CYP2C9

cytochrome P450 family 2 subfamily C member 9, the group of Cytochrome P450 family 2

Basic information

Region (hg38): 10:94938657-94990091

Previous symbols: [ "CYP2C10" ]

Links

ENSG00000138109 ∙ NCBI:1559 ∙ OMIM:601130 ∙ HGNC:2623 ∙ Uniprot:P11712 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Drug metabolism, CYP2C9-related	AD	Pharmacogenomic	Selection and dosing of medications may be affected by the presence of variants	General	10073515; 10901705; 19228618; 19300499; 19715737; 19794412; 20089352; 20402581; 21562147; 23089672

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP2C9 gene.

• not provided (11 variants)
• Inborn genetic diseases (11 variants)
• Lesinurad response (6 variants)
• Flurbiprofen response (6 variants)
• Piroxicam response (6 variants)
• Warfarin response (2 variants)
• Phenytoin response (2 variants)
• not specified (1 variants)
• Tolbutamide response (1 variants)
• - (1 variants)
• Glipizide response (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP2C9 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	1	3
missense			11	4	2	17
nonsense						0
start loss						0
frameshift				1		1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	11	7	3

Variants in CYP2C9

This is a list of pathogenic ClinVar variants found in the CYP2C9 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-94938725-C-A		not specified	Uncertain significance (May 04, 2022)
10-94938785-C-T		not specified	Uncertain significance (Jun 21, 2023)
10-94941928-A-T		not specified	Uncertain significance (May 25, 2022)
10-94941939-A-G		not specified	Uncertain significance (May 25, 2022)
10-94941953-T-C			Likely benign (Jul 21, 2018)
10-94941955-A-G		not specified	Uncertain significance (Feb 23, 2023)
10-94942234-G-A			Benign (Aug 21, 2021)
10-94942290-C-T		Warfarin response • not specified • Lesinurad response • Flurbiprofen response • Piroxicam response • Phenytoin response	Likely benign; drug response; other (Feb 11, 2019)
10-94942290-C-C		-	no classification for the single variant (-)
10-94942309-G-A		Lesinurad response • Flurbiprofen response • Piroxicam response	Benign/Likely benign; drug response (Jul 03, 2023)
10-94947843-T-G		not specified	Uncertain significance (Apr 13, 2022)
10-94947919-T-G		Warfarin response	Pathogenic (Oct 15, 2001)
10-94947928-C-T		not specified	Uncertain significance (Dec 11, 2023)
10-94949217-A-G			Benign (Mar 10, 2020)
10-94949241-A-G		not specified	Uncertain significance (Sep 22, 2023)
10-94949281-GA-G		Flurbiprofen response • Piroxicam response • Lesinurad response	Benign/Likely benign; drug response; other (Apr 14, 2021)
10-94972174-C-T		not specified	Uncertain significance (Mar 24, 2023)
10-94972191-A-G		not specified	Uncertain significance (Aug 02, 2021)
10-94972974-T-G		Pulmonary disease, chronic obstructive, susceptibility to	association (Jul 05, 2022)
10-94981224-C-T		Piroxicam response • Flurbiprofen response • Lesinurad response	Benign/Likely benign; drug response (Jan 18, 2024)
10-94981252-A-T		not specified	Uncertain significance (Apr 04, 2023)
10-94981296-A-C		Warfarin response • Phenytoin response • Glipizide response • Tolbutamide response • Flurbiprofen response • Piroxicam response • Lesinurad response	drug response; other (Feb 11, 2019)
10-94981296-A-A		-	no classification for the single variant (-)
10-94981301-C-G		Lesinurad response • Flurbiprofen response • Piroxicam response	Benign/Likely benign; drug response; other (Jan 20, 2020)
10-94981315-G-T		not specified	Uncertain significance (Jan 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP2C9	protein_coding	protein_coding	ENST00000260682	9	50733

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.27e-10	0.100	125665	0	78	125743	0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.94	381	250	1.52	0.0000130	3242
Missense in Polyphen		125	82.504	1.5151		1094
Synonymous	-4.07	141	91.4	1.54	0.00000459	929
Loss of Function	0.295	16	17.3	0.924	7.43e-7	248

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000507	0.000507
Ashkenazi Jewish	0.00	0.00
East Asian	0.00131	0.00131
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.00131	0.00131
South Asian	0.000856	0.000850
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics (PubMed:25994031). This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031). {ECO:0000269|PubMed:25994031}.
• Pathway: Celecoxib Pathway, Pharmacokinetics;Rosiglitazone Pharmacokinetic Pathway;Retinol metabolism - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human);Drug metabolism - cytochrome P450 - Homo sapiens (human);Arachidonic acid metabolism - Homo sapiens (human);Linoleic acid metabolism - Homo sapiens (human);Chemical carcinogenesis - Homo sapiens (human);Imatinib Pathway, Pharmacokinetics/Pharmacodynamics;Losartan Pathway, Pharmacokinetics;Statin Pathway - Generalized, Pharmacokinetics;Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics;Fluvastatin Pathway, Pharmacokinetics;Warfarin Pathway, Pharmacokinetics;Phenytoin Pathway, Pharmacokinetics;Tamoxifen Pathway, Pharmacokinetics;Gefitinib Pathway, Pharmacokinetics;Anti-diabetic Drug Nateglinide Pathway, Pharmacokinetics;Clopidogrel Pathway, Pharmacokinetics;Fluoxetine Pathway, Pharmacokinetics;Zidovudine Pathway, Pharmacokinetics/Pharmacodynamics;Caffeine Pathway, Pharmacokinetics;Nevirapine Pathway, Pharmacokinetics;Sorafenib Pharmacokinetics;Valproic Acid Pathway, Pharmacokinetics;Doxepin Pathway, Pharmacokinetics;Ibuprofen Pathway, Pharmacokinetics;Cyclophosphamide Pathway, Pharmacokinetics;Ifosfamide Pathway, Pharmacokinetics;Ibuprofen Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Rosiglitazone Metabolism Pathway;Fluoxetine Action Pathway;Ibuprofen Metabolism Pathway;Clopidogrel Metabolism Pathway;Celecoxib Action Pathway;Clopidogrel Action Pathway;Valproic Acid Metabolism Pathway;Cyclophosphamide Action Pathway;Ifosfamide Action Pathway;Sorafenib Metabolism Pathway;Doxepin Metabolism Pathway;Fluoxetine Metabolism Pathway;Celecoxib Metabolism Pathway;Nevirapine Metabolism Pathway;Caffeine Metabolism;Cyclophosphamide Metabolism Pathway;Ifosfamide Metabolism Pathway;Constitutive Androstane Receptor Pathway;Pregnane X Receptor pathway;Vitamin D Receptor Pathway;Nuclear Receptors Meta-Pathway;Nuclear Receptors in Lipid Metabolism and Toxicity;Cannabinoid receptor signaling;Valproic acid pathway;Liver steatosis AOP;Metabolism of Tetrahydrocannabinol (THC);Oxidation by Cytochrome P450;Arachidonate Epoxygenase - Epoxide Hydrolase;Tamoxifen metabolism;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE);Arachidonic acid metabolism;Xenobiotics;Tyrosine metabolism;Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET);Androgen and estrogen biosynthesis and metabolism;Cytochrome P450 - arranged by substrate type;Leukotriene metabolism;Biological oxidations;Metabolism;Biosynthesis of maresin-like SPMs;Biosynthesis of maresins;Biosynthesis of DHA-derived SPMs;Biosynthesis of specialized proresolving mediators (SPMs);Fatty acid metabolism;Linoleate metabolism;C21-steroid hormone biosynthesis and metabolism;Xenobiotics metabolism;Tryptophan degradation;CYP2E1 reactions;Arachidonic acid metabolism (Consensus)

Recessive Scores

• pRec: 0.383

Intolerance Scores

• loftool: 0.903
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.71

Haploinsufficiency Scores

• pHI: 0.0918
• hipred: N
• hipred_score: 0.112

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.937

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cyp2c66

Gene ontology

• Biological process: organic acid metabolic process;xenobiotic metabolic process;steroid metabolic process;monoterpenoid metabolic process;drug metabolic process;epoxygenase P450 pathway;urea metabolic process;monocarboxylic acid metabolic process;drug catabolic process;exogenous drug catabolic process;long-chain fatty acid biosynthetic process;cellular amide metabolic process;oxidation-reduction process;oxidative demethylation;omega-hydroxylase P450 pathway
• Cellular component: cytoplasm;endoplasmic reticulum membrane;organelle membrane;intracellular membrane-bounded organelle
• Molecular function: monooxygenase activity;iron ion binding;drug binding;arachidonic acid epoxygenase activity;steroid hydroxylase activity;oxidoreductase activity;oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen;heme binding;caffeine oxidase activity