NAGS Gene: N-Acetylglutamate Synthase - Function, Mutations, and Associated Diseases

The NAGS gene encodes N-acetylglutamate synthase (NAGS), a mitochondrial enzyme that catalyzes the formation of N-acetylglutamate (NAG) from glutamate and acetyl-CoA. NAG is an essential allosteric activator of carbamoyl phosphate synthetase I (CPS1), the first and rate-limiting enzyme of the urea cycle. NAGS deficiency leads to hyperammonemia and is inherited in an autosomal recessive pattern.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Urea cycle and metabolism of arginine

• proline

• glutamate

• aspartate and asparagine (KEGG: map00220)

• Metabolism of amino acids and derivatives (Reactome: R-HSA-71291)

N-acetylglutamate synthase (NAGS) is a mitochondrial enzyme composed of 534 amino acids. It catalyzes the formation of N-acetylglutamate (NAG), an essential allosteric activator of carbamoyl phosphate synthetase I (CPS1). The enzyme is primarily expressed in the liver and small intestine. Mutations in NAGS cause NAGS deficiency, a rare autosomal recessive disorder characterized by hyperammonemia, lethargy, and coma. Treatment includes N-carbamylglutamate, a synthetic analog of NAG.