Comprehensive overview of the global pharmacogenetic and functional variability in NUDT15

NUDT15 (alleles *2 to *8, loss-of-function variants)

NUDT15 (nudix hydrolase 15) → hydrolyzes active thioguanine-triphosphate metabolites → protection against DNA incorporation; LOF variants → accumulation → myelotoxicity; CPIC Level A especially for Asian populations (*3 frequency ~10-15%)

Comprehensive review of global pharmacogenetic and functional variability in NUDT15, a key gene in thiopurine metabolism. The review covers alleles *2 to *8, their allele frequencies in world populations, functional impacts (enzymatic activity), and clinical implications. Allele *3 (p.Arg139Cys) is the most common and most deleterious, present in 10-15% of East Asians vs 0.5-1% of Europeans. NUDT15 genotyping is CPIC Level A for thiopurines.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

NUDT15 is underused in routine practice outside pediatric hematological malignancies, even though it is CPIC Level A for all thiopurine indications (IBD, transplants, leukemias). The review provides an allele database usable by laboratory physicians implementing PGx panels in precision medicine.

comprehensive global NUDT15 review +2; thiopurine CPIC Level A +2; significant ethnic disparities (Asian populations) +2; Human Genomics +1