NAT2*6 is assigned decreased function based on definitive evidence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the NAT2*6 allele as "slow" . Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". NAT2*6 is characterized by the core SNVs c.590G>A (p.R197Q) and c.803G>A (p.R268K). c.803G>A defines NAT2*4, formerly considered the reference allele, which has repeatedly exhibited increased function in vivo and in vitro. The functional SNV c.590G>A (p.R197Q) has been studied for more than 25 years and has shown decreased N-acetylation activity in numerous clinical and in vitro studies using various substrates. Clinical studies have demonstrated that individuals homozygous for NAT2*6 or heterozygous for NAT2*6 in combination with another decreased function allele exhibit decreased acetylation activity toward caffeine metabolites (8102597, 7668286, 9891107, 10744128, 20801937, 22970273, 24221535, 28653770), isoniazid (2376572, 9154882, 9321764, 19336229, 35928262), sulphonamides (1872889, 15032315, 16570187, 18167504, 21946899), and dapsone (10762005). Individuals homozygous for NAT2*6 or heterozygous for NAT2*6 in combination with another decreased function allele exhibit increased hydralazine exposure (24702251, 31257615). Seven out of nine variant effect predictors tested by CPIC staff predict that c.590G>A (p.R197Q) impairs protein function. In vitro studies have shown that NAT2*6 exhibits decreased thermostability and decreased protein expression (11337936, 17434923, 8081359) as well as decreased acetylation toward various substrates (7669073, 33815485). Several studies indicate the existence of an ultra-slow acetylator phenotype in individuals homozygous for the NAT2*6 allele compared with other NAT2 decreased function alleles (29018032, 28653770, 24221535, 33815485, 7668286, 22970273, 28752039, 16570187, 28516247).