rs72558186

badMag 6.5

This is a splice donor variant variant in the CYP2C19 gene.

Key Literature Trait Associations

Drug Metabolism (CYP2C19)

CYP2C19*7 is a rare loss-of-function allele caused by a T>A splice donor site mutation (c.819+2T>A) in intron 5 of CYP2C19. Carriers have severely reduced or absent CYP2C19 enzymatic activity, impairing the bioactivation of clopidogrel and metabolism of PPIs, antidepressants, and antifungals. CPIC guidelines classify CYP2C19*7 as a no-function allele.

Chaudhry AS et al. “The CYP2C19 Intron 2 Branch Point SNP is the Ancestral Polymorphism Contributing to the Poor Metabolizer Phenotype in Livers with CYP2C19*35 and CYP2C19*2 Alleles.” Drug Metabolism and Disposition: the Biological Fate of Chemicals (2015)

Allele A

OR —

p —

N 104

Candidate gene study

African (Ethiopian)

Scott SA et al. “Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update.” Clinical Pharmacology and Therapeutics 94(3):317-323 (2013)

Allele A

OR —

p —

Major Consortium Study

Lee CR et al. “Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update.” Clinical Pharmacology and Therapeutics (2022)

Allele A

OR —

p —

Major Consortium Study

multi-ancestry

Biswas M et al. “Global distribution of CYP2C19 risk phenotypes affecting safety and effectiveness of medications.” The Pharmacogenomics Journal (2021)

Allele A

OR —

p —

Candidate gene study

multi-ancestry

Clopidogrel response

CYP2C19 is the principal enzyme responsible for bioactivating the prodrug clopidogrel into its active thiol metabolite. Carriers of no-function alleles such as rs72558186 (*35) — as poor or intermediate metabolizers — show substantially reduced platelet inhibition and elevated cardiovascular event rates. A multicenter study in 567 Black patients showed an adjusted hazard ratio of 2.00 for major atherothrombotic events in intermediate/poor metabolizers versus normal metabolizers. CPIC guidelines recommend alternative P2Y12 inhibitors (prasugrel, ticagrelor) for ACS/PCI patients carrying CYP2C19 loss-of-function alleles.

Tunehag KR et al. “CYP2C19 Genotype Is Associated With Adverse Cardiovascular Outcomes in Black Patients Treated With Clopidogrel Undergoing Percutaneous Coronary Intervention.” Journal of the American Heart Association (2024)

Allele A

OR 2.00

p 8.0e-3

N 567

Preliminary work

African American

Lee CR et al. “Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update.” Clinical Pharmacology and Therapeutics (2022)

Allele A

OR —

p —

Major Consortium Study

multi-ancestry

Voriconazole pharmacokinetics

CYP2C19 is the primary metabolic route for voriconazole, and carriers of no-function alleles such as *35 exhibit on average 4-fold higher drug exposure compared to normal metabolizers. This elevated exposure significantly increases the risk of neurotoxicity and hepatotoxicity. Therapeutic drug monitoring is standard of care for voriconazole, and CPIC/DPWG guidelines recommend dose reduction or increased monitoring frequency for CYP2C19 poor metabolizers to prevent toxicity while maintaining efficacy.

Dean L et al. “Voriconazole Therapy and CYP2C19 Genotype.” (2012)

Allele A

OR —

p —

Candidate gene study

multi-ancestry

SSRI antidepressant response

CYP2C19 poor metabolizers carrying no-function alleles such as *35 have significantly elevated plasma concentrations of escitalopram, citalopram, and sertraline due to reduced first-pass and systemic metabolism. In a UK Biobank study of over 40,000 SSRI users, CYP2C19 poor metabolizers prescribed escitalopram showed increased odds of medication switching, adverse effects after first prescription, and shorter treatment duration compared to normal metabolizers; similar patterns were seen with citalopram. DPWG and CPIC guidelines recommend dose reductions for escitalopram and citalopram in poor metabolizers to minimize QTc-prolongation and other side effects.

Wong WLE et al. “The Effects of CYP2C19 Genotype on Proxies of SSRI Antidepressant Response in the UK Biobank.” Pharmaceuticals (basel, Switzerland) (2023)

Allele A

OR —

p —

N 40,285

Major Consortium Study

European

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ClinVar annotation

Drug Response★★★★

1 submitter5 publications

CYP2C19: no function; Citalopram response; Clopidogrel response; Escitalopram response; Sertraline response; Voriconazole response

View on ClinVar →

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Research that mentions this SNP (1)

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Interindividual Variability in the Hepatic Expression of the Human Breast Cancer Resistance Protein (BCRP/ABCG2): Effect of Age, Sex, and Genotype

AssociationN=1,000Bhagwat Prasad et al.(2013)· Journal of Pharmaceutical Sciences

Case-control study of 1,000 Han Chinese individuals (450 epilepsy cases, 550 controls) examining associations between STX1B polymorphisms and epilepsy treatment response. The rs140820592 variant showed significant association with reduced epilepsy risk (OR=0.542, p=0.004) and drug-resistant epilepsy risk (OR=0.260, p=0.004), with eQTL analysis confirming rs140820592 regulates STX1B expression in brain tissues.

Traits studied:Drug-resistant epilepsyDrug-responsive epilepsyEpilepsyImatinib response in chronic myelogenous leukemiaPraziquantel responseTacrolimus metabolism

rs72558186

Key Literature Trait Associations

Drug Metabolism (CYP2C19)

Clopidogrel response

Voriconazole pharmacokinetics

SSRI antidepressant response

ClinVar annotation

Research that mentions this SNP (1)

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