title: A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis.
abstract: The progressive familial intrahepatic cholestases (PFIC) are a group of inherited disorders with severe cholestatic liver disease from early infancy. A subgroup characterized by normal serum cholesterol and gamma-glutamyltranspeptidase (gammaGT) levels is genetically heterogeneous with loci on chromosomes 2q (PFIC2) and 18q. The phenotype of the PFIC2-linked group is consistent with defective bile acid transport at the hepatocyte canalicular membrane. The PFIC2 gene has now been identified by mutations in a positional candidate, BSEP, which encodes a liver-specific ATP-binding cassette (ABC) transporter, sister of p-glycoprotein (SPGP). The product of the orthologous rat gene has been shown to be an effective bile acid transporter in vitro. These data provide evidence that SPGP is the human bile salt export pump (BSEP).
authors.affiliation: Department of Paediatrics, University College London Medical School, UK.
authors.forename: S S
authors.initials: SS
authors.lastname: Strautnieks
authors.forename: L N
authors.initials: LN
authors.lastname: Bull
authors.forename: A S
authors.initials: AS
authors.lastname: Knisely
authors.forename: S A
authors.initials: SA
authors.lastname: Kocoshis
authors.forename: N
authors.initials: N
authors.lastname: Dahl
authors.forename: H
authors.initials: H
authors.lastname: Arnell
authors.forename: E
authors.initials: E
authors.lastname: Sokal
authors.forename: K
authors.initials: K
authors.lastname: Dahan
authors.forename: S
authors.initials: S
authors.lastname: Childs
authors.forename: V
authors.initials: V
authors.lastname: Ling
authors.forename: M S
authors.initials: MS
authors.lastname: Tanner
authors.forename: A F
authors.initials: AF
authors.lastname: Kagalwalla
authors.forename: A
authors.initials: A
authors.lastname: Németh
authors.forename: J
authors.initials: J
authors.lastname: Pawlowska
authors.forename: A
authors.initials: A
authors.lastname: Baker
authors.forename: G
authors.initials: G
authors.lastname: Mieli-Vergani
authors.forename: N B
authors.initials: NB
authors.lastname: Freimer
authors.forename: R M
authors.initials: RM
authors.lastname: Gardiner
authors.forename: R J
authors.initials: RJ
authors.lastname: Thompson
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002780:Cholestasis, Intrahepatic / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003241:Consanguinity; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D051381:Rats; D017386:Sequence Homology, Amino Acid
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C490548:Abcb11 protein, rat; D001647:Bile Acids and Salts; D018076:DNA, Complementary