HMGCR
Chr 5AR3-hydroxy-3-methylglutaryl-CoA reductase
Also known as: LDLCQ3, LGMDR28, MYPLG
HMG-CoA reductase catalyzes the rate-limiting step in cholesterol synthesis by converting HMG-CoA to mevalonic acid, playing a critical role in cellular cholesterol homeostasis. Mutations cause cerebrotendinous xanthomatosis and other sterol biosynthesis disorders with autosomal recessive inheritance, affecting the nervous system, tendons, and cardiovascular system. This gene is highly constrained against loss-of-function variants, indicating that complete loss of function is likely incompatible with normal development.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
HMGCR · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
GPR146 and Cholesterol Metabolism
NOT YET RECRUITINGMulti-Center Study of the Effects of Simvastatin on Hepatic Decompensation and Death in Subjects Presenting With High-Risk Compensated Cirrhosis
ACTIVE NOT RECRUITINGEffect of Breastfeeding on Lipid Profile and Cardiovascular Risk Markers in Women With Familial Hypercholesterolemia
ACTIVE NOT RECRUITINGCholesterol Lowering and Residual Risk in Diabetes, Type 1
RECRUITINGExternal Resources
Links to major genomics databases and tools