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General Information
D-2-hydroxyglutaric aciduria 2
FlyBase ID
Disease Ontology Term
Parent Disease

This report describes D-2-hydroxyglutaric aciduria 2 (D2HGA2), which is a sub-type of D-2-hydroxyglutaric aciduria (D2HGA); D2HGA2 exhibits autosomal dominant inheritance. The human gene implicated in this disease is IDH2, which is a mitochondrial NADP-dependent isocitrate dehydrogenase. There is a single fly ortholog, Dmel\Idh, for which classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\Idh is a high scoring ortholog of a second isocitrate dehydrogenase gene in humans, IDH1, which is associated with susceptibility to malignant glioma (OMIM:137800). Somatic mutations of both IDH1 and IDH2 have been implicated in the development of multiple cancers; see the report for 'cancer, multiple, IDH1,2-related,' FBhh0000525.

Neither human gene, IDH2 nor IDH1, has been introduced into flies.

Variant(s) implicated in human disease tested (as analogous mutation in fly gene): R163Q in the fly Idh gene (corresponds to R140Q in the human IDH2 gene). Ubiquitous expression of a transgenic gene carrying the R163Q variant results in elevation of D-2-hydroxyglutarate levels. Amorphic mutations of Dmel\Idh are homozygous lethals. Genetic and physical interactions have been described for Dmel\Idh; see below and in the FlyBase gene report for Idh.

[updated Sep. 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: D-2-hydroxyglutaric aciduria
Symptoms and phenotype

D-2-hydroxyglutaric aciduria is a neurometabolic disorder. Symptoms are varible, ranging from asymptomatic to developmental delay, epilepsy, hypotonia (weak muscle tone), and dysmorphic features. Severe cases are characterized by early infantile-onset epileptic encephalopathy and, often, cardiomyopathy. [from OMIM:600721, OMIM:613657; 2015.12.21]

Specific Disease Summary: D-2-hydroxyglutaric aciduria 2
OMIM report


Human gene(s) implicated


Symptoms and phenotype

See general description of D-2-hydroxyglutaric aciduria, above.


The transmission pattern of D-2-hydroxyglutaric aciduria-2 in the families reported by Kranendijk et al. (2010; pubmed:20847235) is consistent with autosomal dominant inheritance. D2HGA2 appears to be caused by heterozygous mutations in the mitochondrial isocitrate dehydrogenase-2 (IDH2) gene. [from OMIM:613657; 2015.12.21]

Cellular phenotype and pathology
Molecular information

Isocitrate dehydrogenase-2 (IDH2) is a mitochondrial NADP-dependent isocitrate dehydrogenase. By providing NADPH for NADPH-dependent antioxidant enzymes, IDH2 plays a role in controlling the mitochondrial redox balance and mitigating cellular oxidative damage (Park et al., 2008; pubmed:18484410). [from OMIM:147650; 2015.12.21]

External links
Disease synonyms
D-2-hydroxyglutaric aciduria
2-hydroxyglutaric aciduria
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 2 human to 1 Drosophila. Two human genes, IDH1 and IDH2, are orthologous to the fly gene Dmel\Idh.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      Isocitrate dehydrogenase (Idh) encodes a cytosolic enzyme that catalyzes the oxidative decarboxylation of isocitrate to 2-oxoglutarate, with the concomitant reduction of NADP[+] to NADPH. It functions, along with Men, Zw, and Pgd, in a small network of NADP reducing enzymes. [Date last reviewed: 2019-03-07]
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      Lower-scoring ortholog of IDH2; higher-scoring ortholog of second human gene, IDH1 (1 Drosphila to 2 human). Dmel\Idh shares 65% identity and 80% similarity with the human IDH2 gene; it shares 72% identity and 87% similarity with the human IDH1 gene.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Synthetic Gene(s) Used (0)
      Summary of Physical Interactions (3 groups)
      Interacting group
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
      Models Based on Experimental Evidence ( 2 )
      Modifiers Based on Experimental Evidence ( 0 )
      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
      Selected mammalian transgenes
      Publicly Available Stocks
      Selected Drosophila transgenes
      Publicly Available Stocks
      RNAi constructs available
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele class
      Publicly Available Stocks
      loss of function allele
      P-element activity
      loss of function allele
      natural population
      loss of function allele
      natural population
      loss of function allele
      natural population
      amorphic allele - molecular evidence
      Delta2-3 transposase
      References (4)