NADK2 Gene (Protein Coding)

NAD Kinase 2, Mitochondrial

GC05M036194
GIFtS:
38
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 2014] See more...

Aliases for NADK2 Gene

Aliases for NADK2 Gene

  • NAD Kinase 2, Mitochondrial 2 3 4 5
  • MNADK 2 3 4
  • NAD Kinase Domain-Containing Protein 1, Mitochondrial 3 4
  • Mitochondrial NAD Kinase 2 4
  • C5orf33 3 4
  • NADKD1 3 4
  • Chromosome 5 Open Reading Frame 33 2
  • NAD Kinase Domain Containing 1 2
  • EC 2.7.1.23 4
  • FLJ30596 2
  • DECRD 3
  • NADK2 5

External Ids for NADK2 Gene

Previous HGNC Symbols for NADK2 Gene

  • C5orf33
  • NADKD1

Summaries for NADK2 Gene

Entrez Gene Summary for NADK2 Gene

  • 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 2014]

GeneCards Summary for NADK2 Gene

NADK2 (NAD Kinase 2, Mitochondrial) is a Protein Coding gene. Diseases associated with NADK2 include 2,4-Dienoyl-Coa Reductase Deficiency and Hyperlysinemia, Type I. Among its related pathways are Metabolism and NAD metabolism. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and NAD+ kinase activity.

UniProtKB/Swiss-Prot Summary for NADK2 Gene

  • 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(+) kinase activity and may not be relevant in vivo.

Additional gene information for NADK2 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NADK2 Gene

Genomics for NADK2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for NADK2 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH05J036238 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 607.8 +0.8 823 5.1 RNF2 SP1 CREB1 GATAD2A CTCF HNRNPL PRDM10 REST ZNF629 TFE3 NADK2 NIPBL OFD1P17 RANBP3L NADK2-AS1 SLC1A3 SKP2
GH05J036213 Promoter 0.3 EPDnew 611.2 +29.1 29065 0.1 NADK2 RANBP3L RNU6-1305P lnc-SKP2-2 lnc-RANBP3L-2 piR-52879-014 SKP2
GH05J036225 Promoter 0.3 EPDnew 600.4 +16.7 16719 0.1 NADK2 RNU6-1305P NADK2-AS1 SKP2
GH05J036691 Promoter/Enhancer 1.6 FANTOM5 ENCODE CraniofacialAtlas dbSUPER 11.3 -450.1 -450114 2 CTCF LARP7 ZNF143 REST RAD21 ZNF501 TRIM22 EZH2 TCF7 CEBPB ENSG00000250155 SLC1A3 NADK2 RANBP3L NIPBL piR-35674-411 LOC107986413
GH05J036682 Promoter/Enhancer 1 Ensembl ENCODE dbSUPER 11.3 -441.7 -441715 2.8 CEBPB RCOR1 POLR2A CHD2 MYC MAX GATA2 ENSG00000250155 SLC1A3 NADK2 RANBP3L LOC107986413 piR-35674-411 NIPBL
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NADK2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NADK2

Genomic Locations for NADK2 Gene

Genomic Locations for NADK2 Gene
chr5:36,192,589-36,242,279
(GRCh38/hg38)
Size:
49,691 bases
Orientation:
Minus strand
chr5:36,192,694-36,242,381
(GRCh37/hg19)
Size:
49,688 bases
Orientation:
Minus strand

Genomic View for NADK2 Gene

Genes around NADK2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NADK2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NADK2 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for NADK2 Gene

Proteins for NADK2 Gene

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  • Protein details for NADK2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q4G0N4-NAKD2_HUMAN
    Recommended name:
    NAD kinase 2, mitochondrial
    Protein Accession:
    Q4G0N4
    Secondary Accessions:
    • B5MC93
    • Q6UTX5
    • Q96NM0

    Protein attributes for NADK2 Gene

    Size:
    442 amino acids
    Molecular mass:
    49433 Da
    Quaternary structure:
    • Homodimer.

    Alternative splice isoforms for NADK2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NADK2 Gene

Protein Expression for NADK2 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for NADK2 Gene

  • Ubiquitination at Lys104
  • Modification sites at PhosphoSitePlus

Other Protein References for NADK2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for NADK2 Gene

Domains & Families for NADK2 Gene

Gene Families for NADK2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for NADK2 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for NADK2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ55867 (B7Z8V7_HUMAN)
  • UPF0465 protein C5orf33 (CE033_HUMAN)
  • C5orf33 protein (Q49AR0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q4G0N4

UniProtKB/Swiss-Prot:

NAKD2_HUMAN :
  • Belongs to the NAD kinase family.
Family:
  • Belongs to the NAD kinase family.
genes like me logo Genes that share domains with NADK2: view

Function for NADK2 Gene

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Molecular function for NADK2 Gene

UniProtKB/Swiss-Prot 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(+) kinase activity and may not be relevant in vivo.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + NAD(+) = ADP + H(+) + NADP(+); Xref=Rhea:RHEA:18629, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57540, ChEBI:CHEBI:58349, ChEBI:CHEBI:456216; EC=2.7.1.23; Evidence={ECO:0000269|PubMed:23212377};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=0.022 mM for NAD(+) {ECO:0000269|PubMed:23212377}; KM=1.7 mM for ATP {ECO:0000269|PubMed:23212377}; KM=1.2 mM for tetrapolyphosphate {ECO:0000269|PubMed:23212377}; Vmax=0.091 umol/min/mg enzyme {ECO:0000269|PubMed:23212377};
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by NADH, NADPH and NADP(+).

Enzyme Numbers (IUBMB) for NADK2 Gene

Phenotypes From GWAS Catalog for NADK2 Gene

Gene Ontology (GO) - Molecular Function for NADK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0003951 NAD+ kinase activity IBA,IDA 23212377
GO:0005524 ATP binding IEA --
GO:0016301 kinase activity IEA --
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with NADK2: view
genes like me logo Genes that share phenotypes with NADK2: view

Human Phenotype Ontology for NADK2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NADK2 Gene

MGI Knock Outs for NADK2:
  • Nadk2 Nadk2<tm1a(EUCOMM)Wtsi>
  • Nadk2 Nadk2<tm1b(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

miRNA for NADK2 Gene

miRTarBase miRNAs that target NADK2

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NADK2

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for NADK2 Gene

Localization for NADK2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NADK2 Gene

Mitochondrion.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NADK2 gene
Compartment Confidence
mitochondrion 5
cytosol 2
plasma membrane 1
extracellular 1
peroxisome 1
nucleus 1

Gene Ontology (GO) - Cellular Components for NADK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IBA,IDA 23212377
GO:0005759 mitochondrial matrix TAS --
genes like me logo Genes that share ontologies with NADK2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for NADK2 Gene

Pathways & Interactions for NADK2 Gene

PathCards logo

SuperPathways for NADK2 Gene

genes like me logo Genes that share pathways with NADK2: view

Pathways by source for NADK2 Gene

Gene Ontology (GO) - Biological Process for NADK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006741 NADP biosynthetic process IEA --
GO:0016310 phosphorylation IEA --
GO:0019674 NAD metabolic process TAS --
genes like me logo Genes that share ontologies with NADK2: view

No data available for SIGNOR curated interactions for NADK2 Gene

Drugs & Compounds for NADK2 Gene

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  1. Drug

(3) Drugs for NADK2 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
NAD Experimental Pharma Agonist, Full agonist, Activator 0
NADP Experimental Pharma 0
ATP Investigational Nutra Agonist, Activator, Partial agonist, Antagonist, Full agonist, Gating inhibitor, Pore Blocker, Potentiation 0

(1) Additional Compounds for NADK2 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
 Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist 58-64-0
genes like me logo Genes that share compounds with NADK2: view

Transcripts for NADK2 Gene

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  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
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mRNA/cDNA for NADK2 Gene

4 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NADK2

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NADK2 Gene

No ASD Table

Relevant External Links for NADK2 Gene

GeneLoc Exon Structure for
NADK2

Expression for NADK2 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NADK2 Gene

mRNA expression in normal human tissues for NADK2 Gene
mRNA expression by BioGPS for NADK2 GenemRNA expression by GTEx for NADK2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NADK2 Gene

This gene is overexpressed in Liver (x7.6).

Protein differential expression in normal tissues from HIPED for NADK2 Gene

This gene is overexpressed in Liver (11.6), Gallbladder (8.0), and Fetal Liver (7.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NADK2 Gene



Protein tissue co-expression partners for NADK2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NADK2

mRNA Expression by UniProt/SwissProt for NADK2 Gene:

Q4G0N4-NAKD2_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for NADK2 Gene

  • Nervous system(4.7)
  • Liver(4.6)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NADK2 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • eye
  • head
  • skull
Limb:
  • lower limb
  • upper limb
General:
  • spinal cord
genes like me logo Genes that share expression patterns with NADK2: view

Orthologs for NADK2 Gene

This gene was present in the common ancestor of animals.

Orthologs for NADK2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia NADK2 31
  • 100 (a)
 OneToOne
NADKD1 30
  • 99.7 (n)
Dog
(Canis familiaris)
 Mammalia NADK2 30
  • 93.51 (n)
Cow
(Bos Taurus)
 Mammalia NADKD1 30
  • 91.78 (n)
NADK2 31
  • 91 (a)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Nadk2 30
  • 89.4 (n)
Mouse
(Mus musculus)
 Mammalia Nadk2 30 17 31
  • 89.22 (n)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia NADK2 31
  • 81 (a)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia NADK2 31
  • 80 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves NADKD1 30
  • 79.09 (n)
NADK2 31
  • 74 (a)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia NADK2 31
  • 73 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia nadk2 30
  • 72.07 (n)
Str.11200 30
African clawed frog
(Xenopus laevis)
 Amphibia Xl.2638 30
Zebrafish
(Danio rerio)
 Actinopterygii nadk2 30 31
  • 66.43 (n)
 OneToOne
Dr.13238 30
Rainbow Trout
(Oncorhynchus mykiss)
 Actinopterygii Omy.7246 30
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP006767 30
  • 46.75 (n)
Fruit Fly
(Drosophila melanogaster)
 Insecta CG8080 30 31
  • 46.65 (n)
 OneToOne
Worm
(Caenorhabditis elegans)
 Secernentea Y17G7B.10 30 31
  • 51.25 (n)
 OneToOne
Sea Squirt
(Ciona savignyi)
 Ascidiacea CSA.2100 31
  • 42 (a)
 OneToMany
-- 31
  • 33 (a)
 OneToMany
Species where no ortholog for NADK2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for NADK2 Gene

ENSEMBL:
Gene Tree for NADK2 (if available)
TreeFam:
Gene Tree for NADK2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NADK2: view image

Paralogs for NADK2 Gene

(1) SIMAP similar genes for NADK2 Gene using alignment to 4 proteins:

  • NAKD2_HUMAN
  • B7Z8V7_HUMAN
  • D6RHI4_HUMAN
  • H0Y9H7_HUMAN

Pseudogenes.org Pseudogenes for NADK2 Gene

genes like me logo Genes that share paralogs with NADK2: view

No data available for Paralogs for NADK2 Gene

Variants for NADK2 Gene

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Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NADK2 Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
640415 Uncertain Significance: 2,4-Dienoyl-CoA reductase deficiency 36,219,679(-) C/T SYNONYMOUS_VARIANT
658874 Uncertain Significance: 2,4-Dienoyl-CoA reductase deficiency 36,241,699(-) GC/AT MISSENSE_VARIANT,INTRON_VARIANT
664623 Uncertain Significance: 2,4-Dienoyl-CoA reductase deficiency 36,241,751(-) C/T SYNONYMOUS_VARIANT,INTRON_VARIANT
676272 Benign: not provided 36,241,905(-) G/A FIVE_PRIME_UTR_VARIANT,INTRON_VARIANT
715274 Conflicting Interpretations: 2,4-Dienoyl-CoA reductase deficiency; not provided 36,227,517(-) T/C MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for NADK2 Gene

Structural Variations from Database of Genomic Variants (DGV) for NADK2 Gene

Variant ID Type Subtype PubMed ID
esv3604707 CNV gain 21293372
esv3604713 CNV gain 21293372
nsv1015638 CNV gain 25217958
nsv830262 CNV gain 17160897

Variation tolerance for NADK2 Gene

Residual Variation Intolerance Score: 57.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.14; 51.48% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NADK2 Gene

Human Gene Mutation Database (HGMD)
NADK2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NADK2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NADK2 Gene

Disorders for NADK2 Gene

MalaCards: The human disease database

(5) MalaCards diseases for NADK2 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
2,4-dienoyl-coa reductase deficiency
  • decrd
hyperlysinemia, type i
  • lysine:alpha-ketoglutarate reductase deficiency
hyperprolinemia, type i
  • hyrpro1
hyperprolinemia, type ii
  • hyrpro2
multiple acyl-coa dehydrogenase deficiency
  • madd
- elite association - COSMIC cancer census association via MalaCards
Search NADK2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

NAKD2_HUMAN
  • 2,4-dienoyl-CoA reductase deficiency (DECRD) [MIM:616034]: A rare, autosomal recessive, inborn error of polyunsaturated fatty acids and lysine metabolism, resulting in mitochondrial dysfunction. Affected individuals have a severe encephalopathy with neurologic and metabolic abnormalities beginning in early infancy. Laboratory studies show increased C10:2 carnitine levels and hyperlysinemia. {ECO:0000269 PubMed:24847004}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for NADK2

ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with NADK2: view

No data available for Genatlas for NADK2 Gene

Publications for NADK2 Gene

  1. Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. (PMID: 24847004) Houten SM … Wanders RJ (Human molecular genetics 2014) 3 4
  2. MNADK, a novel liver-enriched mitochondrion-localized NAD kinase. (PMID: 23616928) Zhang R (Biology open 2013) 2 3
  3. Identification and characterization of a human mitochondrial NAD kinase. (PMID: 23212377) Ohashi K … Murata K (Nature communications 2012) 3 4
  4. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4
  5. An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. (PMID: 29568061) Liu X … Varjosalo M (Nature communications 2018) 3

ExternalLinks

View latest publications for NADK2 gene in Mastermind

Products for NADK2 Gene

  • Signalway Proteins for NADK2

Sources for NADK2 Gene