IDH1 Gene: Isocitrate Dehydrogenase (NADP(+)) 1
A key metabolic enzyme frequently mutated in glioma and acute myeloid leukemia, with diagnostic and prognostic significance.
Gene Information Card
| Symbol | IDH1 |
|---|---|
| Full Name | Isocitrate dehydrogenase (NADP(+)) 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q34 |
| NCBI Gene ID | 3417 ncbi.nlm.nih.gov/gene/3417 |
| Ensembl ID | ENSG00000138413 |
| UniProt ID | O75874 |
| OMIM ID | 147700 |
| HGNC ID | 5382 |
| Aliases | IDH, IDP, IDCD, HEL-216, HEL-S-26 |
Description
The IDH1 gene encodes the cytosolic isocitrate dehydrogenase 1 enzyme, which catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (2-oxoglutarate), producing NADPH from NADP+. This enzyme plays a critical role in cellular metabolism, lipid synthesis, and protection against oxidative stress. Mutations in IDH1, particularly at arginine 132, confer a neomorphic activity that produces the oncometabolite 2-hydroxyglutarate (2-HG), leading to epigenetic dysregulation and tumorigenesis. IDH1 mutations are common in low-grade gliomas, secondary glioblastomas, and acute myeloid leukemia, and are associated with distinct clinical outcomes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glioma (low-grade, secondary glioblastoma) | Heterozygous mutations at R132 (e.g., R132H) result in neomorphic enzyme activity producing 2-hydroxyglutarate (2-HG), which competitively inhibits alpha-ketoglutarate-dependent dioxygenases, leading to DNA and histone hypermethylation, altered gene expression, and blocked cellular differentiation. | COSMIC, ClinVar, multiple studies |
| Acute myeloid leukemia (AML) | Recurrent somatic mutations at R132 (e.g., R132C, R132H) produce 2-HG, which disrupts hematopoietic differentiation and promotes leukemogenesis via epigenetic alterations. | COSMIC, ClinVar, multiple studies |
| Ollier disease and Maffucci syndrome (somatic mosaic) | Somatic mosaic mutations in IDH1 (and IDH2) are found in enchondromas and spindle cell hemangiomas, leading to 2-HG production and altered chondrocyte differentiation. | OMIM, ClinVar |
| D-2-hydroxyglutaric aciduria (rare, germline) | Germline mutations in IDH1 (e.g., R132H) can cause metabolic disorder with accumulation of D-2-hydroxyglutarate, leading to neurological symptoms. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 20.1 | High |
| Kidney | 15.3 | High |
| Heart | 12.8 | Medium |
| Brain | 10.5 | Medium |
| Lung | 8.2 | Medium |
| Skeletal Muscle | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 25.4 | High expression |
| A549 (lung cancer) | 12.1 | Medium expression |
| MCF7 (breast cancer) | 9.8 | Medium expression |
| K562 (leukemia) | 7.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R132H | Missense (G>A) | ~70% of IDH1 mutations in glioma | Neomorphic: produces 2-HG; associated with better prognosis in glioma |
| R132C | Missense (C>T) | ~15% of IDH1 mutations in glioma; common in AML | Neomorphic: produces 2-HG; similar oncogenic effect |
| R132G | Missense (C>G) | ~5% of IDH1 mutations | Neomorphic: produces 2-HG |
| R132S | Missense (C>A) | ~3% of IDH1 mutations | Neomorphic: produces 2-HG |
| R132L | Missense (G>T) | ~2% of IDH1 mutations | Neomorphic: produces 2-HG |
Mutation functional classification
Loss of Function (LOF)
Loss of normal catalytic activity (conversion of isocitrate to alpha-KG) is observed, but the oncogenic effect is primarily due to gain of neomorphic activity.
Gain of Function (GOF)
Gain of neomorphic activity: mutant IDH1 reduces alpha-KG to 2-hydroxyglutarate (2-HG) using NADPH, leading to accumulation of 2-HG, an oncometabolite.
Dominant Negative (DN)
Not typically classified as dominant negative; mutations are heterozygous and act via gain-of-function, but the mutant subunit can dimerize with wild-type, altering activity.
View complete mutation data：
Gene Ontology (GO)
| • isocitrate dehydrogenase (NADP+) activity | • oxidoreductase activity |
| • magnesium ion binding | • manganese ion binding |
| • NADP binding | • cytoplasm |
| • peroxisome | • cytosol |
| • carbohydrate metabolic process | • glyoxylate cycle |
| • NADPH regeneration | • response to oxidative stress |
Pathways
• Isocitrate metabolism
• Glyoxylate cycle
• 2-oxoglutarate (alpha-KG) metabolic process
• NADPH regeneration
• Glutathione metabolism (indirect)
• Hypoxia-inducible factor (HIF) signaling (via 2-HG inhibition)
Protein Summary
The IDH1 protein is a homodimeric cytosolic enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, producing NADPH. It plays a key role in cellular defense against oxidative stress and in lipid metabolism. Mutations at arginine 132 alter the enzyme's active site, enabling the conversion of alpha-ketoglutarate to 2-hydroxyglutarate (2-HG), an oncometabolite that competitively inhibits alpha-KG-dependent dioxygenases, leading to epigenetic alterations and tumorigenesis. The protein is a target for cancer therapy, with specific inhibitors (e.g., ivosidenib) approved for AML and under investigation for gliomas.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IDH1 Knockout HEK293 Cell Line | EDJ-KQ17797 | Human | 3417 | Details Get a Quote |
| IDH1 Knockout A-549 Cell Line | EDJ-KQ19888 | Human | 3417 | Details Get a Quote |
| IDH1 Knockout HCT 116 Cell Line | EDJ-KQ19889 | Human | 3417 | Details Get a Quote |
| IDH1 Knockout HeLa Cell Line | EDJ-KQ19890 | Human | 3417 | Details Get a Quote |
| IDH1 (p.R132H) Point Mutation in HCT 116 Cell Line | EDC03179 | Human | 3417 | Details Get a Quote |
| IDH1 (c.851-13C>T )Point Mutation in HAP1 Cell Line | EDC03509 | Human | 3417 | Details Get a Quote |
| IDH1 and IDH2 Overexpression U-87MG Stable Cell Line | EDC01492 | Human | 3417 and 3148 | Details Get a Quote |
| IDH1（p.R132H）Point Mutation in U-87MG Cell Line | EDC90384 | Human | 3417 | Details Get a Quote |
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