PepFold

SNP Database

rs3892097CYP2D6 CYP2D6*4 (splicing defect)

Drug response · ~22% in Caucasians

rs3892097 is the defining variant of the CYP2D6*4 allele, the most common loss-of-function allele in Europeans. It creates a splice-site mutation that produces a non-functional enzyme, rendering carriers poor metabolizers of ~25% of clinical drugs.

Molecular Mechanism

The G>A substitution at the intron 3/exon 4 boundary disrupts mRNA splicing, producing a truncated, non-functional CYP2D6 protein. Homozygous *4/*4 individuals cannot metabolize codeine to morphine, tamoxifen to endoxifen, or many SSRIs to their active forms.

Peptide Therapeutic Relevance

While CYP2D6 is not a traditional peptide therapy target, peptide-based enzyme modulators and allosteric regulators are emerging research areas. PepFold generates exploratory candidates targeting CYP2D6 active site regions.

Gene: CYP2D6 (Cytochrome P450 2D6)

Phase I drug metabolism enzyme responsible for ~25% of clinical drugs. Highly polymorphic with >100 known alleles ranging from gene deletion to ultra-rapid multiplication.

Chromosome 22q13.2

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

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