TPMT*8 is assigned decreased function based on moderate evidence. Clinically, erythrocytes from individuals genotyped TPMT*1/*8 exhibited intermediate enzymatic activity (9931346, 27564568, 39182670). Erythrocytes from individuals genotyped TPMT*8/*33 or TPMT*8/*8 also exhibited intermediate enzymatic activity (33118454), while individuals genotyped TPMT*3A/*8 or TPMT *3C/*8 exhibited decreased activity by 16% and 42%, respectively, relative to normal metabolizers. Despite these observations, thiopurine dose intensity is not significantly different between individuals genotyped TPMT*1/*8 and TPMT*1/*1 (27564568, 29785012, 34412101). In vitro studies in mammalian cell systems found that TPMT.8 protein expression is comparable (16220112) or increased (18708949) compared to TPMT.1. These results are corroborated by a study which found TPMT.8 protein abundance is comparable to TPMT.1 (29785012). Enzyme kinetic analysis indicates that TPMT.8 activity is decreased by 28% relative to TPMT.1 (16220112), while another study found that TPMT.8 enzymatic activity is not statistically different from TPMT.1 and that TPMT.8 has increased affinity for 6-TG (18708949). Recombinant TPMT.8 expressed and purified from bacterial cells exhibited identical biophysical characteristics to TPMT.1 (30023734). Ten out of ten variant effect predictors tested by CPIC staff predict that the TPMT*8-defining SNV, c.644G>A (p.R215H), does not impair protein function. Despite conflicting in vitro evidence, the experts agreed to assign decreased function based on the available clinical data.