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NUDT15 enzyme

The enzyme NUDT15 (full name: nudixhydrolase 15) plays a role in breaking down drugs from the thiopurine group. The enzyme NUDT15 is involved in the metabolisation of, amongst other things, the anti-tumour drugs mercaptopurine and thioguanine, as well as immunosuppressants like azathioprine. These drugs are used in the treatment of cancer and Crohn’s disease, in the event of organ transplants and to treat inflammatory diseases such as rheumatoid arthritis and inflammation of the bowel, liver or skin, for example.

Genetic predisposition
The activity of the enzyme NUDT15 varies from one individual to another. This variation can be partly explained by genetic variations. In people with NUDT15 deficiency (reduced activity) drugs from the thiopurine group can build up in the body and cause side effects. Reduced activity of the enzyme NUDT15 is found in roughly 20-25% of the Asian population; the enzyme is completely inactive in around 1% of Asians. Mutations are much rarer in Europeans, around 1.5% of whom exhibit reduced activity.
When a genotype is determined variations in the NUDT15 gene are indicated by two so-called alleles. Each allele has a name consisting of an asterisk (*) and a number. An example of a possible NUDT15 genotype is NUDT15*1/*3.
At iGene we determine the following variants (alleles) of the NUDT15 gene:
NUDT15*3, NUDT15*4, NUDT15*5 and other (classified as NUDT15*1). The mutation that distinguishes NUDT152 from NUDT153 cannot currently be determined, which means that NUDT153 is the sum of NUDT152 and NUDT15*3. This has no implications from a functional perspective.

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