PRNP (Major prion protein) variants and mutations

PRNP (also known as Major prion protein) is a human protein-coding gene encoding a major prion protein. Its normal cellular form is enriched in the nervous system, but misfolding into self-propagating conformations can template further protein conversion. This process causes prion diseases, while germline pathogenic variants underlie inherited Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease, and fatal familial insomnia. This analysis covers 617 PRNP variants and mutations. Of these, 80% have computational variant effect predictions. Disease context includes Gerstmann-Straussler-Scheinker syndrome, Creutzfeldt Jacob disease, and Huntington disease-like 1. Example PRNP variants include M1?, A2E, and A2V.

Variant analysis overview

Gene: PRNP
Protein: Major prion protein
UniProt accession: P04156
Organism: Homo sapiens
Variants analyzed: 617
Variant scope: all variants
Completed: 2026-08-18

Variant and mutation evidence

Variant composition: 350 unspecified-consequence records; 119 synonymous variants; 104 missense variants; 11 stop-gained variants; 15 frameshift variants; 1 in-frame insertions; 11 in-frame deletions; 1 stop retained variant; 5 substitution
Prediction scores: 491 variants have prediction scores (80% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: Gerstmann-Straussler-Scheinker syndrome, Creutzfeldt Jacob disease, Huntington disease-like 1, fatal familial insomnia, inherited Creutzfeldt-Jakob disease, dementia, neurodegenerative disease, hereditary disease, prion disease, cerebral amyloid angiopathy, inherited prion disease, sporadic Creutzfeld Jacob disease.

Protein structure and variant hotspots

Protein features: 12 binding sites; 2 post-translational modification sites.
PTM context: 4 variants overlap post-translational modification sites.

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 PRNP variants

Examples include M1?, A2E, A2V, A2A, N3K, N3N, L4F, L4H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

PRNP analysis run — PRNP (617 variants) — completed 2026-08-18