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

Gene ID: 3419, updated on 11-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (78149362..78171945)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (76011920..76034530)
105.20220307 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

Expression

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  • Project title: 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. A novel missense variant in IDH3A causes autosomal recessive retinitis pigmentosa. Peter VG, et al. Ophthalmic Genet, 2019 Apr. PMID 31012789
  2. 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
  3. 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
  4. IDH3α regulates one-carbon metabolism in glioblastoma. May JL, et al. Sci Adv, 2019 Jan. PMID 30613765, Free PMC Article
  5. Aberrant IDH3α expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis. Zeng L, et al. Oncogene, 2015 Sep 3. PMID 25531325

See all (83) 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
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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

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 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 
Component Evidence Code Pubs
part_of isocitrate dehydrogenase complex (NAD+) IPI
Inferred from Physical Interaction
more info
 PubMed 
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
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_2023_10

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

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

    UniProtKB/TrEMBL
    B4DJB4

  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

  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

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