PCSK9 (Proprotein convertase subtilisin/kexin type 9) variants and mutations

PCSK9 (also known as Proprotein convertase subtilisin/kexin type 9) is a human protein-coding gene encoding a proprotein convertase subtilisin/kexin type 9 protein. By binding hepatic LDL receptors and promoting their lysosomal degradation, it reduces receptor recycling and raises circulating LDL cholesterol. Gain-of-function variants cause autosomal dominant hypercholesterolemia, whereas loss-of-function variants lower LDL cholesterol and cardiovascular risk. This analysis covers 1,359 PCSK9 variants and mutations. Of these, 98% have computational variant effect predictions. Disease context includes familial hypercholesterolemia, Hypercholesterolemia, and hypercholesterolemia, autosomal dominant, 3. Example PCSK9 variants include M1R, G2D, and G2S.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, PharmGKB, MaveDB, LitVar.

Notable PCSK9 variants

Examples include M1R, G2D, G2S, G2C, G2V, G2G, T3I, T3N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.