Defective ABCG8 (in ABCG5:ABCG8) does not transport sterols from cytosol to extracellular region

Stable Identifier
Reaction [transition]
Homo sapiens
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ATP-binding cassette sub-family G member 8 (ABCG8 aka sterolin-2), is a "half transporter", that forms a complex with another half transporter ABCG5 in the endoplasmic reticulum. This complex translocates to the plasma membrane to mediate the ATP-dependent intestinal absorption and facilitation of biliary secretion of cholesterol and phytosterols (eg sitosterol). Defects in either of these half transporters result in loss of enterocyte discrimination between cholesterol and sitosterol causing sterol accumulation and predisposition for atherosclerosis. Defects in ABCG8 are the cause of gallbladder disease 4 (GBD4; MIM:611465) and sitosterolemia (MIM:210250). A mutation causing GBD4 is D19H (Buch et al. 2007). Mutations causing sitosterolemia include W361*, G574R, Y658*, R263Q and P231T (Berge et al. 2000).
Literature References
PubMed ID Title Journal Year
11099417 Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters

Graf, GA, Hobbs, HH, Barnes, R, Kwiterovich, P, Shan, B, Grishin, NV, Schultz, J, Tian, H, Yu, L, Berge, KE

Science 2000
17632509 A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease

Schreiber, S, Seeger, M, Buch, S, Fölsch, UR, Hampe, J, Höll, C, Lammert, F, Völzke, H, Tepel, J, Wittig, M, Miquel, JF, Franke, A, Schafmayer, C, Krawczak, M, Kluck, C, Timm, B, Becker, C, Lu, T, ElSharawy, A, Fändrich, F, Bässmann, I, Egberts, J, Nürnberg, P, Nervi, F, Brosch, M, von Eller-Eberstein, H, Rosskopf, D

Nat. Genet. 2007
Catalyst Activity

sterol transporter activity of mutant ABCG8:ABCG5 [plasma membrane]

Normal reaction
Functional status

Loss of function of mutant ABCG8:ABCG5 [plasma membrane]

Name Identifier Synonyms
lipid metabolism disorder DOID:3146 dyslipidemia, fatty acid metabolism disorder
atherosclerosis DOID:1936
cholelithiasis DOID:10211
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