CYP2C19 Cytochrome P450 2C19
CYP2C19 is a liver enzyme that activates or clears several widely used medicines, including clopidogrel, most proton-pump inhibitors, escitalopram and voriconazole.
What does CYP2C19 do?
CYP2C19 is a liver enzyme that activates or clears several widely used medicines, including clopidogrel, most proton-pump inhibitors, escitalopram and voriconazole. Two common no-function alleles (*2 and *3) and one increased-function allele (*17) make CYP2C19 activity vary widely between people, and between populations: roughly 2-5% of Europeans but 13-15% of East Asians are poor metabolisers. CPIC publishes prescribing guidance keyed to the resulting phenotype.
What do the CYP2C19 metaboliser phenotypes mean?
Each person carries two CYP2C19 alleles. Each allele has a function and an activity score; the two scores are added and the total is mapped to a phenotype as follows.
| Phenotype | How it is assigned | What it means |
|---|---|---|
| Ultrarapid Metabolizer | activity score ≥ 3 (*17/*17) | Two increased-function alleles: faster than normal clearance of CYP2C19 substrates. |
| Rapid Metabolizer | activity score 2.5 or 1.5 (one *17 allele) | One increased-function allele: somewhat faster clearance. |
| Normal Metabolizer | activity score 2 (*1/*1) | Two normal-function alleles: the reference against which drug doses are designed. |
| Intermediate Metabolizer | activity score 0.5 – 1 | One no-function or decreased-function allele: reduced clearance, reduced activation of prodrugs. |
| Poor Metabolizer | activity score 0 (*2/*2, *2/*3, *3/*3) | Two no-function alleles: little or no enzyme activity. |
Which CYP2C19 star alleles are there, and how common are they?
| Allele | Function | Activity score | Defining variants | Frequency (EUR / EAS / AFR / SAS / AMR) | Note |
|---|---|---|---|---|---|
| *1 | normal function | 1 | reference | 63.0% / 38.0% / 65.0% / 45.0% / 60.0% | Wild-type/reference allele. Normal enzyme activity. |
| *2 | no function | 0 | rs4244285 681G>A (splicing defect, exon 5) | 15.0% / 30.0% / 15.0% / 35.0% / 12.0% | Most common loss-of-function allele worldwide. Splicing defect abolishes enzyme activity. Particularly prevalent in South/East Asian populations. |
| *3 | no function | 0 | rs4986893 636G>A (premature stop codon W212X) | 0.1% / 5.0% / 0.1% / 0.5% / 0.2% | Second most common loss-of-function allele, predominantly in East Asian populations (5-8% in Chinese/Japanese). Premature stop codon. |
| *4 | no function | 0 | rs28399504 1A>G (initiation codon mutation) | 0.2% / 0.1% / 0.2% / 0.1% / 0.1% | Rare loss-of-function allele. Mutation in initiation codon prevents translation. |
| *5 | no function | 0 | rs56337013 1297C>T (R433W) | 0.1% / 0.1% / 0.1% / 0.1% / 0.1% | Rare loss-of-function allele. Missense mutation R433W disrupts protein folding. |
| *6 | no function | 0 | rs72552267 395G>A (R132Q) | 0.1% / 0.1% / 0.1% / 0.1% / 0.1% | Rare loss-of-function allele. Missense mutation R132Q. |
| *7 | no function | 0 | rs72558186 IVS5+2T>A (splicing defect) | 0.1% / 0.1% / 0.1% / 0.1% / 0.1% | Rare loss-of-function allele. Splice site mutation. |
| *8 | no function | 0 | rs41291556 358T>C (W120R) | 0.1% / 0.1% / 0.1% / 0.1% / 0.1% | Rare loss-of-function allele. Missense mutation W120R. |
| *9 | decreased function | 0.5 | rs17884712 431G>A (R144H) | 0.5% / 0.1% / 0.5% / 0.3% / 0.3% | Decreased function allele. Missense mutation R144H reduces but does not abolish activity. |
| *10 | decreased function | 0.5 | rs6413438 680C>T (P227L) | 0.1% / 0.1% / 0.1% / 0.1% / 0.1% | Decreased function allele. Missense mutation P227L. |
| *17 | increased function | 1.5 | rs12248560 -806C>T (promoter variant) | 21.0% / 1.0% / 18.0% / 15.0% / 15.0% | Increased function allele. Promoter variant increases transcription. Common in Europeans (~21%), rare in East Asians (~1%). Associated with ultrarapid metabolism of clopidogrel, PPIs, and SSRIs. |
| *35 | no function | 0 | rs12769205 332-1G>A (splicing defect) | 15.0% / 30.0% / 15.0% / 35.0% / 12.0% | Loss-of-function allele. Typically in LD with *2 (rs4244285). The *35 defining variant may be linked to *2 on the same haplotype. |
Which drugs does CYP2C19 affect?
- Clopidogrel Antiplatelet CPIC level A
- Clopidogrel is a prodrug: CYP2C19 converts it into the active metabolite that blocks platelets. People with reduced CYP2C19 activity make less of it and have higher rates of stent thrombosis and recurrent heart attack on standard clopidogrel.
- Proton Pump Inhibitors (PPIs) Acid Suppressant CPIC level A
- Omeprazole, lansoprazole, pantoprazole and related PPIs are cleared mainly by CYP2C19. Rapid and ultrarapid metabolisers clear them faster and may get less acid suppression; poor metabolisers have higher exposure.
- Escitalopram/Citalopram SSRI Antidepressant CPIC level A
- Escitalopram and citalopram are cleared by CYP2C19. Poor metabolisers reach higher blood levels, with more side effects including QT prolongation; ultrarapid metabolisers may have subtherapeutic levels.
- Voriconazole Antifungal CPIC level A
- Voriconazole is largely cleared by CYP2C19 and has a narrow therapeutic window. Ultrarapid metabolisers risk treatment failure from low exposure; poor metabolisers risk toxicity from high exposure.
Can a 23andMe or AncestryDNA file tell you your CYP2C19 type?
23andMe and AncestryDNA chips genotype the defining variants of *2, *3 and *17 directly (rs4244285, rs4986893, rs12248560), so CYP2C19 is one of the better-covered pharmacogenes on consumer data. Rare alleles are not tested, and a call is only as good as the chip's read at each position.
Upload your 23andMe, AncestryDNA or WeGene raw file → · Ask G2: “What is my CYP2C19 metaboliser status and which of my medicines does it affect?”
Genetic associations describe risk across populations, not a diagnosis for any one person. Most variants shift risk modestly and act alongside lifestyle, environment and other genes. Consumer DNA chips do not read every position and can be wrong at any single one. For general education only; talk to a clinician or genetic counsellor before acting on anything here, and never change a prescribed medicine without your prescriber.