NUDT15*6 is assigned no function based on moderate evidence. In vitro studies using a bacterial expression system found that NUDT15.6 exhibits decreased enzymatic activity using TGTP or TdGTP as substrates compared to NUDT15.1 (26878724, 33753169). Additionally, NUDT15.6 exhibits reduced protein thermostability compared to NUDT15.1 (26878724, 33753169). The destabilizing effects of c.55_56insGAGTCG (p.V18_V19insGV) were confirmed using an experimentally derived crystal structure of NUDT15.6 (33753169). NUDT15*1/*6 patients have been shown to tolerate lower doses of thiopurines (32221476, 34665987) and one patient genotyped NUDT15*3/*6 tolerated a significantly lower thiopurine dose (32873882) compared to NUDT15*1/*1 patients. Patients carrying a NUDT15*6 allele also exhibit increased incidence of adverse reactions and increased therapy interruption compared to NUDT15*1/*1 patients (28903549, 30728528, 37454061, 34665987, 36873097, 30806694). NUDT15*6 is characterized by the in-frame insertion c.55_56insGAGTCG (p.V18_V19insGV), which is predicted to impair protein function by CADD and PhD-SNPg