Gene NUDT15

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Also known as

nudix hydrolase 15, MTH2, MutT homolog 2

Overview

NUDT15 (Nudix Hydrolase 15) encodes an enzyme that dephosphorylates thiopurine nucleotides, playing a critical role in the metabolism of thiopurine drugs like azathioprine, mercaptopurine, and thioguanine. By inactivating these active metabolites, NUDT15 helps regulate thiopurine cytotoxicity. The enzyme is important for protecting cells from excessive thiopurine-induced damage.

Variants in NUDT15, particularly R139C (rs116855232), significantly reduce enzyme activity and are associated with severe thiopurine-induced myelosuppression. This variant is common in East Asian populations (approximately 10% frequency) and is now included in pharmacogenomic guidelines for thiopurine dosing. Testing NUDT15 before starting thiopurine therapy can prevent life-threatening bone marrow toxicity.

Understanding your NUDT15 genetic status is essential for safe thiopurine therapy. This information is critically important for patients being considered for thiopurine drugs used to treat autoimmune diseases, inflammatory bowel disease, and certain leukemias.

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