NQO1 P187S - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

NQO1 P187S

(NQO1 Pro187Ser)


Short summary

 

Variant evidence
Computational 3

GVGD: GV 0.00; GD 73.35; Class C65
Variant Effect Predictor (Ensembl ):
SIFT=deleterious(0.04);
PolyPhen=possibly_damaging(0.253);
Condel=deleterious(0.804)
Mutation Tasting prediction: Polymorphism p value: 0.007316; no protein features affected.

Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pharmacogenetic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • A @ chr16:69745145: 19.7% (2121/10758) in EVS
  • A @ chr16:68302645: 22.7% (29/128) in GET-Evidence
  • Frequency shown in summary reports: 19.7% (2121/10758)

Publications
 

Blanco JG, Leisenring WM, Gonzalez-Covarrubias VM, Kawashima TI, Davies SM, Relling MV, Robison LL, Sklar CA, Stovall M, Bhatia S. Genetic polymorphisms in the carbonyl reductase 3 gene CBR3 and the NAD(P)H:quinone oxidoreductase 1 gene NQO1 in patients who developed anthracycline-related congestive heart failure after childhood cancer. Cancer. 2008 Jun 15;112(12):2789-95. PubMed PMID: 18457324.

 

Fagerholm R, Hofstetter B, Tommiska J, Aaltonen K, Vrtel R, Syrjäkoski K, Kallioniemi A, Kilpivaara O, Mannermaa A, Kosma VM, Uusitupa M, Eskelinen M, Kataja V, Aittomäki K, von Smitten K, Heikkilä P, Lukas J, Holli K, Bartkova J, Blomqvist C, Bartek J, Nevanlinna H. NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer. Nat Genet. 2008 Jul;40(7):844-53. Epub 2008 May 30. PubMed PMID: 18511948.

 

Genomes
 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
het A @ chr16:69745145

 

hu0E64A1 - CGI sample GS01173-DNA_B02 from PGP sample 94378523
hom A @ chr16:69745145

 

 

hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
het A @ chr16:69745145

 

 

hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
hom A @ chr16:69745145

 

hu43860C - CGI sample GS00253-DNA_A01_200_37
het A @ chr16:69745145

 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het A @ chr16:69745145

 

 

 

hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
het A @ chr16:69745145

 

hu92FD55 - CGI sample GS01669-DNA_A04 from PGP sample 08188426
hom A @ chr16:69745145

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
het A @ chr16:69745145

 

 

huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
het A @ chr16:69745145

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het A @ chr16:69745145

 

huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het A @ chr16:69745145

 

huCA017E - CGI sample GS01175-DNA_B01 from PGP sample 86206034
het A @ chr16:69745145

 

huD37D14 - CGI sample GS01175-DNA_A04 from PGP sample 13272228
het A @ chr16:69745145

 

GS06985 - var-GS06985-1100-36-ASM
het A @ chr16:68302646

 

GS06994 - var-GS06994-1100-36-ASM
het A @ chr16:68302646

 

GS07357 - var-GS07357-1100-36-ASM
het A @ chr16:68302646

 

GS12004 - var-GS12004-1100-36-ASM
het A @ chr16:68302646

 

GS18526 - var-GS18526-1100-36-ASM
het A @ chr16:68302646

 

GS18537 - var-GS18537-1100-36-ASM
hom A @ chr16:68302646

 

GS18555 - var-GS18555-1100-36-ASM
het A @ chr16:68302646

 

GS18558 - var-GS18558-1100-36-ASM
het A @ chr16:68302646

 

GS18942 - var-GS18942-1100-36-ASM
het A @ chr16:68302646

 

GS18956 - var-GS18956-1100-36-ASM
het A @ chr16:68302646

 

GS19238 - var-GS19238-1100-36-ASM
het A @ chr16:68302646

 

GS19670 - var-GS19670-1100-36-ASM
het A @ chr16:68302646

 

GS19700 - var-GS19700-1100-36-ASM
hom A @ chr16:68302646

 

GS19704 - var-GS19704-1100-36-ASM
het A @ chr16:68302646

 

GS19735 - var-GS19735-1100-36-ASM
het A @ chr16:68302646

 

GS21767 - var-GS21767-1100-36-ASM
het A @ chr16:68302646

 

NA12878

 

Other external references
 

    dbSNP
  • rs1800566
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [1-methyloxy-4-sulfone-benzene; cisplatin; dicumarol; doxorubicin]
    This variant causes the NQO1 protein to be rapidly degraded. Also, the NQO1*2 variant is in the active site of NQO1, leading to decreased NQO1 activity.
    www.pharmgkb.org/search/annotatedGene/nqo1/v
  • [Breast Neoplasms]
    [epirubicin]
    This homozygous variant predicts poor survival among two independent series of women with breast cancer. This effect is particularly evident after anthracycline-based adjuvant chemotherapy with epirubicin and in p53-aberrant tumors.
    www.ncbi.nlm.nih.gov/pubmed/18511948
  • [Cardiomyopathies; Drug Toxicity; Heart Failure]
    Risk or phenotype-associated allele: C/T. Phenotype: There was no association between the NQO1*2 polymorphism and the risk of anthracycline-related CHF. Study size: 145. Study population/ethnicity: Nested case-control study was conducted within a cohort of 1979 patients enrolled in the Childhood Cancer Survivor Study who received treatment with anthracyclines and had available DNA. Significance metric(s): OR = 1.04; p = 0.97. Type of association: CO; TOX; ADR.
    www.ncbi.nlm.nih.gov/pubmed/18457324
    PolyPhen-2
  • Score: 0.215 (possibly damaging)

Other in silico analyses
 

  • NBLOSUM100 score = 3
  • GET-Evidence autoscore = 2

Edit history
 

Gene search

"GENE" or "GENE A123C":

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