NAT2 Gene - N-Acetyltransferase 2: Function, Variants, and Clinical Significance

The NAT2 gene encodes N-acetyltransferase 2, a phase II drug-metabolizing enzyme that catalyzes the N-acetylation and O-acetylation of arylamine and hydrazine substrates. This enzyme is primarily expressed in the liver and gut, and its activity is highly polymorphic, leading to distinct acetylator phenotypes (slow, intermediate, rapid) that influence drug response and toxicity. NAT2 is involved in the metabolism of numerous drugs, including isoniazid, sulfamethoxazole, procainamide, and dapsone, as well as carcinogenic arylamines found in tobacco smoke and diet.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Drug metabolism – other enzymes (KEGG: hsa00983)

• Metabolism of xenobiotics by cytochrome P450 (KEGG: hsa00980)

• Phase II conjugation (Reactome: R-HSA-156588)

N-acetyltransferase 2 (NAT2) is a 290-amino acid cytosolic enzyme that transfers an acetyl group from acetyl-CoA to arylamine and hydrazine substrates. The protein is highly polymorphic, with over 50 known alleles. The most common slow acetylator variants (NAT2*5, *6, *7) result in decreased protein stability or catalytic activity. NAT2 plays a critical role in the detoxification and activation of drugs and carcinogens, making it a key pharmacogenomic marker.