Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1)

Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) is a ubiquitously expressed nuclear enzyme responsible for the final, rate-limiting step in nicotinamide adenine dinucleotide (NAD+) biosynthesis, catalyzing the condensation of nicotinamide mononucleotide (NMN) or nicotinic acid mononucleotide (NaMN) with ATP to produce NAD+ or NaAD[1][2][3][4]. NMNAT1 maintains the nuclear pool of NAD+, supporting critical DNA repair (via PARP1), deacetylation (via SIRT1), chromatin remodeling, and cell survival[2][3][4]. It is neuroprotective, important for axonal integrity, and required for normal retinal development and function—where its deficiency causes early-onset, severe retinal degeneration (e.g., Leber congenital amaurosis)[4][5]. NMNAT1 is also associated with certain cancers, where its activity helps mediate resistance to chemotherapy and influences tumor cell survival[1][2][3]. Its essential cellular roles, and links to disease, highlight NMNAT1 as a therapeutic target in oncology and neurodegeneration, though safety concerns exist due to its basal importance in many cell types[1][5].

Other names

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1NMN adenylyltransferase 1NaMN adenylyltransferase 1PNAT1Nicotinamide-nucleotide adenylyltransferase 1Nicotinate-nucleotide adenylyltransferase 1Pyridine nucleotide adenylyltransferase 1Leber congenital amaurosis 9 (LCA9)SHILCA

Catalytic inhibition (blocking NAD+ synthesis for cancer therapy)[1][3]; Modulation of NAD+ pool influencing DNA repair, Sirtuin and PARP1 activities[2][3]