IDH2 Gene: Isocitrate Dehydrogenase (NADP(+)) 2
Key enzyme in cellular metabolism, frequently mutated in glioma and acute myeloid leukemia
Gene Information Card
| Symbol | IDH2 |
|---|---|
| Full Name | Isocitrate dehydrogenase (NADP(+)) 2, mitochondrial |
| Gene Type | protein coding |
| Chromosomal Location | 15q26.1 |
| NCBI Gene ID | 3418 ncbi.nlm.nih.gov/gene/3418 |
| Ensembl ID | ENSG00000182054 |
| UniProt ID | P48735 |
| OMIM ID | 147650 |
| HGNC ID | 5383 |
| Aliases | IDHM; IDP; mNADP-IDH; isocitrate dehydrogenase 2 (NADP+), mitochondrial |
Description
The IDH2 gene encodes the mitochondrial isocitrate dehydrogenase 2 enzyme, which catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (2-oxoglutarate) while reducing NADP+ to NADPH. This enzyme plays a critical role in cellular metabolism, redox balance, and epigenetic regulation. Mutations in IDH2, particularly at arginine residues R140 and R172, are oncogenic and lead to neomorphic enzyme activity that produces the oncometabolite 2-hydroxyglutarate (2-HG), which competitively inhibits alpha-ketoglutarate-dependent dioxygenases, resulting in DNA and histone hypermethylation and altered cell differentiation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glioma | IDH2 mutations (R172) produce 2-HG, which inhibits TET enzymes and histone demethylases, leading to hypermethylation and block of differentiation. | COSMIC; PMID: 21817013 |
| Acute myeloid leukemia (AML) | IDH2 mutations (R140, R172) cause 2-HG accumulation, impairing hematopoietic differentiation and promoting leukemogenesis. | COSMIC; PMID: 20946881 |
| D-2-hydroxyglutaric aciduria 2 | Germline loss-of-function mutations in IDH2 cause accumulation of D-2-hydroxyglutarate, leading to metabolic encephalopathy. | OMIM; PMID: 20522425 |
| Ollier disease and Maffucci syndrome | Somatic mosaic IDH2 mutations (R172) are found in enchondromas and spindle cell hemangiomas, producing 2-HG and altering chondrocyte differentiation. | PMID: 21764749 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 10.2 | Medium |
| Kidney | 8.5 | Medium |
| Heart | 7.8 | Medium |
| Brain | 6.9 | Medium |
| Skeletal muscle | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 12.3 | Hepatocellular carcinoma cell line |
| K-562 | 9.8 | Chronic myelogenous leukemia cell line |
| A549 | 8.1 | Lung carcinoma cell line |
| MCF7 | 7.2 | Breast adenocarcinoma cell line |
| U-87 MG | 6.5 | Glioblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R140Q | Missense | ~10% in AML | Neomorphic: produces 2-HG |
| R172K | Missense | ~5% in glioma | Neomorphic: produces 2-HG |
| R172S | Missense | Rare | Neomorphic: produces 2-HG |
| R140W | Missense | Rare | Neomorphic: produces 2-HG |
Mutation functional classification
Loss of Function (LOF)
Germline loss-of-function mutations (e.g., in D-2-hydroxyglutaric aciduria) reduce normal enzyme activity, leading to metabolic imbalance.
Gain of Function (GOF)
Somatic missense mutations at R140 and R172 confer neomorphic activity, producing 2-HG from alpha-ketoglutarate.
Dominant Negative (DN)
Not typically described; mutant IDH2 acts as a gain-of-function rather than dominant-negative.
View complete mutation data：
Gene Ontology (GO)
| • isocitrate dehydrogenase (NADP+) activity | • oxidoreductase activity |
| • magnesium ion binding | • manganese ion binding |
| • mitochondrial matrix | • tricarboxylic acid cycle |
| • NADPH regeneration | • 2-oxoglutarate metabolic process |
Pathways
• Tricarboxylic acid (TCA) cycle
• 2-hydroxyglutarate production (mutant)
• NADPH regeneration
• Glutathione metabolism
Protein Summary
IDH2 is a mitochondrial enzyme that exists as a homodimer and catalyzes the conversion of isocitrate to alpha-ketoglutarate, producing NADPH. It is essential for cellular defense against oxidative stress and for lipid and amino acid metabolism. Mutant IDH2 enzymes acquire the ability to reduce alpha-ketoglutarate to 2-HG, an oncometabolite that disrupts epigenetic regulation and cellular differentiation, contributing to tumorigenesis in gliomas and AML. Therapeutic inhibitors such as enasidenib target mutant IDH2 and are used in AML treatment.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IDH2 Knockout HEK293 Cell Line | EDJ-KQ17826 | Human | 3418 | Details Get a Quote |
| IDH2 Knockout A-549 Cell Line | EDJ-KQ20273 | Human | 3418 | Details Get a Quote |
| IDH2 Knockout HCT 116 Cell Line | EDJ-KQ20274 | Human | 3418 | Details Get a Quote |
| IDH2 Knockout HeLa Cell Line | EDJ-KQ20275 | Human | 3418 | Details Get a Quote |
| IDH2 (p.R140W) Point Mutation in HCT 116 Cell Line | EDC03138 | Human | 3418 | Details Get a Quote |
| IDH2 (p.R140Q) Point Mutation in HCT 116 Cell Line | EDC03137 | Human | 3418 | Details Get a Quote |
| IDH2 (p.R172M) Point Mutation in HCT 116 Cell Line | EDC03184 | Human | 3418 | Details Get a Quote |
| IDH2 (c.1272-31A>G )Point Mutation in HAP1 Cell Line | EDC03510 | Human | 3418 | Details Get a Quote |
| IDH1 and IDH2 Overexpression U-87MG Stable Cell Line | EDC01492 | Human | 3417 and 3148 | Details Get a Quote |
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