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{{Infokutija gen}}
'''Komplementarna grupa A  [[Fanconijeva anemija|Fanconijeve anemje]]''', znana i kao '''FAA''', '''FACA''' i '''FANCA''', jest [[protein]] koji je kod [[ljudi]] [[kodon|kodiran]] [[gen]]om '''FANCA''' sa [[hromosom 16|hromosoma 16]].<ref name="entrez">{{cite web | title = Entrez Gene: FANCA Fanconi anemia, complementation group A| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2175}}</ref> Pripada porodici gena komplementarne grupe [[Fanconijeva anemija|Fanconijeve anemije]] (FANC) od kojih je 12 komplementacijskih grupa  prepoznato i pretpostavlja se da djeluje kao [[popravka DNK|popravak]], nakon replikacije ili [[kontrolna tačka ćelijskog ciklusa|kontrolne tačke ćelijskog ciklusa]]. [[FANCA proteini]] su uključeni u popravku međulančanih unakrsnih veza [[DNK]] i u održavanju normalne [[hromosom]]ske stabilnosti koja reguliše [[ćelijska diferencijacija|diferencijaciju]] hematopoetskih [[matične ćelije|matičnih ćelija]] u zrele [[krvne ćelije]].<ref name="dokal">{{cite journal | author = Dokal I | title = Fanconi's anaemia and related bone marrow failure syndromes | journal = Br. Med. Bull. | volume = 77–78 | pages = 37–53 | year = 2006 | pmid = 16968690 | doi = 10.1093/bmb/ldl007 | doi-access = free }}</ref>

Mutacije koje uključuju  gen FANCA povezane su s mnogim somatskim i kongenitalnim defektima, prvenstveno uključujući [[fenotip]]ske varijacije zvane [[Fanconijeva anemija]], [[aplazijska anemija]] i oblike [[karcinom]]a kao što su [[karcinom skvamoznih ćelijaa|karcinom skvamoznih ćelija]] i [[akutna mijeloidna leukemija]].<ref name="FA">{{cite journal |vauthors=Tischkowitz MD, Hodgson SV | title = Fanconi anaemia | journal = J. Med. Genet. | volume = 40 | issue = 1 | pages = 1–10 |date=januar 2003 | pmid = 12525534 | pmc = 1735271 | doi = 10.1136/jmg.40.1.1 }}</ref>

== Funkcija ==
Grupa za komplemenata za Fanconijevu anemiju (FANC)  uključuje FANCA, [[FANCB]], [[FANCC]], FANCD1 (takođe zvana [[BRCA2]]), [[FANCD2]], [[FANCE]], [[FANCF ]], [[FANCG]] i [[FANCL]]. Prethodno definirana grupa FANCH je ista kao i FANCA. Članovi grupe za komplementaciju Fanconijeve anemije ne dijele sličnost sekvenci; oni su povezani svojim sklapanjem u zajednički jedarni [[proteinski kompleks]]. Gen FANCA kodira protein za komplementacionu grupu A. [[Alternativna prerada]] rezultira višestrukim varijantama transkripta koje kodiraju različite [[izoforme]].<ref name="entrez"/>
{|
|{{Infokutija protein
| Symbol          = Fanc-A
| Ime             = Protein grupe A Fanconijeve anemije
| image           = FANCM_structures_sml.jpg
| width           = 
| caption         = Struktura Fanc proteina
| Pfam            = PF03511
| Pfam_clan       = 
| InterPro        = IPR003516
| SMART           = 
| PROSITE         = 
| MEROPS          = 
| SCOP            = 
| TCDB            = 
| OPM family      = 
| OPM protein     = 
| CAZy            = 
| CDD             = 
}}
|}

==Aminokiselinska sekvenca==	
Dužina [[polipeptid]]nog lanca je  1.455 [[aminokiselina]], a [[molekularna masa|molekulska težina]]  162.775 [[dalton (jedinica)|Da]].<ref name="entrez"/>
{{legenda aminokiselina}} 
<table  style="font-family:monospace;">
<tr style="text-align:right;"><th>10</th><th></th><th>20</th><th></th><th>30</th><th></th><th>40</th><th></th><th>50</th></tr>
<tr style="background-color: #eee;"><td>MSDSWVPNSA</td><td style="background-color: #f9f9f9;"></td><td>SGQDPGGRRR</td><td style="background-color: #f9f9f9;"></td><td>AWAELLAGRV</td><td style="background-color: #f9f9f9;"></td><td>KREKYNPERA</td><td style="background-color: #f9f9f9;"></td><td>QKLKESAVRL</td></tr>
<tr style="background-color: #eee;"><td>LRSHQDLNAL</td><td style="background-color: #f9f9f9;"></td><td>LLEVEGPLCK</td><td style="background-color: #f9f9f9;"></td><td>KLSLSKVIDC</td><td style="background-color: #f9f9f9;"></td><td>DSSEAYANHS</td><td style="background-color: #f9f9f9;"></td><td>SSFIGSALQD</td></tr>
<tr style="background-color: #eee;"><td>QASRLGVPVG</td><td style="background-color: #f9f9f9;"></td><td>ILSAGMVASS</td><td style="background-color: #f9f9f9;"></td><td>VGQICTAPAE</td><td style="background-color: #f9f9f9;"></td><td>TSHPVLLTVE</td><td style="background-color: #f9f9f9;"></td><td>QRKKLSSLLE</td></tr>
<tr style="background-color: #eee;"><td>FAQYLLAHSM</td><td style="background-color: #f9f9f9;"></td><td>FSRLSFCQEL</td><td style="background-color: #f9f9f9;"></td><td>WKIQSSLLLE</td><td style="background-color: #f9f9f9;"></td><td>AVWHLHVQGI</td><td style="background-color: #f9f9f9;"></td><td>VSLQELLESH</td></tr>
<tr style="background-color: #eee;"><td>PDMHAVGSWL</td><td style="background-color: #f9f9f9;"></td><td>FRNLCCLCEQ</td><td style="background-color: #f9f9f9;"></td><td>MEASCQHADV</td><td style="background-color: #f9f9f9;"></td><td>ARAMLSDFVQ</td><td style="background-color: #f9f9f9;"></td><td>MFVLRGFQKN</td></tr>
<tr style="background-color: #eee;"><td>SDLRRTVEPE</td><td style="background-color: #f9f9f9;"></td><td>KMPQVTVDVL</td><td style="background-color: #f9f9f9;"></td><td>QRMLIFALDA</td><td style="background-color: #f9f9f9;"></td><td>LAAGVQEESS</td><td style="background-color: #f9f9f9;"></td><td>THKIVRCWFG</td></tr>
<tr style="background-color: #eee;"><td>VFSGHTLGSV</td><td style="background-color: #f9f9f9;"></td><td>ISTDPLKRFF</td><td style="background-color: #f9f9f9;"></td><td>SHTLTQILTH</td><td style="background-color: #f9f9f9;"></td><td>SPVLKASDAV</td><td style="background-color: #f9f9f9;"></td><td>QMQREWSFAR</td></tr>
<tr style="background-color: #eee;"><td>THPLLTSLYR</td><td style="background-color: #f9f9f9;"></td><td>RLFVMLSAEE</td><td style="background-color: #f9f9f9;"></td><td>LVGHLQEVLE</td><td style="background-color: #f9f9f9;"></td><td>TQEVHWQRVL</td><td style="background-color: #f9f9f9;"></td><td>SFVSALVVCF</td></tr>
<tr style="background-color: #eee;"><td>PEAQQLLEDW</td><td style="background-color: #f9f9f9;"></td><td>VARLMAQAFE</td><td style="background-color: #f9f9f9;"></td><td>SCQLDSMVTA</td><td style="background-color: #f9f9f9;"></td><td>FLVVRQAALE</td><td style="background-color: #f9f9f9;"></td><td>GPSAFLSYAD</td></tr>
<tr style="background-color: #eee;"><td>WFKASFGSTR</td><td style="background-color: #f9f9f9;"></td><td>GYHGCSKKAL</td><td style="background-color: #f9f9f9;"></td><td>VFLFTFLSEL</td><td style="background-color: #f9f9f9;"></td><td>VPFESPRYLQ</td><td style="background-color: #f9f9f9;"></td><td>VHILHPPLVP</td></tr>
<tr style="background-color: #eee;"><td>GKYRSLLTDY</td><td style="background-color: #f9f9f9;"></td><td>ISLAKTRLAD</td><td style="background-color: #f9f9f9;"></td><td>LKVSIENMGL</td><td style="background-color: #f9f9f9;"></td><td>YEDLSSAGDI</td><td style="background-color: #f9f9f9;"></td><td>TEPHSQALQD</td></tr>
<tr style="background-color: #eee;"><td>VEKAIMVFEH</td><td style="background-color: #f9f9f9;"></td><td>TGNIPVTVME</td><td style="background-color: #f9f9f9;"></td><td>ASIFRRPYYV</td><td style="background-color: #f9f9f9;"></td><td>SHFLPALLTP</td><td style="background-color: #f9f9f9;"></td><td>RVLPKVPDSR</td></tr>
<tr style="background-color: #eee;"><td>VAFIESLKRA</td><td style="background-color: #f9f9f9;"></td><td>DKIPPSLYST</td><td style="background-color: #f9f9f9;"></td><td>YCQACSAAEE</td><td style="background-color: #f9f9f9;"></td><td>KPEDAALGVR</td><td style="background-color: #f9f9f9;"></td><td>AEPNSAEEPL</td></tr>
<tr style="background-color: #eee;"><td>GQLTAALGEL</td><td style="background-color: #f9f9f9;"></td><td>RASMTDPSQR</td><td style="background-color: #f9f9f9;"></td><td>DVISAQVAVI</td><td style="background-color: #f9f9f9;"></td><td>SERLRAVLGH</td><td style="background-color: #f9f9f9;"></td><td>NEDDSSVEIS</td></tr>
<tr style="background-color: #eee;"><td>KIQLSINTPR</td><td style="background-color: #f9f9f9;"></td><td>LEPREHMAVD</td><td style="background-color: #f9f9f9;"></td><td>LLLTSFCQNL</td><td style="background-color: #f9f9f9;"></td><td>MAASSVAPPE</td><td style="background-color: #f9f9f9;"></td><td>RQGPWAALFV</td></tr>
<tr style="background-color: #eee;"><td>RTMCGRVLPA</td><td style="background-color: #f9f9f9;"></td><td>VLTRLCQLLR</td><td style="background-color: #f9f9f9;"></td><td>HQGPSLSAPH</td><td style="background-color: #f9f9f9;"></td><td>VLGLAALAVH</td><td style="background-color: #f9f9f9;"></td><td>LGESRSALPE</td></tr>
<tr style="background-color: #eee;"><td>VDVGPPAPGA</td><td style="background-color: #f9f9f9;"></td><td>GLPVPALFDS</td><td style="background-color: #f9f9f9;"></td><td>LLTCRTRDSL</td><td style="background-color: #f9f9f9;"></td><td>FFCLKFCTAA</td><td style="background-color: #f9f9f9;"></td><td>ISYSLCKFSS</td></tr>
<tr style="background-color: #eee;"><td>QSRDTLCSCL</td><td style="background-color: #f9f9f9;"></td><td>SPGLIKKFQF</td><td style="background-color: #f9f9f9;"></td><td>LMFRLFSEAR</td><td style="background-color: #f9f9f9;"></td><td>QPLSEEDVAS</td><td style="background-color: #f9f9f9;"></td><td>LSWRPLHLPS</td></tr>
<tr style="background-color: #eee;"><td>ADWQRAALSL</td><td style="background-color: #f9f9f9;"></td><td>WTHRTFREVL</td><td style="background-color: #f9f9f9;"></td><td>KEEDVHLTYQ</td><td style="background-color: #f9f9f9;"></td><td>DWLHLELEIQ</td><td style="background-color: #f9f9f9;"></td><td>PEADALSDTE</td></tr>
<tr style="background-color: #eee;"><td>RQDFHQWAIH</td><td style="background-color: #f9f9f9;"></td><td>EHFLPESSAS</td><td style="background-color: #f9f9f9;"></td><td>GGCDGDLQAA</td><td style="background-color: #f9f9f9;"></td><td>CTILVNALMD</td><td style="background-color: #f9f9f9;"></td><td>FHQSSRSYDH</td></tr>
<tr style="background-color: #eee;"><td>SENSDLVFGG</td><td style="background-color: #f9f9f9;"></td><td>RTGNEDIISR</td><td style="background-color: #f9f9f9;"></td><td>LQEMVADLEL</td><td style="background-color: #f9f9f9;"></td><td>QQDLIVPLGH</td><td style="background-color: #f9f9f9;"></td><td>TPSQEHFLFE</td></tr>
<tr style="background-color: #eee;"><td>IFRRRLQALT</td><td style="background-color: #f9f9f9;"></td><td>SGWSVAASLQ</td><td style="background-color: #f9f9f9;"></td><td>RQRELLMYKR</td><td style="background-color: #f9f9f9;"></td><td>ILLRLPSSVL</td><td style="background-color: #f9f9f9;"></td><td>CGSSFQAEQP</td></tr>
<tr style="background-color: #eee;"><td>ITARCEQFFH</td><td style="background-color: #f9f9f9;"></td><td>LVNSEMRNFC</td><td style="background-color: #f9f9f9;"></td><td>SHGGALTQDI</td><td style="background-color: #f9f9f9;"></td><td>TAHFFRGLLN</td><td style="background-color: #f9f9f9;"></td><td>ACLRSRDPSL</td></tr>
<tr style="background-color: #eee;"><td>MVDFILAKCQ</td><td style="background-color: #f9f9f9;"></td><td>TKCPLILTSA</td><td style="background-color: #f9f9f9;"></td><td>LVWWPSLEPV</td><td style="background-color: #f9f9f9;"></td><td>LLCRWRRHCQ</td><td style="background-color: #f9f9f9;"></td><td>SPLPRELQKL</td></tr>
<tr style="background-color: #eee;"><td>QEGRQFASDF</td><td style="background-color: #f9f9f9;"></td><td>LSPEAASPAP</td><td style="background-color: #f9f9f9;"></td><td>NPDWLSAAAL</td><td style="background-color: #f9f9f9;"></td><td>HFAIQQVREE</td><td style="background-color: #f9f9f9;"></td><td>NIRKQLKKLD</td></tr>
<tr style="background-color: #eee;"><td>CEREELLVFL</td><td style="background-color: #f9f9f9;"></td><td>FFFSLMGLLS</td><td style="background-color: #f9f9f9;"></td><td>SHLTSNSTTD</td><td style="background-color: #f9f9f9;"></td><td>LPKAFHVCAA</td><td style="background-color: #f9f9f9;"></td><td>ILECLEKRKI</td></tr>
<tr style="background-color: #eee;"><td>SWLALFQLTE</td><td style="background-color: #f9f9f9;"></td><td>SDLRLGRLLL</td><td style="background-color: #f9f9f9;"></td><td>RVAPDQHTRL</td><td style="background-color: #f9f9f9;"></td><td>LPFAFYSLLS</td><td style="background-color: #f9f9f9;"></td><td>YFHEDAAIRE</td></tr>
<tr style="background-color: #eee;"><td>EAFLHVAVDM</td><td style="background-color: #f9f9f9;"></td><td>YLKLVQLFVA</td><td style="background-color: #f9f9f9;"></td><td>GDTSTVSPPA</td><td style="background-color: #f9f9f9;"></td><td>GRSLELKGQG</td><td style="background-color: #f9f9f9;"></td><td>NPVELITKAR</td></tr>
<tr style="background-color: #eee;"><td>LFLLQLIPRC</td><td style="background-color: #f9f9f9;"></td><td>PKKSFSHVAE</td><td style="background-color: #f9f9f9;"></td><td>LLADRGDCDP</td><td style="background-color: #f9f9f9;"></td><td>EVSAALQSRQ</td><td style="background-color: #f9f9f9;"></td><td>QAAPDADLSQ</td></tr>
<tr style="background-color: #eee;"><td>EPHLF</td></tr>
</table>

=== Gen i protein ===

Kod ljudi, gen FANCA je dugačak 79 kilobaza (kb) i nalazi se na [[hromosom 16|hromosomu 16]] (16q24.3). FANCA protein se sastoji od 1.455 [[aminokiselina]].<ref>{{cite web|title=FANCA Gene protein-coding|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=FANCA|access-date=24. 10. 2013}}</ref>  Unutar ćelija, glavna svrha FANCA pripada njegovom navodnom uključivanju u multipodjedinični FA kompleks koji se sastoji od FANCA, [[FANCB]], [[FANCC]], [[FANCE]], [[FANCF]], [[FANCG]] , FANCL/PHF9 i FANCM. U kompleksu sa FANCF, FANCG i FANCL, FANCA je u interakciji sa HES1. Ova interakcija je predložena kao ključna za stabilnost i jedarnu lokalizaciju jedarnih  FA [[proteinski kompleks|kompleksnih proteina]]. Kompleks sa FANCC i FANCG može takođe uključivati EIF2AK2 i HSP70.<ref name=uniprot>{{cite web|title=(FANCA_HUMAN)|url=https://www.uniprot.org/uniprot/O15360|access-date=24. 10. 2013}}</ref> U ćelijama je uključenost FANCA u ovaj 'FA core kompleks' potrebna za aktivaciju [[FANCD2]] proteina u monoubikvitiniranu izoformu (FANCD2-Ub) kao odgovor na [[oštećenje DNK]], katalizujući aktivaciju FA/put odgovora na oštećenje BRCA DNK,<ref name="D'andrea">{{cite journal |vauthors=D'Andrea AD, Grompe M | title = The Fanconi anaemia/BRCA pathway | journal = Nat. Rev. Cancer | volume = 3 | issue = 1 | pages = 23–34 |date=januar 2003 | pmid = 12509764 | doi = 10.1038/nrc970 | s2cid = 52331376 }}</ref> dovodećii do [[popravka DNK|popravke]].<ref name="pmid11239454">{{cite journal |vauthors=Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M, D'Andrea AD | title = Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway | journal = Mol. Cell | volume = 7 | issue = 2 | pages = 249–62 |date=februar 2001 | pmid = 11239454 | doi = 10.1016/S1097-2765(01)00173-3 | doi-access = free }}</ref>

FANCA se vezuje za jednolančanu (ssDNA) i dvolančanu (dsDNK) DNK; međutim, kada se [[test]]ira u elektroforetskom pomaku mobilnosti, njegov afinitet za [[ssDNK]] je značajno veći nego za [[dsDNK]]. FANCA se također vezuje za RNK sa većim afinitetom od svog DNK dvojnika.<ref name=Fenghua>{{cite journal |vauthors=Yuan F, Qian L, Zhao X, Liu JY, Song L, D'Urso G, Jain C, Zhang Y | title = Fanconi anemia complementation group A (FANCA) protein has intrinsic affinity for nucleic acids with preference for single-stranded forms | journal = J. Biol. Chem. | volume = 287 | issue = 7 | pages = 4800–7 |date=februar 2012 | pmid = 22194614 | pmc = 3281618 | doi = 10.1074/jbc.M111.315366 | doi-access = free }}</ref> FANCA zahtijeva određeni broj [[nukleotid]]a za optimalno vezivanje, s tim da je minimum za FANCA prepoznavanje otprilike 30 i za DNK i za [[RNK]]. Yuan et al. (2012) otkrili su testiranjem afiniteta FANCA sa različitim DNK strukturama da 5'-preklop ili 5'-rep na DNK olakšava njegovu interakciju sa FANCA-om, dok komplementarni [[C-terminal]]ni fragment Q772X, C772-1455, zadržava diferenciranu aktivnost vezivanja [[nukleinske kiseline]] (tj. davanje prednosti RNK prije ssDNK i dsDNK), što ukazuje da se [[DNK-vezujući domen|domen koji se vezuje za nukleinsku kiselinu]] FANCA nalazi prvenstveno na [[C-kraj]]u, lokaciji gdje su pronađene mnoge mutacije koje uzrokuju bolesti.<ref name=Fenghua/>

FANCA je sveprisutno eksprimirana na niskim nivoima u svim ćelijama<ref name=vandevrugt>{{cite journal |vauthors=van de Vrugt HJ, Cheng NC, de Vries Y, Rooimans MA, de Groot J, Scheper RJ, Zhi Y, Hoatlin ME, Joenje H, Arwert F | title = Cloning and characterization of murine fanconi anemia group A gene: Fanca protein is expressed in lymphoid tissues, testis, and ovary | journal = Mamm. Genome | volume = 11 | issue = 4 | pages = 326–31 |date=april 2000 | pmid = 10754110 | doi =10.1007/s003350010060 | s2cid = 11568640 }}</ref> sa subćelijskom lokalizacijom prvenstveno u [[ćelijsko jedro|jedru]] ali i u [[citoplazma|citoplazmi]]<ref name=walsh>{{cite journal |vauthors=Walsh CE, Yountz MR, Simpson DA | title = Intracellular localization of the Fanconi anemia complementation group A protein | journal = Biochem. Biophys. Res. Commun. | volume = 259 | issue = 3 | pages = 594–9 |date=juni 1999 | pmid = 10364463 | doi = 10.1006/bbrc.1999.0768 }}</ref> što odgovara njegovoj navodnoj ulozi čuvara u putevima odgovora na [[oštećenje DNK]] i formiranju FA kompleksa. Raspodjela proteina u različitim tkivima još nije dobro shvaćena. Imunohemijska studija mišjeg tkiva pokazuje da je FANCA prisutna na višem nivou u [[limfa|limfoidnim]] tkivima, [[sjemenici]]ma i [[jajnici]]ma,<ref name=vandevrugt/> a iako je značaj ovoga nejasan, sugerira da bi prisustvo FA proteina moglo biti povezano sa [[ćelijska proliferacija|ćelijskom proliferacijom]]. Naprimjer, u ljudskim besmrtnim [[limfoblast]]ima i [[leukemija|leukemijskim]] ćelijama, FA proteini se lahko mogu otkriti [[imunoprecipitacija]]ma.<ref name=aberrant>{{cite journal |vauthors=Xie Y, de Winter JP, Waisfisz Q, Nieuwint AW, Scheper RJ, Arwert F, Hoatlin ME, Ossenkoppele GJ, Schuurhuis GJ, Joenje H | title = Aberrant Fanconi anaemia protein profiles in acute myeloid leukaemia cells | journal = Br. J. Haematol. | volume = 111 | issue = 4 | pages = 1057–64 |date=decembar 2000 | pmid = 11167740 | doi = 10.1111/j.1365-2141.2000.02450.x | s2cid = 45590851 | doi-access = free }}</ref>

== Klinički značaj ==

[[Mutacije]] u ovom genu su najčešći uzrok [[Fanconijeva anemija|Fanconijeve anemije]].<ref name="entrez"/><ref name=dokal/><ref name=FA/> Fanconijeva anemija je nasljedni [[autosomno nasljeđivanje|autosomno recesivni poremećaj]], čija su glavna obilježja [[aplazijska anemija]] u djetinjstvu, višestruke kongenitalne abnormalnosti, sklonost [[leukemija|leukemiji]] i drugim tipovima [[karcinom]]a, te ćelijska preosjetljivost na međulančane agense za umrežavanje DNK.<ref name=FA/> Općenito, ćelije pacijenata sa Fanconijevom anemijom pokazuju značajno veću učestalost spontanog lomljenja hromosoma i preosetljivost na klastogeni efekat agenasa za umrežavanje DNK kao što su [[diepoksibutan]] (DEB) i [[mitomicin- C]] (MMC),  u poređenju sa normalnim ćelijama. Primarni dijagnostički test za Fanconijevu anemiju zasniva se na povećanom lomu hromosoma koji se vidi u pogođenim ćelijama nakon izlaganja ovim agensima – DEB/MMC stres test. Ostale karakteristike ćelijskog [[fenotip]]a  Fanconijeve anemije također uključuju abnormalnu kinetiku [[ćelijski ciklus|ćelijskog ciklusa]] (produžena G2 faza), preosjetljivost na [[kisik]], povećanu učestalost [[apoptoza]] i ubrzano skraćivanje [[telomera]].<ref name=dokal/><ref name = pmid14499622/>

FANCA mutacije su daleko najčešći uzrok Fanconijeve anemije, čineći između 60-70% svih slučajeva. FANCA je klonirana 1996<ref name=consortium>{{cite journal|last=The Fanconi Anaemia/Breast Cancer Consortium.|title=Positional cloning of the Fanconi anaemia group A gene.|journal=Nat. Genet.|year=1996|volume=14|issue=3|pages=324–8|doi=10.1038/ng1296-488b |pmid=8896564|doi-access=free}}</ref> i jedan je od najvećih FA gena. Zabilježene su stotine različitih [[mutacija]].<ref name=wijker>{{cite journal |author1=Wijker M |author2=Morgan NV |author3=Herterich S |author4=van Berkel CG |author5=Tipping AJ |author6=Gross HJ |author7=Gille JJ |author8=Pals G |author9=Savino M |author10=Altay C |author11=Mohan S |author12=Dokal I |author13=Cavenagh J |author14=Marsh J |author15=van Weel M |author16=Ortega JJ |author17=Schuler D |author18=Samochatova E |author19=Karwacki M |author20=Bekassy AN |author21=Abecasis M |author22=Ebell W |author23=Kwee ML |author24=de Ravel T |author25=CG Mathew | title = Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene | journal = Eur. J. Hum. Genet. | volume = 7 | issue = 1 | pages = 52–9 |date=januar 1999 | pmid = 10094191 | doi = 10.1038/sj.ejhg.5200248 |doi-access=free }}</ref><ref name=levran>{{cite journal |vauthors=Levran O, Erlich T, Magdalena N, Gregory JJ, Batish SD, Verlander PC, Auerbach AD | title = Sequence variation in the Fanconi anemia gene FAA | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 24 | pages = 13051–6 |date=novembar 1997 | pmid = 9371798 | pmc = 24261 | doi =10.1073/pnas.94.24.13051 | bibcode = 1997PNAS...9413051L  | doi-access = free }}</ref> sa 30% [[tačkasta mutacija|tačkastih mutacija]], 30% mikrodelecija ili mikroinsercija od 1-5 [[baztni par|baznih parova]] i 40% velikih [[delecija (genetika)|delecija]], uklanjajući iz gena do 31 [[egzon]]a.<ref name="pmid10521298">{{cite journal |vauthors=Morgan NV, Tipping AJ, Joenje H, Mathew CG | title = High frequency of large intragenic deletions in the Fanconi anemia group A gene | journal = Am. J. Hum. Genet. | volume = 65 | issue = 5 | pages = 1330–41 |date=novembar 1999 | pmid = 10521298 | pmc = 1288285 | doi = 10.1086/302627 }}</ref> Ove velike delecije imaju visoku [[korelacija|korelaciju]] sa specifičnim tačkama prekida i nastaju kao rezultat [[Alu-sekvenca|Alu]] posredovane rekombinacije. Vrlo relevantno zapažanje je da različite mutacije proizvode [[fenotip]]ove Fanconijeve anemije različite težine.

[[Homozigot]]ni pacijenti za nulte mutacije u ovom genu imaju raniji početak [[anemija]] od onih s mutacijama koje proizvode izmijenjen ili netačan protein.<ref name=Adachi>{{cite journal |vauthors=Adachi D, Oda T, Yagasaki H, Nakasato K, Taniguchi T, D'Andrea AD, Asano S, Yamashita T | title = Heterogeneous activation of the Fanconi anemia pathway by patient-derived FANCA mutants | journal = Hum. Mol. Genet. | volume = 11 | issue = 25 | pages = 3125–34 |date=decembar 2002 | pmid = 12444097 | doi =10.1093/hmg/11.25.3125  | citeseerx = 10.1.1.325.8547 }}</ref>  Međutim, kako su većina pacijenata [[složeni heterozigot]], dijagnostički skrining za mutacije je težak. Određene mutacije osnivača također se mogu pojaviti u nekim populacijama, kao što je delecijska mutacija egzona 12-31, koja čini 60% mutacija kod  [[Afrika]]naca.<ref name=tipping>{{cite journal |vauthors=Tipping AJ, Pearson T, Morgan NV, Gibson RA, Kuyt LP, Havenga C, Gluckman E, Joenje H, de Ravel T, Jansen S, Mathew CG | title = Molecular and genealogical evidence for a founder effect in Fanconi anemia families of the Afrikaner population of South Africa | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 10 | pages = 5734–9 |date=maj 2001 | pmid = 11344308 | pmc = 33282 | doi = 10.1073/pnas.091402398 |bibcode = 2001PNAS...98.5734T | doi-access = free }}</ref>

== Interakcije ==

Pokazalo se da FANCA [[interakcija protein-protein|intereaguje]] sa:
{{refbegin|2}}
* [[BRCA1]],
* [[CHUK]],
* [[ERCC4]],<ref name=pmid12571280>{{cite journal |vauthors=Sridharan D, Brown M, Lambert WC, McMahon LW, Lambert MW | title = Nonerythroid alphaII spectrin is required for recruitment of FANCA and XPF to nuclear foci induced by DNA interstrand cross-links | journal = J. Cell Sci. | volume = 116 | issue = Pt 5 | pages = 823–35 | year = 2003 | pmid = 12571280 | doi =10.1242/jcs.00294 | doi-access = free }}</ref> 
* [[FANCE]],
* [[FANCF]],<ref name = pmid15262960>{{cite journal |vauthors=Léveillé F, Blom E, Medhurst AL, Bier P, Laghmani el H, Johnson M, Rooimans MA, Sobeck A, Waisfisz Q, Arwert F, Patel KJ, Hoatlin ME, Joenje H, de Winter JP | title = The Fanconi anemia gene product FANCF is a flexible adaptor protein | journal = J. Biol. Chem. | volume = 279 | issue = 38 | pages = 39421–30 | year = 2004 | pmid = 15262960 | doi = 10.1074/jbc.M407034200 | doi-access = free }}</ref> 
* [[FANCG]],<ref name = pmid11157805>{{cite journal |vauthors=Medhurst AL, Huber PA, Waisfisz Q, de Winter JP, Mathew CG | title = Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway | journal = Hum. Mol. Genet. | volume = 10 | issue = 4 | pages = 423–9 | year = 2001 | pmid = 11157805 | doi =10.1093/hmg/10.4.423 | doi-access = free }}</ref><ref name = pmid16189514>{{cite journal |vauthors=Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | year = 2005 | pmid = 16189514 | doi = 10.1038/nature04209 |bibcode = 2005Natur.437.1173R | s2cid = 4427026 }}</ref><ref name = pmid15138265>{{cite journal |vauthors=Park SJ, Ciccone SL, Beck BD, Hwang B, Freie B, Clapp DW, Lee SH | title = Oxidative stress/damage induces multimerization and interaction of Fanconi anemia proteins | journal = J. Biol. Chem. | volume = 279 | issue = 29 | pages = 30053–9 | year = 2004 | pmid = 15138265 | doi = 10.1074/jbc.M403527200 | doi-access = free }}</ref><ref name = pmid11918676>{{cite journal |vauthors=van de Vrugt HJ, Koomen M, Berns MA, de Vries Y, Rooimans MA, van der Weel L, Blom E, de Groot J, Schepers RJ, Stone S, Hoatlin ME, Cheng NC, Joenje H, Arwert F | title = Characterization, expression and complex formation of the murine Fanconi anaemia gene product Fancg | journal = Genes Cells | volume = 7 | issue = 3 | pages = 333–42 | year = 2002 | pmid = 11918676 | doi =10.1046/j.1365-2443.2002.00518.x | s2cid = 23489983 | doi-access = free }}</ref><ref name = pmid11739169>{{cite journal |vauthors=Yagasaki H, Adachi D, Oda T, Garcia-Higuera I, Tetteh N, D'Andrea AD, Futaki M, Asano S, Yamashita T | title = A cytoplasmic serine protein kinase binds and may regulate the Fanconi anemia protein FANCA | journal = Blood | volume = 98 | issue = 13 | pages = 3650–7 | year = 2001 | pmid = 11739169 | doi =10.1182/blood.V98.13.3650 | doi-access = free }}</ref><ref name = pmid12649160>{{cite journal |vauthors=Gordon SM, Buchwald M | title = Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems | journal = Blood | volume = 102 | issue = 1 | pages = 136–41 | year = 2003 | pmid = 12649160 | doi = 10.1182/blood-2002-11-3517 }}</ref><ref name = pmid10567393>{{cite journal |vauthors=Kruyt FA, Abou-Zahr F, Mok H, Youssoufian H | title = Resistance to mitomycin C requires direct interaction between the Fanconi anemia proteins FANCA and FANCG in the nucleus through an arginine-rich domain | journal = J. Biol. Chem. | volume = 274 | issue = 48 | pages = 34212–8 | year = 1999 | pmid = 10567393 | doi =10.1074/jbc.274.48.34212 | doi-access = free }}</ref><ref name = pmid14697762>{{cite journal |vauthors=Blom E, van de Vrugt HJ, de Vries Y, de Winter JP, Arwert F, Joenje H | title = Multiple TPR motifs characterize the Fanconi anemia FANCG protein | journal = DNA Repair (Amst.) | volume = 3 | issue = 1 | pages = 77–84 | year = 2004 | pmid = 14697762 | doi =10.1016/j.dnarep.2003.09.007 }}</ref><ref name = pmid10961856>{{cite journal |vauthors=Kuang Y, Garcia-Higuera I, Moran A, Mondoux M, Digweed M, D'Andrea AD | title = Carboxy terminal region of the Fanconi anemia protein, FANCG/XRCC9, is required for functional activity | journal = Blood | volume = 96 | issue = 5 | pages = 1625–32 | year = 2000 | pmid = 10961856 | doi = 10.1182/blood.V96.5.1625}}</ref><ref name = pmid10468606>{{cite journal |vauthors=Waisfisz Q, de Winter JP, Kruyt FA, de Groot J, van der Weel L, Dijkmans LM, Zhi Y, Arwert F, Scheper RJ, Youssoufian H, Hoatlin ME, Joenje H | title = A physical complex of the Fanconi anemia proteins FANCG/XRCC9 and FANCA | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 18 | pages = 10320–5 | year = 1999 | pmid = 10468606 | pmc = 17886 | doi =10.1073/pnas.96.18.10320 |bibcode = 1999PNAS...9610320W | doi-access = free }}</ref><ref name = pmid11050007>{{cite journal |vauthors=Garcia-Higuera I, Kuang Y, Denham J, D'Andrea AD | title = The fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex | journal = Blood | volume = 96 | issue = 9 | pages = 3224–30 | year = 2000 | pmid = 11050007 | doi = 10.1182/blood.V96.9.3224}}</ref> 
* [[Fanconi anemia, complementation group C|FANCC]],<ref name = pmid10627486>{{cite journal |vauthors=Reuter T, Herterich S, Bernhard O, Hoehn H, Gross HJ | title = Strong FANCA/FANCG but weak FANCA/FANCC interaction in the yeast 2-hybrid system | journal = Blood | volume = 95 | issue = 2 | pages = 719–20 | year = 2000 | pmid = 10627486 | doi = 10.1182/blood.V95.2.719}}</ref><ref name = pmid12973351>{{cite journal | vauthors = Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, Oostra AB, Yan Z, Ling C, Bishop CE, Hoatlin ME, Joenje H, Wang W | title = A novel ubiquitin ligase is deficient in Fanconi anemia | journal = Nat. Genet. | volume = 35 | issue = 2 | pages = 165–70 | year = 2003 | pmid = 12973351 | doi = 10.1038/ng1241 | s2cid = 10149290 }}</ref><ref name = pmid12239156>{{cite journal |vauthors=Taniguchi T, D'Andrea AD | title = The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC | journal = Blood | volume = 100 | issue = 7 | pages = 2457–62 | year = 2002 | pmid = 12239156 | doi = 10.1182/blood-2002-03-0860 | doi-access = free}}</ref><ref name = pmid11063725>{{cite journal |vauthors=de Winter JP, van der Weel L, de Groot J, Stone S, Waisfisz Q, Arwert F, Scheper RJ, Kruyt FA, Hoatlin ME, Joenje H | title = The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG | journal = Hum. Mol. Genet. | volume = 9 | issue = 18 | pages = 2665–74 | year = 2000 | pmid = 11063725 | doi =10.1093/hmg/9.18.2665 | doi-access = free }}</ref><ref name = pmid10373536>{{cite journal |vauthors=Garcia-Higuera I, Kuang Y, Näf D, Wasik J, D'Andrea AD | title = Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex | journal = Mol. Cell. Biol. | volume = 19 | issue = 7 | pages = 4866–73 | year = 1999 | pmid = 10373536 | pmc = 84285 | doi = 10.1128/mcb.19.7.4866}}</ref><ref name = pmid15082718>{{cite journal |vauthors=Thomashevski A, High AA, Drozd M, Shabanowitz J, Hunt DF, Grant PA, Kupfer GM | title = The Fanconi anemia core complex forms four complexes of different sizes in different subcellular compartments | journal = J. Biol. Chem. | volume = 279 | issue = 25 | pages = 26201–9 | year = 2004 | pmid = 15082718 | doi = 10.1074/jbc.M400091200 | doi-access = free }}</ref><ref name = pmid10551855>{{cite journal |vauthors=McMahon LW, Walsh CE, Lambert MW | title = Human alpha spectrin II and the Fanconi anemia proteins FANCA and FANCC interact to form a nuclear complex | journal = J. Biol. Chem. | volume = 274 | issue = 46 | pages = 32904–8 | year = 1999 | pmid = 10551855 | doi =10.1074/jbc.274.46.32904 | doi-access = free }}</ref> 
* [[IKK2]],<ref name = pmid12210728>{{cite journal |vauthors=Otsuki T, Young DB, Sasaki DT, Pando MP, Li J, Manning A, Hoekstra M, Hoatlin ME, Mercurio F, Liu JM | title = Fanconi anemia protein complex is a novel target of the IKK signalsome | journal = J. Cell. Biochem. | volume = 86 | issue = 4 | pages = 613–23 | year = 2002 | pmid = 12210728 | doi = 10.1002/jcb.10270 | s2cid = 42471384 | url = https://zenodo.org/record/1229210 }}</ref> 
* [[SMARCA4]]<ref name = pmid14499622>{{cite journal |vauthors=Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA | title = Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport | journal = Exp. Cell Res. | volume = 289 | issue = 2 | pages = 211–21 | year = 2003 | pmid = 14499622 | doi =10.1016/S0014-4827(03)00261-1 }}</ref> 
* [[SNX5]]<ref name = pmid10600472>{{cite journal |vauthors=Otsuki T, Kajigaya S, Ozawa K, Liu JM | title = SNX5, a new member of the sorting nexin family, binds to the Fanconi anemia complementation group A protein | journal = Biochem. Biophys. Res. Commun. | volume = 265 | issue = 3 | pages = 630–5 | year = 1999 | pmid = 10600472 | doi = 10.1006/bbrc.1999.1731 }}</ref> 
* [[SPTAN1]]<ref name = pmid10551855/><ref name = pmid11401546>{{cite journal |vauthors=McMahon LW, Sangerman J, Goodman SR, Kumaresan K, Lambert MW | title = Human alpha spectrin II and the FANCA, FANCC, and FANCG proteins bind to DNA containing psoralen interstrand cross-links | journal = Biochemistry | volume = 40 | issue = 24 | pages = 7025–34 | year = 2001 | pmid = 11401546 | doi =10.1021/bi002917g }}</ref> i
* [[HES1]]<ref>{{cite journal|last=Tremblay CS.|title=HES1 is a novel interactor of the Fanconi anemia core complex.|journal=Blood|year=2008|volume=112|issue=5|pages=2062–2070|pmid = 18550849 | doi =10.1182/blood-2008-04-152710|display-authors=etal|pmc=5154739}}</ref>
{{refend}}

== Reference==
{{reflist|35em}}

==Vanjski linkovi==
{{popravak DNK}}

[[Kategorija:Geni na hromosomu 16]]
[[Kategorija:Ljudski proteini]]
[[Kategorija:Proteomika]]
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