title: Molecular basis of intrahepatic cholestasis.
abstract: Intrahepatic cholestasis, or impairment of bile flow, is an important manifestation of inherited and acquired liver disease. In recent years, human genetic and molecular studies have identified several genes, the disruption of which results in cholestasis. ATP8B1 (FIC1), ABCB11 (BSEP), and ABCB4 (MDR3) are disrupted in forms of progressive familial intrahepatic cholestasis (PFIC) and related disorders. Mutations in BAAT, TJP2 (ZO-2), and EPHX1 have been identified in patients with hypercholanemia. A CLDN1 mutation was recently reported in patients with ichthyosis, leukocyte vacuoles, alopecia and sclerosing cholangitis (ILVASC), and North American Indian childhood cirrhosis (NAIC) is associated with a missense mutation in CIRH1A. Alagille syndrome patients carry mutations in JAG1, and mutations in VPS33B have been identified in patients with arthrogryposis, renal dysfunction and cholestasis syndrome (ARC). Identification of these genes, and characterization of the proteins they encode, is enhancing our understanding of the biology of the enterohepatic circulation in health and disease.
authors.affiliation: Liver Center Laboratory and Department of Medicine, San Francisco General Hospital, San Francisco, California 94110, USA.
authors.forename: Victoria E H
authors.initials: VE
authors.lastname: Carlton
authors.forename: Ludmila
authors.initials: L
authors.lastname: Pawlikowska
authors.forename: Laura N
authors.initials: LN
authors.lastname: Bull
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000217:Acyltransferases / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics; D016738:Alagille Syndrome / Q000235:genetics; D000818:Animals; D002135:Calcium-Binding Proteins; D002780:Cholestasis, Intrahepatic / Q000235:genetics / Q000503:physiopathology*; D062445:Claudin-1; D005621:Friedreich Ataxia / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008099:Liver / Q000378:metabolism / Q000503:physiopathology*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D011506:Proteins / Q000235:genetics; D000072099:Serrate-Jagged Proteins; D019108:Tight Junctions / Q000235:genetics; D033921:Vesicular Transport Proteins
chemical_list: C093491:ABCB11 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C568108:CLDN1 protein, human; D002135:Calcium-Binding Proteins; D062445:Claudin-1; C568113:Cldn1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011506:Proteins; D000072099:Serrate-Jagged Proteins; C411584:VPS33B protein, human; D033921:Vesicular Transport Proteins; C095122:multidrug resistance protein 3; D000217:Acyltransferases; C026953:bile acid-CoA amino acid N-acyltransferase; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human