PKP1 (Plakophilin-1) variants and mutations

PKP1 (also known as Plakophilin-1) is a human protein-coding gene encoding a plakophilin-1 protein. It strengthens desmosomal adhesion by linking cadherins to intermediate filaments, particularly in stratified epithelia. Biallelic loss-of-function variants cause ectodermal dysplasia-skin fragility syndrome with trauma-induced blistering, palmoplantar keratoderma, and abnormal hair. This analysis covers 1,386 PKP1 variants and mutations. Of these, 58% have computational variant effect predictions. Disease context includes epidermolysis bullosa simplex due to plakophilin deficiency, seborrheic keratosis, and skin aging. Example PKP1 variants include M1?, N2S, and H3H.

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, MaveDB, LitVar.

Notable PKP1 variants

Examples include M1?, N2S, H3H, S4*, S4L, S4W, S4T, P5L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.