CYP2C19
Cytochrome P450 2C19: A key pharmacogene in drug metabolism and response
Gene Information Card
| Symbol | CYP2C19 |
|---|---|
| Full Name | Cytochrome P450 Family 2 Subfamily C Member 19 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q23.33 |
| NCBI Gene ID | 1557 ncbi.nlm.nih.gov/gene/1557 |
| Ensembl ID | ENSG00000165841 |
| UniProt ID | P33261 |
| OMIM ID | 124020 |
| HGNC ID | 2613 |
| Aliases | CPCJ, CYP2C, CYPIIC17, P450C2C, P450IIC17 |
Description
CYP2C19 encodes a member of the cytochrome P450 superfamily of enzymes, which are involved in the metabolism of various endogenous compounds and xenobiotics. This enzyme is responsible for the metabolism of several clinically important drugs, including the antiplatelet agent clopidogrel, proton pump inhibitors (e.g., omeprazole), antidepressants (e.g., citalopram), and the antimalarial proguanil. Genetic polymorphisms in CYP2C19 significantly affect enzyme activity, leading to variable drug response and adverse effects. The most common loss-of-function alleles are CYP2C19*2 (c.681G>A; rs4244285) and CYP2C19*3 (c.636G>A; rs4986893), which are associated with poor metabolizer phenotypes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiovascular Disease (clopidogrel response) | CYP2C19 poor metabolizer status reduces conversion of clopidogrel to its active metabolite, leading to diminished antiplatelet effect and increased risk of stent thrombosis and major adverse cardiovascular events. | ClinVar, FDA drug label |
| Gastroesophageal Reflux Disease (PPI response) | CYP2C19 poor metabolizers have higher plasma concentrations of proton pump inhibitors (e.g., omeprazole), leading to enhanced acid suppression and increased risk of adverse effects such as vitamin B12 deficiency and Clostridium difficile infection. | ClinVar, FDA drug label |
| Peptic Ulcer Disease (Helicobacter pylori eradication) | CYP2C19 genotype influences the efficacy of PPI-based triple therapy for H. pylori eradication; extensive metabolizers may require higher doses. | NCBI Gene, literature |
| Drug-induced liver injury | Certain CYP2C19 variants may predispose individuals to hepatotoxicity from drugs like isoniazid and valproic acid. | OMIM, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Small intestine | 3.2 | Medium |
| Duodenum | 2.8 | Medium |
| Stomach | 1.1 | Low |
| Kidney | 0.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 8.4 | Hepatocellular carcinoma cell line |
| Caco-2 | 2.1 | Colorectal adenocarcinoma cell line |
| HepaRG | 15.3 | Differentiated hepatocyte-like cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| CYP2C19*2 (rs4244285) | SNP (c.681G>A) | 15-25% in Caucasians; 30-50% in Asians | Loss-of-function; aberrant splicing leading to truncated inactive protein |
| CYP2C19*3 (rs4986893) | SNP (c.636G>A) | <1% in Caucasians; 5-15% in Asians | Loss-of-function; premature stop codon |
| CYP2C19*17 (rs12248560) | SNP (c.-806C>T) | 15-25% in Caucasians; 5-10% in Africans | Gain-of-function; increased transcription leading to ultrarapid metabolizer phenotype |
| CYP2C19*4 (rs28399504) | SNP (c.1A>G) | Rare | Loss-of-function; initiation codon mutation |
Mutation functional classification
Loss of Function (LOF)
CYP2C19*2 and CYP2C19*3 are the most common loss-of-function alleles, resulting in reduced or absent enzyme activity. Poor metabolizers (two loss-of-function alleles) have significantly impaired drug metabolism.
Gain of Function (GOF)
CYP2C19*17 is a gain-of-function allele associated with increased transcription and enzyme activity, leading to ultrarapid metabolizer phenotype and potentially reduced drug efficacy for prodrugs like clopidogrel.
Dominant Negative (DN)
No dominant-negative effects have been described for CYP2C19 variants.
View complete mutation data：
Gene Ontology (GO)
| • monooxygenase activity (GO:0004497) | • iron ion binding (GO:0005506) |
| • steroid hydroxylase activity (GO:0008395) | • oxidoreductase activity (GO:0016491) |
| • heme binding (GO:0020037) | • oxidation-reduction process (GO:0055114) |
Pathways
• Drug metabolism - cytochrome P450 (KEGG: hsa00982)
• Metabolism of xenobiotics by cytochrome P450 (KEGG: hsa00980)
• Clopidogrel metabolism (Reactome: R-HSA-211981)
• Omeprazole metabolism (Reactome: R-HSA-211999)
Protein Summary
CYP2C19 is a 490-amino acid microsomal hemoprotein belonging to the cytochrome P450 family. It is primarily expressed in the liver and to a lesser extent in the intestinal mucosa. The enzyme catalyzes the oxidative metabolism of a wide range of drugs, including the activation of the prodrug clopidogrel and the hydroxylation of proton pump inhibitors. Its activity is highly variable due to genetic polymorphisms, which are clinically relevant for drug dosing and therapeutic outcomes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYP2C19 Knockout HEK293 Cell Line | EDJ-KQ3879 | Human | 1557 | Details Get a Quote |
| CYP2C19 Knockout HeLa Cell Line | EDJ-KQ53046 | Human | 1557 | Details Get a Quote |
| CYP2C19 Knockout A-549 Cell Line | EDJ-KQ61510 | Human | 1557 | Details Get a Quote |
| CYP2C19 Knockout HCT 116 Cell Line | EDJ-KQ70004 | Human | 1557 | Details Get a Quote |
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