Thiopurine S-methyltransferase (TPMT)

Thiopurine S-methyltransferase is a cytosolic enzyme encoded by the *TPMT* gene. It catalyzes the S-methylation of thiopurines—drugs such as azathioprine, 6‑mercaptopurine, and 6‑thioguanine—using S‑adenosyl-L‑methionine as a methyl donor. This reaction inactivates these drugs by converting them into non-toxic metabolites. The enzyme plays a critical role in determining individual responses to thiopurines; genetic polymorphisms can lead to reduced or absent enzymatic activity. Individuals with low or absent TPMT activity are at high risk for severe bone marrow suppression when treated with standard doses of thiopurines. Testing for TPMT activity or genotype is recommended prior to initiating therapy with these agents to avoid potentially life-threatening adverse effects such as myelosuppression and increased susceptibility to infection[1][2][3][5].

Other names

Thiopurine methyltransferaseS-adenosyl-L-methionine:thiopurine S-methyltransferaseTPMT_HUMAN

Catalyzes the S-methylation and inactivation of thiopurine drugs, reducing their cytotoxicity[1][3][5][6].