A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis.
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.
Bull
L N
LN
Department of Psychiatry and Liver Center, University of California San Francisco, 94143, USA.
van Eijk
M J
MJ
Pawlikowska
L
L
DeYoung
J A
JA
Juijn
J A
JA
Liao
M
M
Klomp
L W
LW
Lomri
N
N
Berger
R
R
Scharschmidt
B F
BF
Knisely
A S
AS
Houwen
R H
RH
Freimer
N B
NB
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D015152:Blotting, Northern; D002779:Cholestasis / Q000235:genetics*; D002780:Cholestasis, Intrahepatic / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods; D005060:Europe; D005260:Female; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017384:Sequence Deletion; D014481:United States / Q000208:ethnology
D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human