PRNP M129V - GET-Evidence


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(PRNP Met129Val)

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Short summary

This variant is associated with some protective effects for prion disease — individuals homozygous for this variant are less susceptible to Creutzfeldt-Jakob, and Papua New Guinea individuals heterozygotes at this site are less susceptible to kuru.

Variant evidence
Computational -
Functional -
Case/Control 5

High significance evidence

See Mead S et al. 2009 (19081515).

Familial -
Clinical importance
Severity 4
Treatability 1

Prion diseases are extremely rare



Low clinical importance, Likely protective

(The "low clinical importance, likely" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern


Summary of published research, and additional commentary


Allele frequency

  • G @ chr20:4680251: 34.0% (3653/10758) in EVS
  • G @ chr20:4628250: 24.2% (31/128) in GET-Evidence
  • Frequency shown in summary reports: 34.0% (3653/10758)


Shibao C, Garland EM, Gamboa A, Vnencak-Jones CL, Van Woeltz M, Haines JL, Yu C, Biaggioni I. PRNP M129V homozygosity in multiple system atrophy vs. Parkinson's disease. Clin Auton Res. 2008 Feb;18(1):13-9. Epub 2008 Jan 30. PubMed PMID: 18236005.

Found no correlation between codon 129 and MSA.

Mead S, Poulter M, Uphill J, Beck J, Whitfield J, Webb TE, Campbell T, Adamson G, Deriziotis P, Tabrizi SJ, Hummerich H, Verzilli C, Alpers MP, Whittaker JC, Collinge J. Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study. Lancet Neurol. 2009 Jan;8(1):57-66. PubMed PMID: 19081515; PubMed Central PMCID: PMC2643048.

Homozygosity for this variant was associated with a significant protective effect for Creutzfeldt-Jakob (p = 2.7e-4 in replication group). Heterozygous version (and not homozygous) of this variant was also found to be protective against kuru by, it is theorized, extending incubation time (2.2e-9). In general, this GWAS study “confirms the strong association of PRNP codon 129 (rs1799990) across acquired and sporadic prion diseases as the outstanding genetic risk factor in human prion disease”.


hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het G @ chr20:4680251


hu0D879F - CGI sample GS00253-DNA_G01_200_37
het G @ chr20:4680251


hu604D39 - CGI sample GS00253-DNA_B02_200_37
het G @ chr20:4680251



huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het G @ chr20:4680251


GS06994 - var-GS06994-1100-36-ASM
hom G @ chr20:4628251


GS07357 - var-GS07357-1100-36-ASM
het G @ chr20:4628251


GS10851 - var-GS10851-1100-36-ASM
hom G @ chr20:4628251


GS18501 - var-GS18501-1100-36-ASM
het G @ chr20:4628251


GS18504 - var-GS18504-1100-36-ASM
het G @ chr20:4628251


GS18505 - var-GS18505-1100-36-ASM
het G @ chr20:4628251


Added in this revision:

GS18517 - var-GS18517-1100-36-ASM
het G @ chr20:4628251
















Other external references

  • rs1799990
  • GeneTests records for the PRNP gene
    Familial Creutzfeldt-Jakob Disease
    Fatal Familial Insomnia
    Genetic Prion Diseases
    Gerstmann-Straussler-Scheinker Disease
    Huntington Disease-Like 1
  • Creutzfeldt-Jakob disease (rs1799990-A)
    Mead 11-Dec-08 in Lancet Neurol
    OR or beta: NR NR
    p-value: 2.00E-21
    Initial sample: 117 CJD cases, 3,083 controls
    Replication sample: 506 sCJD cases, 28 iCJD cases, 151 Kuru cases, 125 Kuru-resistant cases, up to 1,137 controls
  • [Creutzfeldt-Jakob Syndrome]
    GWAS results: Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study. (Initial Sample Size: 117 CJD cases, 3,083 controls; Replication Sample Size: 506 sCJD cases, 28 iCJD cases, 151 Kuru cases, 125 Kuru-resistant cases, up to 1,137 controls); (Region: 20p13; Reported Gene(s): PRNP; Risk Allele: rs1799990-A); (p-value= 2E-21).This variant is associated with Creutzfeldt-Jakob disease.; Web Resource:
  • Score: 0.628 (possibly damaging)

Other in silico analyses

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 4

Edit history

Gene search

"GENE" or "GENE A123C":

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