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    NADK2 NAD kinase 2, mitochondrial [ Homo sapiens (human) ]

    Gene ID: 133686, updated on 28-Oct-2024

    Summary

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    Official Symbol
    NADK2provided by HGNC
    Official Full Name
    NAD kinase 2, mitochondrialprovided by HGNC
    Primary source
    HGNC:HGNC:26404
    See related
    Ensembl:ENSG00000152620 MIM:615787; AllianceGenome:HGNC:26404
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    DECRD; MNADK; NADKD1; C5orf33
    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 2014]
    Expression
    Broad expression in liver (RPKM 62.0), brain (RPKM 14.1) and 22 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NADK2 in Genome Data Viewer
    Location:
    5p13.2
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (36192589..36242279, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (36440876..36490588, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (36192691..36242381, complement)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene LMBR1 domain containing 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:36151273-36152256 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22476 Neighboring gene RNA, U6 small nuclear 1305, pseudogene Neighboring gene microRNA 580 Neighboring gene S-phase kinase associated protein 2 Neighboring gene NADK2 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15972 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22477 Neighboring gene uncharacterized LOC124900962 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22478 Neighboring gene RAN binding protein 3 like Neighboring gene NANOG hESC enhancer GRCh37_chr5:36359316-36360151 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:36417632-36418831 Neighboring gene Sharpr-MPRA regulatory region 12809 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:36422736-36423935 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:36442158-36443357 Neighboring gene RNA, 5S ribosomal pseudogene 181

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Crystal structure of human NADK2 reveals a dimeric organization and active site occlusion by lysine acetylation. Mary C, et al. Mol Cell, 2022 Sep 1. PMID 35868311, Free PMC Article
    2. Lysine Restriction and Pyridoxal Phosphate Administration in a NADK2 Patient. Tort F, et al. Pediatrics, 2016 Nov. PMID 27940755
    3. Clinical heterogeneity of mitochondrial NAD kinase deficiency caused by a NADK2 start loss variant. Pomerantz DJ, et al. Am J Med Genet A, 2018 Mar. PMID 29388319, Free PMC Article
    4. Mitochondrial NADP(H) generation is essential for proline biosynthesis. Zhu J, et al. Science, 2021 May 28. PMID 33888598, Free PMC Article
    5. Identification and characterization of a human mitochondrial NAD kinase. Ohashi K, et al. Nat Commun, 2012. PMID 23212377, Free PMC Article

    See all (36) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The mitochondrial NAD kinase functions as a major metabolic regulator upon increased energy demand.
      Title: The mitochondrial NAD kinase functions as a major metabolic regulator upon increased energy demand.
    2. Crystal structure of human NADK2 reveals a dimeric organization and active site occlusion by lysine acetylation.
      Title: Crystal structure of human NADK2 reveals a dimeric organization and active site occlusion by lysine acetylation.
    3. Deleting MNADK (NADK2) in mice reduced fat oxidation upon energy demand triggered by endurance exercise or fasting. NADK2 is a major metabolic regulator upon increased energy demand.
      Title: The mitochondrial NAD kinase functions as a major metabolic regulator upon increased energy demand.
    4. Mitochondrial NADP(H) generation is essential for proline biosynthesis.
      Title: Mitochondrial NADP(H) generation is essential for proline biosynthesis.
    5. Our findings also clarify the mechanism underlying NADK2 deficiency and suggest that this disease should be ruled out in cases of hyperlysinemia, especially those with visual loss, and neurological phenotypes.
      Title: Clinical heterogeneity of mitochondrial NAD kinase deficiency caused by a NADK2 start loss variant.
    6. The use of whole exome sequencing has allowed us to identify a new homozygous mutation in NADK2, leading to a premature stop codon and absence of protein. To our knowledge this is the second reported individual with mutations in NADK2.
      Title: Lysine Restriction and Pyridoxal Phosphate Administration in a NADK2 Patient.
    7. An autosomal recessive defect in NADK2 causes mitochondrial NADPH deficiency with secondary deficiencies in several mitochondrial processes including polyunsaturated fatty acid oxidation and lysine degradation.
      Title: Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia.
    8. exhibits NAD kinase activity, utilizing ATP or inorganic polyphosphate, and is localized in mitochondria of HEK293A cells
      Title: Identification and characterization of a human mitochondrial NAD kinase.
    9. MNADK is localized to mitochondria in Hep G2 cells, and a recombinant MNADK showed NAD kinase activity. MNADK is abundant in mitochondrion-rich tissues, such as liver. MNADK expression was suppressed in human liver tumors. Identification of MNADK immediately suggests a model in which NADK and MNADK are responsible for de novo synthesis of NADP(+) in cytosol and mitochondria, respectively.
      Title: MNADK, a novel liver-enriched mitochondrion-localized NAD kinase.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Progressive encephalopathy with leukodystrophy due to DECR deficiency
    MedGen: C1857252 OMIM: 616034 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ30596, MGC43298

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables NAD+ kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables NAD+ kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in NAD metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in NAD metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in NADP biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    NAD kinase 2, mitochondrial
    Names
    NAD kinase domain-containing protein 1, mitochondrial
    NP_001078880.1
    NP_001274269.1
    NP_001274270.1
    NP_694558.1
    XP_005248298.1
    XP_024310128.1
    XP_047272661.1
    XP_047272662.1
    XP_054207567.1
    XP_054207568.1
    XP_054207569.1
    XP_054207570.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_041784.1 RefSeqGene

      Range
      5355..54691
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001085411.3 → NP_001078880.1  NAD kinase 2, mitochondrial isoform 1

      See identical proteins and their annotated locations for NP_001078880.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC008807, AI377881, BC062567, BM990433, BX648388, HY336341
      Consensus CDS
      CCDS47197.1
      UniProtKB/Swiss-Prot
      B5MC93, Q4G0N4, Q6UTX5, Q96NM0
      Related
      ENSP00000371362.4, ENST00000381937.9
      Conserved Domains (1) summary
      cl01255
      Location:96 → 318
      DAGK_cat; Diacylglycerol kinase catalytic domain

    2. NM_001287340.2 → NP_001274269.1  NAD kinase 2, mitochondrial isoform 2

      See identical proteins and their annotated locations for NP_001274269.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in its 5' UTR and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1. Both variants 2 and 3 encode the same isoform.
      Source sequence(s)
      AI377881, AK055158, BC062567, BM990433, BX648388, HY336341
      Consensus CDS
      CCDS3917.1
      UniProtKB/TrEMBL
      A0A0C4DGV3
      Related
      ENSP00000380499.1, ENST00000397338.5
      Conserved Domains (1) summary
      cl01255
      Location:2 → 155
      DAGK_cat; Diacylglycerol kinase catalytic domain

    3. NM_001287341.2 → NP_001274270.1  NAD kinase 2, mitochondrial isoform 3

      See identical proteins and their annotated locations for NP_001274270.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in its 5' UTR, initiates translation at a downstream start codon, and contains an alternate in-frame exon in the central coding region, compared to variant 1. The encoded isoform (3) is shorter, compared to isoform 1.
      Source sequence(s)
      AC008807, AK304009, BC062567, BM990433, BX648388, HY336341
      Consensus CDS
      CCDS75235.1
      UniProtKB/TrEMBL
      A0A0C4DGV3, B7Z8V7
      Related
      ENSP00000422250.1, ENST00000506945.5
      Conserved Domains (1) summary
      cl01255
      Location:2 → 177
      DAGK_cat; Diacylglycerol kinase catalytic domain

    4. NM_153013.5 → NP_694558.1  NAD kinase 2, mitochondrial isoform 2

      See identical proteins and their annotated locations for NP_694558.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in its 5' UTR and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1. Both variants 2 and 3 encode the same isoform.
      Source sequence(s)
      AC008807, AK304009, BC062567, BM990433, BX648388, HY336341
      Consensus CDS
      CCDS3917.1
      UniProtKB/TrEMBL
      A0A0C4DGV3
      Related
      ENSP00000282512.3, ENST00000282512.7
      Conserved Domains (1) summary
      cl01255
      Location:2 → 155
      DAGK_cat; Diacylglycerol kinase catalytic domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      36192589..36242279 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047416706.1 → XP_047272662.1  NAD kinase 2, mitochondrial isoform X3

    2. XM_024454360.2 → XP_024310128.1  NAD kinase 2, mitochondrial isoform X2

      UniProtKB/TrEMBL
      A0A0C4DGV3, B7Z8V7
      Conserved Domains (1) summary
      cl01255
      Location:2 → 177
      DAGK_cat; Diacylglycerol kinase catalytic domain

    3. XM_005248241.5 → XP_005248298.1  NAD kinase 2, mitochondrial isoform X1

      Conserved Domains (1) summary
      cl01255
      Location:96 → 340
      DAGK_cat; Diacylglycerol kinase catalytic domain

    4. XM_047416705.1 → XP_047272661.1  NAD kinase 2, mitochondrial isoform X2

      UniProtKB/TrEMBL
      B7Z8V7

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      36440876..36490588 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054351595.1 → XP_054207570.1  NAD kinase 2, mitochondrial isoform X3

    2. XM_054351593.1 → XP_054207568.1  NAD kinase 2, mitochondrial isoform X2

      UniProtKB/TrEMBL
      B7Z8V7

    3. XM_054351592.1 → XP_054207567.1  NAD kinase 2, mitochondrial isoform X1

    4. XM_054351594.1 → XP_054207569.1  NAD kinase 2, mitochondrial isoform X2

      UniProtKB/TrEMBL
      B7Z8V7
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q4G0N4.2 GenPept UniProtKB/Swiss-Prot:Q4G0N4

    Gene LinkOut

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