma)], CPOX
[coproporphyrinogen oxidase], CPS1 [carbamoyl-phosphate synthetase 1, mitochondrial], CPT1A [carnitine palm itoyltransferase 1A (liver)], CR1 [complement component (3b/4b) receptor 1 (Knops blood group)], CR2 [complement component (3d/Epstein Barr virus) receptor 2], CRABP1 [cellular retinoic acid binding protein 1], CRABP2 [cellular retinoic acid binding protein 2], CRAT [carnitine 0-acetyltransferase], CRB1 [crumbs homolog 1 (Drosophila)], CREB1 [cAMP responsive element binding protein 1], CREBBP [CREB binding protein], CRELD1 [cysteine-rich with EGF-like domains 1], CRH [corticotropin releasing hormone], CRIP1 [cysteine-rich protein 1 (intestinal)], CRK [v-crk sarcoma virus CT10 oncogene homolog (avian)], CRKL [v-crk sarcoma virus CT10 oncogene homolog (avian)-like], CRLF1 [cytokine receptor-like factor 1], CRLF2 [cytokine receptor-like factor 2], CRLF3 [cytokine receptor-like factor 3], CRMP1 [collapsin response mediator protein 1], CRP [C-reactive protein, pentraxin-related], CRTC1 [CREB regulated transcription coactivator 1], CRX
[cone-rod homeobox], CRYAA [crystallin, alpha A], CRYAB [crystallin, alpha B], CS [citrate synthase], CSAD [cysteine sulfinic acid decarboxylase], CSF1 [colony stimulating factor 1 (macrophage)], CSF1 R [colony stimulating factor 1 receptor], CSF2 [colony stimulating factor 2 (granulocyte-macrophage)], CSF2RA [colony stimulating factor 2 receptor, alpha, low-affinity (granulocyte-macrophage)], CSF3 [colony stimulating factor 3 (granulocyte)], CSF3R [colony stimulating factor 3 receptor (granulocyte)], CSH2 [chorionic somatomammotropin hormone 2], CSK [c-src tyrosine kinase], CSMD1 [CUB and Sushi multiple domains 1], CSMD3 [CUB and Sushi multiple domains 3], CSNK1 D [casein kinase 1, delta], CSNK1 E [casein kinase 1, epsilon], CSNK2A1 [casein kinase 2, alpha 1 polypeptide], CSPG4 [chondroitin sulfate proteoglycan 4], CSPG5 [chondroitin sulfate proteoglycan 5 (neuroglycan C)], CST3 [cystatin C], CST7 [cystatin F
(leukocystatin)], CSTB [cystatin B (stefin B)], CTAG1 B [cancer/testis antigen 1 B], CTBP1 [C-terminal binding protein 1], CTCF [CCCTC-binding factor (zinc finger protein)], CTDSP1 [CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase 1], CTF1 [cardiotrophin 1], CTGF [connective tissue growth factor], CTLA4 [cytotoxic T-lymphocyte-associated protein 4], CTNNA1 [catenin (cadherin-associated protein), alpha 1, 102kDa], CTNNAL1 [catenin (cadherin-associated protein), alpha-like 1], CTNNB1 [catenin (cadherin-associated protein), beta 1, 88kDa], CTNND1 [catenin (cadherin-associated protein), delta 1], CTNND2 [catenin (cadherin-associated protein), delta 2 (neural plakophilin-related arm-repeat protein)], CTNS [cystinosis, nephropathic], CTRL
[chymotrypsin-like], CTSB [cathepsin B], CTSC [cathepsin C], CTSD [cathepsin D], CTSG [cathepsin G], CTSH [cathepsin H], CTSL1 [cathepsin L1], CTSS
[cathepsin S], CTTN [cortactin], CTTNBP2 [cortactin binding protein 2], CUL4B
[cullin 4B], CUL5 [cullin 5], CUX2 [cut-like homeobox 2], CX3CL1 [chemokine (C-X3-C motif) ligand 1], CX3CR1 [chemokine (C-X3-C motif) receptor 1], CXADR
[coxsackie virus and adenovirus receptor], CXCL1 [chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha)], CXCL10 [chemokine (C-X-C motif) ligand 10], CXCL12 [chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)], CXCL16 [chemokine (C-X-C motif) ligand 16], CXCL2 [chemokine (C-X-C motif) ligand 2], CXCL5 [chemokine (C-X-C motif) ligand 5], CXCR1 [chemokine (C-X-C motif) receptor 1], CXCR2 [chemokine (C-X-C motif) receptor 2], CXCR3 [chemokine (C-X-C motif) receptor 3], CXCR4 [chemokine (C-X-C motif) receptor 4], CXCR5 [chemokine (C-X-C motif) receptor 5], CYB5A
[cytochrome b5 type A (microsomal)], CYBA [cytochrome b-245, alpha polypeptide], CYBB [cytochrome b-245, beta polypeptide], CYCS [cytochrome c, somatic], CYFIP1 [cytoplasmic FMR1 interacting protein 1], CYLD
[cylindromatosis (turban tumor syndrome)], CYP11A1 [cytochrome P450, family 11, subfamily A, polypeptide 1 ], CYP11 B1 [cytochrome P450, family 11, subfamily B, polypeptide 1], CYP11B2 [cytochrome P450, family 11, subfamily B, polypeptide 2], CYP17A1 [cytochrome P450, family 17, subfamily A, polypeptide 1], CYP19A1 [cytochrome P450, family 19, subfamily A, polypeptide 1], CYP1A1 [cytochrome P450, family 1, subfamily A, polypeptide 1], CYP1A2 [cytochrome P450, family 1, subfamily A, polypeptide 2], CYP1 B1 [cytochrome P450, family 1, subfamily B, polypeptide 1], CYP21A2 [cytochrome P450, family 21, subfamily A, polypeptide 2], CYP2A6 [cytochrome P450, family 2, subfamily A, polypeptide 6], CYP2B6 [cytochrome P450, family 2, subfamily B, polypeptide 6], CYP2C9 [cytochrome P450, family 2, subfamily C, polypeptide 9], CYP2D6 [cytochrome P450, family 2, subfamily D, polypeptide 6], CYP2E1 [cytochrome P450, family 2, subfamily E, polypeptide 1], CYP3A4 [cytochrome P450, family 3, subfamily A, polypeptide 4], CYP7A1 [cytochrome P450, family 7, subfamily A, polypeptide 1], CYR61 [cysteine-rich, angiogenic inducer, 61], CYSLTR1 [cysteinyl leukotriene receptor 1], CYSLTR2 [cysteinyl leukotriene receptor 2], DAB1 [disabled homolog 1 (Drosophila)], DAGLA [diacylglycerol lipase, alpha], DAGLB
[diacylglycerol lipase, beta], DAO [D-amino-acid oxidase], DAOA [D-amino acid oxidase activator], DAPK1 [death-associated protein kinase 1], DAPK3 [death-associated protein kinase 3], DAXX [death-domain associated protein], DBH
[dopamine beta-hydroxylase (dopamine beta-monooxygenase)], DBI [diazepam binding inhibitor (GABA receptor modulator, acyl-Coenzyme A binding protein)], DBN1 [drebrin 1], DCAF6 [DDB1 and CUL4 associated factor 6], DCC [deleted in colorectal carcinoma], DCDC2 [doublecortin domain containing 2], DCK
[deoxycytidine kinase], DCLK1 [doublecortin-like kinase 1], DCN [decorin], DCTN1 [dynactin 1 (p150, glued homolog, Drosophila)], DCTN2 [dynactin 2 (p50)], DCTN4 [dynactin 4 (p62)], DCUN1D1 [DCN1, defective in cullin neddylation 1, domain containing 1 (S. cerevisiae)], DCX [doublecortin], DDB1 [damage-specific DNA binding protein 1, 127kDa], DDC [dopa decarboxylase (aromatic L-amino acid decarboxylase)], DDIT3 [DNA-damage-inducible transcript 3], DDIT4 [DNA-damage-inducible transcript 4], DDIT4L [DNA-damage-inducible transcript 4-like], DDR1 [discoidin domain receptor tyrosine kinase 1 ], DDX10 [DEAD (Asp-Glu-Ala-Asp) box polypeptide 10], DDX17 [DEAD
(Asp-Glu-Ala-Asp) box polypeptide 17], DEFB4A [defensin, beta 4A], DEK [DEK
oncogene], DES [desmin], DEXI [Dexi homolog (mouse)], DFFA [DNA
fragmentation factor, 45kDa, alpha polypeptide], DFNB31 [deafness, autosomal recessive 31], DGCR6 [DiGeorge syndrome critical region gene 6], DGUOK
[deoxyguanosine kinase], DHCR7 [7-dehydrocholesterol reductase], DHFR
[dihydrofolate reductase], DIAPH1 [diaphanous homolog 1 (Drosophila)], DICER1 [dicer 1, ribonuclease type III], DIO1 [deiodinase, iodothyronine, type I], D102 [deiodinase, iodothyronine, type II], DIP2A [DIP2 disco-interacting protein 2 homolog A (Drosophila)], DIRAS3 [DIRAS family, GTP-binding RAS-like 3], DISC1 [disrupted in schizophrenia 1], DISC2 [disrupted in schizophrenia 2 (non-protein coding)], DKC1 [dyskeratosis congenita 1, dyskerin], DLG1 [discs, large homolog 1 (Drosophila)], DLG2 [discs, large homolog 2 (Drosophila)], DLG3 [discs, large homolog 3 (Drosophila)], DLG4 [discs, large homolog 4 (Drosophila)], DLGAP1 [discs, large (Drosophila) homolog-associated protein 1], DLGAP2 [discs, large (Drosophila) homolog-associated protein 2], DLK1 [delta-like 1 homolog (Drosophila)], DLL1 [delta-like 1 (Drosophila)], DLX1 [distal-less homeobox 1], DLX2 [distal-less homeobox 2], DLX3 [distal-less homeobox 3], DLX4 [distal-less homeobox 4], DLX5 [distal-less homeobox 5], DLX6 [distal-less homeobox 6], DMBT1 [deleted in malignant brain tumors 1], DMC1 [DMC1 dosage suppressor of mckl homolog, meiosis-specific homologous recombination (yeast)], DMD [dystrophin], DMPK [dystrophia myotonica-protein kinase], DNAI2 [dynein, axonemal, intermediate chain 2], DNAJC28 [DnaJ
(Hsp40) homolog, subfamily C, member 28], DNAJC30 [DnaJ (Hsp40) homolog, subfamily C, member 30], DNASE1 [deoxyribonuclease I], DNER [delta/notch-like EGF repeat containing], DNLZ [DNL-type zinc finger], DNM1 [dynamin 1], DNM3 [dynamin 3], DNMT1 [DNA (cytosine-5-)-methyltransferase 1], DNMT3A
[DNA (cytosine-5-)-methyltransferase 3 alpha], DNMT3B [DNA (cytosine-5-)-methyltransferase 3 beta], DNTT [deoxynucleotidyltransferase, terminal], DOC2A
[double C2-like domains, alpha], DOCK1 [dedicator of cytokinesis 1], DOCK3 [dedicator of cytokinesis 3], DOCK4 [dedicator of cytokinesis 4], DOCK7 [dedicator of cytokinesis 7], DOK7 [docking protein 7], DONSON [downstream neighbor of SON], DOPEY1 [dopey family member 1], DOPEY2 [dopey family member 2], DPF1 [D4, zinc and double PHD fingers family 1], DPF3 [D4, zinc and double PHD fingers, family 3], DPH1 [DPH1 homolog (S. cerevisiae)], DPP1 0 [dipeptidyl-peptidase 10], DPP4 [dipeptidyl-peptidase 4], DPRXP4 [divergent-paired related homeobox pseudogene 4], DPT [dermatopontin], DPYD
[dihydropyrimidine dehydrogenase], DPYSL2 [dihydropyrimidinase-like 2], DPYSL3 [dihydropyrimidinase-like 3], DPYSL4 [dihydropyrimidinase-like 4], DPYSL5 [dihydropyrimidinase-like 5], DRD1 [dopamine receptor D1], DRD2 [dopamine receptor D2], DRD3 [dopamine receptor D3], DRD4 [dopamine receptor D4], DRD5 [dopamine receptor D5], DRG1 [developmentally regulated GTP binding protein 1], DRGX [dorsal root ganglia homeobox], DSC2 [desmocollin 2], DSCAM [Down syndrome cell adhesion molecule], DSCAML1 [Down syndrome cell adhesion molecule like 1], DSCR3 [Down syndrome critical region gene 3], DSCR4 [Down syndrome critical region gene 4], DSCR6 [Down syndrome critical region gene 6], DSERG1 [Down syndrome encephalopathy related protein 1], DSG1 [desmoglein 1], DSG2 [desmoglein 2], DSP
[desmoplakin], DST [dystonin], DSTN [destrin (actin depolymerizing factor)], DTNBP1 [dystrobrevin binding protein 1], DULLARD [dullard homolog (Xenopus laevis)], DUSP1 [dual specificity phosphatase 1 ], DUSP13 [dual specificity phosphatase 13], DUSP6 [dual specificity phosphatase 6], DUT [deoxyuridine triphosphatase], DVL1 [dishevelled, dsh homolog 1 (Drosophila)], DYRK1A [dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A], DYRK3 [dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 3], DYSF [dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive)], DYX1 C1 [dyslexia susceptibility 1 candidate 1], E2F1 [E2F transcription factor 1], EARS2 [glutamyl-tRNA synthetase 2, mitochondrial (putative)], EBF4 [early B-cell factor 4], [endothelin converting enzyme 1], ECHS1 [enoyl Coenzyme A hydratase, short chain, 1, mitochondrial], EDN1 [endothelin 1], EDN2 [endothelin 2], EDN3 [endothelin 3], EDNRA [endothelin receptor type A], EDNRB [endothelin receptor type B], EEF1A1 [eukaryotic translation elongation factor 1 alpha 1], EEF2 [eukaryotic translation elongation factor 2], EEF2K [eukaryotic elongation factor-2 kinase], EFHA1 [EF-hand domain family, member Al], EFNA1 [ephrin-Al], EFNA2 [ephrin-A2], EFNA3 [ephrin-A3], EFNA4 [ephrin-A4], EFNA5 [ephrin-A5], EFNB2 [ephrin-B2], EFNB3 [ephrin-B3], EFS [embryonal Fyn-associated substrate], EGF [epidermal growth factor (beta-urogastrone)], EGFR [epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)], EGLN1 [egl nine homolog 1 (C. elegans)], EGR1 [early growth response 1], EGR2 [early growth response 2], EGR3 [early growth response 3], EHHADH
[enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase], EHMT2 [euchromatic histone-lysine N-methyltransferase 2], EID1 [EP300 interacting inhibitor of differentiation 1], EIFIAY [eukaryotic translation initiation factor 1A, Y-linked], EIF2AK2 [eukaryotic translation initiation factor 2-alpha kinase 2], EIF2AK3 [eukaryotic translation initiation factor 2-alpha kinase 3], EIF2B2 [eukaryotic translation initiation factor 2B, subunit 2 beta, 39kDa], EIF2B5 [eukaryotic translation initiation factor 2B, subunit 5 epsilon, 82kDa], EIF2S1 [eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa], [eukaryotic translation initiation factor 2, subunit 2 beta, 38kDa], EIF3M
[eukaryotic translation initiation factor 3, subunit M], EIF4E [eukaryotic translation initiation factor 4E], EIF4EBP1 [eukaryotic translation initiation factor 4E
binding protein 1], EIF4G1 [eukaryotic translation initiation factor 4 gamma, 1], [eukaryotic translation initiation factor 4H], ELANE [elastase, neutrophil expressed], ELAVL1 [ELAV (embryonic lethal, abnormal vision, Drosophila)-like 1 (Hu antigen R)], ELAVL3 [ELAV (embryonic lethal, abnormal vision, Drosophila)-like 3 (Hu antigen C)], ELAVL4 [ELAV (embryonic lethal, abnormal vision, Drosophila)-like 4 (Hu antigen D)], ELF5 [E74-like factor 5 (ets domain transcription factor)], ELK1 [ELK1, member of ETS oncogene family], ELMO1 [engulfment and cell motility 1], ELN [elastin], ELP4 [elongation protein 4 homolog (S. cerevisiae)], EMP2 [epithelial membrane protein 2], EMP3 [epithelial membrane protein 3], EMX1 [empty spiracles homeobox 1], EMX2 [empty spiracles homeobox 2], EN1 [engrailed homeobox 1], EN2 [engrailed homeobox 2], ENAH [enabled homolog (Drosophila)], ENDOG [endonuclease G], ENG
[endoglin], ENO1 [enolase 1, (alpha)], ENO2 [enolase 2 (gamma, neuronal)], ENPEP [glutamyl aminopeptidase (aminopeptidase A)], ENPP1 [ectonucleotide pyrophosphatase/phosphodiesterase 1], ENPP2 [ectonucleotide pyrophosphatase/phosphodiesterase 2], ENSA [endosulfine alpha], ENSG00000174496 [], ENSG00000183653 [], ENSG00000215557 [], ENTPD1 [ectonucleoside triphosphate diphosphohydrolase 1], EP300 [E1A binding protein p300], EPCAM [epithelial cell adhesion molecule], EPHA1 [EPH receptor Al], EPHA1 0 [EPH receptor Al 0], EPHA2 [EPH receptor A2], EPHA3 [EPH receptor A3], EPHA4 [EPH receptor A4], EPHA5 [EPH receptor A5], EPHA6 [EPH
receptor A6], EPHA7 [EPH receptor A7], EPHA8 [EPH receptor A8], EPHB1 [EPH receptor B1], EPHB2 [EPH receptor B2 ], EPHB3 [EPH receptor B3], EPHB4 [EPH receptor B4], EPHB6 [EPH receptor B6], EPHX2 [epoxide hydrolase 2, cytoplasmic], EPM2A [epilepsy, progressive myoclonus type 2A, Lafora disease (laforin)], EPO [erythropoietin], EPOR [erythropoietin receptor], EPRS [glutamyl-prolyl-tRNA synthetase], EPS15 [epidermal growth factor receptor pathway substrate 15], ERBB2 [v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)], ERBB3 [v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian)], ERBB4 [v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian)], ERC2 [ELKS/RAB6-interacting/CAST family member 2], ERCC2 [excision repair cross-complementing rodent repair deficiency, complementation group 2], ERCC3 [excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)], ERCC5 [excision repair cross-complementing rodent repair deficiency, complementation group 5], ERCC6 [excision repair cross-complementing rodent repair deficiency, complementation group 6], ERCC8 [excision repair cross-complementing rodent repair deficiency, complementation group 8], EREG

[epiregulin], ERG [v-ets erythroblastosis virus E26 oncogene homolog (avian)], ERVWE1 [endogenous retroviral family W, env(C7), member 1], ESD [esterase D/formylglutathione hydrolase], ESR1 [estrogen receptor 1], ESR2 [estrogen receptor 2 (ER beta)], ESRRA [estrogen-related receptor alpha], ESRRB
[estrogen-related receptor beta], ETS1 [v-ets erythroblastosis virus E26 oncogene homolog 1 (avian)], ETS2 [v-ets erythroblastosis virus E26 oncogene homolog 2 (avian)], ETV1 [ets variant 1 ], ETV4 [ets variant 4], ETV5 [ets variant 5], ETV6 [ets variant 6], EVL [EnahNasp-like], EXOC4 [exocyst complex component 4], EXOC8 [exocyst complex component 8], EXT1 [exostoses (multiple) 1], EXT2 [exostoses (multiple) 2], EZH2 [enhancer of zeste homolog (Drosophila)], EZR [ezrin], F12 [coagulation factor XII (Hageman factor)], F2 [coagulation factor II (thrombin)], F2R [coagulation factor II (thrombin) receptor], F2RL1 [coagulation factor II (thrombin) receptor-like 1], F3 [coagulation factor III
(thromboplastin, tissue factor)], F7 [coagulation factor VII (serum prothrombin conversion accelerator)], F8 [coagulation factor VIII, procoagulant component], F9 [coagulation factor IX], FAAH [fatty acid amide hydrolase], FABP3 [fatty acid binding protein 3, muscle and heart (mammary-derived growth inhibitor)], FABP4 [fatty acid binding protein 4, adipocyte], FABP5 [fatty acid binding protein 5 (psoriasis-associated)], FABP7 [fatty acid binding protein 7, brain], FADD
[Fas (TNFRSF6)-associated via death domain], FADS2 [fatty acid desaturase 2], FAM120C [family with sequence similarity 120C], FAM165B [family with sequence similarity 165, member B], FAM3C [family with sequence similarity 3, member C], FAM53A [family with sequence similarity 53, member A], FARP2 [FERM, RhoGEF and pleckstrin domain protein 2], FARSA [phenylalanyl-tRNA
synthetase, alpha subunit], FAS [Fas (TNF receptor superfamily, member 6)], FASLG [Fas ligand (TNF superfamily, member 6)], FASN [fatty acid synthase], FASTK [Fas-activated serine/threonine kinase], FBLN1 [fibulin 1], FBN1 [fibrillin 1], FBP1 [fructose-1 [6-bisphosphatase 1], FBXO45 [F-box protein 45], FBXW5 [F-box and WD repeat domain containing 5], FBXW7 [F-box and WD repeat domain containing 7], FCER2 [Fc fragment of IgE, low affinity II, receptor for (CD23)], FCGR1A [Fc fragment of IgG, high affinity Ia, receptor (CD64)], FCGR2A [Fc fragment of IgG, low affinity Ila, receptor (CD32)], FCGR2B [Fc fragment of IgG, low affinity Ilb, receptor (CD32)], FCGR3A [Fc fragment of IgG, low affinity Ilia, receptor (CD16a)], FCRL3 [Fc receptor-like 3], FDFT1 [farnesyl-diphosphate farnesyltransferase 1 ], FDX1 [ferredoxin 1 ], FDXR [ferredoxin reductase], FECH [ferrochelatase (protoporphyria)], FEM1A [fem-1 homolog a (C. elegans)], FER [fer (fps/fes related) tyrosine kinase], FES [feline sarcoma oncogene], FEZ1 [fasciculation and elongation protein zeta 1 (zygin I)], FEZ2 [fasciculation and elongation protein zeta 2 (zygin II)], FEZF1 [FEZ family zinc finger 1 ], FEZF2 [FEZ family zinc finger 2], FGF1 [fibroblast growth factor 1 (acidic)], FGF19 [fibroblast growth factor 19], FGF2 [fibroblast growth factor (basic)], FGF20 [fibroblast growth factor 20], FGF3 [fibroblast growth factor (murine mammary tumor virus integration site (v-int-2) oncogene homolog)], FGF4 [fibroblast growth factor 4], FGF5 [fibroblast growth factor 5], FGF7 [fibroblast growth factor 7 (keratinocyte growth factor)], FGF8 [fibroblast growth factor 8 (androgen-induced)], FGF9 [fibroblast growth factor 9 (glia-activating factor)], FGFBP1 [fibroblast growth factor binding protein 1], FGFR1 [fibroblast growth factor receptor 1 ], FGFR2 [fibroblast growth factor receptor 2], FGFR3 [fibroblast growth factor receptor 3], FGFR4 [fibroblast growth factor receptor 4], FHIT [fragile histidine triad gene], FHL1 [four and a half LIM domains 1], [four and a half LIM domains 2], FIBP [fibroblast growth factor (acidic) intracellular binding protein ], FIGF [c-fos induced growth factor (vascular endothelial growth factor D)], FIGNL1 [fidgetin-like 1], FKBP15 [FK506 binding protein 15, 133kDa], FKBP1 B [FK506 binding protein 1 B, 12.6 kDa], FKBP5 [FK506 binding protein 5], FKBP6 [FK506 binding protein 6, 36kDa], FKBP8 [FK506 binding protein 8, 38kDa], FKTN [fukutin], FLCN [folliculin], FLG
[filaggrin], FL11 [Friend leukemia virus integration 1], FLNA [filamin A, alpha], FLNB [filamin B, beta], FLNC [filamin C, gamma], FLT1 [fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)], FLT3 [fms-related tyrosine kinase 3], FMN1 [formin 1], FMNL2 [formin-like 2], FMR1 [fragile X mental retardation 1], FN1 [fibronectin 1], [folate hydrolase (prostate-specific membrane antigen) 1], FOLR1 [folate receptor 1 (adult)], FOS [FBJ murine osteosarcoma viral oncogene homolog], FOSB [FBJ murine osteosarcoma viral oncogene homolog B], FOXC2 [forkhead box C2 (MFH-1, mesenchyme forkhead 1)], FOXG1 [forkhead box G1], FOXL2 [forkhead box L2], FOXM1 [forkhead box M1], FOXO1 [forkhead box 01], FOXO3 [forkhead box 03], FOXP2 [forkhead box P2], FOXP3 [forkhead box P3], FPR1 [formyl peptide receptor 1], FPR2 [formyl peptide receptor 2], FRMD7 [FERM domain containing 7], FRS2 [fibroblast growth factor receptor substrate 2], FRS3 [fibroblast growth factor receptor substrate 3], FRYL [FRY-like], [fascin homolog 1, actin-bundling protein (Strongylocentrotus purpuratus)], FSHB
[follicle stimulating hormone, beta polypeptide], FSHR [follicle stimulating hormone receptor], FST [follistatin], FSTL1 [follistatin-like 1], FSTL3 [follistatin-like 3 (secreted glycoprotein)], FTCD [formiminotransferase cyclodeaminase], FTH1 [ferritin, heavy polypeptide 1], FTL [ferritin, light polypeptide], FTMT
[ferritin mitochondrial], FTSJ1 [FtsJ homolog 1 (E. coli)], FUCA1 [fucosidase, alpha-L-1, tissue], FURIN [furin (paired basic amino acid cleaving enzyme)], FUT1 [fucosyltransferase 1 (galactoside 2-alpha-L-fucosyltransferase, H blood group)], FUT4 [fucosyltransferase 4 (alpha (1 [3) fucosyltransferase, myeloid-specific)], FXN [frataxin], FXR1 [fragile X mental retardation, autosomal homolog 1], FXR2 [fragile X mental retardation, autosomal homolog 2], FXYD1 [FXYD domain containing ion transport regulator 1], FYB [FYN binding protein (FYB-1 20/130)], FYN [FYN oncogene related to SRC, FGR, YES], FZD1 [frizzled homolog 1 (Drosophila)], FZD10 [frizzled homolog 10 (Drosophila)], FZD2 [frizzled homolog 2 (Drosophila)], FZD3 [frizzled homolog 3 (Drosophila)], FZD4 [frizzled homolog 4 (Drosophila)], FZD5 [frizzled homolog 5 (Drosophila)], FZD6 [frizzled homolog 6 (Drosophila)], FZD7 [frizzled homolog 7 (Drosophila)], FZD8 [frizzled homolog 8 (Drosophila)], FZD9 [frizzled homolog 9 (Drosophila)], FZR1 [fizzy/cell division cycle 20 related 1 (Drosophila)], G6PD [glucose-6-phosphate dehydrogenase], GAA [glucosidase, alpha; acid], GAB1 [GRB2-associated binding protein 1], GABARAP [GABA(A) receptor-associated protein], GABBR1 [gamma-aminobutyric acid (GABA) B receptor, 1], GABBR2 [gamma-aminobutyric acid (GABA) B receptor, 2], GABPA [GA binding protein transcription factor, alpha subunit 60kDa], GABRA1 [gamma-aminobutyric acid (GABA) A receptor, alpha 1], GABRA2 [gamma-aminobutyric acid (GABA) A receptor, alpha 2], GABRA3 [gamma-aminobutyric acid (GABA) A receptor, alpha 3], GABRA4 [gamma-aminobutyric acid (GABA) A receptor, alpha 4], GABRA5 [gamma-aminobutyric acid (GABA) A receptor, alpha 5], GABRA6 [gamma-aminobutyric acid (GABA) A
receptor, alpha 6], GABRB1 [gamma-aminobutyric acid (GABA) A receptor, beta 1], GABRB2 [gamma-aminobutyric acid (GABA) A receptor, beta 2], GABRB3 [gamma-aminobutyric acid (GABA) A receptor, beta 3], GABRD [gamma-aminobutyric acid (GABA) A receptor, delta], GABRE [gamma-aminobutyric acid (GABA) A receptor, epsilon], GABRG1 [gamma-aminobutyric acid (GABA) A
receptor, gamma 1], GABRG2 [gamma-aminobutyric acid (GABA) A receptor, gamma 2], GABRG3 [gamma-aminobutyric acid (GABA) A receptor, gamma 3], GABRP [gamma-aminobutyric acid (GABA) A receptor, pi], GAD1 [glutamate decarboxylase 1 (brain, 67kDa)], GAD2 [glutamate decarboxylase 2 (pancreatic islets and brain, 65kDa)], GAL [galanin prepropeptide], GALE [UDP-galactose-4-epimerase], GALK1 [galactokinase 1 ], GALT [galactose-1 -phosphate uridylyltransferase], GAP43 [growth associated protein 43], GAPDH
[glyceraldehyde-3-phosphate dehydrogenase], GARS [glycyl-tRNA synthetase], GART [phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase], GAS1 [growth arrest-specific 1], GAS6 [growth arrest-specific 6], GAST [gastrin], GATA1 [GATA
binding protein 1 (globin transcription factor 1)], GATA2 [GATA binding protein 2], GATA3 [GATA binding protein 3], GATA4 [GATA binding protein 4], GATA6 [GATA binding protein 6], GBA [glucosidase, beta, acid], GBE1 [glucan (1 [4-alpha-), branching enzyme 1], GBX2 [gastrulation brain homeobox 2], GC [group-specific component (vitamin D binding protein)], GCG [glucagon], GCH1 [GTP
cyclohydrolase 1], GCNT1 [glucosaminyl (N-acetyl) transferase 1, core 2], GDAP1 [ganglioside-induced differentiation-associated protein 1], GDF1 [growth differentiation factor 1], GDF11 [growth differentiation factor 11], GDF15 [growth differentiation factor 15], GDF7 [growth differentiation factor 7], GDI1 [GDP
dissociation inhibitor 1], GDI2 [GDP dissociation inhibitor 2], GDNF [glial cell derived neurotrophic factor], GDPD5 [glycerophosphodiester phosphodiesterase domain containing 5], GEM [GTP binding protein overexpressed in skeletal muscle], GFAP [glial fibrillary acidic protein], GFER [growth factor, augmenter of liver regeneration], GFI1 B [growth factor independent 1 B transcription repressor], GFRA1 [GDNF family receptor alpha 1], GFRA2 [GDNF family receptor alpha 2], GFRA3 [GDNF family receptor alpha 3], GFRA4 [GDNF family receptor alpha 4], GGCX [gamma-glutamyl carboxylase], GGNBP2 [gametogenetin binding protein 2], GGT1 [gamma-glutamyltransferase 1], GGT2 [gamma-glutamyltransferase 2], GH1 [growth hormone 1], GHR [growth hormone receptor], GHRH [growth hormone releasing hormone], GHRHR [growth hormone releasing hormone receptor], GHRL [ghrelin/obestatin prepropeptide], GHSR [growth hormone secretagogue receptor], GIPR [gastric inhibitory polypeptide receptor], GIT1 [G
protein-coupled receptor kinase interacting ArfGAP 1 ], GJA1 [gap junction protein, alpha 1, 43kDa], GJA4 [gap junction protein, alpha 4, 37kDa], GJA5 [gap junction protein, alpha 5, 40kDa], GJB1 [gap junction protein, beta 1, 32kDa], GJB2 [gap junction protein, beta 2, 26kDa], GJB6 [gap junction protein, beta 6, 30kDa], GLA [galactosidase, alpha], GLB1 [galactosidase, beta 1], GLDC
[glycine dehydrogenase (decarboxylating)], GLI1 [GLI family zinc finger 1 ], [GLI family zinc finger 2], GLI3 [GLI family zinc finger 3], GLIS1 [GLIS
family zinc finger 1 ], GLIS2 [GLIS family zinc finger 2], GLO1 [glyoxalase I], GLRA2 [glycine receptor, alpha 2], GLRB [glycine receptor, beta], GLS [glutaminase], GLUD1 [glutamate dehydrogenase 1], GLUD2 [glutamate dehydrogenase 2], GLUL
[glutamate-ammonia ligase (glutamine synthetase)], GLYAT [glycine-N-acyltransferase], GMFB [glia maturation factor, beta], GMNN [geminin, DNA
replication inhibitor], GMPS [guanine monphosphate synthetase], GNA1 1 [guanine nucleotide binding protein (G protein), alpha 11 (Gq class)], GNA12 [guanine nucleotide binding protein (G protein) alpha 12], GNA13 [guanine nucleotide binding protein (G protein), alpha 13], GNA14 [guanine nucleotide binding protein (G protein), alpha 14], GNA15 [guanine nucleotide binding protein (G protein), alpha 15 (Gq class)], GNAI1 [guanine nucleotide binding protein (G
protein), alpha inhibiting activity polypeptide 1], GNAI2 [guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2], GNAI3 [guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3], GNAL [guanine nucleotide binding protein (G protein), alpha activating activity polypeptide, olfactory type], GNAO1 [guanine nucleotide binding protein (G protein), alpha activating activity polypeptide 0], GNAQ
[guanine nucleotide binding protein (G protein), q polypeptide], GNAS [GNAS
complex locus], GNAT1 [guanine nucleotide binding protein (G protein), alpha transducing activity polypeptide 1], GNAT2 [guanine nucleotide binding protein (G protein), alpha transducing activity polypeptide 2], GNAZ [guanine nucleotide binding protein (G protein), alpha z polypeptide], GNB1 [guanine nucleotide binding protein (G protein), beta polypeptide 1], GNB1L [guanine nucleotide binding protein (G protein), beta polypeptide 1-like], GNB2 [guanine nucleotide binding protein (G protein), beta polypeptide 2], GNB2L1 [guanine nucleotide binding protein (G protein), beta polypeptide 2-like 1], GNB3 [guanine nucleotide binding protein (G protein), beta polypeptide 3], GNB4 [guanine nucleotide binding protein (G protein), beta polypeptide 4], GNB5 [guanine nucleotide binding protein (G protein), beta 5], GNG10 [guanine nucleotide binding protein (G protein), gamma 10], GNG11 [guanine nucleotide binding protein (G protein), gamma 11], GNG12 [guanine nucleotide binding protein (G protein), gamma 12], GNG13 [guanine nucleotide binding protein (G protein), gamma 13], GNG2 [guanine nucleotide binding protein (G protein), gamma 2], GNG3 [guanine nucleotide binding protein (G protein), gamma 3], GNG4 [guanine nucleotide binding protein (G protein), gamma 4], GNG5 [guanine nucleotide binding protein (G protein), gamma 5], GNG7 [guanine nucleotide binding protein (G protein), gamma 7], GNLY [granulysin], GNRH1 [gonadotropin-releasing hormone 1 (luteinizing-releasing hormone)], GNRHR [gonadotropin-releasing hormone receptor], GOLGA2 [golgin A2], GOLGA4 [golgin A4], GOT2 [glutamic-oxaloacetic transaminase 2, mitochondrial (aspartate aminotransferase 2)], GP1 BA [glycoprotein lb (platelet), alpha polypeptide], GP5 [glycoprotein V
(platelet)], GP6 [glycoprotein VI (platelet)], GP9 [glycoprotein IX
(platelet)], GPC1 [glypican 1], GPC3 [glypican 3], GPD1 [glycerol-3-phosphate dehydrogenase 1 (soluble)], GPHN [gephyrin], GPI [glucose phosphate isomerase], GPM6A
[glycoprotein M6A], GPM6B [glycoprotein M6B], GPR161 [G protein-coupled receptor 161 ], GPR182 [G protein-coupled receptor 182], GPR56 [G protein-coupled receptor 56], GPRC6A [G protein-coupled receptor, family C, group 6, member A], GPRIN1 [G protein regulated inducer of neurite outgrowth 1], GPT
[glutamic-pyruvate transaminase (alanine aminotransferase)], GPT2 [glutamic pyruvate transaminase (alanine aminotransferase) 2], GPX1 [glutathione peroxidase 1], GPX3 [glutathione peroxidase 3 (plasma)], GPX4 [glutathione peroxidase 4 (phospholipid hydroperoxidase)], GRAP [GRB2-related adaptor protein], GRB10 [growth factor receptor-bound protein 10], GRB2 [growth factor receptor-bound protein 2], GRB7 [growth factor receptor-bound protein 7], GREM1 [gremlin 1, cysteine knot superfamily, homolog (Xenopus laevis)], GRIA1 [glutamate receptor, ionotropic, AMPA 1], GRIA2 [glutamate receptor, ionotropic, AMPA 2], GRIA3 [glutamate receptor, ionotrophic, AMPA 3], GRID2 [glutamate receptor, ionotropic, delta 2], GRID2IP [glutamate receptor, ionotropic, delta (Grid2) interacting protein], GRIK1 [glutamate receptor, ionotropic, kainate 1], GRIK2 [glutamate receptor, ionotropic, kainate 2], GRIN1 [glutamate receptor, ionotropic, N-methyl D-aspartate 1], GRIN2A [glutamate receptor, ionotropic, N-methyl D-aspartate 2A], GRIP1 [glutamate receptor interacting protein 1], [glucocorticoid receptor DNA binding factor 1], GRM1 [glutamate receptor, metabotropic 1], GRM2 [glutamate receptor, metabotropic 2], GRM5 [glutamate receptor, metabotropic 5], GRM7 [glutamate receptor, metabotropic 7], GRM8 [glutamate receptor, metabotropic 8], GRN [granulin], GRP [gastrin-releasing peptide], GRPR [gastrin-releasing peptide receptor], GSK3B [glycogen synthase kinase 3 beta], GSN [gelsolin], GSR [glutathione reductase], GSS [glutathione synthetase], GSTA1 [glutathione S-transferase alpha 1], GSTM1 [glutathione S-transferase mu 1], GSTP1 [glutathione S-transferase pi 1], GSTT1 [glutathione S-transferase theta 1], GSTZ1 [glutathione transferase zeta 1], GTF2B [general transcription factor IIB], GTF2E2 [general transcription factor IIE, polypeptide 2, beta 34kDa], GTF2H1 [general transcription factor IIH, polypeptide 1, 62kDa], GTF2H2 [general transcription factor IIH, polypeptide 2, 44kDa], GTF2H3 [general transcription factor IIH, polypeptide 3, 34kDa], GTF2H4 [general transcription factor IIH, polypeptide 4, 52kDa], GTF2I [general transcription factor Ili], GTF2IRD1 [GTF2I repeat domain containing 1], GTF2IRD2 [GTF2I repeat domain containing 2], GUCA2A [guanylate cyclase activator 2A (guanylin)], GUCY1A3 [guanylate cyclase 1, soluble, alpha 3], GUSB [glucuronidase, beta], GYPA [glycophorin A (MNS blood group)], GYPC [glycophorin C (Gerbich blood group)], GZF1 [GDNF-inducible zinc finger protein 1], GZMA [granzyme A
(granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)], GZMB
[granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1)], H19 [H19, imprinted maternally expressed transcript (non-protein coding)], H1 FO [H1 histone family, member 0], H2AFX [H2A histone family, member X], H2AFY [H2A histone family, member Y], H6PD [hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase)], HADHA [hydroxyacyl-Coenzyme A
dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), alpha subunit], HAMP [hepcidin antimicrobial peptide], HAND1 [heart and neural crest derivatives expressed 1], HAND2 [heart and neural crest derivatives expressed 2], HAP1 [huntingtin-associated protein 1], HAPLNI [hyaluronan and proteoglycan link protein 1], HARS [histidyl-tRNA
synthetase], HAS1 [hyaluronan synthase 1], HAS2 [hyaluronan synthase 2], HAS3 [hyaluronan synthase 3], HAX1 [HCLS1 associated protein X-1], HBA2 [hemoglobin, alpha 2], HBB [hemoglobin, beta], HBEGF [heparin-binding EGF-like growth factor], HBG1 [hemoglobin, gamma A], HBG2 [hemoglobin, gamma G], HCCS [holocytochrome c synthase (cytochrome c heme-lyase)], HCK

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Claims (20)

1. A method for editing a chromosomal sequence, the method comprising:
(a) introducing into a cell comprising the chromosomal sequence at least one nucleic acid encoding a zinc finger nuclease that recognizes a target sequence in the chromosomal sequence and is able to cleave a cleavage site in the chromosomal sequence, and, optionally, (i) at least one donor polynucleotide comprising a donor sequence for integration, an upstream sequence, and a downstream sequence, wherein the donor sequence is flanked by the upstream sequence and the downstream sequence, and wherein the upstream sequence and the downstream sequence share substantial sequence identity with either side of the cleavage site, or (ii) at least one exchange polynucleotide comprising an exchange sequence that is substantially identical to a portion of the chromosomal sequence at the cleavage site and further comprising at least one nucleotide change; and (b) culturing the cell to allow expression of the zinc finger nuclease such that the zinc finger nuclease introduces a double-stranded break into the chromosomal sequence at the cleavage site, and wherein the double-stranded break is repaired by (i) a non-homologous end-joining repair process such that a mutation is introduced into the chromosomal sequence, or, optionally, (ii) a homology-directed repair process such that the donor sequence is integrated into the chromosomal sequence or the exchange sequence is exchanged with the portion of the chromosomal sequence.

2. The method of claim 1, wherein the cell is an embryo.

3. The method of claim 2, wherein the embryo is a one cell embryo.

4. The method of claim 1, wherein more than one nucleic acid encoding a zinc finger nuclease is introduced into the cell.

5. The method of claim 1, wherein the nucleic acid encoding a zinc finger nuclease is an RNA.

6. The method of claim 5, wherein the RNA is capped.

7. The method of claim 5, wherein the RNA is polyadenylated.

8. The method of claim 1, wherein more than one of a polynucleotide chosen from the donor polynucleotides, the exchange polynucleotides, or any combination thereof are introduced into the cell.

9. The method of claim 1, wherein the cell is a cultured cell, a primary cell, or a stem cell.

10. The method of claim 1, wherein the cell is a human cell, a mammalian cell, a vertebrate cell, an invertebrate cell, or a fungal cell.

11. A non-human animal, the animal being created by the method of claim 1.

12. The non-human animal of claim 11, wherein the animal is a rodent.

13. The non-human animal of claim 11, wherein the animal is a livestock animal.

14. The non-human animal of claim 11, wherein the animal is a companion animal.

15. A cell, the cell being created using the method of claim 1.

16. The cell of claim 15, wherein the cell is an embryo.

17. The cell of claim 16, wherein the embryo is a one cell embryo.

18. The cell of claim 15, wherein the cell is a cultured cell, a primary cell, or a stem cell.

19. An embryo, the embryo comprising at least one nucleic acid encoding a zinc finger nuclease that recognizes a target sequence in the chromosomal sequence and is able to cleave a cleavage site in the chromosomal sequence, and, optionally, (i) at least one donor polynucleotide comprising a donor sequence for integration, an upstream sequence, and a downstream sequence, wherein the donor sequence is flanked by the upstream sequence and the downstream sequence, and wherein the upstream sequence and the downstream sequence share substantial sequence identity with either side of the cleavage site, or (ii) at least one exchange polynucleotide comprising an exchange sequence that is substantially identical to a portion of the chromosomal sequence at the cleavage site and which further comprises at least one nucleotide change.

20. The embryo of claim 19, wherein the embryo is a one cell embryo.