FB2025_01 , released February 20, 2025
Human Disease Model Report: synaptic transmission defects, IDH3A-related
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General Information
Name
synaptic transmission defects, IDH3A-related
FlyBase ID
FBhh0000916
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes a model of IDH3A loss and its impact on synaptic transmission, addressing the general question of mechanisms by which neural activity is integrated with metabolism. IDH3A encodes isocitrate dehydrogenase 3A, an NAD(+)-dependent form of the enzyme that localizes to the mitochondrial matrix. There is a high-scoring ortholog in Drosophila, Dmel\Idh3a, for which loss-of-function mutations, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated. Several lower-scoring orthologs of IDH3A also exist in Drosophila.

A UAS construct of the human Hsap\IDH3A gene has been introduced into flies. Functional complementation (heterologous rescue) has been demonstrated for the lethal phenotype of Idh3a loss-of-function alleles.

A tagged Dmel\Idh3a protein has been shown to localize with complex V in mitochondria in all tissues assessed. Animals homozygous for Idh3a loss-of-function mutations die during the third larval instar stage; in larval neuromuscular junctions, an increase in spontaneous vesicle release frequency and decrease in evoked release are observed. Clonal loss of Idh3a in the eye causes loss of synaptic transmission in photoreceptors. The similarity of Idh3a LOF phenotypes with those of Dmel\Syt1 has prompted experiments that support a model of metabolic regulation of Syt1-effected synaptic transmission via the product of Idh3a, alpha-ketoglutarate.

[updated Nov. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: synaptic transmission defects, IDH3A-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (2-oxoglutarate). IDH3A encodes the catalytic subunit of an NAD(+)-dependent form of isocitrate dehydrogenase that localizes to the mitochondrial matrix. [Gene Cards, IDH3A; 2018.11.06]

(FlyBase Curators, 2013-)
External links
Disease synonyms
neuromuscular junction disease
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
IDH3A; isocitrate dehydrogenase (NAD(+)) 3 catalytic subunit alpha
D. melanogaster ortholog (based on DIOPT)
Dmel\Idh3a
(DIOPT, 2013-)
Dmel\CG32026
(DIOPT, 2013-)
Dmel\CG3483
(DIOPT, 2013-)
Comments on ortholog(s)

One to many: 1 human to 3 Drosophila; additional paralogous genes in both species.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Dmel\Idh3a
    Gene Snapshot
    Contributions welcome
    Molecular function (GO)
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    Highest-scoring ortholog of human IDH3A (3 Drosophila to 1 human); Dmel\Idh3a shares 68% identity and 81% similarity with the human gene.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    H. sapiens (Human)
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (77 groups)
      Idh3a
      protein-protein
      Interacting group
      Assay
      References
      Idh3a - Actn
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Agpat3
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - α-Spec
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Argk1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - βCOP
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - boca
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - bor
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - CCT3
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - CCT4
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - CCT6
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - CCT7
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - CCT8
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - CG1371
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - CG2065
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - CG3008
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - CG5854
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - CG9467
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - CG31729
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - CG33303
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Chc
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Cnx99A
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - cPges
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Cyp12d1-p
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Cyt-c1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Etfb
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Fatp1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - fax
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Gfat2
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Glt
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - GluProRS
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Gp93
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Gp210
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Idh3g
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Ipo9
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Kap-α3
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Karyβ3
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Kdsr
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Kr-h2
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - lic
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Mcad
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - mEFTu1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Mpcp2
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - MRP
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Nacα
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Nfs1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Ost48
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - OstΔ
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Past1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Pcb
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Pi3K68D
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Pih1D1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Pp2A-29B
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Prm
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - r
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Rab5
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Rdh1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - RpLP0
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - RpS5a
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - RpS10b
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Rpt1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Rpt6
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - scf
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - ScsβA
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - ScsβG
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Sec61α
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Sec63
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - SERCA
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - SerRS
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Spindly
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Tapδ
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Tecr
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - TER94
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Tm2
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - UQCR-6.4
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - UQCR-C2
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - Vps4
      experimental knowledge based
      (Guruharsha et al., 2011)
      Idh3a - wal
      experimental knowledge based
      (Guruharsha et al., 2011)
      Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)
      Idh3a
      Models Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Evidence
      References
      Idh3a1
      model of  neuromuscular junction disease
      CEA
      (Ugur et al., 2017)
      Modifiers Based on Experimental Evidence ( 2 )
      Hsap\IDH3A
      Models Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 1 )
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Related mammalian, viral, bacterial, or synthetic transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Hsap\IDH3AUAS.cUa
      PBac{UAS-hIDH3A.U}
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Idh3aUAS.cUa
      PBac{UAS-Idh3a.U}
      y1 w*; PBac{UAS-Idh3a.U}VK00033
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Idh3aGD5222
      P{GD5222}
      w1118; P{GD5222}v41192
      Idh3aGD16641
      P{GD16641}
      Idh3aKK107912
      P{KK107912}
      P{KK107912}VIE-260B
      Idh3aNIG.12233R
      P{NIG.12233R}
      P{NIG.12233R}2
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      Idh3a3
      ethyl methanesulfonate
      y1 w* Idh3a3 P{neoFRT}19A/FM7c, P{GAL4-Kr.C}DC1, P{UAS-GFP.S65T}DC5, sn+
      Idh3a1
      ethyl methanesulfonate
      y1 w* Idh3a1 P{neoFRT}19A/FM7c, P{GAL4-Kr.C}DC1, P{UAS-GFP.S65T}DC5, sn+
      References (3)