CYP2C9 Gene: Cytochrome P450 Family 2 Subfamily C Member 9
Key drug-metabolizing enzyme affecting warfarin dosing and drug response
Gene Information Card
| Symbol | CYP2C9 |
|---|---|
| Full Name | Cytochrome P450 family 2 subfamily C member 9 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q23.33 |
| NCBI Gene ID | 1559 ncbi.nlm.nih.gov/gene/1559 |
| Ensembl ID | ENSG00000138109 |
| UniProt ID | P11712 |
| OMIM ID | 601130 |
| HGNC ID | 2623 |
| Aliases | CYP2C10, CYPIIC9, P450IIC9 |
Description
CYP2C9 encodes a member of the cytochrome P450 superfamily of enzymes. These enzymes are involved in the metabolism of many endogenous and exogenous compounds, including drugs and fatty acids. CYP2C9 is primarily expressed in the liver and is responsible for the oxidative metabolism of approximately 15% of clinically used drugs, including warfarin, phenytoin, and nonsteroidal anti-inflammatory drugs (NSAIDs). Genetic variants in CYP2C9 can lead to altered enzyme activity, affecting drug efficacy and toxicity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Warfarin sensitivity | Reduced enzyme activity due to CYP2C9*2 and *3 variants leads to decreased warfarin clearance and increased bleeding risk. | ClinVar, CPIC guidelines |
| Phenytoin toxicity | Impaired metabolism of phenytoin in carriers of reduced-function alleles can cause neurotoxicity. | ClinVar, literature |
| Drug-induced liver injury | Certain CYP2C9 variants may predispose to toxicity from drugs like diclofenac. | Literature, PharmGKB |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High (nTPM ~ 100) | High expression |
| Small intestine | Moderate (nTPM ~ 20) | Moderate expression |
| Kidney | Low (nTPM ~ 5) | Low expression |
| Lung | Low (nTPM ~ 2) | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | High | Liver cancer cell line |
| Caco-2 | Moderate | Colorectal adenocarcinoma |
| A549 | Low | Lung carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| CYP2C9*2 (rs1799853) | SNP (c.430C>T, p.Arg144Cys) | ~12% in Caucasians | Reduced enzyme activity (~30% of wild-type) |
| CYP2C9*3 (rs1057910) | SNP (c.1075A>C, p.Ile359Leu) | ~8% in Caucasians | Markedly reduced activity (~5-10% of wild-type) |
| CYP2C9*5 (rs28371686) | SNP (c.1080C>G, p.Asp360Glu) | ~1-3% in African populations | Reduced activity |
| CYP2C9*6 (rs9332131) | Deletion (c.818delA) | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
CYP2C9*2, *3, *5, *6 variants result in reduced or absent enzyme activity, leading to impaired drug metabolism.
Gain of Function (GOF)
No common gain-of-function variants are well-documented; some rare variants may increase activity but are not clinically significant.
Dominant Negative (DN)
Not applicable; CYP2C9 is a monomeric enzyme, and variants do not exert dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • heme binding | • iron ion binding |
| • monooxygenase activity | • oxidoreductase activity |
| • arachidonic acid epoxygenase activity | • steroid hydroxylase activity |
| • membrane | • endoplasmic reticulum membrane |
Pathways
• Arachidonic acid metabolism
• Linoleic acid metabolism
• Drug metabolism - cytochrome P450
• Chemical carcinogenesis
Protein Summary
CYP2C9 is a microsomal cytochrome P450 enzyme that catalyzes the oxidative metabolism of a wide range of drugs and endogenous compounds. The protein is a 55 kDa heme-containing monooxygenase localized to the endoplasmic reticulum. It exhibits substrate specificity for weakly acidic compounds, including S-warfarin, phenytoin, tolbutamide, and many NSAIDs. Genetic polymorphisms significantly affect interindividual variability in drug response and toxicity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYP2C9 Knockout HEK293 Cell Line | EDJ-KQ2527 | Human | 1559 | Details Get a Quote |
| CYP2C9 Knockout HeLa Cell Line | EDJ-KQ53048 | Human | 1559 | Details Get a Quote |
| CYP2C9 Knockout A-549 Cell Line | EDJ-KQ61512 | Human | 1559 | Details Get a Quote |
| CYP2C9 Knockout HCT 116 Cell Line | EDJ-KQ70005 | Human | 1559 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
