LDLR

HIGH

LDL receptor

Chromosome: 19p13.2

Gene Overview

LDLR encodes the low-density lipoprotein receptor, a cell-surface glycoprotein that binds and internalizes LDL cholesterol particles. The receptor mediates endocytosis of cholesterol-carrying lipoproteins, regulating plasma cholesterol homeostasis. Mutations in LDLR cause familial hypercholesterolemia (FH), characterized by severely elevated LDL-C and premature coronary artery disease. GWAS have identified common variants near LDLR that modestly affect LDL-C levels and CAD risk. The gene is transcriptionally regulated by SREBP-2 in response to cellular cholesterol demand. Expression is highest in liver, adrenal cortex, and steroidogenic tissues.

Molecular Function

  • LDL binding
  • receptor-mediated endocytosis
  • cholesterol uptake
  • apoB-100 recognition

Protein class: LDL receptor family

Regulatory Annotation

Promoter activity: SREBP-2 binding elements drive cholesterol-responsive transcription; sterol regulatory element (SRE) in promoter.

Enhancer associations: CAD-associated variants map to regulatory regions modulating LDLR expression in hepatic and vascular cell types.

Methylation sensitivity: CpG methylation inversely correlates with LDLR expression in some tissues.

eQTL tissues: liver, adipose tissue

Tissue Expression Context

liverTPM range: 80-250GTEx vv8
adrenal glandTPM range: 40-120GTEx vv8

Pathways

Linked Diseases & Exposures

Diseases

Exposures

Mechanistic Hypotheses

Reduced LDLR function elevates circulating LDL-C; oxidized LDL accumulates in arterial intima, triggering foam cell formation and atherosclerosis progression.

FH patients and LDLR-deficient mice develop accelerated atherosclerosis; statins upregulate LDLR and reduce CAD events.

HIGH

Confidence Rating

Overall evidence confidence for this gene entry: HIGH

References

  1. 1.Brown MS, Goldstein JL (1986). The LDL receptor. Science. doi:10.1126/science.3513311
  2. 2.GTEx Consortium (2020). GTEx Consortium. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science. doi:10.1126/science.aaz1776
  3. 3.Khera AV, et al. (2016). Genetic risk, adherence to a healthy lifestyle, and coronary disease. New England Journal of Medicine. doi:10.1056/NEJMoa1605086