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    IDH3A isocitrate dehydrogenase (NAD(+)) 3 catalytic subunit alpha [ Homo sapiens (human) ]

    Gene ID: 3419, updated on 10-Dec-2024

    Summary

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    Official Symbol
    IDH3Aprovided by HGNC
    Official Full Name
    isocitrate dehydrogenase (NAD(+)) 3 catalytic subunit alphaprovided by HGNC
    Primary source
    HGNC:HGNC:5384
    See related
    Ensembl:ENSG00000166411 MIM:601149; AllianceGenome:HGNC:5384
    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
    RP90
    Summary
    Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. NAD(+)-dependent isocitrate dehydrogenases catalyze the allosterically regulated rate-limiting step of the tricarboxylic acid cycle. Each isozyme is a heterotetramer that is composed of two alpha subunits, one beta subunit, and one gamma subunit. The protein encoded by this gene is the alpha subunit of one isozyme of NAD(+)-dependent isocitrate dehydrogenase. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in heart (RPKM 59.2), adrenal (RPKM 37.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See IDH3A in Genome Data Viewer
    Location:
    15q25.1
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (78149362..78171945)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (76011920..76034530)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (78441704..78464287)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9910 Neighboring gene calcium and integrin binding family member 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6705 Neighboring gene uncharacterized LOC124903534 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6706 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9911 Neighboring gene acyl-CoA synthetase bubblegum family member 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9912 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6707 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:78500283-78500794 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9913 Neighboring gene DNAJA4 divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6708 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6709 Neighboring gene uncharacterized LOC105370910 Neighboring gene Sharpr-MPRA regulatory region 12554 Neighboring gene DnaJ heat shock protein family (Hsp40) member A4

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Diphosphopyridine nucleotide dependent isocitrate dehydrogenase from pig heart. Charactgerization of the active substrate and modes of regulation. Cohen PF, et al. Biochemistry, 1972 Apr 11. PMID 4336621
    2. A novel missense variant in IDH3A causes autosomal recessive retinitis pigmentosa. Peter VG, et al. Ophthalmic Genet, 2019 Apr. PMID 31012789
    3. Structure and allosteric regulation of human NAD-dependent isocitrate dehydrogenase. Sun P, et al. Cell Discov, 2020 Dec 22. PMID 33349631, Free PMC Article
    4. Assignment of the human mitochondrial NAD+ -specific isocitrate dehydrogenase alpha subunit (IDH3A) gene to 15q25.1-->q25.2by in situ hybridization. Huh TL, et al. Genomics, 1996 Mar 1. PMID 8833160
    5. Characterization of a cDNA clone for human NAD(+)-specific isocitrate dehydrogenase alpha-subunit and structural comparison with its isoenzymes from different species. Kim YO, et al. Biochem J, 1995 May 15. PMID 7755589, Free PMC Article

    See all (97) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Subcellular Proteome Analysis Reveals Apoptotic Vulnerability of T-Cell Acute Lymphoblastic Leukemia.
      Title: Subcellular Proteome Analysis Reveals Apoptotic Vulnerability of T-Cell Acute Lymphoblastic Leukemia.
    2. Association between IDH mutational status and tumor-associated epilepsy or venous thromboembolism in patients with grade II and III astrocytoma.
      Title: Association between IDH mutational status and tumor-associated epilepsy or venous thromboembolism in patients with grade II and III astrocytoma.
    3. IDH3alpha is elevated in glioblastoma patient samples compared to normal brain tissue and promotes glioblastoma progression in orthotopic glioma mouse models. On molecular levels, IDH3alpha ablation reduces TCA cycle turnover and shunts energy metabolism. In addition, IDH3alpha affects one-carbon metabolism and regulates nucleotide production as well as DNA methylation through effect on cSHMT.
      Title: IDH3α regulates one-carbon metabolism in glioblastoma.
    4. This study highlights the importance of including this rarely-mutated gene in the molecular diagnostic set-ups for inherited retinal degenerations, and further delineates the phenotypic spectrum elicited by mutations in IDH3A.
      Title: A novel missense variant in IDH3A causes autosomal recessive retinitis pigmentosa.
    5. The silencing of IDH3a significantly delayed tumor growth by suppressing the HIF-1-mediated Warburg effect and angiogenesis.
      Title: Aberrant IDH3α expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis.
    6. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    7. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: A three-stage genome-wide association study of general cognitive ability: hunting the small effects.
    8. active sites of the human NAD-IDH are shared between alpha and gamma subunits and between alpha and beta subunits
      Title: Identification of Mn2+-binding aspartates from alpha, beta, and gamma subunits of human NAD-dependent isocitrate dehydrogenase.
    9. for IDH, a normal alpha subunit is required for catalytic activity and alpha-Arg88 likely participates in the isocitrate site, whereas the beta and gamma subunits have roles in the nucleotide functions of this allosteric enzyme
      Title: Evaluation by mutagenesis of the importance of 3 arginines in alpha, beta, and gamma subunits of human NAD-dependent isocitrate dehydrogenase.
    10. Asp181 is essential for nicotinamide-adenine dinucleotide (NAD)-specific IDH alpha subunit catalysis and may also facilitate the binding of substrates.
      Title: Role of alpha-Asp181, beta-Asp192, and gamma-Asp190 in the distinctive subunits of human NAD-specific isocitrate dehydrogenase.
    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
    Retinitis pigmentosa 90
    MedGen: C5436588 OMIM: 619007 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)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Tandem affinity purification and mass spectrometry analysis identify isocitrate dehydrogenase 3 (NAD+) alpha subunit (IDH3A), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Gag-Pol gag-pol Tandem affinity purification and mass spectrometry analysis identify isocitrate dehydrogenase 3 (NAD+) alpha subunit (IDH3A), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Nef nef Tandem affinity purification and mass spectrometry analysis identify isocitrate dehydrogenase 3 (NAD+) alpha subunit (IDH3A), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Pol gag-pol HIV-1 Pol is identified to have a physical interaction with isocitrate dehydrogenase 3 (NAD+) alpha (IDH3A) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    Pr55(Gag) gag Tandem affinity purification and mass spectrometry analysis identify isocitrate dehydrogenase 3 (NAD+) alpha subunit (IDH3A), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed

    Go to the HIV-1, Human Interaction Database

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables NAD binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables isocitrate dehydrogenase (NAD+) activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables isocitrate dehydrogenase (NAD+) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables isocitrate dehydrogenase (NAD+) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in carbohydrate metabolic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in isocitrate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in tricarboxylic acid cycle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in tricarboxylic acid cycle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tricarboxylic acid cycle TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    part_of isocitrate dehydrogenase complex (NAD+) IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of isocitrate dehydrogenase complex (NAD+) IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    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
    		  
    located_in mitochondrion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in nucleus HDA PubMed 

    General protein information

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    Preferred Names
    isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial
    Names
    H-IDH alpha
    NAD(+)-specific ICDH subunit alpha
    NAD(H)-specific isocitrate dehydrogenase alpha subunit
    NAD+-specific ICDH
    isocitrate dehydrogenase (NAD(+)) 3 alpha
    isocitrate dehydrogenase (NAD+) alpha chain
    isocitrate dehydrogenase 3 (NAD(+)) alpha
    isocitrate dehydrogenase 3 (NAD+) alpha
    isocitric dehydrogenase subunit alpha
    NP_005521.1
    XP_024305679.1
    XP_047288384.1
    XP_047288385.1
    XP_047288386.1
    XP_054233780.1
    XP_054233781.1
    XP_054233782.1

    NCBI Reference Sequences (RefSeq)

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    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.

    mRNA and Protein(s)

    1. NM_005530.3 → NP_005521.1  isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial precursor

      See identical proteins and their annotated locations for NP_005521.1

      Status: REVIEWED

      Source sequence(s)
      AC090260
      Consensus CDS
      CCDS10297.1
      UniProtKB/Swiss-Prot
      D3DW83, P50213, Q9H3X0
      UniProtKB/TrEMBL
      Q53GF8
      Related
      ENSP00000299518.2, ENST00000299518.7
      Conserved Domains (1) summary
      TIGR00175
      Location:29 → 362
      mito_nad_idh; isocitrate dehydrogenase, NAD-dependent, mitochondrial type

    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_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      78149362..78171945
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047432429.1 → XP_047288385.1  isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial isoform X1

      UniProtKB/TrEMBL
      B4DJB4, Q53GF8

    2. XM_047432428.1 → XP_047288384.1  isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial isoform X1

      UniProtKB/TrEMBL
      B4DJB4, Q53GF8

    3. XM_047432430.1 → XP_047288386.1  isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial isoform X2

      UniProtKB/TrEMBL
      B7Z9J8, E7EWD2

    4. XM_024449911.2 → XP_024305679.1  isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial isoform X1

      UniProtKB/TrEMBL
      B4DJB4, Q53GF8
      Conserved Domains (1) summary
      TIGR00175
      Location:1 → 312
      mito_nad_idh; isocitrate dehydrogenase, NAD-dependent, mitochondrial type

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      76011920..76034530
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054377805.1 → XP_054233780.1  isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial isoform X1

      UniProtKB/TrEMBL
      B4DJB4, Q53GF8

    2. XM_054377807.1 → XP_054233782.1  isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial isoform X3

    3. XM_054377806.1 → XP_054233781.1  isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial isoform X2

      UniProtKB/TrEMBL
      B7Z9J8, E7EWD2
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P50213.1 GenPept UniProtKB/Swiss-Prot:P50213

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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