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CYP2C9*3

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Interpretation:
drug response; other​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
10
First in ClinVar:
Apr 4, 2013
Most recent Submission:
Nov 6, 2020
Last evaluated:
Feb 11, 2019
Accession:
VCV000008408.11
Variation ID:
8408
Description:
single nucleotide variant
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CYP2C9*3

Allele ID
23447
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
10q23.33
Genomic location
10: 94981296 (GRCh38) GRCh38 UCSC
10: 96741053 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_000771.4:c.1075A>C MANE Select NP_000762.2:p.Ile359Leu missense
NC_000010.11:g.94981296A>C
NC_000010.10:g.96741053A>C
... more HGVS
Protein change
I359L
Other names
NM_000771.3(CYP2C9):c.1075A>C (p.Ile359Leu)
CYP2C9, ILE359LEU (rs1057910)
1075A>C
Canonical SPDI
NC_000010.11:94981295:A:C
Functional consequence
-
Global minor allele frequency (GMAF)
0.04852 (C)

Allele frequency
1000 Genomes Project 0.04852
Trans-Omics for Precision Medicine (TOPMed) 0.04520
Exome Aggregation Consortium (ExAC) 0.06371
The Genome Aggregation Database (gnomAD) 0.04900
Links
PharmGKB Clinical Annotation: 655384720
PharmGKB Clinical Annotation: 769181841
PharmGKB Clinical Annotation: 827862258
PharmGKB Clinical Annotation: 981238437
ClinGen: CA119590
Genetic Testing Registry (GTR): GTR000562560
UniProtKB: P11712#VAR_008345
OMIM: 601130.0001
dbSNP: rs1057910
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
other 1 criteria provided, single submitter Jul 10, 2015 RCV000339502.4
drug response 1 criteria provided, single submitter Feb 11, 2019 RCV000788094.3
drug response 1 criteria provided, single submitter Feb 11, 2019 RCV000787930.3
drug response 1 criteria provided, single submitter Feb 11, 2019 RCV000788100.3
drug response 2 no assertion criteria provided Jun 15, 2012 RCV000008917.5
drug response 2 no assertion criteria provided Sep 24, 2020 RCV000008918.4
drug response 1 no assertion criteria provided Jun 15, 2012 RCV000008919.4
drug response 1 no assertion criteria provided Dec 30, 2010 RCV000008916.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CYP2C9 - - GRCh38
GRCh37
17 45

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter More information
drug response
(Feb 11, 2019)
criteria provided, single submitter
Method: curation
Flurbiprofen response
Drug used for Pain , Inflammation , Osteoarthritis , Rheumatoid Arthritis , Bursitis , and Tendinitis
Affected status: yes
Allele origin: germline
Medical Genetics Summaries
Accession: SCV000926949.1
First in ClinVar: Jul 21, 2019
Last updated: Jul 21, 2019
Publications:
PubMed (5)
Other databases
https://dailymed.nlm.nih.gov/dai… https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e5c06f1-f279-4f2f-b10d-0f70005a27e6
Comment:
The dose of flurbiprofen should be reduced in individuals with 2 decreased function alleles (CYP2C9 poor metabolizers) to avoid abnormally high plasma levels due to … (more)
drug response
(Feb 11, 2019)
criteria provided, single submitter
Method: curation
Lesinurad response
Drug used for Gout
Affected status: yes
Allele origin: germline
Medical Genetics Summaries
Accession: SCV000927092.1
First in ClinVar: Jul 24, 2019
Last updated: Jul 24, 2019
Publications:
PubMed (1)
PubMed: 30742400
Other databases
https://dailymed.nlm.nih.gov/dai… https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ef9e7711-f478-4e35-bf4e-6021c8457e3b
Comment:
Lesinurad should be used with caution in individuals with 2 decreased function alleles (CYP2C9 poor metabolizers) because of increased exposure and an increased risk of … (more)
drug response
(Feb 11, 2019)
criteria provided, single submitter
Method: curation
Piroxicam response
Drug used for Pain , Inflammation , Osteoarthritis , and Rheumatoid arthritis
Affected status: yes
Allele origin: germline
Medical Genetics Summaries
Accession: SCV000927098.1
First in ClinVar: Jul 24, 2019
Last updated: Jul 24, 2019
Publications:
PubMed (6)
Other databases
https://dailymed.nlm.nih.gov/dai… https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6039e036-c0aa-4249-af50-115f49ad758a
Comment:
Individuals with 2 decreased function alleles (CYP2C9 poor metabolizers) have reduced clearance of piroxicam. Because the standard recommended dose of piroxicam may cause abnormally high … (more)
other
(Jul 10, 2015)
criteria provided, single submitter
Method: clinical testing
not provided
Affected status: unknown
Allele origin: germline
Eurofins NTD LLC (GA)
Accession: SCV000331714.3
First in ClinVar: Dec 06, 2016
Last updated: Dec 06, 2016
Other databases
http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP2C9
Number of individuals with the variant: 113
Zygosity: 1 Homozygote, 108 Single Heterozygote
Sex: mixed
drug response
(Dec 30, 2010)
no assertion criteria provided
Method: literature only
TOLBUTAMIDE POOR METABOLIZER
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000029126.1
First in ClinVar: Apr 04, 2013
Last updated: Apr 04, 2013
Publications:
PubMed (5)
PubMed: 20555338887322093525711020864515805193
Comment on evidence:
The ile359-to-leu (I359L) substitution results from a 1075A-C transversion in the CYP2C9 gene and is also known as rs1057910 and CYP2C9*3. The variant leads to … (more)
drug response
(Jun 15, 2012)
no assertion criteria provided
Method: literature only
WARFARIN SENSITIVITY
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000029127.1
First in ClinVar: Apr 04, 2013
Last updated: Apr 04, 2013
Publications:
PubMed (5)
PubMed: 20555338887322093525711020864515805193
Comment on evidence:
The ile359-to-leu (I359L) substitution results from a 1075A-C transversion in the CYP2C9 gene and is also known as rs1057910 and CYP2C9*3. The variant leads to … (more)
drug response
(Jun 15, 2012)
no assertion criteria provided
Method: literature only
PHENYTOIN POOR METABOLIZER
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000029128.1
First in ClinVar: Apr 04, 2013
Last updated: Apr 04, 2013
Publications:
PubMed (5)
PubMed: 20555338887322093525711020864515805193
Comment on evidence:
The ile359-to-leu (I359L) substitution results from a 1075A-C transversion in the CYP2C9 gene and is also known as rs1057910 and CYP2C9*3. The variant leads to … (more)
drug response
(Jun 15, 2012)
no assertion criteria provided
Method: literature only
GLIPIZIDE POOR METABOLIZER
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000029129.1
First in ClinVar: Apr 04, 2013
Last updated: Apr 04, 2013
Publications:
PubMed (5)
PubMed: 20555338887322093525711020864515805193
Comment on evidence:
The ile359-to-leu (I359L) substitution results from a 1075A-C transversion in the CYP2C9 gene and is also known as rs1057910 and CYP2C9*3. The variant leads to … (more)
drug response
(Sep 24, 2020)
no assertion criteria provided
Method: case-control
Phenytoin response
Drug used for status epilepticus
Affected status: yes
Allele origin: germline
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV001441534.1
First in ClinVar: Nov 06, 2020
Last updated: Nov 06, 2020
Publications:
PubMed (2)
PubMed: 2509916432779747
Comment:
May cause toxicity/ADR and poor metabolism/PK
drug response
(Aug 31, 2010)
no assertion criteria provided
Method: research
Warfarin response
Drug used for hemorrhage
Affected status: no
Allele origin: unknown
Pharmacogenomics Lab,Chungbuk National University
Accession: SCV000889937.1
First in ClinVar: Sep 08, 2019
Last updated: Sep 08, 2019
Number of individuals with the variant: 12

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update. Karnes JH Clinical pharmacology and therapeutics 2021 PMID: 32779747
Piroxicam Therapy and CYP2C9 Genotype. Pratt VM - 2019 PMID: 30742401
Lesinurad Therapy and CYP2C9 Genotype. Pratt VM - 2019 PMID: 30742400
Flurbiprofen Therapy and CYP2C9 Genotype. Pratt VM - 2019 PMID: 30742399
Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with CYP2C8*3 and CYP2C9. Calvo AM Journal of pain research 2017 PMID: 28740425
CYP2C9 genotype vs. metabolic phenotype for individual drug dosing--a correlation analysis using flurbiprofen as probe drug. Vogl S PloS one 2015 PMID: 25775139
Effects of CYP2C9*1/*3 genotype on the pharmacokinetics of flurbiprofen in Korean subjects. Lee YJ Archives of pharmacal research 2015 PMID: 25712887
Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Caudle KE Clinical pharmacology and therapeutics 2014 PMID: 25099164
Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements. Ross KA Journal of human genetics 2010 PMID: 20555338
Genetically based impairment in CYP2C8- and CYP2C9-dependent NSAID metabolism as a risk factor for gastrointestinal bleeding: is a combination of pharmacogenomics and metabolomics required to improve personalized medicine? Agúndez JA Expert opinion on drug metabolism & toxicology 2009 PMID: 19422321
Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms. Pilotto A Gastroenterology 2007 PMID: 17681167
Impact of CYP2C9*3/*3 genotype on the pharmacokinetics and pharmacodynamics of piroxicam. Perini JA Clinical pharmacology and therapeutics 2006 PMID: 17112811
Influence of CYP2C9 genotypes on the pharmacokinetics and pharmacodynamics of piroxicam. Perini JA Clinical pharmacology and therapeutics 2005 PMID: 16198655
Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Tate SK Proceedings of the National Academy of Sciences of the United States of America 2005 PMID: 15805193
Differences in flurbiprofen pharmacokinetics between CYP2C9*1/*1, *1/*2, and *1/*3 genotypes. Lee CR European journal of clinical pharmacology 2003 PMID: 12698304
Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. Kidd RS Pharmacogenetics 1999 PMID: 10208645
Genetic association between sensitivity to warfarin and expression of CYP2C9*3. Steward DJ Pharmacogenetics 1997 PMID: 9352571
The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Sullivan-Klose TH Pharmacogenetics 1996 PMID: 8873220
DailyMed Drug Label, FLURBIPROFEN, 2021 - - - -
DailyMed Drug Label, ZURAMPIC, 2018 - - - -
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CYP2C9 - - - -
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e5c06f1-f279-4f2f-b10d-0f70005a27e6 - - - -
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6039e036-c0aa-4249-af50-115f49ad758a - - - -
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ef9e7711-f478-4e35-bf4e-6021c8457e3b - - - -

Text-mined citations for rs1057910...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jan 21, 2023