TPMT*3B is assigned no function based on definitive evidence. Erythrocytes from individuals heterozygous for TPMT*3B exhibited intermediate enzymatic activity (9246020, 23585236, 33928426, 31005613, 12217596, 16691038), while erythrocytes from individuals heterozygous for TPMT*3B in combination with another no function allele exhibited low enzymatic activity (31005613). Patients carrying TPMT*3B alleles exhibited increased plasma concentrations of TGNs, increased DNA-incorporated thioguanine, decreased plasma concentrations of methylated metabolites, and tolerated lower doses of thiopurines (23585236, 29387964, 33928426, 33205673). In vitro studies demonstrate that TPMT.3B exhibited decreased protein expression, decreased protein stability, and enzymatic activity is decreased by 75-100% relative to TPMT.1 in yeast (9177237, 8644731) and mammalian (16220112, 18708949, 8561894) cells. TPMT.3B decreased protein expression is attributed to rapid degradation by the proteasome (16220112, 9177237) as well as TPMT.3B aggresome formation (15967990). Seven out of ten variant effect predictors tested by CPIC staff predict that the TPMT*3B-defining SNV, c.460G>A (p.A154T), impairs protein function.