|Name:||ATPase, Class I, type 8B, member 1|
|PubMed (9500542):|| Bull LN, van Eijk MJ, Pawlikowska L, DeYoung JA, Juijn JA, Liao M, Klomp LW,Lomri N, Berger R, Scharschmidt BF, Knisely AS, Houwen RH, Freimer NB. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis.Nat Genet. 1998 Mar;18(3):219-24. PMID: 9500542 [PubMed - indexed for MEDLINE]|
Cholestasis, or impaired bile flow, is an important but poorly understood manifestation of liver disease. Two clinically distinct forms of inherited cholestasis, benign recurrent intrahepatic cholestasis (BRIC) and progressive familial intrahepatic cholestasis type 1 (PFIC1), were previously mapped to 18q21. Haplotype analysis narrowed the candidate region for both diseases to the same interval of less than 1 cM, in which we identified a gene mutated in BRIC and PFIC1 patients. This gene (called FIC1) is the first identified human member of a recently described subfamily of P-type ATPases; ATP-dependent aminophospholipid transport is the previously described function of members of this subfamily. FIC1 is expressed in several epithelial tissues and, surprisingly, more strongly in small intestine than in liver. Its protein product is likely to play an essential role in enterohepatic circulation of bile acids; further characterization of FIC1 will facilitate understanding of normal bile formation and cholestasis.
|PubMed (7655458):|| Carlton VE, Knisely AS, Freimer NB. Mapping of a locus for progressive familial intrahepatic cholestasis (Bylerdisease) to 18q21-q22, the benign recurrent intrahepatic cholestasis region.Hum Mol Genet. 1995 Jun;4(6):1049-53. PMID: 7655458 [PubMed - indexed for MEDLINE]|
A locus for progressive familial intrahepatic cholestasis (PFIC), also known as Byler disease, has been mapped to a 19 cM region of chromosome 18 by a search for shared segments, using patients from the Amish kindred in which the disorder was originally described. A similar liver disease, benign recurrent intrahepatic cholestasis (BRIC), recently has been mapped to the same region, suggesting that these two diseases are caused by mutations in the same gene. Although PFIC and BRIC are clinically distinct diseases, episodic attacks of jaundice and pruritus, with elevated concentrations of bile acid in serum, are seen in both disorders. In PFIC patients, these attacks result in progressive liver damage and death. The clinical and biochemical features of PFIC and BRIC are suggestive of a defect in primary bile acid secretion. The biology of bile secretion is of great interest because of its vital importance in digestion of dietary fats as well as in secretion of xenobiotics and metabolic waste products. Cloning of the gene (or genes) responsible for PFIC and BRIC will likely provide important insights into this pathway.
>sp|O43520|AT8B1_HUMAN Probable phospholipid-transporting ATPase IC OS=Homo sapiens GN=ATP8B1 PE=1 SV=3 MSTERDSETTFDEDSQPNDEVVPYSDDETEDELDDQGSAVEPEQNRVNREAEENREPFRKECTWQVKANDRKYHEQPHFM NTKFLCIKESKYANNAIKTYKYNAFTFIPMNLFEQFKRAANLYFLALLILQAVPQISTLAWYTTLVPLLVVLGVTAIKDL VDDVARHKMDKEINNRTCEVIKDGRFKVAKWKEIQVGDVIRLKKNDFVPADILLLSSSEPNSLCYVETAELDGETNLKFK MSLEITDQYLQREDTLATFDGFIECEEPNNRLDKFTGTLFWRNTSFPLDADKILLRGCVIRNTDFCHGLVIFAGADTKIM KNSGKTRFKRTKIDYLMNYMVYTIFVVLILLSAGLAIGHAYWEAQVGNSSWYLYDGEDDTPSYRGFLIFWGYIIVLNTMV PISLYVSVEVIRLGQSHFINWDLQMYYAEKDTPAKARTTTLNEQLGQIHYIFSDKTGTLTQNIMTFKKCCINGQIYGDHR DASQHNHNKIEQVDFSWNTYADGKLAFYDHYLIEQIQSGKEPEVRQFFFLLAVCHTVMVDRTDGQLNYQAASPDEGALVN AARNFGFAFLARTQNTITISELGTERTYNVLAILDFNSDRKRMSIIVRTPEGNIKLYCKGADTVIYERLHRMNPTKQETQ DALDIFANETLRTLCLCYKEIEEKEFTEWNKKFMAASVASTNRDEALDKVYEEIEKDLILLGATAIEDKLQDGVPETISK LAKADIKIWVLTGDKKETAENIGFACELLTEDTTICYGEDINSLLHARMENQRNRGGVYAKFAPPVQESFFPPGGNRALI ITGSWLNEILLEKKTKRNKILKLKFPRTEEERRMRTQSKRRLEAKKEQRQKNFVDLACECSAVICCRVTPKQKAMVVDLV KRYKKAITLAIGDGANDVNMIKTAHIGVGISGQEGMQAVMSSDYSFAQFRYLQRLLLVHGRWSYIRMCKFLRYFFYKNFA FTLVHFWYSFFNGYSAQTAYEDWFITLYNVLYTSLPVLLMGLLDQDVSDKLSLRFPGLYIVGQRDLLFNYKRFFVSLLHG VLTSMILFFIPLGAYLQTVGQDGEAPSDYQSFAVTIASALVITVNFQIGLDTSYWTFVNAFSIFGSIALYFGIMFDFHSA GIHVLFPSAFQFTGTASNALRQPYIWLTIILAVAVCLLPVVAIRFLSMTIWPSESDKIQKHRKRLKAEEQWQRRQQVFRR GVSTRRSAYAFSHQRGYADLISSGRSIRKKRSPLDAIVADGTAEYRRTGDS