EPHX1 H139R - GET-Evidence

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

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Curation:
Currentness:

EPHX1 H139R

(EPHX1 His139Arg)


Short summary

 

Variant evidence
Computational 2

PolyPhen: Benign, score 0.000
SIFT: Tolerated 1.00
GVGD: GV 28.82; GD 0.00; Class C0
Variant Effect Predictor (Ensembl ):
SIFT=tolerated(0.93);
PolyPhen=benign(0)
Mutation Tasting Prediction: Polymorphism, P value: 0.999999; protein features (might be) 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

  • G @ chr1:226026406: 24.8% (2666/10758) in EVS
  • G @ chr1:224093028: 17.7% (22/124) in GET-Evidence
  • Frequency shown in summary reports: 24.8% (2666/10758)

Publications
 

Nakajima Y, Saito Y, Shiseki K, Fukushima-Uesaka H, Hasegawa R, Ozawa S, Sugai K, Katoh M, Saitoh O, Ohnuma T, Kawai M, Ohtsuki T, Suzuki C, Minami N, Kimura H, Goto Y, Kamatani N, Kaniwa N, Sawada J. Haplotype structures of EPHX1 and their effects on the metabolism of carbamazepine-10,11-epoxide in Japanese epileptic patients. Eur J Clin Pharmacol. 2005 Mar;61(1):25-34. Epub 2005 Feb 4. PubMed PMID: 15692831.

 

Vibhuti A, Arif E, Deepak D, Singh B, Qadar Pasha MA. Genetic polymorphisms of GSTP1 and mEPHX correlate with oxidative stress markers and lung function in COPD. Biochem Biophys Res Commun. 2007 Jul 20;359(1):136-42. Epub 2007 May 22. PubMed PMID: 17532303.

 

Pautas E, Moreau C, Gouin-Thibault I, Golmard JL, Mahé I, Legendre C, Taillandier-Hériche E, Durand-Gasselin B, Houllier AM, Verrier P, Beaune P, Loriot MA, Siguret V. Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients. Clin Pharmacol Ther. 2010 Jan;87(1):57-64. Epub 2009 Sep 30. PubMed PMID: 19794411.

 

Azzato EM, Chen RA, Wacholder S, Chanock SJ, Klebanoff MA, Caporaso NE. Maternal EPHX1 polymorphisms and risk of phenytoin-induced congenital malformations. Pharmacogenet Genomics. 2010 Jan;20(1):58-63. PubMed PMID: 19952982.

 

Edvardsen H, Brunsvig PF, Solvang H, Tsalenko A, Andersen A, Syvanen AC, Yakhini Z, Børresen-Dale AL, Olsen H, Aamdal S, Kristensen VN. SNPs in genes coding for ROS metabolism and signalling in association with docetaxel clearance. Pharmacogenomics J. 2010 Feb 16. [Epub ahead of print] PubMed PMID: 20157331.

 

Genomes
 

hu011C57 - CGI sample GS01669-DNA_B05 from PGP sample 86486261
het G @ chr1:226026406

 

hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
het G @ chr1:226026406

 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het G @ chr1:226026406

 

 

hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
het G @ chr1:226026406

 

hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
het G @ chr1:226026406

 

 

hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
het G @ chr1:226026406

 

hu92C40A - CGI sample GS01175-DNA_G03 from PGP sample 92527586
het G @ chr1:226026406

 

huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
het G @ chr1:226026406

 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het G @ chr1:226026406

 

huFFAD87 - CGI sample GS01669-DNA_H05 from PGP sample 10971581
het G @ chr1:226026406

 

GS18502 - var-GS18502-1100-36-ASM
het G @ chr1:224093029

 

GS18504 - var-GS18504-1100-36-ASM
het G @ chr1:224093029

 

GS18505 - var-GS18505-1100-36-ASM
het G @ chr1:224093029

 

GS19020 - var-GS19020-1100-36-ASM
het G @ chr1:224093029

 

GS19025 - var-GS19025-1100-36-ASM
het G @ chr1:224093029

 

GS19129 - var-GS19129-1100-36-ASM
het G @ chr1:224093029

 

GS19238 - var-GS19238-1100-36-ASM
het G @ chr1:224093029

 

GS19239 - var-GS19239-1100-36-ASM
het G @ chr1:224093029

 

GS19700 - var-GS19700-1100-36-ASM
het G @ chr1:224093029

 

GS19701 - var-GS19701-1100-36-ASM
het G @ chr1:224093029

 

GS19834 - var-GS19834-1100-36-ASM
het G @ chr1:224093029

 

Other external references
 

    dbSNP
  • rs2234922
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [Craniofacial Abnormalities]
    [phenytoin]
    Risk or phenotype-associated allele: G. Phenotype: In a logistic regression model adjusted for history of phenytoin use during the first trimester and maternal epilepsy, the maternal EPHX1 139 R (rs2234922A/G) allele was associated with craniofacial abnormalities in the child. Study size: 157 pregnancies. Study population/ethnicity: phenytoin use during the first trimester and maternal epilepsy. metric(s): per rare allele OR: 2.33, 95% CI: 1.09-5.00, P=0.03. Type of association: GN.
    www.ncbi.nlm.nih.gov/pubmed/19952982
  • [warfarin]
    Risk or phenotype-associated allele: undetermined. Phenotype: The variant allele was not associated with warfarin maintenance dose variability (p = 0.5311). Study size: 283. Study population/ethnicity: Hospitalized Caucasian patients aged 75 years or older, recruited Sep 2002-Nov 2004 in Ivry, France, and Oct 2005-Mar 2008 from 14 French centers. Significance metric(s): not significant. Type of association: GN; PK.
    www.ncbi.nlm.nih.gov/pubmed/19794411
  • [Epilepsy]
    [carbamazepine]
    Significantly increased and decreased carbamazepine-10,11-diol/carbamazepine-10,11-epoxide ratios were observed with the block 2 *2 haplotype harboring only 337T>C (Y113H) and the block 3 *2 haplotype harboring 416A>G (H139R), IVS3-114G>C and mostly 1071C>T (N357N). The allele frequencies for H139R (416A>G) was 0.135 in this study of 96 Japanese epileptic patients.
    www.ncbi.nlm.nih.gov/pubmed/15692831
  • [docetaxel]
    Risk or phenotype-associated allele: A. Phenotype: The AA homozygote was associated with higher clearance of docetaxel. Study size: 31. Study population/ethnicity: Patients with Non-Small-Cell Lung Carcinoma. Significance metric(s): Type of association: PK.
    www.ncbi.nlm.nih.gov/pubmed/20157331
    PolyPhen-2
  • Score: 0 (benign)
    Web search results (100 hits -- see all)
  • Microsomal epoxide hydrolase genotype and risk of myocardial ...
    mutagens and an amino acid substitution (H139R) in exon 4 of the EPHX1 gene is ... large case-control study design we found that the EPHX1 H139R polymorphism ...
    ccp.ucr.ac.cr/bvp/pdf/salud/hcampos-10.pdf
  • EPHX1 [PharmGKB]
    EPHX1: Y113H; NM_000120.2: c.337T>C; NT_004559.13: g.2221786T>C. Related Drugs: ... EPHX1: H139R; NM_000120.2: c.416A>G; NT_004559.13: g.2228559A>G ...
    www.pharmgkb.org/do/serve?objId=PA27829&objCls=Gene
  • Rs2234922 - SNPedia
    EPHX1: H139R, NM_000120.2: c.416A>G, NT_004559.13: g.2228559A>G ... The allele frequencies for H139R (416A>G) was 0.135 in this study of 96 Japanese ...
    www.snpedia.com/index.php?title=Rs2234922
  • carbamazepine [PharmGKB]
    The allele frequencies for H139R (416A>G) was 0.135 in this study of 96 Japanese ... EPHX1: H139R; NM_000120.2: c.416A>G; NT_004559.13: g.2228559A>G ...
    www.pharmgkb.org/do/serve?objId=PA448785
  • Lack of increased genetic damage in 1,3-butadiene-exposed ...
    The genotype of EPHX1 was examined because the recent report by Abdel-Rahman et ... The EPHX1 H139R polymorphism did, however, influence the level of hyperdiploidy ...
    www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1249498
  • WikiGenes - EPHX1 - epoxide hydrolase 1, microsomal (xenobiotic)
    The world's first wiki where authorship really matters. Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts.
    www.wikigenes.org/e/gene/e/2052.html
  • Functional analysis of human microsomal epoxide hydrolase ...
    encodes allelic variation at least two amino acid positions, Y113H and H139R. ... Y113H and H139R variant alleles exert only modest impact on. EPHX1-specific enzymatic ...
    www.personal.psu.edu/faculty/c/j/cjo10/PDFs/CBI-mEH-2004.pdf
  • Lack of increased genetic damage in 1,3-butadiene-exposed ...
    The genotype of EPHX1 was examined because. the recent report by Abdel-Rahman et al. ... EPHX1 at position 139 (H139R), in order to provide. a more complete phenotypic picture of ...
    ehs.sph.berkeley.edu/superfund/pdfs/04_zhang_1.pdf

Other in silico analyses
 

  • NBLOSUM100 score = 1
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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