Related Experiment Video
Updated: Aug 7, 2026

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
Published on: April 1, 2019
Clinical Functional Assignment of TPMT and NUDT15 Alleles by the Clinical Pharmacogenetics Implementation Consortium
Bailey M Tibben1, Maud Maillard1,2, Victoria M Pratt3,4
1Department of Pharmacy and Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
None:
The Clinical Pharmacogenetics Implementation Consortium (CPIC) TPMT/NUDT15 Pharmacogene Curation Expert Panel (PCEP) conducted a comprehensive review of clinical, laboratory, and computational evidence to determine the clinical function assignments for TPMT and NUDT15 star alleles. These genes are critical for the metabolism of thiopurines, which are widely used in the treatment of cancer and autoimmune disorders. Standardized allele function assignment is essential for predicting metabolizer phenotypes and pharmacogenetics-guided thiopurine dosing. The work presented here includes the first designation of decreased function alleles for both TPMT and NUDT15, reflecting new clinical data that demonstrate partial loss of enzymatic activity and reduced dose tolerance. The panel also reclassified several alleles previously assigned uncertain or unknown function. The functional assignments were informed by a standardized framework incorporating clinical data, such as thiopurine tolerance and toxicity, as well as in vitro protein activity, ex vivo enzymatic measurements, and in silico variant effect prediction tools. These updates enhance the precision of genotype-to-phenotype mapping and support more personalized thiopurine therapy across diverse patient populations.
Related Concept Videos
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Pharmacogenomics: Identification of New Drug Targets
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Metabolism: Overview
