rs4244285 — CYP2C19 CYP2C19*2 (splicing defect)
Drug response · ~15% Caucasians, ~30% East Asians
rs4244285 defines the CYP2C19*2 allele, the most common loss-of-function variant affecting clopidogrel (Plavix) activation. Poor metabolizers have up to 3.6x increased risk of cardiovascular events on standard clopidogrel therapy.
Molecular Mechanism
The G>A mutation at position 681 in exon 5 creates an aberrant splice site, producing a truncated non-functional enzyme. Since clopidogrel is a prodrug requiring CYP2C19 activation, poor metabolizers cannot generate the active metabolite needed for antiplatelet effect.
Peptide Therapeutic Relevance
Peptide-based antiplatelet agents could bypass the CYP2C19 activation requirement entirely. PepFold generates candidates targeting the P2Y12 receptor directly, offering metabolism-independent alternatives.
Gene: CYP2C19 (Cytochrome P450 2C19)
Metabolizes proton pump inhibitors, clopidogrel, certain antidepressants, and antifungals. Pharmacogenomic testing is recommended before clopidogrel therapy by CPIC guidelines.
Chromosome 10q23.33
Condition: Drug Metabolism Disorders (CYP450 Pharmacogenomics)
Genetic variation in cytochrome P450 enzymes (CYP2D6, CYP2C19, CYP2C9) creates a spectrum from ultra-rapid to poor metabolizers. This affects ~25% of all prescribed medications and is the foundation of clinical pharmacogenomics.
Prevalence: 7-10% of Caucasians are CYP2D6 poor metabolizers; 2-5% are CYP2C19 poor metabolizers
Related Variants
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