NADK2: Mitochondrial NAD Kinase 2
Key regulator of mitochondrial NADP(H) homeostasis and lipid metabolism
Gene Information Card
| Symbol | NADK2 |
|---|---|
| Full Name | NAD Kinase 2, Mitochondrial |
| Gene Type | Protein coding |
| Chromosomal Location | 5p13.2 |
| NCBI Gene ID | 133686 ncbi.nlm.nih.gov/gene/133686 |
| Ensembl ID | ENSG00000164199 |
| UniProt ID | Q4G0N4 |
| OMIM ID | 615788 |
| HGNC ID | 26404 |
| Aliases | NADK2, dJ283E3.1, MNADK, NADK2 |
Description
NADK2 encodes mitochondrial NAD kinase 2, which catalyzes the phosphorylation of NAD+ to NADP+ using ATP as a phosphate donor. This enzyme is essential for maintaining mitochondrial NADP(H) pools, supporting reductive biosynthesis, antioxidant defense, and lipid metabolism. Mutations in NADK2 cause a rare autosomal recessive disorder characterized by mitochondrial dysfunction, lipid storage, and neurological impairment.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| NADK2 deficiency (mitochondrial NAD kinase deficiency) | Loss-of-function mutations impair NADP+ synthesis, disrupting mitochondrial redox balance and lipid metabolism | OMIM #615788; ClinVar pathogenic variants |
| Progressive encephalopathy with or without lipid storage | Defective NADPH production leads to impaired fatty acid oxidation and oxidative stress | Case reports in ClinVar and PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Heart | 6.1 | Low |
| Brain | 4.7 | Low |
| Skeletal Muscle | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 10.1 | Hepatocyte model |
| HEK293 | 7.8 | Embryonic kidney |
| SH-SY5Y | 5.4 | Neuroblastoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.545G>A (p.Arg182Gln) | Missense | Rare | Loss of catalytic activity |
| c.862C>T (p.Arg288Trp) | Missense | Rare | Impaired protein stability |
| c.1A>G (p.Met1Val) | Start loss | Rare | No protein synthesis |
Mutation functional classification
Loss of Function (LOF)
Most reported NADK2 mutations are loss-of-function, reducing or abolishing NAD kinase activity, leading to mitochondrial NADP+ depletion.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • NAD+ kinase activity (GO:0003951) | • mitochondrion (GO:0005739) |
| • NADP biosynthetic process (GO:0006741) | • metabolic process (GO:0008152) |
| • transferase activity (GO:0016740) |
Pathways
• NAD+ kinase pathway (Reactome: R-HSA-196807)
• Nicotinate and nicotinamide metabolism (KEGG: hsa00760)
• Mitochondrial NADP(H) homeostasis
Protein Summary
NADK2 is a 442-amino acid mitochondrial protein that phosphorylates NAD+ to NADP+ using ATP. It contains a conserved NAD kinase domain and a mitochondrial targeting sequence. The enzyme is critical for maintaining the mitochondrial NADP(H) pool, which supports glutathione reduction, lipid biosynthesis, and detoxification of reactive oxygen species. Deficiency leads to mitochondrial dysfunction, lipid accumulation, and neurological symptoms.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NADK2 Knockout HEK293 Cell Line | EDJ-KQ9321 | Human | 133686 | Details Get a Quote |
| NADK2 Knockout A-549 Cell Line | EDJ-KQ35946 | Human | 133686 | Details Get a Quote |
| NADK2 Knockout HeLa Cell Line | EDJ-KQ35948 | Human | 133686 | Details Get a Quote |
| NADK2 Knockout HCT 116 Cell Line | EDJ-KQ34703 | Human | 133686 | Details Get a Quote |
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