NADK2 (NAD kinase 2, mitochondrial)

Gene

• Entrez ID: 133686
• Gene name: NAD kinase 2, mitochondrial
• Gene symbol: NADK2
• Synonyms (NCBI Gene): C5orf33, DECRD, MNADK, NADKD1
• Chromosome: 5
• Chromosome location: 5p13.2
• Summary: This gene encodes a mitochondrial kinase that catalyzes the phosphorylation of NAD to yield NADP. Mutations in this gene result in 2,4-dienoyl-CoA reductase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs190440332	T>C	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant, 5 prime UTR variant
rs587777772	G>A	Pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT041747	hsa-miR-484	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0003951	Function	NAD+ kinase activity	IBA
GO:0003951	Function	NAD+ kinase activity	IDA	23212377
GO:0003951	Function	NAD+ kinase activity	IEA
GO:0005524	Function	ATP binding	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	23212377
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006741	Process	NADP+ biosynthetic process	IEA
GO:0016301	Function	Kinase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016773	Function	Phosphotransferase activity, alcohol group as acceptor	IEA
GO:0019674	Process	NAD+ metabolic process	IBA
GO:0019674	Process	NAD+ metabolic process	IDA	23212377
GO:0019674	Process	NAD+ metabolic process	IEA
GO:0042803	Function	Protein homodimerization activity	IDA	23212377

Other IDs

• MIM: 615787
• HGNC: 26404
• e!Ensembl: ENSG00000152620

Protein

• UniProt ID: Q4G0N4
• Protein name: NAD kinase 2, mitochondrial (EC 2.7.1.23) (Mitochondrial NAD kinase) (NAD kinase domain-containing protein 1, mitochondrial)
• Protein function: Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor. Also has weak NADH kinase activity in vitro; however NADH kinase activity is much weaker than the NAD(+
• PDB: 7N29, 7R4J, 7R4K, 7R4L, 7R4M
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01513	NAD_kinase	70 → 324	ATP-NAD kinase	Family

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:23212377}.
• Sequence:

  MTCYRGFLLGSCCRVAGGRAAALRGPGAGGPAARPRLGGDGGGRRHLGQGQPRELAGCGS
  RADGGFRPSRVVVVAKTTRYEFEQQRYRYAELSEEDLKQLLALKGSSYSGLLERHHIHTK
  NVEHIIDSLRNEGIEVRLVKRREYDEETVRWADAVIAAGGDGTMLLAASKVLDRLKPVIG
  VNTDPERSEGHLCLPVRYTHSFPEALQKFYRGEFRWLWRQRIRLYLEGTGINPVPVDLHE
  QQLSLNQHNRALNIERAHDERSEASGPQLLPVRALNEVFIGESLSSRASYYEISVDDGPW
  EKQKSSGLNLCTGTGSKAWSFNINRVATQAVEDVLNIAKRQGNLSLPLNRELVEKVTNEY
  NESLLYSPEEPKILFSIREPIANRVFSSSRQRCFSSKVCVRSRCWDACMVVDGGTSFEFN
  DGAIASMMINKEDELRTVLLEQ

• Sequence length: 442

Pathways

KEGG:

Nicotinate and nicotinamide metabolism
Metabolic pathways
Biosynthesis of cofactors

Reactome:

Nicotinate metabolism

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Progressive encephalopathy with leukodystrophy due to DECR deficiency	Likely pathogenic; Pathogenic	rs587777772, rs1746670652	RCV000144251 RCV001030439	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
2,4-DIENOYL-COA REDUCTASE DEFICIENCY	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bardet-Biedl syndrome 10	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MULTINODULAR GOITER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NADK2-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
2,4-Dienoyl-CoA Reductase Deficiency	2,4-dienoyl-CoA reductase deficiency	CLINGEN_DG	23212377, 24847004, 27940755, 28923496		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
2,4-Dienoyl-CoA Reductase Deficiency	2,4-dienoyl-CoA reductase deficiency	ORPHANET_DG	24847004		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
2,4-Dienoyl-CoA Reductase Deficiency	2,4-dienoyl-CoA reductase deficiency	GENOMICS_ENGLAND_DG	27940755, 29388319		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
2,4-Dienoyl-CoA Reductase Deficiency	2,4-dienoyl-CoA reductase deficiency	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Central visual impairment	Central Visual Impairment	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Choreoathetosis	Choreoathetosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	BEFREE	28923496		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperlysinemias	Hyperlysinemia	BEFREE	24847004, 29388319		★☆☆☆☆ Found in Text Mining only
Hyperlysinemias	Hyperlysinemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	BEFREE	27940755		★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leukodystrophy	Leukodystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neonatal Hypotonia	Hypotonia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	28923496		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pancreatitis	Pancreatitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Progressive encephalopathy with leukodystrophy due to DECR deficiency	Progressive Encephalopathy With Leukodystrophy	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Quadriplegia	Quadriplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Apnea, Central	Sleep Apnea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	BEFREE	28923496		★☆☆☆☆ Found in Text Mining only