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Published on: April 4, 2018
Clinical Function Assignment of NAT2 Alleles by the Clinical Pharmacogenetics Implementation Consortium Pharmacogene
Bailey M Tibben1, David W Hein2, Michelle Whirl-Carrillo3
1Department of Pharmacy and Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
Clinical Pharmacology and Therapeutics
|August 1, 2026
Summary
The Clinical Pharmacogenetics Implementation Consortium (CPIC) standardized the function of 59 arylamine N-acetyltransferase 2 (NAT2) alleles. This work clarifies NAT2 genetic variability for improved clinical pharmacogenetic testing and drug response prediction.
Area of Science:
- Pharmacogenomics
- Enzyme kinetics
- Drug metabolism
Background:
- Arylamine N-acetyltransferase 2 (NAT2) is a crucial enzyme in phase II drug metabolism, exhibiting significant genetic polymorphism.
- NAT2 genetic variations lead to diverse metabolizer phenotypes (rapid vs. poor), impacting drug efficacy and safety across populations.
Purpose of the Study:
- To standardize clinical function assignments for NAT2 genetic variants (star alleles) using established terminology.
- To facilitate the clinical implementation of NAT2 pharmacogenetic testing by providing clear genotype-phenotype correlations.
Main Methods:
- The Clinical Pharmacogenetics Implementation Consortium (CPIC) NAT2 Pharmacogene Curation Expert Panel (PCEP) reviewed extensive in vitro and clinical literature.
- Allele function was assessed based on genotype-phenotype concordance and biochemical activity.
- CPIC's standard terminology (increased, decreased, uncertain, unknown function) was applied to 59 cataloged NAT2 star alleles.
Main Results:
- Two NAT2 alleles (*1, *4) were assigned increased function (rapid metabolizers).
- Forty NAT2 alleles were assigned decreased function (slow metabolizers).
- Ten alleles were assigned uncertain function, and seven were assigned unknown function.
Conclusions:
- Standardized functional assignments for NAT2 alleles are essential for accurate pharmacogenetic test interpretation.
- Clear genotype-to-phenotype mappings improve the clinical utility of NAT2 testing for predicting drug response.
- This CPIC initiative provides a robust framework for understanding NAT2 pharmacogenetics in diverse populations.
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