SCARB1 (Scavenger Receptor Class B Member 1 / SR-B1 HDL Receptor Gene)
SCARB1 (scavenger receptor class B member 1; HGNC:1664, NCBI Gene ID 949) is a human locus mapped to chromosome band 12q24.31 that encodes horseshoe-loop glycoprotein Scavenger Receptor Class B Type I / SR-B1 (509 aa). SCARB1 acts in selective hepatic cholesteryl ester uptake from HDL & steroidogenic cholesterol delivery, together with APOA1 (Apolipoprotein A-I Gene), ABCA1 (Cholesterol Efflux Transporter), and ABCG1 (HDL Cholesterol Efflux Transporter). Encodes SR-B1, the physiological high-density lipoprotein receptor mediating selective cholesteryl ester uptake in the liver and steroidogenic glands.
Approved Symbol
SCARB1
Chromosomal Locus
12q24.31
Encoded Product
Horseshoe-loop glycoprotein Scavenger Receptor Class B Type I / SR-B1 (509 aa)
Loss-of-function p.Pro376Leu variant raises plasma HDL-C to extreme levels while paradoxically increasing CHD risk
Gene Structure & Expression
Genomic Organization & Cytogenetic Locus: 13-exon gene on chromosome 12q24.31 encoding a 509-amino-acid CD36-family membrane glycoprotein with short cytoplasmic N- and C-termini (which bind the PDZ adaptor PDZK1 in hepatocytes), two transmembrane domains, and a large heavily glycosylated extracellular domain containing a hydrophobic lipid-transfer tunnel.
Cellular & Tissue Expression Profile: Abundantly expressed on the sinusoidal microvillar surface of hepatic hepatocytes and in trophic-hormone-stimulated steroidogenic cells of the adrenal cortex (zona fasciculata/reticularis), ovarian corpus luteum and granulosa/theca cells, and testicular Leydig cells.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Unlike LDLR—which internalizes and degrades the entire LDL particle—SR-B1 binds spherical ApoA-I-rich HDL particles at the cell surface and channels hydrophobic cholesteryl esters down a concentration gradient through its non-aqueous ectodomain tunnel directly into the plasma membrane bilayer, releasing the cholesterol-depleted HDL shell back into circulation for further reverse cholesterol transport.
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: Human carriers of the rare loss-of-function missense mutation p.Pro376Leu (P376L) exhibit profoundly elevated plasma HDL-cholesterol (>95th percentile) due to blocked hepatic clearance, yet suffer a significantly increased risk of coronary heart disease—proving clinically that reverse cholesterol transport flux rather than static HDL-cholesterol concentration determines atheroprotection.
Therapeutic & Clinical Pharmacology: Also functions as a co-receptor for hepatitis C virus (HCV) E2 glycoprotein entry into hepatocytes and facilitates cellular uptake of lipid-conjugated siRNAs and vitamin E/carotenoids.