• nucleobase, nucleoside, nucleotide and nucleic acid metabolic process • metabolic process
RNA expression pattern
More reference expression data
NM_000367 (mRNA) NP_000358 (protein)
NM_016785 (mRNA) NP_058065 (protein)
Chr 6: 18.24 - 18.26 Mb
Chr 13: 47.04 - 47.05 Mb
Thiopurine methyltransferase or thiopurine S-methyltransferase (TPMT) is an enzyme (EC 220.127.116.11) that methylates thiopurine compounds. The methyl donor is S-adenosyl-L-methionine, which is converted to S-adenosyl-L-homocysteine.
This gene encodes the enzyme that metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct. Thiopurine drugs such as 6-mercaptopurine are used as chemotherapeutic agents. Genetic polymorphisms that affect this enzymatic activity are correlated with variations in sensitivity and toxicity to such drugs within individuals. A pseudogene for this locus is located on chromosome 18q.
TPMT is best known for its role in the metabolism of the drugs 6-mercaptopurine, azathioprine and 6-thioguanine. TPMT catalyzes the S-methylation of thiopurine drugs, including 6MP. Defects in the TPMT gene leads to decreased methylation and decreased inactivation of 6MP leading to enhanced bone marrow toxicity. 
Measurement of TPMT activity is encouraged prior to commencing azathioprine or 6-mercaptopurine, as patients with low activity (10% prevalence) or especially absent activity (prevalence 0.3%) are at a heightened risk of drug-induced bone marrow toxicity due to accumulation of the unmetabolised drug. Reuther et al found that about 5% of all thiopurine therapies will fail due to toxicity. This intolerant group could be anticipated by routine measurement of TPMT activity. There appears to be a great deal of variation in TPMT mutation, with ethnic differences in mutation types accounting for variable responses to 6MP.
^ Pharmacogenomics in Drug-Metabolizing Enzymes Catalyzing Anticancer Drugs for Personalized Cancer Chemotherapy. Ken-ichi Fujita,; Yasutsuna Sasaki, Current Drug Metabolism, Volume 8, Number 6, August 2007 , pp. 554-562(9)
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