Defective ABCG5 (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 5 (ABCG5 aka sterolin-1), is a "half transporter", that forms a complex with another half transporter ABCG8 (aka sterolin-2) 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 ABCG5 are the cause of sitosterolemia (MIM:210250), characterised by unrestricted intestinal absorption of both cholesterol and plant-derived sterols causing hypercholesterolemia and premature coronary atherosclerosis. Mutations causing sitosterolemia include R408*, R243*, R389H, R419H, Q16* and R446* (Berge et al. 2000, Lee et al. 2001, Rios et al. 2010, Mannucci et al. 2007).

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
17976197 Beta-sitosterolaemia: a new nonsense mutation in the ABCG5 gene

Gnasso, A, Pisciotta, L, Bertolini, S, Bertucci, P, Mannucci, L, Irace, C, Liberatoscioli, L, Federici, G, Cortese, C, Guardamagna, O

Eur. J. Clin. Invest. 2007
11138003 Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption

Hazard, S, Patel, SB, Salen, G, Hidaka, H, Dean, M, Pegoraro, R, Kojima, H, Lu, K, Allikmets, R, Yu, H, Srivastava, AK, Shulenin, S, Lee, MH, Sakuma, N

Nat. Genet. 2001
20719861 Identification by whole-genome resequencing of gene defect responsible for severe hypercholesterolemia

Stein, E, Hobbs, HH, Cohen, JC, Shendure, J, Rios, J

Hum. Mol. Genet. 2010
Catalyst Activity

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

Normal reaction
Functional status

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

Name Identifier Synonyms
lipid metabolism disorder DOID:3146 dyslipidemia, fatty acid metabolism disorder
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