NMNAT1 Gene: Function, Mutations, and Associated Diseases | Biomedical Resource

The NMNAT1 gene encodes nicotinamide nucleotide adenylyltransferase 1, a key enzyme in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). This enzyme catalyzes the final step of NAD+ synthesis, transferring an adenylyl group from ATP to nicotinamide mononucleotide (NMN) to form NAD+. NMNAT1 is ubiquitously expressed but shows high activity in the retina, where it plays a critical role in photoreceptor survival and function. Mutations in NMNAT1 are associated with Leber congenital amaurosis type 9 (LCA9), a severe retinal dystrophy presenting in infancy. The enzyme is also implicated in axonal protection and cellular stress responses.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• NAD+ biosynthesis pathway (nicotinamide adenine dinucleotide metabolism)

• Nicotinate and nicotinamide metabolism (KEGG:00760)

• Axonal protection pathway (Wallerian degeneration)

NMNAT1 is a 279-amino acid protein with a molecular weight of approximately 32 kDa. It belongs to the nucleotidyltransferase family and contains a conserved motif for ATP and NMN binding. The enzyme is localized in the nucleus and cytoplasm, with high expression in the retina. It catalyzes the formation of NAD+ from ATP and NMN, a rate-limiting step in NAD+ biosynthesis. NMNAT1 also has chaperone-like activity and can protect axons from degeneration. Mutations that reduce its enzymatic activity lead to photoreceptor cell death, underlying LCA9.