rs116855232

This is a missense variant in the NUDT15 gene.

Key Literature Trait Associations

Thiopurine Toxicity

NUDT15*3 (R139C) abolishes NUDT15 nucleotide diphosphatase activity, which normally degrades thiopurine active metabolites. This variant is critical in East Asian populations where TPMT variants are rare but NUDT15*3 frequency is 7-10%. Homozygous carriers have extreme sensitivity to azathioprine and mercaptopurine, with near-certain severe myelosuppression at standard doses. CPIC recommends combined TPMT + NUDT15 genotyping before initiating thiopurine therapy.

Relling MV et al. “Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing.” Clinical Pharmacology and Therapeutics 89(3):387-391 (2011)
Allele T
OR —
p —
Candidate gene study
▶

GWAS Catalog Trait Associations (1)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

trait in response to thiopurine, Decreased total leukocyte count

Yang SK et al. “A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia.” Nature Genetics 46(9):1017-20 (2014)
Allele T
OR 35.63
p 5.0e-94
N 340
Small GWAS
East Asian
Kim HS et al. “A coding variant in FTO confers susceptibility to thiopurine-induced leukopenia in East Asian patients with IBD.” Gut 66(11):1926-1935 (2017)
Allele T
OR 3.90
p 1.0e-22
N 267
Small GWAS
East Asian
▶

ClinVar annotation

Drug Response★★★★
3 submitters32 publications

Thiopurines, poor metabolism of, 2; mercaptopurine response - Dosage; azathioprine response - Toxicity; NUDT15-related disorder

View on ClinVar →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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