NUDIX-Type Motif 15 (NUDT15)

NUDT15 is an enzyme that helps to break down thiopurines in the body. Thiopurines include three medications: 6-mercaptopurine (6-MP), 6-thioguanine (6-TG) and azathioprine. 6-MP and 6-TG are often used to treat leukemia or lymphoma. Azathioprine is used often to treat non-malignant immunologic disorders. Like many drugs, their effectiveness and side effects can vary from person to person. One of the reasons why this difference occurs is because each person’s ability to metabolize thiopurines is different based on variations in the NUDT15 gene.

Patients who are tested for NUDT15 can be classified into one of three possible groups of enzyme function. Knowing the NUDT15 enzyme function that an individual has can help clinicians use different starting doses of thiopurines to attempt to decrease side effects (due to low blood counts). Thiopurine dosing is also affected by the TPMT genotype test result.

Priority genotypes

• Poor metabolizers — These patients have little to no NUDT15 enzyme function. Approximately 2% of people of Asian descent are NUDT15 poor metabolizers while fewer than 1% of individuals of European, Hispanic, or African descent are NUDT15 poor metabolizers.
  • Patients should receive substantially lower doses than normal to minimize the side effect of low blood counts.

Routine genotype

Most medicines affected by NUDT15 do not need to be adjusted based on the following NUDT15 phenotypes:

• Normal metabolizers — These patients have normal NUDT15 enzyme function. Approximately 78% of people of Asian descent are NUDT15 normal metabolizers. About 90% of people of Hispanic descent and at least 99% of people of European or African descent are NUDT15 normal metabolizers. No change in starting thiopurine dose is recommended based on the NUDT15 phenotype.
• Intermediate metabolizers — These patients have more NUDT15 enzyme function than poor metabolizers, but less NUDT15 enzyme function than normal metabolizers. Approximately 20% of people of Asian descent are NUDT15 intermediate metabolizers while only 10% of individuals of Hispanic descent and 0-1% of people of European or African descent are NUDT15 intermediate metabolizers. Based on current evidence, no change in the thiopurine dose is recommended. However, as we learn more about NUDT15 enzyme function and thiopurines, these patients may require reduced doses of thiopurine medications.