CJD_PRNP

Gene
PRNP
Disease
CJD
Inheritance
AD
Classification
Moderate
Total Score
9
Publications Reviewed
6
Publication Span
34.09 years
Last Updated
08/14/2025
Curator(s)
Macayla Weiner, Laurel Hiatt

Description

PRNP octapeptide repeat insertions (OPRIs) in the exon 2/N-terminal coding repeat region are associated with autosomal dominant genetic Creutzfeldt-Jakob disease/inherited prion disease. Uploaded sources describe the normal five-octapeptide repeat structure, familial CJD/CJD-GSS cases with expanded alleles, published OPRI genetic CJD case summaries across 1–7 additional repeats, and newer 5-OPRI reports with atypical frontotemporal dementia-like or Huntington disease-like presentations.

Genetic evidence

Total: 7.5

Singular EvidenceProbandsPMID:298871396Review summarized published genetic CJD cases with PRNP octapeptide-repeat insertions across 1–7 additional-repeat haplotypes, including 5-OPRI, 6-OPRI, and 7-OPRI groups with variable age at onset, disease duration, family history, and diagnostic findings.
Collective EvidenceSegregationPMID:16837081.5Goldfarb et al. screened familial spongiform encephalopathy kindreds and identified expanded PRNP octapeptide-repeat alleles in affected CJD/CJD-GSS families: 10 repeats in Kel, 12 repeats in three tested affected Ald family members with four unaffected relatives carrying normal alleles, and 13 repeats in Che, including the proband and one at-risk niece while another niece was normal.
2 rows

Experimental evidence

Total: 1.5

FunctionBiochemical functionPMID:373797240.5In an HD-phenocopy screening cohort, one patient with inherited prion disease carried PRNP 5-OPRI and Met/Met at codon 129; the authors reported neuropathologically proven prion disease and protease-resistant PrP fragments. This is PRNP OPRI-associated prion biochemistry/pathology rather than a mechanistic functional assay.
FunctionProtein interactionPMID:299396370.5Gene-level, not OPRI-specific: the clinical CJD review describes pathogenic PrPSc associating with normal cellular PrP and converting alpha-helical PrPC into protease-resistant beta-pleated aggregates; no PRNP OPRI-specific protein-interaction assay was provided.
FunctionRegulatory impactPMID:36977684 PMID:38467784 PMID:16837080.5
3 rows

Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.