Annotated PGx Gene Information for CYP2C19
Submitted by: Jason Robarge, Rebecca Fletcher, Anne Nguyen (COBRA), Caroline F. Thorn (PharmGKB)
Reviewed by: Under Review
Submitted date: September 30, 2006
| Gene HGNC Name: | CYP2C19 |
|---|---|
| Introductory Information: | Cytochrome P450 2C19, CYP2C19, is responsible for the metabolism of a large number of clinically relevant drugs, including the anticonvulsant mephenytoin, anti-ulcer drugs such as omeprazole, certain antidepressants, and the antimalarial drug proguanil [reviewed by Desta et al, PMID: 12222994]. The drug-interaction table maintained by the COBRA group has a regularly updated list of drugs that interact with CYP2C19 categorized into substrates, inhibitors and inducers, and links to the supporting literature. CYP2C19 protein is mainly present in the liver although activity has been observed in intestine [PMID: 11181505]. A variant response to mephenytoin 4-hydroxylation lead to the phenotypic classification of individuals into poor metabolizers (PM) and extensive metabolizers (EM). It was observed that the PM phenotype was more common in Asians than Whites [PMID: 4042523]. Genetic variation in CYP2C19 was shown to be responsible for the PM phenotype [PMID: 8195181]. The two main haplotypes, CYP2C19*2 and CYP2C19*3, account for 99% of PM in Asians and approximately 87% of White PMs [PMID: 9435198]. Over 20 other variants and haplotypes have been reported. The Human Cytochrome P450 Allele Nomenclature Committee website lists all of the reported genetic variants and their approved haplotype names. The AmpliChip CYP450 Test (Roche Diagnostics) is an FDA approved diagnostic test that detects variation in CYP2C19 and CYP2D6. |
| Key PubMed IDs: | 4042523; 8195181; 8110777; 9435198 |
| Reviews: | 12222994 |
| Key Pathways: | Antiestrogen Pathway (Tamoxifen PK); Cyclophosphamide Pathway (PK); Phenytoin PK Pathway (PharmGKB); Statin Pathway (Fluvastatin PK); Warfarin Pathway (PK) |
| Drugs/Substrates: | Substrates: lansoprazole; omeprazole; pantoprazole; rabeprazole; phenytoin; mephenytoin; phenobarbitone; amitriptyline; carisoprodol; citalopram; clomipramine; cyclophosphamide; hexobarbital; imipramine; indomethacin; mephobarbital; moclobemide; nelfinavir; nilutamide; primidone; progesterone; proguanil; propranolol; teniposide; warfarin Inhibitors: chloramphenicol; cimetidine; felbamate; fluoxetine; fluvoxamine; indomethacin; ketoconazole; lansoprazole; modafinil; omeprazole; oxcarbazepine; probenecid; ticlopidine; topiramate; Inducers: carbamazepine; norethindrone; prednisone; rifampin |
| Phenotypes/Diseases: | Phenotypes: Mephenytoin poor metabolizer (OMIM: 124020); Omeprazole poor metabolizer (OMIM: 124020); Proguanil poor metabolizer (OMIM: 124020) |
| Important Haplotypes | CYP2C19*2, CYP2C19*3 |
| Important Variants | CYP2C19:636G>A, CYP2C19:681G>A |