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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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IDH1
isocitrate dehydrogenase (NADP(+)) 1
Chromosome 2 · 2q34
NCBI Gene: 3417Ensembl: ENSG00000138413.15HGNC: HGNC:5382UniProt: A0A024R3Y6
984PubMed Papers
21Diseases
8Drugs
6Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly Studied
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolcytoplasmprotein bindingisocitrate dehydrogenase (NADP+) activityacute myeloid leukemiaEnchondromatosischolangiocarcinomaMaffucci syndrome
✦AI Summary

IDH1 (isocitrate dehydrogenase 1) catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate to 2-ketoglutarate, generating NADPH—a critical cofactor for biosynthetic pathways 1. The enzyme functions in cytosolic and mitochondrial compartments, participating in the tricarboxylic acid cycle and cellular metabolism. Wild-type IDH1 is essential for normal metabolic homeostasis. However, somatic IDH1 mutations—particularly R132H—occur frequently in gliomas (77% of diffuse astrocytomas, 89% of oligodendrogliomas) 2. These mutations cause a neomorphic enzyme activity that converts α-ketoglutarate to 2-hydroxyglutarate (2HG), an oncometabolite driving tumorigenesis 3. IDH1 mutations are similarly common in cytogenetically normal acute myeloid leukemia and associated cartilaginous tumors, characterizing Ollier disease and Maffucci syndrome 4. Clinically, IDH1 mutation status serves as a prognostic biomarker: glioma patients with IDH1 mutations show significantly improved overall and progression-free survival 2. Accordingly, IDH1 inhibitors like olutasidenib have been FDA-approved for treating relapsed/refractory acute myeloid leukemia with susceptible IDH1 mutations 5. Conversely, the IDH1-R132H mutation aggravates cisplatin-induced kidney injury through ferroptosis mechanisms 6, highlighting context-dependent clinical significance.

Sources cited
1
IDH1 catalyzes NADP(+)-dependent oxidative decarboxylation of isocitrate to 2-ketoglutarate and generates NADPH for biosynthesis
PMID: 10521434
2
IDH1 mutations are present in 77% of diffuse astrocytomas and 89% of oligodendrogliomas; mutations correlate with improved overall and progression-free survival in gliomas
PMID: 35996504
3
IDH1 mutations produce 2-hydroxyglutarate (2HG), an oncometabolite with multiple downstream effects promoting tumorigenesis
PMID: 20171147
4
IDH1 mutations characterize low-grade diffuse gliomas, cartilaginous tumors, cytogenetically normal acute myeloid leukemia, and Ollier/Maffucci syndromes
PMID: 32727816
5
Olutasidenib, an IDH1 inhibitor, was FDA-approved for treating relapsed/refractory acute myeloid leukemia with susceptible IDH1 mutations
PMID: 36848032
6
The IDH1-R132H mutation aggravates cisplatin-induced acute kidney injury by promoting ferroptosis through disrupting NDUFA1 and FSP1 interaction
PMID: 39306640
Disease Associationsⓘ21
acute myeloid leukemiaOpen Targets
0.77Strong
EnchondromatosisOpen Targets
0.65Moderate
cholangiocarcinomaOpen Targets
0.65Moderate
Maffucci syndromeOpen Targets
0.65Moderate
glioblastoma multiformeOpen Targets
0.63Moderate
metaphyseal chondromatosis with D-2-hydroxyglutaric aciduriaOpen Targets
0.62Moderate
gliomaOpen Targets
0.59Moderate
Ollier diseaseOpen Targets
0.55Moderate
astrocytomaOpen Targets
0.48Moderate
glioma susceptibility 1Open Targets
0.48Moderate
low grade gliomaOpen Targets
0.47Moderate
acute myeloid leukemia by FAB classificationOpen Targets
0.47Moderate
oligodendrogliomaOpen Targets
0.45Moderate
melanomaOpen Targets
0.45Moderate
pilocytic astrocytomaOpen Targets
0.44Moderate
cutaneous melanomaOpen Targets
0.44Moderate
osteosarcomaOpen Targets
0.43Moderate
prostate adenocarcinomaOpen Targets
0.43Moderate
neoplasmOpen Targets
0.42Moderate
hepatocellular carcinomaOpen Targets
0.41Moderate
GliomaUniProt
Pathogenic Variants6
NM_005896.4(IDH1):c.395G>A (p.Arg132His)Pathogenic
Glioblastoma multiforme, somatic|Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria|not provided|Glioma susceptibility 1|Enchondromatosis|Metaphyseal chondromatosis|Neoplasm|Acute myeloid leukemia with NPM1 somatic mutations|Astrocytoma IDH-mutant|Oligodendroglioma
★★☆☆2024→ Residue 132
NM_005896.4(IDH1):c.394C>T (p.Arg132Cys)Pathogenic
Acute myeloid leukemia|not provided|Enchondromatosis|Enchondromatosis;Maffucci syndrome|Glioma susceptibility 1|Maffucci syndrome|Neoplasm|Juvenile type testicular granulosa cell tumor|Medulloblastoma
★★☆☆2023→ Residue 132
NM_005896.4(IDH1):c.395G>T (p.Arg132Leu)Pathogenic
Neoplasm|not provided|Astrocytoma IDH-mutant
★☆☆☆2025→ Residue 132
NM_005896.4(IDH1):c.394C>A (p.Arg132Ser)Pathogenic
not provided|Acute myeloid leukemia|Hepatocellular carcinoma|Neoplasm|Medulloblastoma SHH activated|Cholangiocarcinoma
★☆☆☆2024→ Residue 132
NM_005896.4(IDH1):c.890G>T (p.Cys297Phe)Likely pathogenic
Paroxysmal extreme pain disorder
★☆☆☆2021→ Residue 297
NM_005896.4(IDH1):c.565A>G (p.Ile189Val)Likely pathogenic
not specified|Enchondromatosis
★☆☆☆→ Residue 189
View on ClinVar ↗
Drug Targets8
BAY1436032Phase I
Isocitrate dehydrogenase [NADP] cytoplasmic inhibitor
acute myeloid leukemia by FAB classification
DS-1001BPhase II
Isocitrate dehydrogenase [NADP] cytoplasmic inhibitor
grade II glioma
IDH305Phase II
Isocitrate dehydrogenase [NADP] cytoplasmic inhibitor
Paraganglioma
IVOSIDENIBApproved
Isocitrate dehydrogenase [NADP] cytoplasmic inhibitor
OLUTASIDENIBApproved
Isocitrate dehydrogenase [NADP] cytoplasmic inhibitor
acute myeloid leukemia by FAB classification
SAFUSIDENIBUNKNOWN
Isocitrate dehydrogenase [NADP] cytoplasmic inhibitor
neoplasm
VORASIDENIBApproved
Isocitrate dehydrogenase [NADP] cytoplasmic inhibitor
oligodendroglioma
VORASIDENIB CITRATEUNKNOWN
Isocitrate dehydrogenase [NADP] cytoplasmic inhibitor
neoplasm
Related Genes
PTENProtein interaction100%ACLYProtein interaction100%ACO1Protein interaction100%ACO2Protein interaction100%ASLProtein interaction100%GPTProtein interaction100%
Tissue Expression6 tissues
Liver
100%
Ovary
20%
Lung
16%
Heart
14%
Brain
12%
Bone Marrow
6%
Gene Interaction Network
Click a node to explore
IDH1PTENACLYACO1ACO2ASLGPT
PROTEIN STRUCTURE
Preparing viewer…
PDB6BKX · 1.65 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.83LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.58 [0.42–0.83]
RankingsWhere IDH1 stands among ~20K protein-coding genes
  • #166of 20,598
    Most Researched984 · top 1%
  • #441of 1,025
    FDA-Approved Drug Targets3
  • #3,281of 5,498
    Most Pathogenic Variants6
  • #7,061of 17,882
    Most Constrained (LOEUF)0.83
Genes detectedIDH1
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
[Astrocytoma, IDH-Mutant].
PMID: 37743331
No Shinkei Geka · 2023
1.00
2
Low-grade glioma.
PMID: 25468226
Cancer Treat Res · 2015
0.90
3
Management of isocitrate dehydrogenase 1/2 mutated acute myeloid leukemia.
PMID: 38600315
Leukemia · 2024
0.82
4
Olutasidenib: First Approval.
PMID: 36848032
Drugs · 2023
0.80
5
IDH1/2 mutation detection in gliomas.
PMID: 25008158
Brain Tumor Pathol · 2015
0.80