PRNP M129V - GET-Evidence

Curation:
Currentness:

PRNP M129V

(PRNP Met129Val)


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 3

PolyPhen: Possibly damaging 0.583
SIFT: Affect protein function 0.01
GVGD: GV 0.00; GD 20.52; Class C15
Variant Effect Predictor (Ensembl ):
SIFT=deleterious(0.01);
PolyPhen=benign(0.019);
Condel=deleterious(0.900)
Mutation Tasting Prediction: Polymorphism, P value: 0. 768693; protein features (might be) affected (aa 23-230 REGION Interaction with GRB2, ERI3 and SYN1 (By similarity) gets lost)

Functional -
Case/Control 5

High significance evidence

See 19081515.

Familial -
 
Clinical importance
Severity 4
Treatability 1
Penetrance

Prion diseases are extremely rare

 

Impact

Low clinical importance, protective

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

Inheritance pattern

other

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)

Publications
 

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.

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PubMed PMID: 19081515

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”.

Genomes
 

 

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

 

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

 

GS18537 - var-GS18537-1100-36-ASM
het G @ chr20:4628251

 

GS19025 - var-GS19025-1100-36-ASM
het G @ chr20:4628251

 

GS19026 - var-GS19026-1100-36-ASM
het G @ chr20:4628251

 

GS19648 - var-GS19648-1100-36-ASM
het G @ chr20:4628251

 

GS19670 - var-GS19670-1100-36-ASM
het G @ chr20:4628251

 

GS19701 - var-GS19701-1100-36-ASM
het G @ chr20:4628251

 

GS19703 - var-GS19703-1100-36-ASM
het G @ chr20:4628251

 

GS19704 - var-GS19704-1100-36-ASM
het G @ chr20:4628251

 

GS20502 - var-GS20502-1100-36-ASM
hom G @ chr20:4628251

 

Other external references
 

    dbSNP
  • rs1799990
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the PRNP gene
    Familial Creutzfeldt-Jakob Disease
    Fatal Familial Insomnia
    Genetic Prion Diseases
    Gerstmann-Straussler-Scheinker Disease
    Huntington Disease-Like 1
    5-Oxoprolinuria
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PRNP
    GWAS
  • 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
    www.ncbi.nlm.nih.gov/pubmed/19081515
    PharmGKB
  • [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.
    www.ncbi.nlm.nih.gov/pubmed/19081515; Web Resource:http://www.genome.gov/gwastudie
    PolyPhen-2
  • 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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