NMNAT3
Nicotinamide mononucleotide adenylyltransferase 3 is an enzyme that in humans is encoded by the NMNAT3 gene.
NMNAT3 is the third of three protein isoforms of nicotinamide-nucleotide adenylyltransferase found in humans. As with the other NMNATs, NMNAT3 is an enzyme that catalyzes nicotinamide adenine dinucleotide synthesis. NMNAT3 levels are highest in liver, heart, skeletal muscle, and erythrocytes.
NMNAT3 is localized in mitochondria or cytoplasm, depending upon the cell type. Knockdown of NMNAT3 gene expression in cell culture strongly reduces mitochondrial function. NMNAT3 is essential for maintaining NAD in red blood cells.
The catechin epigallocatechin gallate found in tea can activate NMNAT3 by more than 40%.
Until January 2026, mutations in the NMNAT3 gene had not been associated with any known human disease, although it had been discovered that NMNAT3 deficiency causes hemolytic anemia in mice. In January 2026, researchers at the University Medical Center Utrecht in Utrecht, The Netherlands, were the first to link NMNAT3 deficiency to disease in vivo, in a patient with unexplained hereditary hemolytic anemia. The patient was successfully treated by supplementing NAD.