Table 1.

Genetic models of NADK and NADK2 and their phenotype.

Organism	Genotype	Phenotype	References
Saccharomyces cerevisiae	POS5, UTR1 and YEF1	●Triple mutant: Lethal ●POS5 mutant: Sensitive to oxidative stress, defects in iron homeostasis and amino acid biosynthesis ●UTR1 mutant: Retarded growth in iron deficient medium	[41,82]
Drosophila melanogaster	CG6145/NADK RNAi	Lower lipid storage in fat body, reduced mitochondrial mass and ROS (mitochondrial) level, mitochondrial cristae disruption	[43]
Mus musculus	C57BL/6N-Nadkem2(IMPC)Bay (Endonuclease-mediated mutation 2, Baylor College of Medicine)	●Homozygotes: Embryonic/preweaning lethality and complete penetrance ●Heterozygotes: Low total body fat amount ●Elevated lean body mass and bone mineral content	Nadk Mouse Gene Details | NAD kinase | International Mouse Phenotyping Consortium (mousephenotype.org) and Nadk < em2(IMPC)Bay > Endonuclease-mediated Allele Detail MGI Mouse (MGI:6257722) (jax.org)
	Chemically-induced NADK2 point mutations S326L and S330P	Severe neuromuscular disease Short lifespan	[83]
	NADK2-KO (C57BL/6NTac background)	●Increased serum concentrations of lysine and C10:2 carnitine ●Development of non-alcoholic fatty liver disease under atherogenic high fat diet ●Increased ROS in liver ●Fatty acid oxidation defects under starvation	[65]
Homo sapiens (Clinical studies)	a homozygous nonsense mutation, c.1018C > T (NM_001085411.1), in exon 10 of NADK2, which leads to a premature stop codon at position 340 (p.R340X) and start loss mutation in the NADK2 gene	Developmental defects, hyperlysinemia, severe mitochondrial dysfunction, metabolic defects, metabolic acidosis, CNS anomalies, ataxia, and incoordination	[66,75]
	Gain-of-function mutation: NADK(I90F)	Pro-tumor effects due to increased kinase activities and induction of NADP(H) level-dependent enhanced antioxidant defense response	[62]