Free for academic non-profit institutions. Other users need a Commercial license
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. Each NADP(+)-dependent isozyme is a homodimer. The protein encoded by this gene is the NADP(+)-dependent isocitrate dehydrogenase found in the mitochondria. It plays a role in intermediary metabolism and energy production. This protein may tightly associate or interact with the pyruvate dehydrogenase complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
IDH2 mutations have been observed in a number of cancer types, including sarcomas, hematologic malignancies, colon cancer and brain cancer. Mutations in the two isocitrate dehydrogenase enzymes involved in cytoplasmic (IDH1) and mitochondrial (IDH2) conversion of alpha-ketoglutarate to D-2-hydroxyglutarate have been described as mutually exclusive in many of these cancer types. The most frequent mutations involve R132 (IDH1) and R172 (IDH2) involve the active site and result in neomorphic enzyme activity. Although IDH2 (R172) mutations are associated with poorer overall prognosis in AML patients, its utility as a prognostic marker in MDS is still under debate. Additionally, IDH2 (R140) has been associated with improved overall survival in AML. IDH2 mutations have been associated with improved prognosis in gliomas.
IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) is a Protein Coding gene. Diseases associated with IDH2 include D-2-Hydroxyglutaric Aciduria 2 and D-2-Hydroxyglutaric Aciduria 1. Among its related pathways are Metabolism and Carbon metabolism. Gene Ontology (GO) annotations related to this gene include magnesium ion binding and oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. An important paralog of this gene is IDH1.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000287 | magnesium ion binding | ISS | -- |
GO:0004448 | isocitrate dehydrogenase activity | IEA | -- |
GO:0004450 | isocitrate dehydrogenase (NADP+) activity | IDA,ISS | -- |
GO:0016491 | oxidoreductase activity | IEA | -- |
GO:0016616 | oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005739 | mitochondrion | IBA,IDA | -- |
GO:0005759 | mitochondrial matrix | TAS | -- |
GO:0005777 | peroxisome | IEA | -- |
GO:0005829 | cytosol | IEA | -- |
GO:0070062 | extracellular exosome | HDA | 23533145 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Carbon metabolism | ||
2 | Pyruvate metabolism and Citric Acid (TCA) cycle |
.01
|
|
3 | Metabolism |
.40
|
|
4 | Glucose / Energy Metabolism | ||
5 | Central carbon metabolism in cancer |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005975 | carbohydrate metabolic process | NAS | 8954790 |
GO:0006097 | glyoxylate cycle | IEA | -- |
GO:0006099 | tricarboxylic acid cycle | TAS | -- |
GO:0006102 | isocitrate metabolic process | ISS | -- |
GO:0006103 | 2-oxoglutarate metabolic process | ISS | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
enasidenib | Approved, Investigational | Pharma | Target, inhibitor | 0 | ||
Venetoclax | Approved, Investigational | Pharma | Bcl-2 inhibitor,potent and selective | 245 | ||
Cytarabine | Approved, Experimental, Investigational | Pharma | 1335 | |||
Daunorubicin | Approved | Pharma | DNA topoisomerase II inhibitor | 383 | ||
Etoposide | Approved | Pharma | Topo II inhibitor, Topoisomerase 2 Inhibitors | 1461 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
Hydrogen Ion |
|
|
||||
Oxalosuccinic acid |
|
1948-82-9 |
|
Compound | Action | Cas Number |
---|---|---|
AGI-6780 | IDH2/R140Q mutation inhibitor | 1432660-47-3 |
ExUns: | 1a | · | 1b | ^ | 2 | ^ | 3 | ^ | 4a | · | 4b | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8a | · | 8b | ^ | 9 | ^ | 10 | ^ | 11 | ^ | 12 | ^ | 13 | ^ | 14 | ^ | 15 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | - | ||||||||||||||||||||||||||||||
SP2: | - | - | - | - | |||||||||||||||||||||||||||||||
SP3: | - | - | - | ||||||||||||||||||||||||||||||||
SP4: | - | - | |||||||||||||||||||||||||||||||||
SP5: | - | - | |||||||||||||||||||||||||||||||||
SP6: |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | IDH2 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | IDH2 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | IDH2 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Idh2 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Idh2 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | IDH2 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | IDH2 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | IDH2 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | IDH2 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | idh2 30 |
|
||
Str.6413 30 |
|
||||
Zebrafish (Danio rerio) |
Actinopterygii | idh2 30 |
|
||
IDH2 31 |
|
OneToOne | |||
wufb33c06 30 |
|
||||
African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP003168 30 |
|
||
Worm (Caenorhabditis elegans) |
Secernentea | C34F6.8 32 |
|
|
|
F59B8.2 32 |
|
|
|||
idh-2 30 31 |
|
OneToOne | |||
A. gosspyii yeast (Eremothecium gossypii) |
Saccharomycetes | AGOS_AAL022W 30 |
|
||
K. Lactis Yeast (Kluyveromyces lactis) |
Saccharomycetes | KLLA0F12342g 30 |
|
||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | IDP2 30 31 33 |
|
ManyToMany | |
IDP3 31 |
|
ManyToMany | |||
IDP1 31 |
|
ManyToMany | |||
Thale Cress (Arabidopsis thaliana) |
eudicotyledons | ICDH 30 |
|
||
Rice (Oryza sativa) |
Liliopsida | Os01g0248400 30 |
|
||
Os.2326 30 |
|
||||
Barley (Hordeum vulgare) |
Liliopsida | Hv.4559 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.7852 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 15 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
641910 | Uncertain Significance: D-2-hydroxyglutaric aciduria 2 | 90,085,050(-) | G/A | MISSENSE_VARIANT | |
643998 | Uncertain Significance: D-2-hydroxyglutaric aciduria 2 | 90,088,449(-) | G/C | MISSENSE_VARIANT | |
657276 | Uncertain Significance: D-2-hydroxyglutaric aciduria 2 | 90,087,235(-) | T/C | MISSENSE_VARIANT | |
712843 | Likely Benign: D-2-hydroxyglutaric aciduria 2 | 90,091,619(-) | C/T | SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT,INTRON_VARIANT | |
715534 | Likely Benign: D-2-hydroxyglutaric aciduria 2 | 90,091,640(-) | G/A | SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT,INTRON_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv112e55 | CNV | gain | 17911159 |
esv2760054 | CNV | gain | 17122850 |
esv3569864 | CNV | gain | 25503493 |
esv3637213 | CNV | gain | 21293372 |
nsv1038313 | CNV | gain | 25217958 |
nsv1052652 | CNV | gain | 25217958 |
nsv442384 | CNV | gain | 18776908 |
Disorder | Aliases | PubMed IDs |
---|---|---|
d-2-hydroxyglutaric aciduria 2 |
|
|
d-2-hydroxyglutaric aciduria 1 |
|
|
multiple enchondromatosis, maffucci type |
|
|
enchondromatosis, multiple, ollier type |
|
|
brain stem glioma |
|
|