TPMT*6 is assigned no function based on moderate evidence. Erythrocytes from an individual genotyped TPMT*1/*6 exhibited intermediate enzymatic activity toward 6-MP (9246020). An individual carrying TPMT*6 experienced severe leukopenia following standard azathioprine dosing (39696474). In vitro studies using mammalian cell expression systems demonstrate that TPMT.6 protein expression is substantially decreased compared to TPMT.1 (16220112). Additionally, TPMT.6 exhibited reduced substrate affinity for 6-TG, reduced clearance of 6-TG and 6-MP, and enzymatic activity was decreased by 60-80% in vitro (16220112, 18708949). Recombinant TPMT.6 expressed and purified from bacterial cells exhibited decreased protein stability, however activity was unaffected when using 6-MP as a substrate (30023734). Despite conflicting in vitro evidence, the experts agreed to assign no function based on the available clinical data. Five out of ten variant effect predictors tested by CPIC staff predict that the TPMT*6-defining SNV, c.539A>T (p.Y180F), impairs protein function.