PKP2 (Plakophilin-2) variants and mutations

PKP2 (also known as Plakophilin-2) is a human protein-coding gene encoding a plakophilin-2 protein. It organizes cardiac desmosomes and helps maintain both mechanical adhesion and electrical coupling between cardiomyocytes. Pathogenic variants are a major cause of arrhythmogenic cardiomyopathy and increase susceptibility to ventricular arrhythmias and sudden cardiac death. This analysis covers 762 PKP2 variants and mutations. Of these, 75% have computational variant effect predictions. Disease context includes Arrhythmogenic right ventricular dysplasia, arrhythmogenic right ventricular cardiomyopathy, and cardiomyopathy. Example PKP2 variants include M1L, M1T, and M1V.

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, MaveDB, LitVar.

Notable PKP2 variants

Examples include M1L, M1T, M1V, A3S, P4T, G5A, G11S, Y12C. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.