Alternative titles; symbols
HGNC Approved Gene Symbol: SCARB1
Cytogenetic location: 12q24.31 Genomic coordinates (GRCh38): 12:124,776,856-124,863,864 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 12q24.31 | [High density lipoprotein cholesterol level QTL6] | 610762 | 3 |
SCARB1 encodes an integral membrane receptor with a large hydrophobic tunnel that forms a conduit for cellular uptake of lipophilic molecules. SCARB1 mediates uptake of cholesterol and a variety of lipids, including phospholipids, products of triglycerol hydrolysis, lipophilic vitamins A and D, and carotenoids (summary by Toomey et al., 2017).
Using degenerate PCR, Calvo and Vega (1993) isolated a novel sequence closely related to both the CD36 thrombospondin/collagen receptor (173510) and to lysosomal integral membrane protein II (LIMPII; 602257). This novel gene was termed CLA1 for 'CD36 and LIMPII analogous-1.' Calvo and Vega (1993) isolated 2 alternatively spliced CLA1 cDNAs predicting proteins of 409 and 509 amino acids from a human placenta cDNA library. Calvo and Vega (1993) stated that the full-length CLA1 sequence predicts a glycoprotein having 2 transmembrane domains, 2 short cytoplasmic tails, and a large extracellular loop. They used immunofluorescence to show that the protein is found on the plasma membrane. Northern blot analysis revealed a 2.9-kb mRNA in several cell lines.
By immunohistochemical analysis, Santander et al. (2013) found that Srb1 was expressed in the yolk sac and placenta during early stages of mouse development. Srb1 was expressed in the embryo itself later in gestation.
Calvo et al. (1995) used PCR analysis of human-hamster hybrids to map the CD36L1 gene to human chromosome 12. They stated that CD36, CD36L1, and CD36L2 represent a gene family, but that this family is not clustered in the genome; these genes map to chromosomes 7, 12, and 4, respectively. Cao et al. (1997) mapped the SCARB1 gene to 12q24.2-qter by FISH. From the mapping of a QTL for internal carotid artery intimal medial thickness with chromosome 12 to a site 161 cM from 12pter, it was found by Fox et al. (2004) that SCARB1 is in close proximity.
High density lipoprotein (HDL) and low density lipoprotein (LDL) are cholesterol transport particles whose plasma concentrations are directly (in the case of LDL) and inversely (in the case of HDL) correlated with risk for atherosclerosis. LDL metabolism involves cellular uptake and degradation of the entire particle by a well-characterized receptor (LDLR; 606945). HDL, in contrast, selectively delivers its cholesterol, but not protein, to cells. Acton et al. (1996) showed that the mouse HDL receptor involved in this selective delivery of cholesterol is the class B scavenger receptor they referred to as SR-BI. This receptor binds HDL with high affinity, is expressed primarily in liver and nonplacental steroidogenic tissues, and mediates selective cholesterol uptake by a mechanism distinct from the classic LDL receptor pathway. The authors distinguished this receptor activity from that of other HDL-binding proteins (e.g., 142695). By analogy with the LDL system, a key missing element in the study of HDL metabolism had been a well-defined HDL receptor, which could give a molecular and cellular handle on the system. The class B type I scavenger receptor was the first molecularly well-characterized HDL receptor.
The murine scavenger receptor type B class I (SRBI) has affinity for high density lipoproteins (HDLs) and mediates the selective uptake of cholesterol esters. Murao et al. (1997) noted that SRBI shares 81% sequence identity with the longer (509 amino acid) form of human CLA1. By Northern blot analysis, Murao et al. (1997) demonstrated that the 2.9-kb CLA1 message is expressed most strongly in human adrenal gland and also in liver and testis. Murao et al. (1997) suggested that CLA1, like SRBI, could play a role in the metabolism of HDL. However, CLA1 was also expressed in monocytes and, like SRBI, recognized modified forms of low density lipoproteins as well as native LDL and anionic phospholipids. Murao et al. (1997) found that CLA1 bound selectively to apoptotic thymocytes. Murao et al. (1997) suggested that CLA1 may have 2 distinct roles, functioning both as a mediator of HDL uptake in the liver and steroidogenic tissues, and having an alternative role in leukocytes.
Murao et al. (1997) and Cao et al. (1997) demonstrated that SRBI is expressed in humans at high levels in precisely those tissues that previously had been shown to exhibit the bulk of selective uptake of HDL cholesterol in vivo. The temporal and spatial expression of SRBI during murine embryogenesis was consistent with a role of SRBI in delivering cholesterol to the developing fetus. Additional correlative evidence of a role of SRBI in HDL cholesterol metabolism came from studies of the effects on SRBI expression of hormones, which induce or suppress steroid hormone synthesis. To address the role of SRBI in HDL cholesterol homeostasis, mice were generated bearing an SRBI promoter mutation that resulted in decreased expression of the receptor in homozygous mutant mice (Varban et al., 1998). Hepatic expression of the receptor was reduced by 53% with a corresponding increase in total plasma cholesterol levels of 50 to 70%, attributable almost exclusively to elevated plasma HDL. In addition to the increased HDL cholesteryl esters, HDL phospholipids and apoA1 (107680) levels were elevated and there was an increase in HDL particle size in mutant mice. Metabolic studies using HDL-bearing nondegradable radiolabels in both the protein and lipid components demonstrated that reduced hepatic SRBI expression by half was associated with a decrease of 47% in selective uptake of cholesteryl esters by the liver, and a corresponding reduction of 53% in selective removal of HDL cholesteryl esters from plasma. Taken together, these findings strongly supported a pivotal role for hepatic SRBI expression in regulating plasma HDL levels and indicated that SRBI is the major molecular mediating selective cholesteryl ester uptake by the liver. The inverse correlation between plasma HDL levels and atherosclerosis further suggests that SRBI may influence the development of coronary artery disease. See Krieger (1998) for a comparison of the HDL and LDL receptor systems.
Ikemoto et al. (2000) identified an SRBI-associated protein from rat liver membrane extracts by using an affinity chromatography technique. The protein contains 4 PDZ domains (see 603199 for a discussion of PDZ) and associates with the C terminus of rat SRBI by using its N-terminal first PDZ domain; see 603831.
Scarselli et al. (2002) determined that SCARB1 is a receptor for hepatitis C virus glycoprotein E2. Binding between SCARB1 and E2 was found to be independent of the genotype of the viral isolate.
Using a genomewide RNA interference screen in Drosophila macrophage-like cells using Mycobacterium fortuitum, Philips et al. (2005) identified factors required for general phagocytosis, as well as those needed specifically for mycobacterial infection. One specific factor, Peste (Pes), is a CD36 family member required for uptake of mycobacteria, but not E. coli or S. aureus. Moreover, mammalian class B scavenger receptors (SRs) conferred uptake of bacteria into nonphagocytic cells, with SR-BI and SR-BII (602257) uniquely mediating uptake of M. fortuitum, which suggests a conserved role for class B SRs in pattern recognition and innate immunity.
Vishnyakova et al. (2006) found that transfection of embryonic kidney and HeLa cell lines with CLA1 and its splice variant, CLA2, enhanced uptake of both gram-positive and gram-negative bacteria. Lipopolysaccharide and lipoteichoic acid competed with E. coli K12 for CLA1 and CLA2 binding. Transmission electron microscopy and confocal microscopy analyses revealed cytosolic accumulation of bacteria in cells overexpressing CLA1/CLA2. In the presence of antibiotics, E. coli K12 survived and replicated intracellularly, but synthetic amphipathic helical peptides prevented E. coli K12 invasion. Peritoneal macrophages from mice lacking Cla1/Cla2 showed reduced bacterial uptake, as well as decreased bacterial cytosolic invasion, ubiquitination, and proteasome mobilization, whereas bacterial lysosomal accumulation was unaffected. Vishnyakova et al. (2006) proposed that these CLA1/CLA2-mediated intracellular events may facilitate infection with certain intracellular pathogens, such as hepatitis C virus, and/or represent a mechanism of pathogen recognition, ubiquitination, and degradation.
MicroRNAs (miRNAs) are small noncoding RNAs that typically downregulate gene expression by binding to complementary sequences in the 3-prime UTRs of target mRNAs and either inhibiting translation or directing mRNA degradation. Wang et al. (2013) found that the microRNAs MIR185 (615576), MIR96 (611606), and MIR223 (300694) downregulated expression of SRBI in human hepatic cell lines. The 3-prime UTR of SRBI contains independent binding sites for MIR96, MIR185, and MIR223, and the 3 miRNAs showed an additive effect in inhibiting expression of a reporter gene containing the SRBI 3-prime UTR. Transfection of MIR185 and MIR96 mimics, but not an MIR223 mimic, markedly reduced SRBI mRNA levels in phorbol ester-stimulated human THP-1 macrophage-like cells and suppressed HDLC uptake. In apoE (107741)-knockout mice on a high-fat diet, elevated hepatic Srbi coincided with decreased Mir96 and Mir185 content (the 3-prime UTR of rodent Srbi does not have an Mir223 target site). Wang et al. (2013) concluded that these miRNAs have a role in regulating cholesterol uptake by repressing expression of SRBI.
Huang et al. (2019) showed in mice that Srb1 in endothelial cells mediates the delivery of LDL into arteries and its accumulation by artery wall macrophages, thereby promoting atherosclerosis. LDL particles were colocalized with Srb1 in endothelial cell intracellular vesicles in vivo, and transcytosis of LDL across endothelial monolayers required its direct binding to Srb1 as well as recruitment of the guanine nucleotide exchange factor Dock4 (607679) through an 8-amino-acid cytoplasmic domain of Srb1. Dock4 promoted internalization of Srb1 and transport of LDL by coupling the binding of LDL to Srb1 with activation of Rac1 (602048). The expression of Srb1 and Dock4 was increased in atherosclerosis-prone regions of the mouse aorta before lesion formation, and in human atherosclerotic arteries when compared with normal arteries. Huang et al. (2019) concluded that their findings challenged the long-held concept that atherogenesis involves passive movement of LDL across a compromised endothelial barrier and suggested that interventions that inhibit the endothelial delivery of LDL into artery walls may represent a novel therapeutic category in the battle against cardiovascular disease.
Crystal Structure
Neculai et al. (2013) determined the crystal structure of LIMP2 (602257) and inferred, by homology modeling, the structure of SRBI and CD36 (173510). LIMP2 shows a helical bundle where beta-glucocerebrosidase (GBA; 606463) binds, and where ligands are most likely to bind to SRBI and CD36. Remarkably, the crystal structure also shows the existence of a large cavity that traverses the entire length of the molecule. Mutagenesis of SRBI indicates that the cavity serves as a tunnel through which cholesterol(esters) are delivered from the bound lipoprotein to the outer leaflet of the plasma membrane. Neculai et al. (2013) provided evidence supporting a model whereby lipidic constituents of the ligands attached to the receptor surface are handed off to the membrane through the tunnel, accounting for the selective lipid transfer characteristic of SRBI and CD36.
In 77 subjects who were heterozygous for familial hypercholesterolemia (143890), Tai et al. (2003) examined the association of plasma lipid concentrations with 3 common polymorphisms of the SRBI gene, which is a candidate gene involved in the pathophysiology of atherosclerosis. Two polymorphisms, one in exon 1 and one in exon 8, were associated with variation in plasma concentrations of fasting triglyceride. In addition, the exon 8 polymorphism was associated with change in lipoprotein levels. In agreement with animal studies, the data suggested a role for SRBI in the metabolism of apolipoprotein B (APOB; 107730)-containing lipoproteins in humans. Tai et al. (2003) suggested that this pathway may constitute a backup mechanism to LDL receptor-mediated pathways for the catabolism of these lipoproteins, and could be particularly relevant in subjects with high levels of apoB-containing lipoproteins, such as those occurring in patients with familial hypercholesterolemia.
Decreased HDL cholesterol and raised triglyceride levels are well known risk factors for atherosclerosis. McCarthy et al. (2003) examined polymorphisms in the HDL receptor gene SCARB1 in 371 white patients with coronary artery disease to determine their association with plasma lipids. They found an association between a combination of genotypes in women but not in men. McCarthy et al. (2003) concluded that genetic variants in SCARB1 may be an important determinant of abnormal lipoproteins in women and confer particular susceptibility to coronary artery disease. They referred to the findings of Herrington et al. (2002) that a differential response of HDL cholesterol to hormone replacement therapy is dependent on the presence of genetic variants of the estrogen receptor gene (133430.0004), and suggested that SCARB1 variants may also modulate the effect of hormone replacement therapy on plasma lipid levels in women.
Acton et al. (1999) reported 3 common polymorphisms associated with plasma lipids and body mass index. Osgood et al. (2003) hypothesized that diabetic status may interact with these polymorphisms in determining plasma lipid concentrations and particle size. They evaluated this hypothesis in 2,463 nondiabetic (49% men) and 187 diabetic (64% men) participants in the Framingham Study. After multivariate adjustment, they found a consistent association between the exon 8 polymorphism and high density lipoprotein cholesterol concentration and particle size. Interaction effects were not significant for exon 8 and intron 5 polymorphisms. However, Osgood et al. (2003) found statistically significant interactions between SCARB1 exon 1 genotypes and type 2 diabetes (125853), indicating that diabetic subjects with the less common allele have lower lipid concentrations. The authors concluded that SCARB1 gene variation modulates the lipid profile, particularly in type 2 diabetes, contributing to the metabolic abnormalities in these subjects.
Perez-Martinez et al. (2005) studied if a G-to-A polymorphism in exon 1 of the SCARB1 gene modifies the insulin sensitivity to dietary fat. They studied 59 healthy volunteers. Steady-state plasma glucose after a monounsaturated fatty acid (MUFA) diet was lower in G/A compared with G/G subjects. Plasma nonesterified free fatty acid values were lower in subjects carrying the less common A allele for all the diet periods. The authors concluded that carriers of the G/A genotype have significant increases in insulin sensitivity after a MUFA-rich diet compared with G/G individuals. There were no homozygotes for the A allele.
Teslovich et al. (2010) performed a genomewide association study for plasma lipids in more than 100,000 individuals of European ancestry and reported 95 significantly associated loci (P = less than 5 x 10(-8)), with 59 showing genomewide significant association with lipid traits for the first time. The newly reported associations included SNPs near known lipid regulators (e.g., CYP7A1, 118455; NPC1L1, 608010; and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contributed not only to normal variation in lipid traits but also to extreme lipid phenotypes and had an impact on lipid traits in 3 non-European populations (East Asians, South Asians, and African Americans).
Vergeer et al. (2011) identified a missense mutation, P297S (601040.0001), in the SCARB1 gene that was associated with elevated HDL cholesterol levels (see HDLCQ6, 610762) but no other differences in lipid profile parameters, atherosclerosis, or carotid intima-media thickness. However, carriers of the P297S variant showed decreased platelet aggregation and a reduction in cholesterol efflux from monocyte-macrophages. Carriers also had decreased adrenal steroidogenesis. Khovidhunkit (2011) commented that the study by Vergeer et al. (2011) did not distinguish whether the diminished adrenal function in the carriers of the P297S mutation was primary or secondary, and suggested measuring corticotropin levels to differentiate. Vergeer et al. (2011) replied that there was no difference in median corticotropin levels between the 15 P297S carriers and the 15 noncarriers, indicating that there was no pituitary defect. Vergeer et al. (2011) suggested that the P297S mutation in the SCARB1 cholesterol transporter directly impairs the adrenal uptake of cholesterol as a substrate for steroidogenesis, leading to a primary defect in adrenal function in human carriers.
Brunham et al. (2011) sequenced the SCARB1 gene in 120 Caucasian probands with plasma HDL cholesterol levels at or above the 90th percentile adjusted for age and gender, and in 80 Caucasian individuals with HDLC below the 10th percentile, with no other lipid abnormalities. In 2 probands with high HDLC, they identified 2 missense mutations (601040.0002 and 601040.0003) that segregated with HDL cholesterol levels in each family and were not found in the 80 individuals with low HDLC levels or in the dbSNP or 1000 Genomes Project databases.
In a study of individuals with elevated HDLC levels, Zanoni et al. (2016) identified a missense mutation in the SCARB1 gene (P376L; 601040.0004) that was associated with an increased level of plasma HDLC, but also with an increased risk of coronary heart disease. Functional analysis of the P376L variant showed that the mutant confers almost complete loss of function of SRBI, impairing posttranslational processing of SRBI and abrogating selective HDL cholesterol uptake. Zanoni et al. (2016) stated that their results supported the notion that steady-state concentrations of HDLC are not causally protective against CHD, and that HDL function and cholesterol flux may be more important than absolute levels.
Miettinen et al. (2001) generated Scarb1 knockout mice and observed that null females had abnormal HDLs, ovulated dysfunctional oocytes, and were infertile. Fertility was restored when the structure and/or quantity of abnormal HDL was altered by inactivating the Apoa1 gene or administering the cholesterol-lowering drug probucol. Miettinen et al. (2001) suggested that abnormal lipoprotein metabolism can cause infertility in mice and may contribute to some forms of human female infertility.
Widjaja-Adhi et al. (2015) characterized zeaxanthin uptake and metabolism in single and compound mutant mice lacking Bco2 (611740), Scarb1, Isx (612019), and/or Bco1 (605748). They found that the membrane protein Scarb1 was required for intestinal xanthophyll uptake. The transcription factor Isx downregulated Scarb1 and Bco1 expression by binding to a core DNA element in their promoters. Bco1 was required for xanthophyll absorption in liver and eye. The studies identified Bco1 and Bco2 as the major metabolizing enzymes for beta-carotene and zeaxanthin, respectively, and showed that Bco1-dependent retinoid signaling induced Isx expression in a negative-feedback loop.
Santander et al. (2013) found that the proportion of weaned Srb1 -/- mice obtained by heterozygous intercrossing was lower than the predicted mendelian ratio, with more Srb1 -/- females lost than Srb1 -/- males. A high proportion of Srb1 -/- embryos exhibited defects in neural tube closure and exencephaly, with a sex bias toward females. Embryos with defects in neural tube closure also showed abnormal tongue morphogenesis and defective eyelid closure associated with disorganized eye structures. Nonexencephalic Srb1 -/- embryos did not show detectable developmental abnormalities in brain or other organs. All Srb1 -/- embryos showed a moderate decrease in cholesterol content. Surviving Srb1 -/- animals showed intrauterine growth restriction and were significantly smaller than their wildtype counterparts at birth. Noting that Srb1 is expressed at maternofetal interfaces early in embryonic development, Santander et al. (2013) concluded that maternofetal transport of cholesterol and/or other lipid molecules is required for neural tube closure and fetal growth.
The yellow, orange, and red coloration of the feathers, skin, and beak of birds is most commonly produced through the deposition of carotenoid pigments, which are metabolized from dietary carotenoids. Toomey et al. (2017) found that 'white recessive' canaries had absent or very low concentrations of carotenoids in feathers and skin and other tissues. Selective sweep mapping, linkage analysis, and sequencing identified a homozygous T-to-G transversion at the splice donor site of exon 4 of the Scarb1 gene in white recessive canaries. Yellow and red individuals across several breeds were either homozygous wildtype or heterozygous. White recessive canaries lacked wildtype Scarb1 mRNA, but expressed 3 different splice isoforms. The most common transcript skipped exon 4, which encodes 68 residues in the highly conserved ligand-binding domain. Expression of wildtype Scarb1 in DF1 avian fibroblasts increased cellular uptake of carotenoids compared with controls, whereas mutant Scarb1 significantly reduced carotenoid uptake relative to controls. Toomey et al. (2017) concluded that white recessive canaries express a nonfunctional Scarb1 transcript with respect to carotenoid transport.
Among a cohort of 162 unrelated white participants with an HDL cholesterol level above the 95th percentile (see HDLCQ6, 610762), Vergeer et al. (2011) identified an individual who carried a C-to-T transition at nucleotide 889 of the SCARB1 gene, resulting in a proline-to-serine substitution at codon 297 (P297S). This mutation was not found in 150 normolipidemic controls. The proline at this position is highly conserved across species. Vergeer et al. (2011) investigated 18 further carrier members of the proband's family and compared them to 36 family noncarrier controls matched according to BMI, sex, and age on an aggregate basis. Carriers had significantly increased HDL cholesterol levels (70.4 mg per deciliter vs 53.4 mg per deciliter in noncarriers; p less than 0.001) but no significant differences in levels of other plasma lipids. Vergeer et al. (2011) found no difference in the prevalence of cardiovascular disease between carriers and noncarriers, and no difference in carotid intima-media thickness. Among carriers, Vergeer et al. (2011) identified decreased platelet aggregation in response to different agonists compared with noncarriers, as well as decreased adrenal steroidogenesis. Cholesterol uptake from HDL by primary murine hepatocytes that expressed mutant SRB1 protein was reduced by 56% of that of hepatocytes expressing wildtype SRB1 (p less than 0.001).
In a 50-year-old Caucasian man with HDL cholesterol (HDLC) levels above the 95th percentile when adjusted for age and gender (HDLCQ6; 610762), Brunham et al. (2011) identified heterozygosity for a 776A-G transition in the SCARB1 gene, resulting in a thr175-to-ala (T175A) substitution at a highly conserved residue in the large extracellular loop. The mutation was present in the proband's 2 sons, who also had HDLC levels above the 95th percentile, and in the proband's brother, whose HDLC level was at the 71st percentile but who also had hypertension and was taking medication that might influence the phenotype. The mutation was not found in other family members with HDLC levels less than the 95th percentile, in 80 unrelated Caucasian individuals with HDLC levels below the 10th percentile, or in the dbSNP or 1000 Genomes Project databases.
In a 51-year-old Caucasian man with HDL cholesterol levels above the 95th percentile when adjusted for age and gender (HDLCQ6; 610762), Brunham et al. (2011) identified heterozygosity for a 588C-T transition in the SCARB1 gene, resulting in a ser112-to-phe (S112F) substitution at a highly conserved residue in the large extracellular loop. The mutation was not found in 80 unrelated Caucasian individuals with HDLC levels below the 10th percentile, or in the dbSNP or 1000 Genomes Project databases. However, the proband's 76-year-old mother, who was also heterozygous for S112F, had an HDLC level in the 15th percentile, with early-onset cerebrovascular disease at 55 years of age as well as later coronary artery disease. Analysis of 3 genes known to be associated with low HDLC levels revealed that his mother also carried a heterozygous missense mutation in the ABCA1 gene (V2091I), suggesting that ABCA1 mutations may be dominant to SCARB1 mutations with respect to HDLC.
Among 328 individuals with very high HDLC levels (HDLCQ6; 610762), Zanoni et al. (2016) identified 1 homozygote and 4 heterozygotes for a c.1127C-T (rs74830677) transition in the SCARB1 gene, resulting in a pro376-to-leu (P376L) substitution. No carriers of the P376L variant were found in a group of 398 individuals with low HDLC levels. Analysis of another cohort revealed 11 P376L heterozygotes among 524 individuals with very high HDLC and 3 heterozygotes among 758 individuals with low HDLC; combining the results showed that the P376L variant was significantly overrepresented in individuals with high HDLC (p = 0.000127). The P376L variant was also present in the Global Lipid Genetics Consortium database at a minor allele frequency of approximately 0.0003, and was significantly associated with higher HDLC levels (p = 1.4 x 10(-15)), but not with LDLC or triglycerides. Functional analysis in hepatocyte-like cells generated from pluripotent stem cells from the homozygote and a noncarrier control revealed a profound reduction in selective cholesterol uptake from HDL with the mutant cells compared to controls; similar results were observed in transfected COS-7 cells. Hepatic overexpression of wildtype SCARB1 or the P376L mutant in Scarb1 knockout mice showed much slower clearance of HDL cholesteryl esters with the mutant compared to wildtype. The homozygous individual was a 67-year-old woman who, despite an HDLC level of 152 mg/dL, had increased carotid intimal-media thickness (cIMT) as well as detectable plaque in both carotid arteries. Measurements of cIMT in the heterozygotes were not significantly different from controls, but statistical power was limited due to small sample size. However, analysis of 49,846 CHD cases and 88,149 controls from the CARDIoGRAM Exome Consortium and the CHD Exome+ Consortium showed that P376L carriers had a significantly higher risk of CHD compared to noncarriers (odds ratio, 1.79; p = 0.018). Zanoni et al. (2016) concluded that carriers of the SCARB1 P376L loss-of-function variant have both significantly increased HDLC levels and a significantly increased risk of CHD.
Acton, S., Osgood, D., Donoghue, M., Corella, D., Pocovi, M., Cenarro, A., Mozas, P., Keilty, J., Squazzo, S., Woolf, E. A., Ordovas, J. M. Association of polymorphisms at the SR-BI gene locus with plasma lipid levels and body mass index in a white population. Arterioscler. Thromb. Vasc. Biol. 19: 1734-1743, 1999. [PubMed: 10397692] [Full Text: https://doi.org/10.1161/01.atv.19.7.1734]
Acton, S., Rigotti, A., Landschultz, K. T., Xu, S., Hobbs, H. H., Krieger, M. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 271: 518-650, 1996. [PubMed: 8560269] [Full Text: https://doi.org/10.1126/science.271.5248.518]
Brunham, L. R., Tietjen, I., Bochem, A. E., Singaraja, R. R., Franchini, P. L., Radomski, C., Mattice, M., Legendre, A., Hovingh, G. K., Kastelein, J. J. P., Hayden, M. R. Novel mutations in scavenger receptor BI associated with high HDL cholesterol in humans. Clin. Genet. 79: 575-581, 2011. Note: Erratum: Clin. Genet. 80: 406 only, 2011. [PubMed: 21480869] [Full Text: https://doi.org/10.1111/j.1399-0004.2011.01682.x]
Calvo, D., Dopazo, J., Vega, M. A. The CD36, CLA-1 (CD36L1), and LIMPII (CD36L2) gene family: cellular distribution, chromosomal location, and genetic evolution. Genomics 25: 100-106, 1995. [PubMed: 7539776] [Full Text: https://doi.org/10.1016/0888-7543(95)80114-2]
Calvo, D., Vega, M. A. Identification, primary structure, and distribution of CLA-1, a novel member of the CD36/LIMPII gene family. J. Biol. Chem. 268: 18929-18935, 1993. [PubMed: 7689561]
Cao, G., Garcia, C. K., Wyne, K. L., Schultz, R. A., Parker, K. L., Hobbs, H. H. Structure and localization of the human gene encoding SR-BI/CLA-1: evidence for transcriptional control by steroidogenic factor 1. J. Biol. Chem. 272: 33068-33076, 1997. [PubMed: 9407090] [Full Text: https://doi.org/10.1074/jbc.272.52.33068]
Fox, C. S., Cupples, L. A., Chazaro, I., Polak, J. F., Wolf, P. A., D'Agostino, R. B., Ordovas, J. M., O'Donnell, C. J. Genomewide linkage analysis for internal carotid artery intimal medial thickness: evidence for linkage to chromosome 12. Am. J. Hum. Genet. 74: 253-261, 2004. Note: Erratum: Am. J. Hum. Genet. 74: 1080 only, 2004. [PubMed: 14730480] [Full Text: https://doi.org/10.1086/381559]
Herrington, D. M., Howard, T. D., Hawkins, G. A., Reboussin, D. M., Xu, J., Zheng, S. L., Brosnihan, K. B., Meyers, D. A., Bleecker, E. R. Estrogen-receptor polymorphisms and effects of estrogen replacement on high-density lipoprotein cholesterol in women with coronary disease. New Eng. J. Med. 346: 967-974, 2002. [PubMed: 11919305] [Full Text: https://doi.org/10.1056/NEJMoa012952]
Huang, L., Chambliss, K. L., Gao, X., Yuhanna, I. S., Behling-Kelly, E., Bergaya, S., Ahmed, M., Michaely, P., Luby-Phelps, K., Darehshouri, A., Xu, L., Fisher, E. A., Ge, W.-P., Mineo, C., Shaul, P. W. SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis. Nature 569: 565-569, 2019. [PubMed: 31019307] [Full Text: https://doi.org/10.1038/s41586-019-1140-4]
Ikemoto, M., Arai, H., Feng, D., Tanaka, K., Aoki, J., Dohmae, N., Takio, K., Adachi, H., Tsujimoto, M., Inoue, K. Identification of a PDZ-domain-containing protein that interacts with the scavenger receptor class B type I. Proc. Nat. Acad. Sci. 97: 6538-6543, 2000. [PubMed: 10829064] [Full Text: https://doi.org/10.1073/pnas.100114397]
Khovidhunkit, W. A genetic variant of the scavenger receptor BI in humans. (Letter) New Eng. J. Med. 364: 1375-1376, 2011. [PubMed: 21470028] [Full Text: https://doi.org/10.1056/NEJMc1101847]
Krieger, M. The 'best' of cholesterols, the 'worst' of cholesterols: a tale of two receptors. (Commentary) Proc. Nat. Acad. Sci. 95: 4077-4080, 1998. [PubMed: 9539689] [Full Text: https://doi.org/10.1073/pnas.95.8.4077]
McCarthy, J. J., Lehner, T., Reeves, C., Moliterno, D. J., Newby, L. K., Rogers, W. J., Topol, E. J. Association of genetic variants in the HDL receptor, SR-B1, with abnormal lipids in women with coronary artery disease. J. Med. Genet. 40: 453-458, 2003. [PubMed: 12807968] [Full Text: https://doi.org/10.1136/jmg.40.6.453]
Miettinen, H. E., Rayburn, H., Krieger, M. Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)-deficient mice. J. Clin. Invest. 108: 1717-1722, 2001. [PubMed: 11733567] [Full Text: https://doi.org/10.1172/JCI13288]
Murao, K., Terpstra, V., Green, S. R., Kondratenko, N., Steinberg, D., Quehenberger, O. Characterization of CLA-1, a human homologue of rodent scavenger receptor BI, as a receptor for high density lipoprotein and apoptotic thymocytes. J. Biol. Chem. 272: 17551-17557, 1997. [PubMed: 9211901] [Full Text: https://doi.org/10.1074/jbc.272.28.17551]
Neculai, D., Schwake, M., Ravichandran, M., Zunke, F., Collins, R. F., Peters, J., Neculai, M., Plumb, J., Loppnau, P., Pizarro, J. C., Seitova, A., Trimble, W. S., Saftig, P., Grinstein, S., Dhe-Paganon, S. :Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36. Nature 504: 172-176, 2013. [PubMed: 24162852] [Full Text: https://doi.org/10.1038/nature12684]
Osgood, D., Corella, D., Demissie, S., Cupples, L. A., Wilson, P. W. F., Meigs, J. B., Schaefer, E. J., Coltell, O., Ordovas, J. M. Genetic variation at the scavenger receptor class B type I gene locus determines plasma lipoprotein concentrations and particle size and interacts with type 2 diabetes: the Framingham Study. J. Clin. Endocr. Metab. 88: 2869-2879, 2003. [PubMed: 12788901] [Full Text: https://doi.org/10.1210/jc.2002-021664]
Perez-Martinez, P., Perez-Jimenez, F., Bellido, C., Ordovas, J. M., Moreno, J. A., Marin, C., Gomez, P., Delgado-Lista, J., Fuentes, F., Lopez-Miranda, J. A polymorphism exon 1 variant at the locus of the scavenger receptor class B type I (SCARB1) gene is associated with differences in insulin sensitivity in healthy people during the consumption of an olive oil-rich diet. J. Clin. Endocr. Metab. 90: 2297-2300, 2005. [PubMed: 15671101] [Full Text: https://doi.org/10.1210/jc.2004-1489]
Philips, J. A., Rubin, E. J., Perrimon, N. Drosophila RNAi screen reveals CD36 family member required for mycobacterial infection. Science 309: 1251-1253, 2005. [PubMed: 16020694] [Full Text: https://doi.org/10.1126/science.1116006]
Santander, N. G., Contreras-Duarte, S., Awad, M. F., Lizama, C., Passalacqua, I., Rigotti, A., Busso, D. Developmental abnormalities in mouse embryos lacking the HDL receptor SR-BI. Hum. Molec. Genet. 22: 1086-1096, 2013. Note: Erratum: Hum. Molec. Genet. 22: 2551 only, 2013. [PubMed: 23221804] [Full Text: https://doi.org/10.1093/hmg/dds510]
Scarselli, E., Ansuini, H., Cerino, R., Roccasecca, R. M., Acali, S., Filocamo, G., Traboni, C., Nicosia, A., Cortese, R., Vitelli, A. The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J. 21: 5017-5025, 2002. [PubMed: 12356718] [Full Text: https://doi.org/10.1093/emboj/cdf529]
Tai, E. S., Adiconis, X., Ordovas, J. M., Carmena-Ramon, R., Real, J., Corella, D., Ascaso, J., Carmena, R. Polymorphisms at the SRBI locus are associated with lipoprotein levels in subjects with heterozygous familial hypercholesterolemia. Clin. Genet. 63: 53-58, 2003. [PubMed: 12519372] [Full Text: https://doi.org/10.1034/j.1399-0004.2003.630108.x]
Teslovich, T. M., Musunuru, K., Smith, A. V., Edmondson, A. C., Stylianou, I. M., Koseki, M., Pirruccello, J. P., Ripatti, S., Chasman, D. I., Willer, C. J., Johansen, C. T., Fouchier, S. W., and 197 others. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466: 707-713, 2010. [PubMed: 20686565] [Full Text: https://doi.org/10.1038/nature09270]
Toomey, M. B., Lopes, R. J., Araujo, P. M., Johnson, J. D., Gazda, M. A., Afonso, S., Mota, P. G., Koch, R. E., Hill, G. E., Corbo, J. C., Carneiro, M. High-density lipoprotein receptor SCARB1 is required for carotenoid coloration in birds. Proc. Nat. Acad. Sci. 114: 5219-5224, 2017. [PubMed: 28465440] [Full Text: https://doi.org/10.1073/pnas.1700751114]
Varban, M. L., Rinninger, F., Wang, N., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Gosselin, M. L., Dixon, K. L., Deeds, J. D., Acton, S. L., Tall, A. R., Huszar, D. Targeted mutation reveals a central role for SR-BI in hepatic selective uptake of high density lipoprotein cholesterol. Proc. Nat. Acad. Sci. 95: 4619-4624, 1998. [PubMed: 9539787] [Full Text: https://doi.org/10.1073/pnas.95.8.4619]
Vergeer, M., Korporaal, S. J. A., Franssen, R., Meurs, I., Out, R., Hovingh, G. K., Hoekstra, M., Sierts, J. A., Dallinga-Thie, G. M., Motazacker, M. M., Holleboom, A. G., Van Berkel, T. J. C., Kastelein, J. J. P., Van Eck, M., Kuivenhoven, J. A. Genetic variant of the scavenger receptor BI in humans. New Eng. J. Med. 364: 136-145, 2011. [PubMed: 21226579] [Full Text: https://doi.org/10.1056/NEJMoa0907687]
Vergeer, M., Van Eck, M., Kuivenhoven, J. A. Reply to Khovidhunkit. (Letter) New Eng. J. Med. 364: 1376 only, 2011. [PubMed: 21470031] [Full Text: https://doi.org/10.1056/NEJMc1100699]
Vishnyakova, T. G., Kurlander, R., Bocharov, A. V., Baranova, I. N., Chen, Z., Abu-Asab, M. S., Tsokos, M., Malide, D., Basso, F., Remaley, A., Csako, G., Eggerman, T. L., Patterson, A. P. CLA-1 and its splicing variant CLA-2 mediate bacterial adhesion and cytosolic bacterial invasion in mammalian cells. Proc. Nat. Acad. Sci. 103: 16888-16893, 2006. [PubMed: 17071747] [Full Text: https://doi.org/10.1073/pnas.0602126103]
Wang, L., Jia, X.-J., Jiang, H.-J., Du, Y., Yang, F., Si, S.-Y., Hong, B. MicroRNAs 185, 96, and 223 repress selective high-density lipoprotein cholesterol uptake through posttranscriptional inhibition. Molec. Cell. Biol. 33: 1956-1964, 2013. [PubMed: 23459944] [Full Text: https://doi.org/10.1128/MCB.01580-12]
Widjaja-Adhi, M. A. K., Lobo, G. P., Golczak, M., Von Lintig, J. A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption. Hum. Molec. Genet. 24: 3206-3219, 2015. [PubMed: 25701869] [Full Text: https://doi.org/10.1093/hmg/ddv072]
Zanoni, P., Khetarpal, S. A. Larach, D. B., Hancock-Cerutti, W. F., Millar, J. S., Cuchel, M., DerOhannessian, S., Kontush, A., Surendran, P., Saleheen, D., Trompet, S., Jukema, J. W., and 40 others. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease. Science 351: 1166-1171, 2016. [PubMed: 26965621] [Full Text: https://doi.org/10.1126/science.aad3517]