Somatic mutations in the human isocitrate dehydrogenase genes IDH1 (cytosolic) and IDH2 (mitochondrial) have been observed in multiple cancers, including cytogenetically normal acute myeloid leukemia (CN-AML). There is one orthologous gene in flies, Dmel\Idh, for which classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. IDH2 is also implicated in D-2-hydroxyglutaric aciduria 2 (MIM:613657; FBhh0000103).
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); R195H in the fly Idh gene (corresponds to R132H in the human IDH1 gene).
Amorphic mutations of Dmel\Idh are homozygous lethals. GAL4-UAS expression of mutational lesions analogous to disease-associated mutations in both human genes, IDH1 and IDH2, result in elevation of D-2-hydroxyglutarate levels. Expression of disease-associated mutations in larval blood cells (hemocytes) resulted in higher numbers of circulating blood cells. Other phenotypes observed include neurologic defects, locomotor defective, and melanotic mass phenotypes. 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]
Somatic mutations in the human genes IDH2 or IDH1 have been identified in cytogenetically normal acute myeloid leukemia (CN-AML). While large chromosomal abnormalities can be involved in the development of acute myeloid leukemia, about half of cases do not have these abnormalities; these are classified as CN-AML. Nearly 20% of people with CN-AML have a mutation in the IDH2 gene; approximately 16% have a mutation in the IDH1 gene. [Genetics Home Reference, IDH2, IDH1; 2017.04.17]
IDH1 encodes a dimeric cytosolic NADP-dependent isocitrate dehydrogenase that catalyzes decarboxylation of isocitrate into alpha-ketoglutarate (Nekrutenko et al., 1998; pubmed:9866202). [from MIM:147700; 2017.04.17] IDH2 encodes a mitochondrial version of the enzyme. [from MIM:147650; 2017.04.17]
Many to one: 2 human to 1 Drosophila.
Many to one: 2 human to 1 Drosophila.
High-scoring ortholog of human gene IDH1; lower-scoring ortholog of human gene IDH2 (1 Drosophila to 2 human). Dmel\Idh shares shares 72% identity and 87% similarity with the human IDH1 gene; it shares 65% identity and 80% similarity with the human IDH2 gene.
