rs56337013
neutralMag 5.5This is a variant in the CYP2C19 gene that changes a arginine to an tryptophan.
Key Literature Trait Associations
Drug Metabolism (CYP2C19)
CYP2C19*5 (c.1297C>T, p.Arg433Trp) is a rare loss-of-function allele that produces a non-functional enzyme due to an amino acid substitution in the heme-binding region of CYP2C19. Carriers have reduced capacity to metabolize multiple CYP2C19 substrates including clopidogrel, proton pump inhibitors, and antifungals. CPIC guidelines classify *5 as a no-function allele.
▶ClinVar annotation
CYP2C19: no function; Citalopram response; Clopidogrel response; Escitalopram response; Mephenytoin, poor metabolism of; Sertraline response; Voriconazole response
View on ClinVar →▶Research that mentions this SNP (4)
▶Interindividual Variability in the Hepatic Expression of the Human Breast Cancer Resistance Protein (BCRP/ABCG2): Effect of Age, Sex, and GenotypeAssociationN=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.
▶Influence of neurexin 1 (NRXN1) polymorphisms in clozapine responseReviewRenan P. Souza et al.(2010)· Human Psychopharmacology: Clinical and Experimental
This systematic review of 98 studies examined biological predictors of clozapine response in treatment-resistant schizophrenia patients. Of 379 different gene variants investigated across 70 genetic studies, only three variants (DRD3 Ser9Gly rs6280, HTR2A His452Tyr, and GNB3 C825T) achieved independent replication. Non-genetic predictors included higher prefrontal cortical volumes and lower HVA:5-HIAA ratio in cerebrospinal fluid.
▶Association of Cytochrome P450 2C19 Genotype With the Antiplatelet Effect and Clinical Efficacy of Clopidogrel TherapyAssociationN=656Shuldiner AR et al.(2009)· JAMA
This genome-wide association study identified the CYP2C19*2 loss-of-function variant (rs4244285) as a major determinant of clopidogrel response in 429 Amish individuals. The variant was associated with diminished platelet aggregation response to ADP stimulation (P=4.3×10⁻¹¹) and accounted for 12% of variation in clopidogrel response. In an independent cohort of 227 patients undergoing percutaneous coronary intervention, carriers of CYP2C19*2 had higher cardiovascular event rates (20.9% vs 10.0%, HR=2.42, P=.02).
▶Lack of association of GPX1 and MnSOD genes with symptom severity and response to clozapine treatment in schizophrenia subjectsReviewRenan P. Souza et al.(2009)· Human Psychopharmacology: Clinical and Experimental
A systematic review of 98 studies investigating biological predictors of clozapine response in treatment-resistant schizophrenia. Of 70 genetic studies examining 379 variants, only three genetic variants have independently replicated findings: DRD3 Ser9Gly (rs6280), HTR2A His452Tyr, and GNB3 C825T (rs5442/rs5443). Non-genetic predictors include higher prefrontal cortical structural integrity and activity, and lower HVA:5-HIAA ratio in cerebrospinal fluid.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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