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Updated: Jun 17, 2026

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
A synonymous variant in scavenger receptor, class B, type I gene is associated with lower SR-BI protein expression
Jason Constantineau1, Erin Greason, Michael West
1Department of Medicine, Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States.
Objective:
A synonymous variant within scavenger receptor class B type I gene (SCARB1), exon 8 rs5888, has been associated with altered lipid levels and cardiovascular risk in humans. The objective was to determine if rs5888 decreased SR-BI protein expression and function in vitro.
Methods:
SR-BI RNA secondary structure, turnover, polysomal distribution and protein expression were examined in COS cells transfected with wild-type or rs5888-SR-BI plasmids by selective 2'-hydroxyl acylation and primer extension assays, actinomycin D inhibition, polysomal profiling, and western blotting. SR-BI function in murine macrophages stably expressing wild-type or rs5888-SR-BI was assessed by measuring the specific cell association of (125)I,(3)H-cholesteryl ester (CE) radiolabeled HDL.
Results:
Rs5888 changed RNA secondary structure and led to marked differences in the polysomal profiles compared with wild-type transcript (p<0.02). As compared to wild-type cells, COS cells expressing rs5888 had significantly lower SR-BI protein expression (p<0.04), but no difference in total RNA transcript levels. There were no differences in SR-BI RNA turnover in murine macrophages, whereas specific cell association of (125)I (p<0.0001) or (3)H-CE (p<0.00001) was significantly lower in rs5888 cells.
Conclusions:
The rs5888 variant affected SR-BI RNA secondary structure, protein translation, and was significantly associated with reduced SR-BI protein expression and function in vitro.
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