One enzyme, four prescribing guidelines. CYP2C19 decides how much drug reaches you for a heart medicine, a stomach medicine, an antifungal and most antidepressants — and the same genotype helps with one and hinders another.
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
CYP2C19 is a liver enzyme that breaks down a long list of medicines. It is one of the most variable enzymes in the human body, and the variation is not subtle: some people have none of it, some have more than usual, and both are common.
Three of the positions that define this are on this page:
Two non-functional copies makes a poor metaboliser; two *17 copies an ultrarapid metaboliser; and there are several gradations in between. Whether that is good or bad news depends entirely on which drug you are taking, and this is the point of the page.
For a drug that arrives active and is destroyed by CYP2C19, a poor metaboliser is over-exposed. For a drug that arrives inactive and must be switched on by CYP2C19, a poor metaboliser is under-exposed. Same genotype, opposite consequence.
| Drug | What CYP2C19 does to it | So a poor metaboliser… |
|---|---|---|
| Clopidogrel | Switches it on — it arrives as an inactive prodrug | gets less of the active drug, and less protection |
| Proton pump inhibitors | Switches them off | gets more exposure, and often better acid suppression |
| Voriconazole | Clears it | runs higher trough levels, with more adverse events |
That is why there is no such thing as a “good” CYP2C19 genotype. There is only a genotype and a drug.
CPIC — the body that writes prescribing guidance for genotypes — has published separate guidelines covering CYP2C19 for clopidogrel, for proton pump inhibitors, for voriconazole, and for the serotonin reuptake antidepressants. Few genes carry that many.
Each is linked from the drug pages above and from serotonin reuptake antidepressants.
The *3 allele is substantially more common in East Asian populations than in European ones, and *17 is more common in European and African populations than in East Asian ones. So the fraction of people who are poor metabolisers differs between populations by more than most pharmacogenetic variants do.
That is not a footnote on the guidance. It changes how much a testing programme is worth in a given place, which is why guidelines discuss it rather than stating one universal rule.
It cannot tell you your metaboliser status. CYP2C19 is called from a set of alleles, some of which are structural and none of which a consumer genotype file is designed to type reliably as a diagnostic. Clinical CYP2C19 testing exists, is ordered by a prescriber, and is done in an accredited laboratory.
Nothing here is a reason to change or stop a medicine. If you are on one of the drugs above and something about it is not working — that is a conversation with the person who prescribed it.
Alleles listed here. rs4244285 (CYP2C19*2, c.681G>A, splice defect, no function), rs4986893 (*3, c.636G>A, premature stop, no function) and rs12248560 (*17, c.-806C>T, promoter, increased transcription). Diplotype-to-phenotype translation follows the CPIC/DPWG consensus terms: ultrarapid, rapid, normal, intermediate and poor metaboliser.
Guidelines covering this gene. CPIC has published CYP2C19 guidance for clopidogrel, for proton pump inhibitors (Clin Pharmacol Ther 2021), for voriconazole (2017) and, jointly with CYP2D6, CYP2B6, SLC6A4 and HTR2A, for serotonin reuptake inhibitor antidepressants (2023). The direction of the recommendation depends on whether the drug is a prodrug activated by the enzyme or an active drug cleared by it.
Population frequency. *2 is common in all major populations; *3 is appreciably more frequent in East Asian populations; *17 is more frequent in European and African populations than East Asian. The resulting phenotype distribution differs enough between populations to affect the expected yield of pre-emptive testing.
Clinical use. CYP2C19 genotyping is performed in clinical laboratories as part of pre-emptive or reactive pharmacogenomic testing, and star-allele assignment requires an assay designed for it. Consumer genotyping arrays are not validated for diplotype calling and should not be used to infer metaboliser status for a prescribing decision.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about CYP2C19 Metaboliser Status comes down to these specific, well-studied positions — not a diagnosis.
Research-derived gene–drug associations only — not a prescription, dosing guide, or medical advice. Always follow your prescriber's guidance.
| Gene | Drug | What the research shows |
|---|---|---|
| CYP2C19 | Proton pump inhibitors (omeprazole, lansoprazole, pantoprazole, dexlansoprazole, rabeprazole) | Most proton pump inhibitors are metabolised primarily by CYP2C19 into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy and adverse effects. A poor metaboliser therefore has more drug for longer — which for acid suppression and for Helicobacter pylori eradication usually helps rather than harms, and is the unusual case of a loss-of-function genotype being an advantage. An ultrarapid metaboliser has the opposite problem and may under-respond. CPIC published dosing guidance on this basis in 2021. The class does not depend on the enzyme equally: omeprazole, lansoprazole and pantoprazole rely on it most and carry the strongest evidence rating, dexlansoprazole less so, and rabeprazole is cleared largely by a route that does not involve the enzyme at all — which is why it is the PPI on which a genotype says least. (CPIC Guideline for CYP2C19 and Proton Pump Inhibitor Dosing (Clin Pharmacol Ther 2021, PMID 32770672).) |
| CYP2C19 | Voriconazole | Voriconazole shows wide interpatient variability in serum concentration, due in part to CYP2C19 alleles. Ultrarapid metabolisers have decreased trough concentrations, delaying achievement of target blood levels; poor metabolisers have increased troughs and are at increased risk of adverse drug events. This is a drug with a narrow window where the level is routinely measured anyway, and genotype explains part of why two patients on the same dose land in different places. (CPIC Guidelines for CYP2C19 and Voriconazole Therapy (Clin Pharmacol Ther 2017, PMID 27981572).) |
| CYP2C19 | Serotonin reuptake inhibitor antidepressants | Genetic variation in CYP2D6, CYP2C19 and CYP2B6 influences the metabolism of many antidepressants, which may affect dosing, efficacy and tolerability. The CPIC guideline covers the SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), the SNRIs (desvenlafaxine, duloxetine, levomilnacipran, milnacipran, venlafaxine) and the serotonin modulators vilazodone and vortioxetine, and also considers the pharmacodynamic genes SLC6A4 and HTR2A. Antidepressant response is not reducible to metabolism, and the guidance addresses exposure rather than whether a given drug will work for a given person. (CPIC Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4 and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants (Clin Pharmacol Ther 2023, PMID 37032427).) |
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CYP2C19 Metaboliser Status. MyGeneLog™. https://www.mygenelog.com/conditions/cyp2c19-metaboliser-status
It depends entirely on the drug, and the direction reverses. For clopidogrel, which arrives inactive and has to be switched on by CYP2C19, a poor metaboliser gets less protection. For a proton pump inhibitor, which the enzyme destroys, the same person gets more drug and often better acid suppression. There is no good genotype — only a genotype and a drug.
Not reliably, and it should not be used for a prescribing decision. Metaboliser status is assigned from a set of star alleles by an assay designed for it, in an accredited laboratory. A consumer array covers some of the positions and is not validated for the call.
Because the alleles do. *3 is appreciably more common in East Asian populations and *17 in European and African ones, so the proportion of poor and ultrarapid metabolisers differs — which changes how much a testing programme is worth in a given place. Guidelines say so rather than stating one universal rule.
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