ASS1 Gene: Argininosuccinate Synthase 1 - Function, Mutations, and Disease

The ASS1 gene encodes argininosuccinate synthase 1, a cytosolic enzyme that catalyzes the condensation of citrulline and aspartate to form argininosuccinate, a key step in the urea cycle for ammonia detoxification and in arginine biosynthesis. The enzyme also plays a role in nitric oxide production by providing arginine as a substrate for nitric oxide synthases. Mutations in ASS1 cause citrullinemia type I, an autosomal recessive urea cycle disorder.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Urea cycle (Reactome: R-HSA-70635)

• Arginine and proline metabolism (KEGG: hsa00330)

• Nitric oxide signaling (Reactome: R-HSA-202131)

Argininosuccinate synthase 1 (ASS1) is a 412-amino acid homotetrameric enzyme that catalyzes the ATP-dependent condensation of citrulline and aspartate to form argininosuccinate. It is the rate-limiting enzyme of the urea cycle in the liver and is also expressed in extrahepatic tissues where it supplies arginine for nitric oxide production. The protein contains a conserved N-terminal domain and a C-terminal catalytic domain. Defects in ASS1 cause citrullinemia type I, characterized by hyperammonemia and neurotoxicity.