Document Type

Article

Publication Date

8-2026

Identifier

DOI: 10.1002/cpt.70286; PMCID: PMC13339618

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.

Journal Title

Clinical pharmacology and therapeutics

Volume

120

Issue

2

First Page

313

Last Page

323

MeSH Keywords

Humans; Cytochrome P-450 CYP1A2; Genetic Variation; Terminology as Topic; Pharmacogenetics; Alleles; Polymorphism, Genetic

PubMed ID

41992662

Keywords

Cytochrome P-450 CYP1A2; Genetic Variation; Terminology as Topic; Pharmacogenetics; Alleles; Genetic Polymorphism

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