TPMT*12 is assigned uncertain function based on inadequate evidence. Patients genotyped TPMT*1/*12 exhibited TPMT enzymatic activity that is comparable to TPMT*1/*1 patients and there was no difference in 6-MP dose intensity between TPMT*1/*12 and TPMT*1/*1 patients (27564568). In vitro studies using mammalian cell expression systems found that TPMT.12 protein expression is decreased, enzymatic activity is decreased >50%, and TPMT.12 exhibited decreased affinity for 6-TG and SAM compared to TPMT.1 (16220112, 18708949). TPMT.12 also exhibited an increased rate of protein degradation compared to TPMT.1 (16220112). TPMT.12 enzymatic activity is decreased by 75% compared to TPMT.1 in yeast cells (13679074). An additional in vitro study found that TPMT.12 protein abundance in mammalian cells was comparable to TPMT.1 (29785012). Four out of ten variant effect predictors tested by CPIC staff predict that the TPMT*12-defining SNV, c.374C>T (p.S125L), impairs protein function.