{"gene":{"symbol":"CYP2C19","name":"Cytochrome P450 Family 2 Subfamily C Member 19","protein":"Cytochrome P450 2C19","ncbi_gene_id":"1557","locus":"10q23.33","summary":"CYP2C19 is a hepatic cytochrome P450 enzyme that activates the antiplatelet prodrug clopidogrel and clears proton-pump inhibitors, several antidepressants, diazepam and the antifungal voriconazole. Poor metabolizers convert little clopidogrel to its active form, a difference linked to higher rates of stent thrombosis and recurrent cardiovascular events and the basis of the drug's FDA boxed warning. Star-allele haplotypes map to poor, intermediate, normal, rapid and ultra-rapid metabolizer phenotypes.","function":"CYP2C19 performs oxidative metabolism on a focused but high-stakes set of drugs. For clopidogrel it acts as an activator: clopidogrel is an inactive prodrug and CYP2C19 catalyzes a key step converting it into the active metabolite that blocks platelet aggregation — no active metabolite, no antiplatelet effect. For most other substrates it inactivates the parent drug: proton-pump inhibitors (omeprazole, lansoprazole, pantoprazole), the antidepressants citalopram, escitalopram and sertraline, the benzodiazepine diazepam and the antifungal voriconazole; here a poor metabolizer accumulates higher drug levels, which can mean better acid suppression with a PPI but greater side-effect risk with an antidepressant or voriconazole. Unlike CYP2D6, CYP2C19 sits in a structurally simpler region of chromosome 10 with no common whole-gene duplication or deletion and no high-similarity pseudogene, making it one of the more tractable pharmacogenes to read from a SNP array.","category":"pharmacogene","key_variants":[{"rsid":null,"name":"*1 (reference)","alleles":"Wild-type haplotype","effect":"Normal enzyme activity; reference for phenotype scoring.","frequency_note":null},{"rsid":"rs4244285","name":"*2 (c.681G>A)","alleles":"Plus strand, GRCh37 (as in 23andMe raw data): G reference, A variant, which defines *2. CYP2C19 is on the plus strand, so the letters match the gene. Copies of A at this one position are not a metabolizer status: that needs the other CYP2C19 variants and phasing.","effect":"Splice defect, no functional enzyme; the most common loss-of-function allele worldwide.","frequency_note":"~15% in Europeans, ~17% in Africans, ~29–35% in East Asians."},{"rsid":"rs4986893","name":"*3 (c.636G>A)","alleles":"Plus strand, GRCh37 (as in 23andMe raw data): G reference, A variant (Trp212Ter), which defines *3.","effect":"Premature stop codon, no functional enzyme.","frequency_note":"Rare in Europeans (<1%) but common in East Asians (~5–9%), where *2 and *3 together make poor-metabolizer status much more frequent."},{"rsid":"rs12248560","name":"*17 (c.-806C>T)","alleles":"Plus strand, GRCh37 (as in 23andMe raw data): C reference, T variant (c.-806C>T), found in *17.","effect":"Promoter variant that boosts transcription and raises enzyme activity; drives rapid and ultra-rapid metabolizer phenotypes.","frequency_note":"~21–22% in Europeans, ~17–24% in African-ancestry groups; rare (~2%) in East Asians."}],"phenotypes":["Poor metabolizer (PM): two no-function alleles (e.g. *2/*2, *2/*3)","Intermediate metabolizer (IM): one no-function allele with one normal or increased-function allele (e.g. *1/*2, *2/*17)","Normal metabolizer (NM): two normal-function alleles (*1/*1)","Rapid metabolizer (RM): one normal and one increased-function allele (*1/*17)","Ultra-rapid metabolizer (UM): two increased-function alleles (*17/*17)"],"clinical_relevance":"CYP2C19 has formal, peer-reviewed dosing guidelines from CPIC and DPWG. Clopidogrel: CPIC's 2022 guideline recommends an alternative antiplatelet (prasugrel or ticagrelor) for poor and intermediate metabolizers undergoing percutaneous coronary intervention for acute coronary syndromes, because they form less active metabolite and have higher rates of stent thrombosis and cardiovascular events; clopidogrel carries an FDA boxed warning about reduced effectiveness in poor metabolizers. Proton-pump inhibitors: CPIC suggests considering a 50–100% higher dose for normal and rapid metabolizers treated for H. pylori or erosive esophagitis and a 100% higher starting dose for ultra-rapid metabolizers, while intermediate and poor metabolizers reach higher drug levels. SSRIs (citalopram, escitalopram, sertraline): CPIC provides phenotype-based dosing; poor metabolizers reach higher concentrations, and for citalopram and escitalopram ultra-rapid metabolizers may have reduced response. Voriconazole: CPIC recommends an alternative antifungal not dependent on CYP2C19 for adult poor, rapid and ultra-rapid metabolizers.","consumer_array_caveat":"CYP2C19 is one of the friendlier pharmacogenes for consumer raw data: the two most important alleles are tagged by single, commonly genotyped SNPs and there is no copy-number or pseudogene complication. rs4244285 (*2 marker) is almost always genotyped; rs12248560 (*17 marker) usually; rs4986893 (*3 marker) sometimes, mattering mainly in East Asian populations. A raw file gives genotypes at single positions, not a phased, clinically validated star-allele call, and it will miss rarer alleles. For a real decision about clopidogrel after a stent, the appropriate tool is a CPIC-aware clinical pharmacogenomic test ordered through a clinician.","drugs":[{"drug":"clopidogrel","guideline":"CPIC","level":"CPIC A","summary":"Prodrug activated by CYP2C19. CPIC 2022 recommends an alternative antiplatelet (prasugrel or ticagrelor) for poor and intermediate metabolizers undergoing PCI for acute coronary syndromes. FDA boxed warning about reduced effectiveness in poor metabolizers."},{"drug":"omeprazole","guideline":"CPIC","level":"CPIC A","summary":"Proton-pump inhibitor inactivated by CYP2C19. CPIC suggests considering a 50–100% higher dose for normal and rapid metabolizers treated for H. pylori or erosive esophagitis, and a 100% higher starting dose for ultra-rapid metabolizers. Intermediate and poor metabolizers reach higher drug levels; for chronic therapy (>12 weeks) CPIC suggests considering a 50% dose reduction once efficacy is achieved."},{"drug":"lansoprazole","guideline":"CPIC","level":"CPIC A","summary":"Proton-pump inhibitor inactivated by CYP2C19. CPIC suggests considering a 50–100% higher dose for normal and rapid metabolizers treated for H. pylori or erosive esophagitis, and a 100% higher starting dose for ultra-rapid metabolizers. Intermediate and poor metabolizers reach higher drug levels; for chronic therapy (>12 weeks) CPIC suggests considering a 50% dose reduction once efficacy is achieved."},{"drug":"pantoprazole","guideline":"CPIC","level":"CPIC A","summary":"Proton-pump inhibitor inactivated by CYP2C19. CPIC suggests considering a 50–100% higher dose for normal and rapid metabolizers treated for H. pylori or erosive esophagitis, and a 100% higher starting dose for ultra-rapid metabolizers. Intermediate and poor metabolizers reach higher drug levels; for chronic therapy (>12 weeks) CPIC suggests considering a 50% dose reduction once efficacy is achieved."},{"drug":"citalopram","guideline":"CPIC","level":"CPIC A","summary":"SSRI inactivated by CYP2C19. CPIC (Bousman et al. 2023) recommends considering an antidepressant not predominantly metabolized by CYP2C19 for ultra-rapid and poor metabolizers (strong); if the drug is still used, a lower starting dose, slower titration and a 50% lower maintenance dose for poor metabolizers. For intermediate metabolizers it suggests the usual starting dose with slower titration and a lower maintenance dose (moderate)."},{"drug":"escitalopram","guideline":"CPIC","level":"CPIC A","summary":"SSRI inactivated by CYP2C19. CPIC (Bousman et al. 2023) recommends considering an antidepressant not predominantly metabolized by CYP2C19 for ultra-rapid and poor metabolizers (strong); if the drug is still used, a lower starting dose, slower titration and a 50% lower maintenance dose for poor metabolizers. For intermediate metabolizers it suggests the usual starting dose with slower titration and a lower maintenance dose (moderate)."},{"drug":"sertraline","guideline":"CPIC","level":"CPIC A","summary":"SSRI metabolized by CYP2C19 (and CYP2B6). CPIC recommends the usual starting dose for rapid and ultra-rapid metabolizers; for poor metabolizers, a lower starting dose, slower titration and about 50% lower maintenance dose, or an alternative antidepressant. Recommendations also take CYP2B6 into account."},{"drug":"voriconazole","guideline":"CPIC","level":"CPIC A","summary":"Antifungal inactivated by CYP2C19. CPIC recommends an alternative antifungal not dependent on CYP2C19 for adult ultra-rapid, rapid and poor metabolizers; if voriconazole is still used in a poor metabolizer, a lower dose with therapeutic drug monitoring. In children, rapid metabolizers start at standard dosing with drug-level monitoring."},{"drug":"amitriptyline","guideline":"CPIC","level":"CPIC A","summary":"Tricyclic antidepressant converted by CYP2C19 to nortriptyline. CPIC recommends avoiding amitriptyline in poor metabolizers; if it is used, CPIC suggests considering a 50% lower starting dose with drug-level monitoring (moderate). For rapid and ultra-rapid metabolizers it suggests considering an alternative not metabolized by CYP2C19, or drug-level monitoring if amitriptyline is used (optional); normal and intermediate metabolizers start at the recommended dose. These recommendations apply to the higher doses used for depression, and CYP2D6 phenotype also changes the recommendation."},{"drug":"dexlansoprazole","guideline":"CPIC","level":"CPIC B","summary":"Proton-pump inhibitor inactivated by CYP2C19. CPIC suggests considering a 50–100% higher dose for normal and rapid metabolizers treated for H. pylori or erosive esophagitis, and a 100% higher starting dose for ultra-rapid metabolizers. Intermediate and poor metabolizers reach higher drug levels; for chronic therapy (>12 weeks) CPIC suggests considering a 50% dose reduction once efficacy is achieved. CPIC classifies all of its dexlansoprazole recommendations as optional."},{"drug":"clomipramine","guideline":"CPIC","level":"CPIC B","summary":"Tricyclic antidepressant (tertiary amine) metabolized by CYP2C19. CPIC extrapolates its amitriptyline recommendations to clomipramine, noting fewer supporting data, and classifies them as optional except the usual starting dose for normal metabolizers (strong). Assuming CYP2D6 normal metabolism, CPIC suggests avoiding clomipramine in poor metabolizers, or considering a 50% lower starting dose with drug-level monitoring if it is used; for rapid and ultra-rapid metabolizers, an alternative not metabolized by CYP2C19, or drug-level monitoring if clomipramine is used; and for intermediate metabolizers, the usual starting dose. These recommendations apply to the higher doses used for depression, and other CYP2D6 phenotypes change them."},{"drug":"imipramine","guideline":"CPIC","level":"CPIC B","summary":"Tricyclic antidepressant (tertiary amine) metabolized by CYP2C19. CPIC extrapolates its amitriptyline recommendations to imipramine, noting fewer supporting data, and classifies them as optional except the usual starting dose for normal metabolizers (strong). Assuming CYP2D6 normal metabolism, CPIC suggests avoiding imipramine in poor metabolizers, or considering a 50% lower starting dose with drug-level monitoring if it is used; for rapid and ultra-rapid metabolizers, an alternative not metabolized by CYP2C19, or drug-level monitoring if imipramine is used; and for intermediate metabolizers, the usual starting dose. These recommendations apply to the higher doses used for depression, and other CYP2D6 phenotypes change them."},{"drug":"doxepin","guideline":"CPIC","level":"CPIC B","summary":"Tricyclic antidepressant (tertiary amine) metabolized by CYP2C19. CPIC extrapolates its amitriptyline recommendations to doxepin, noting fewer supporting data, and classifies them as optional except the usual starting dose for normal metabolizers (strong). Assuming CYP2D6 normal metabolism, CPIC suggests avoiding doxepin in poor metabolizers, or considering a 50% lower starting dose with drug-level monitoring if it is used; for rapid and ultra-rapid metabolizers, an alternative not metabolized by CYP2C19, or drug-level monitoring if doxepin is used; and for intermediate metabolizers, the usual starting dose. These recommendations apply to the higher doses used for depression, and other CYP2D6 phenotypes change them."},{"drug":"trimipramine","guideline":"CPIC","level":"CPIC B","summary":"Tricyclic antidepressant (tertiary amine) metabolized by CYP2C19. CPIC extrapolates its amitriptyline recommendations to trimipramine, noting fewer supporting data, and classifies them as optional except the usual starting dose for normal metabolizers (strong). Assuming CYP2D6 normal metabolism, CPIC suggests avoiding trimipramine in poor metabolizers, or considering a 50% lower starting dose with drug-level monitoring if it is used; for rapid and ultra-rapid metabolizers, an alternative not metabolized by CYP2C19, or drug-level monitoring if trimipramine is used; and for intermediate metabolizers, the usual starting dose. These recommendations apply to the higher doses used for depression, and other CYP2D6 phenotypes change them."}],"sources":[{"label":"CPIC — CYP2C19 gene page","url":"https://cpicpgx.org/gene/cyp2c19/"},{"label":"PharmGKB CYP2C19 (PA124)","url":"https://www.pharmgkb.org/gene/PA124"},{"label":"PharmVar CYP2C19","url":"https://www.pharmvar.org/gene/CYP2C19"},{"label":"NCBI Gene 1557","url":"https://www.ncbi.nlm.nih.gov/gene/1557"},{"label":"Lee et al., Clin Pharmacol Ther 2022 (CPIC clopidogrel guideline update)","url":"https://pubmed.ncbi.nlm.nih.gov/35034351/"},{"label":"Lima et al., Clin Pharmacol Ther 2021 (CPIC CYP2C19 and proton pump inhibitor guideline)","url":"https://pubmed.ncbi.nlm.nih.gov/32770672/"},{"label":"Bousman et al., Clin Pharmacol Ther 2023 (CPIC serotonin reuptake inhibitor antidepressant guideline: CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A)","url":"https://pubmed.ncbi.nlm.nih.gov/37032427/"},{"label":"Moriyama et al., Clin Pharmacol Ther 2017 (CPIC CYP2C19 and voriconazole guideline)","url":"https://pubmed.ncbi.nlm.nih.gov/27981572/"},{"label":"FDA label, Plavix (clopidogrel) (boxed warning on CYP2C19 poor metabolizers)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de8b0b67-eb25-4684-83b5-7ad785314227"}],"related_blog":"/blog/pharmacogenomics-europe-guide/","disclaimer":"Educational information only, not medical advice or diagnosis. Consult a clinician before acting on genetic information."},"meta":{"disclaimer":"Educational information only, not medical advice or diagnosis. Consult a clinician before acting on genetic information.","api_version":"2026-09-20","docs":"https://deepdna.ai/docs/","status":"live","data_as_of":"2026-10-25T21:32:19.251Z","freshness":"https://deepdna.ai/api/v1/freshness"}}