ABCB4 missense mutations D243A, K435T, G535D, I490T, R545C, and S978P significantly impair the lipid floppase and likely predispose to secondary pathologies in the human population

• Published in: Cellular and molecular life sciences : CMLS Vol. 74; no. 13; pp. 2513 - 2524
• Main Authors: Andress, Edward J., Nicolaou, Michael, McGeoghan, Farrell, Linton, Kenneth J.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.07.2017; Springer Nature B.V
• Subjects: ABC transporter; Abundance; Adenosine Triphosphatases - metabolism; Amino Acid Substitution - genetics; ATP Binding Cassette Transporter, Subfamily B - genetics; Bile; Bile salts; Binding; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cancer; Cell Biology; Cell Membrane - metabolism; Cholangitis; Cholestasis; Cyclosporine - pharmacology; Cytotoxicity; Detergents; Diseases; Etiology; Exports; Gallbladder diseases; Genetic Predisposition to Disease; Glycosylation; HEK293 Cells; Hepatocytes; Human populations; Humans; Intracellular; Intracellular Space - metabolism; Lecithin; Life Sciences; Lipids - chemistry; Liver; Liver cancer; Liver diseases; Micelles; Missense mutation; Molecular Chaperones - metabolism; Mutant Proteins - metabolism; Mutation; Mutation, Missense - genetics; Original; Original Article; Pathology; Patients; Phosphatidylcholine; Phosphatidylcholines - metabolism; Polymorphism, Single Nucleotide - genetics; Population; Protein Stability - drug effects; Protein Transport - drug effects; Salts; Signal transduction; Signaling; Single-nucleotide polymorphism; Subcellular Fractions - metabolism; Vitamins; Liver cancer; Bile flow; Biliary cirrhosis; Inflammatory liver disease; MDR3; Sclerosing cholangitis; Cholestasis

Bile salts are natural detergents required to solubilise dietary fat and lipid soluble vitamins. They are synthesised in hepatocytes and secreted into the luminal space of the biliary tree by the bile salt export pump (BSEP), an ATP-binding cassette (ABC) transporter in the canalicular membrane. BSE...