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

Stable Identifier
R-HSA-5679101
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane, cytosol, extracellular region
ReviewStatus
5/5
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Defective ABCG8 (in ABCG5:ABCG8) does not transport sterols from cytosol to extracellular region
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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

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

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

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

Nat. Genet. 2007
Participants
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Catalyst Activity

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

Physical Entity
mutant ABCG8:ABCG5 [plasma membrane] (Homo sapiens)
Activity
ABC-type sterol transporter activity (GO:0034041)
Normal reaction
ABCG5:ABCG8 transports sterols from cytosol to extracellular region (Homo sapiens)
Functional status

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

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
lipid metabolism disorder DOID:3146 dyslipidemia, fatty acid metabolism disorder
atherosclerosis DOID:1936
cholelithiasis DOID:10211
Cross References
Mondo
Authored
Jassal, B  (2015-03-02)
Reviewed
Shukla, S  (2015-09-15)
Created
Jassal, B  (2015-03-02)
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