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The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. The protein encoded by this gene functions as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG5. Mutations in this gene may contribute to sterol accumulation and atherosclerosis, and have been observed in patients with sitosterolemia. ABCG5 and ABCG8 function as obligate heterodimers to promote sterol excretion into bile. ABCGG5 and ABCG8 are required to modulate biliary cholesterol secretion in response to cholate and diosgenin. Common DNA sequence polymorphisms in the ABCG8 gene contribute to heritable variation in the plasma concentrations of the plant sterols campesterol and sitosterol. Genetic variations in the ABCG8 gene may play a role in the genetic determination of plasma cholesterol levels and could possibly influence the gender-specific response of plasma cholesterol levels after dietary changes. In a sitosterolemia patient a novel heterozygous mutation has been found in exon 5 of ABCG8 (c.584T>A; Leu195Gln). Role of ABCG5 and ABCG8 in cholesterol secretion and absorption. In patients with hypercholesterolemia, the ABCG8 D19H variant is associated with greater LDLC-lowering response to atorvastatin therapy. Mutations in ATP-binding cassette proteins G5 (ABCG5) and G8 (ABCG8) causing sitosterolemia. Several potential regulatory elements were found for the ABCG5 and ABCG8 genes, and the intergenic region was found to act as a bidirectional promoter.
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