rs1800460

This is a missense variant in the TPMT gene.

Key Literature Trait Associations

Thiopurine Toxicity

TPMT*3B carries an A154T substitution and is usually found in cis with rs1142345 (Y240C) as TPMT*3A, the most common non-functional TPMT allele in Europeans (~5% allele frequency). The A154T change causes protein misfolding and degradation, abolishing TPMT enzymatic activity. CPIC recommends substantial dose reductions of azathioprine and mercaptopurine for carriers of non-functional TPMT alleles.

Allele G
OR
p
Candidate gene study

ClinVar annotation

Likely Benign★★★
6 submitters10 publications

Thiopurine S-methyltransferase deficiency; not provided; TPMT-related disorder

View on ClinVar →

Research that mentions this SNP (1)

Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment
ReviewJürgen Brockmöller et al.(2008)· European Journal of Clinical Pharmacology

This comprehensive review article traces the evolution of pharmacogenetics from single-gene analysis to whole-genome approaches. It discusses validated pharmacogenetic biomarkers with clinical impact including CYP2D6, CYP2C9, CYP2C19, TPMT, DPD, VKORC1, UGT1A1, and ADRB1/ADRB2, providing examples of how genetic variants affect drug metabolism and response. The paper emphasizes the importance of integrating pharmacogenetic information into clinical practice and drug development.

Traits studied:5-fluorouracil toxicityanticoagulant responseantidepressant responseasthmaatrial fibrillationbeta-blocker responsebreast cancerclopidogrel responsecolorectal cancerdrug metabolismdrug responsehypertensionirinotecan toxicitylung cancerproton pump inhibitor metabolismrheumatoid arthritisthiopurine toxicitythrombosis risktype 2 diabeteswarfarin sensitivity

Gene information from NCBI Gene. Variant classifications from ClinVar.

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