CYP2C19

Cytochrome P450, family 2, subfamily C, polypeptide 19
PDB rendering based on 1r9o.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4GQS
Identifiers
Symbols	CYP2C19 ; CPCJ; CYP2C; CYPIIC17; CYPIIC19; P450C2C; P450IIC19
External IDs	OMIM: 124020 MGI: 1306818 HomoloGene: 133565 ChEMBL: 3622 GeneCards: CYP2C19 Gene
EC number	1.14.13.48, 1.14.13.49, 1.14.13.80
Gene ontology Molecular function • monooxygenase activity • iron ion 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 • (S)-limonene 6-monooxygenase activity • (S)-limonene 7-monooxygenase activity • oxygen binding • enzyme binding • heme binding • (R)-limonene 6-monooxygenase activity Cellular component • cytoplasm • endoplasmic reticulum membrane • intracellular membrane-bounded organelle Biological process • xenobiotic metabolic process • steroid metabolic process • monoterpenoid metabolic process • drug metabolic process • arachidonic acid metabolic process • epoxygenase P450 pathway • exogenous drug catabolic process • small molecule metabolic process • heterocycle metabolic process • oxidation-reduction process • omega-hydroxylase P450 pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1557	69888
Ensembl	ENSG00000165841	ENSMUSG00000067229
UniProt	P33261	n/a
RefSeq (mRNA)	NM_000769	NM_001011707
RefSeq (protein)	NP_000760	NP_001011707
Location (UCSC)	Chr 10: 94.76 – 94.85 Mb	Chr 19: 39.11 – 39.19 Mb
PubMed search	[1]	[2]

Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme. This protein, a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics, including many proton pump inhibitors and antiepileptics. In humans, the CYP2C19 protein is encoded by the CYP2C19 gene. CYP2C19 is a liver enzyme that acts on 10-15% of drugs in current clinical use, including the antiplatelet clopidogrel (Plavix), drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam.

CYP2C19 has been annotated as (R)-limonene 6-monooxygenase and (S)-limonene 6-monooxygenase in UniProt.

Function

The gene encodes a member of the cytochrome P450 superfamily of enzymes. These proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize many drugs. Polymorphism within this gene is associated with variable ability to metabolize mephenytoin, known as the poor metabolizer and extensive metabolizer phenotypes. The gene is located within a cluster of cytochrome P450 genes on chromosome no.10 arm q24.

Genetic polymorphism and pharmacogenomics

Genetic polymorphism (mainly CYP2C19*2, CYP2C19*3 and CYP2C19*17) exists for CYP2C19 expression, with approximately 3–5% of Caucasian and 15–20% of Asian populations being poor metabolizers with no CYP2C19 function. This may reduce the efficacy of clopidogrel (Plavix). In patients with an abnormal CYP2C19 variant certain benzodiazepines should be avoided, such as diazepam (Valium), lorazepam (Ativan), oxazepam (Serax), and temazepam (Restoril). On the basis of their ability to metabolize (S)-mephenytoin or other CYP2C19 substrates, individuals can be classified as extensive metabolizers (EM) or poor metabolizers (PM). Eight variant alleles (CYP2C19*2 to CYP2C19*8) that predict PMs have been identified.

Ligands

The following is a table of selected substrates, inducers and inhibitors of CYP2C19. Where classes of agents are listed, there may be exceptions within the class.

Inhibitors of CYP2C19 can be classified by their potency, such as:

• Strong being one that causes at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance.
• Moderate being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.
• Weak being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% decrease in clearance.

Selected inducers, inhibitors and substrates of CYP2C19

Substrates	Inhibitors	Inducers
antidepressants TCAs amitriptyline clomipramine imipramine SSRIs citalopram moclobemide Bupropion antiepileptics diazepam mephenytoin nordazepam phenytoin phenobarbital primidone hexobarbital methylphenobarbital proton pump inhibitors lansoprazole omeprazole pantoprazole rabeprazole esomeprazole clopidogrel (antiplatelet drug) proguanil (prophylactic antimalarial) propranolol (beta blocker) limonene (monoterpene) gliclazide (sulfonylurea) carisoprodol (muscle relaxant) chloramphenicol (bacteriostatic antimicrobial) cyclophosphamide (alkylating antineoplastic agent) indomethacin (NSAID) nelfinavir (antiretroviral) nilutamide (antiandrogen) progesterone (sex hormone) teniposide (chemotherapeutic) warfarin (anticoagulant) tapentadol (analgesic)	Strong: moclobemide (antidepressant) fluvoxamine (SSRI) chloramphenicol (bacteriostatic antimicrobial) fluoxetine (SSRI) Weak: Several anticonvulsants felbamate topiramate Unspecified potency: proton pump inhibitors lansoprazole omeprazole pantoprazole rabeprazole cimetidine (H2-receptor antagonist) indomethacin (NSAID) ketoconazole (antifungal) modafinil (eugeroic) probenecid (uricosuric) ticlopidine (antiplatelet) JWH-018 isoniazid	rifampicin (bactericidal) artemisinin (in malaria) carbamazepine (anticonvulsant, mood stabilizing) norethisterone (contraceptive) prednisone (corticosteroid) Aspirin - Low doses (89mg)

See also

• Cytochrome P450 oxidase

External links

• PharmGKB: Annotated PGx Gene Information for CYP2C19