CYP2C8
Cytochrome P450 Family 2 Subfamily C Member 8: Drug Metabolism and Pharmacogenetics
Gene Information Card
| Symbol | CYP2C8 |
|---|---|
| Full Name | Cytochrome P450 Family 2 Subfamily C Member 8 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q23.33 |
| NCBI Gene ID | 1558 ncbi.nlm.nih.gov/gene/1558 |
| Ensembl ID | ENSG00000138115 |
| UniProt ID | P10632 |
| OMIM ID | 601129 |
| HGNC ID | 2622 |
| Aliases | CPC8, CYPIIC8, P450-2C8 |
Description
CYP2C8 is a member of the cytochrome P450 superfamily of enzymes, which are heme-thiolate monooxygenases involved in the oxidative metabolism of endogenous compounds and xenobiotics. CYP2C8 is primarily expressed in the liver and is responsible for the metabolism of approximately 5% of clinically used drugs, including paclitaxel, cerivastatin, and several nonsteroidal anti-inflammatory drugs (NSAIDs). Genetic polymorphisms in CYP2C8 can lead to altered enzyme activity, affecting drug efficacy and toxicity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Drug-induced liver injury | Reduced metabolism of hepatotoxic drugs due to loss-of-function variants | ClinVar |
| Paclitaxel-induced peripheral neuropathy | Increased exposure to paclitaxel due to decreased clearance | NCBI Gene |
| Cerivastatin-induced rhabdomyolysis | Impaired metabolism of cerivastatin leading to accumulation | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 22.5 | High |
| Kidney | 3.2 | Low |
| Small intestine | 2.1 | Low |
| Heart | 0.8 | Not detected |
| Brain | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.0 | Hepatocellular carcinoma cell line |
| Caco-2 | 1.2 | Colorectal adenocarcinoma cell line |
| HEK293 | 0.3 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs11572103 (CYP2C8*2) | Missense (Ile269Phe) | 1-3% in African populations | Reduced enzyme activity |
| rs10509681 (CYP2C8*3) | Missense (Arg139Lys, Lys399Arg) | 10-15% in Caucasians | Reduced paclitaxel metabolism |
| rs11572080 (CYP2C8*4) | Missense (Ile264Met) | 2-5% in Caucasians | Decreased activity |
Mutation functional classification
Loss of Function (LOF)
CYP2C8*2, *3, *4 variants reduce catalytic activity, leading to decreased clearance of substrates like paclitaxel and NSAIDs.
Gain of Function (GOF)
No well-characterized gain-of-function variants reported.
Dominant Negative (DN)
Not described for CYP2C8.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Drug metabolism - cytochrome P450 (Reactome: R-HSA-211981)
• Metabolism of xenobiotics by cytochrome P450 (KEGG: hsa00980)
• Arachidonic acid metabolism (KEGG: hsa00590)
Protein Summary
CYP2C8 is a 490-amino acid microsomal protein localized to the endoplasmic reticulum. It contains a conserved heme-binding domain essential for electron transfer and substrate oxidation. The enzyme metabolizes a wide range of drugs, including paclitaxel, amodiaquine, and repaglinide, as well as endogenous compounds like arachidonic acid. Structural polymorphisms can alter substrate specificity and catalytic efficiency, impacting drug response and toxicity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYP2C8 Knockout HEK293 Cell Line | EDJ-KQ4398 | Human | 1558 | Details Get a Quote |
| CYP2C8 Knockout HCT 116 Cell Line | EDJ-KQ25650 | Human | 1558 | Details Get a Quote |
| CYP2C8 Knockout HeLa Cell Line | EDJ-KQ53047 | Human | 1558 | Details Get a Quote |
| CYP2C8 Knockout A-549 Cell Line | EDJ-KQ61511 | Human | 1558 | Details Get a Quote |
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