TPMT
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2BZG, 2H11
Identifiers
Aliases	TPMT, entrez:7172, TPMTD, thiopurine S-methyltransferase
External IDs	OMIM: 187680 MGI: 98812 HomoloGene: 313 GeneCards: TPMT
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p22.3 Start 18,128,311 bp[1] End 18,155,077 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13 A5|13 24.5 cM Start 47,175,958 bp[2] End 47,198,213 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in rectum left lobe of thyroid gland right lobe of thyroid gland internal globus pallidus right lobe of liver kidney thoracic diaphragm monocyte kidney tubule islet of Langerhans Top expressed in proximal tubule kidney left lobe of liver secondary oocyte yolk sac cumulus cell epithelium of stomach medial vestibular nucleus Region I of hippocampus proper subiculum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function S-adenosylmethionine-dependent methyltransferase activity transferase activity methyltransferase activity thiopurine S-methyltransferase activity S-adenosyl-L-methionine binding Cellular component cytosol cytoplasm Biological process nucleobase-containing compound metabolic process methylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7172 22017 Ensembl ENSG00000137364 ENSMUSG00000021376 UniProt P51580 O55060 RefSeq (mRNA) NM_000367 NM_001346817 NM_001346818 NM_016785 RefSeq (protein) NP_000358 NP_001333746 NP_001333747 NP_058065 Location (UCSC) Chr 6: 18.13 – 18.16 Mb Chr 13: 47.18 – 47.2 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Thiopurine methyltransferase or thiopurine S-methyltransferase (TPMT) is an enzyme that in humans is encoded by the TPMT gene. A pseudogene for this locus is located on chromosome 18q.^[5][6]

Function

Thiopurine methyltransferase methylates thiopurine compounds. The methyl donor is S-adenosyl-L-methionine, which is converted to S-adenosyl-L-homocysteine. This enzyme metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct.^[5][7]

Clinical significance

Thiopurine drugs such as 6-mercaptopurine are used as chemotherapeutic agents and immunosuppressive drugs. Genetic polymorphisms that affect this enzyme's activity are correlated with variations in sensitivity and toxicity to such drugs. About 1/300 individual is deficient for the enzyme.^[5]

Pharmacology

TPMT is best known for its role in the metabolism of the thiopurine drugs such as azathioprine, 6-mercaptopurine and 6-thioguanine. TPMT catalyzes the S-methylation of thiopurine drugs. Defects in the TPMT gene leads to decreased methylation and decreased inactivation of 6MP leading to enhanced bone marrow toxicity which may cause myelosuppression, anemia, bleeding tendency, leukopenia & infection.^[8][9][10] Allopurinol inhibits thiopurine S-methyltransferase, which can increase the utility of 6-MP.^[11]

Diagnostic use

Measurement of TPMT activity is encouraged prior to commencing the treatment of patients with thiopurine drugs such as azathioprine, 6-mercaptopurine and 6-thioguanine. 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.^[9][12]

Genetic variants of TPMT have also been associated with cisplatin-induced ototoxicity in children.^[13] TPMT is now listed as a pharmacogenomic biomarker for adverse drug reactions to cisplatin by the FDA.^[14]