ReviewClinical pharmacology and therapeutics2026
PharmVar GeneFocus: CYP1A2-Clinical Impact, Genetic Variation, and Updated Nomenclature.
Review in Clinical pharmacology and therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The Pharmacogene Variation Consortium (PharmVar) provides nomenclature for the highly polymorphic human CYP1A2 gene. CYP1A2 plays a crucial role in the biotransformation of several commonly used drugs, including antipsychotics, antidepressants, anxiolytics, and methylxanthines. The activity of CYP1A2 varies significantly among individuals due to genetic and non-genetic factors. This GeneFocus paper offers an overview of the functional significance of CYP1A2 in drug metabolism, CYP1A2 genetic variation, and presents the updated PharmVar star allele-based nomenclature for CYP1A2. Updates include revisions to previously defined star alleles to align with PharmVar standards, as well as the addition of novel star alleles, providing the pharmacogenetic community with a more comprehensive and high-quality catalog of CYP1A2 genetic variation. We highlight that the common -163C>A (rs762551) variant, which previously defined CYP1A2*1F, is now the sole core variant for a newly established group of CYP1A2*30 alleles. Furthermore, the -163C>A variant, which has been associated with increased expression levels in smokers, has been found on various haplotypes in combination with one or more amino acid changing variants, each of which was assigned a unique star number (e.g., CYP1A2*13, *21, *24, and *31). While all alleles containing -163C>A may have increased expression levels in smokers, it remains unknown whether the presence of one or more amino acids negates the effect of increased expression levels on CYP1A2 activity. Systematic nomenclature that comprehensively describes CYP1A2 variability is essential for future research aimed at assessing the relationship between CYP1A2 variation, drug metabolism, and the clinical utility of CYP1A2 pharmacogenetic testing.
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