Variant: VIP

rs1057910 in CYP2C9

Alleles (on + chromosomal strand)
  1. A > C

Clinical Annotations

PharmGKB clinical annotations provide information about variant-drug pairs based on a summary of the individual variant annotations in the database. Therefore, each clinical annotation could represent information from a single paper or multiple papers. The rating system used to assign "Strength of Evidence" levels is described here. The individual variant annotations, including the PMID for each supporting PubMed publication, can be found on the "PGx Research" tab above.

This information is manually curated by PharmGKB. All alleles are displayed on the positive chromosomal strand.

Variant Annotations

PharmGKB variant annotations provide information about variant-drug pairs or variant-disease pairs based on individual PubMed publications. Each annotation represents information from a single paper and the goal is to report the information that the author states, not an interpretation of the paper. The PMID for supporting PubMed publications is found in the "Evidence" field.

Information presented, including study size, allele frequencies and statistics is taken directly from the publication. However, if the author does not correct p-values in cases of multiple hypotheses, curators may apply a Bonferroni correction. Curators attempt to report study size based on the actual number of participants used for the calculation of the association statistics, so the number may vary slightly from what is reported in the abstract of the paper. OMB Race Category information is derived from the paper and mapped to standardized categories. Category definitions may be found by clicking on the "OMB Race Category" link.

List of all variant annotations for this variant.

There are 95 annotations for this variant. Register or sign in to see them.

Variant Overview

PharmGKB Accession ID: PA166153959
Type: SNP
Class: Missense
Clinical Significance: Not reported
Genes: CYP2C9

Primary Locus

Name:
[GRCh37]chr10:96741053
Location:
NC_000010.10 96741053 - 96741053
  • A > C
Sequence Type:
genomic
Source:
dbSnp

Alternate Locations

  1. Name:
    NP_000762.2:p.I359L
    Location:
    NP_000762.2 359 - 359
    • I > L
    Sequence Type:
    protein
    Source:
    dbSnp

Variant Frequencies

Population variation data is sourced from HapMap 3.

Alternate Names

  • NC_000010.10:g.96741053A=
  • NC_000010.10:g.96741053A>C
  • NC_000010.11:g.94981296A=
  • NC_000010.11:g.94981296A>C
  • NG_008385.1:g.47639A=
  • NG_008385.1:g.47639A>C
  • NM_000771.3:c.1075A=
  • NM_000771.3:c.1075A>C
  • NP_000762.2:p.Ile359=
  • NP_000762.2:p.Ile359Leu
  • XM_005269575.1:c.1075A=
  • XM_005269575.1:c.1075A>C
  • XP_005269632.1:p.Ile359=
  • XP_005269632.1:p.Ile359Leu
  • rs17847042
  • rs3198471
  • rs61212474

VIP Variant in CYP2C9

The variant at this position is the defining allele for the CYP2C9*3 haplotype. Other variant positions delineate between haplotypes in the *3 series (see http://www.imm.ki.se/CYPalleles for defining website), but a C allele at this position defines a CYP2C9*3 haplotype. For further information about the CYP2C9*3 haplotype see the Haplotype page.

The catalytic activity of the *3 haplotype is significantly reduced for most CYP2C9 substrates because of both an increase in Km and a reduction in Vmax [Articles:11927841, 15637526, 14597963].
Leu/Leu homozygotes have lower metabolic activity for CYP2C9 substrates in general, including tolbutamide and phenytoin [Article:10761997]. However, much of the supporting data are from in-vitro studies and homozygous individuals are rare [Article:19082874]. In other studies, it has been found that heterozygotes have about half the clearance as wild-type, for the following drugs: S-warfarin, tolbutamide, fluvastatin, glimepiride, tenoxicam, candesartan, celecoxib, phenytoin [Article:15637526].
The clearance of S-ibuprofen is reduced in CYP2C9*3/*3 homozygotes compared with wild-type homogozygotes [Article:15289789]. In in-vivo studies, the CYP2C9*3 haplotype in heterozygote subjects has been associated with a lower clearance and longer half-life of flurbiprofen [Article:12698304].

PopulationN subjectsAllele Frequency of "C"PMID
Chinese (Shanghai)3940.036[Article:12803577]
Korean5740.011[Article:11298075]
Japanese1470.007[Article:16111713]
Japanese1400.054[Article:9631918]
Japanese640.016[Article:16424822]
Vietnamese (Kinh)1570.022[Article:15795654]
Iranian2000.000[Article:17201743]
Turkish4990.100[Article:10510154]
Ashekenazi Jew1000.080[Article:16111713]
Yemenite Jew990.081[Article:16111713]
Moroccan Jew1000.115[Article:16111713]
Libyan Jew890.174[Article:16111713]
Egyptian2470.060[Article:12047484]
Ethiopian1500.020[Article:11678789]
African-American660.008[Article:16424822]
Caucasian1150.109[Article:16424822]
Russian2900.067[Article:12879168]
Croatian2000.095[Article:12950145]
French Caucasians1510.080[Article:12803577]
German1180.050[Article:12445031]
Swedish4300.074[Article:9920790]
Spanish1570.162[Article:11372590]
Italian1570.090[Article:11678789]
Citation Cytochrome P450 2C9-CYP2C9. Pharmacogenetics and genomics. 2010. Van Booven Derek, Marsh Sharon, McLeod Howard, Carrillo Michelle Whirl, Sangkuhl Katrin, Klein Teri E, Altman Russ B. PubMed
Reviewed 11/18/2009
Key Publications:
Drugs / Other Molecules

Appendix

CYP2C9: 359Ile>Leu

Genomic Variant & GenBank ID:15489579 A>C on NT_030059 
mRNA Variant & GenBank ID:1075 A>C on NM_000771 
Protein Variant & GenBank ID:359Ile>Leu on NP_000762 
Key Haplotypes:CYP2C9*3
gp Positionchr10:96731043(hg18)

Connected Chemicals and Chemical Classes

Evidence Drug

Connected Diseases

Evidence Disease

Related Publications

Evidence Publication