IDH1

Chr 2

isocitrate dehydrogenase (NADP(+)) 1

Also known as: HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC, PICD

NCBI Gene: 3417ENSG00000138413UniProt: O75874

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 cytoplasm and peroxisomes. It contains the PTS-1 peroxisomal targeting signal sequence. The presence of this enzyme in peroxisomes suggests roles in the regeneration of NADPH for intraperoxisomal reductions, such as the conversion of 2, 4-dienoyl-CoAs to 3-enoyl-CoAs, as well as in peroxisomal reactions that consume 2-oxoglutarate, namely the alpha-hydroxylation of phytanic acid. The cytoplasmic enzyme serves a significant role in cytoplasmic NADPH production. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]

Primary Disease Associations & Inheritance

{Glioma, susceptibility to, somatic}MIM #137800
401
ClinVar variants
33
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical Summary— IDH1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 230 VUS of 401 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.33LOEUF
pLI 0.000
Z-score 0.40
OE 0.90 (0.63–1.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.60Z-score
OE missense 0.89 (0.79–1.00)
207 obs / 233.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.90 (0.63–1.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.79–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 19 / 21.0Missense obs/exp: 207 / 233.0Syn Z: 0.87

ClinVar Variant Classifications

401 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic4
VUS230
Likely Benign117
Benign21
29
Pathogenic
4
Likely Pathogenic
230
VUS
117
Likely Benign
21
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
27
0
29
Likely Pathogenic
0
4
0
0
4
VUS
0
222
8
0
230
Likely Benign
0
5
0
112
117
Benign
0
3
17
1
21
Total023652113401

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IDH1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Glioma, susceptibility to, somatic}

MIM #137800

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The definition of primary and secondary glioblastoma.
Ohgaki H et al.·Clin Cancer Res
2013Review
The Molecular Taxonomy of Primary Prostate Cancer.
Cancer Genome Atlas Research Network·Cell
2015
IDH1 and IDH2 mutations in gliomas.
Yan H et al.·N Engl J Med
2009
PRMT1 driven PTX3 regulates ferritinophagy in glioma.
Lathoria K et al.·Autophagy
2023
Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation.
Figueroa ME et al.·Cancer Cell
2010
Long-term results from the AGILE study of azacitidine plus ivosidenib vs placebo in newly diagnosed IDH1-mutated AML.
Montesinos P et al.·Blood Adv
2025Clinical trial
Systemic Therapy for Chondrosarcoma.
Rock A et al.·Curr Treat Options Oncol
2022Review
Identifying the target, mechanism, and agonist of α-ketoglutaric acid in delaying mesenchymal stem cell senescence.
Cui Z et al.·Cell Rep
2025Functional
IDH1 Inhibition Potentiates Chemotherapy Efficacy in Pancreatic Cancer.
Zarei M et al.·Cancer Res
2024
Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation.
Serra-Camprubí Q et al.·Clin Cancer Res
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Chronic Myeloid Leukemia, Chronic PhaseWithdrawal;Drug

Efficacy and Safety of TKIs' Withdrawal After a Two-step Dose Reduction in Patients with Chronic Myeloid Leukemia

ACTIVE NOT RECRUITING
NCT04147533Phase PHASE2Masaryk UniversityStarted 2020-06-16
Imatinib withdrawalDasatinibNilotinib
GlioblastomaIDH1 Gene MutationIDH2 Gene Mutation

BGB-290 and Temozolomide in Treating Isocitrate Dehydrogenase (IDH)1/2-Mutant Grade I-IV Gliomas

ACTIVE NOT RECRUITING
NCT03749187Phase PHASE1University of California, San FranciscoStarted 2019-04-03
PARP Inhibitor BGB-290Temozolomide (TMZ)
ChondrosarcomasCartilage Tumours

Diagnostic and Therapeutic Targets in Cartilaginous Tumours

RECRUITING
NCT07315542St. Anne's University Hospital Brno, Czech RepublicStarted 2025-05-01
Tumour tissue analysisMolecular validationLiquid biopsy analysis
Locally Advanced Unresectable Primary Central ChondrosarcomaMetastatic Primary Central ChondrosarcomaUnresectable Primary Central Chondrosarcoma

Testing the Combination of Belinostat and SGI-110 (Guadecitabine) or ASTX727 for the Treatment of Unresectable and Metastatic Conventional Chondrosarcoma

ACTIVE NOT RECRUITING
NCT04340843Phase PHASE2National Cancer Institute (NCI)Started 2020-09-08
BelinostatBiopsy ProcedureBiospecimen Collection
Recurrent Malignant GliomaGlioblastomaAnaplastic Astrocytoma

Comprehensive Analysis of Chemotherapy and Targeted Therapy Outcomes in Recurrent Malignant Gliomas

ACTIVE NOT RECRUITING
NCT07448480Blokhin's Russian Cancer Research CenterStarted 2026-02-01
Bevacizumab-Containing RegimensNon-Bevacizumab RegimensBRAF ± MEK Targeted Therapy
AMLIDH1 MutationTreatment

Venetoclax in Combination With Ivosidenib and Azacitidine for Newly Diagnosed IDH1-Mutated AML

RECRUITING
NCT06611839Phase PHASE1, PHASE2Institute of Hematology & Blood Diseases Hospital, ChinaStarted 2025-10-17
Ivosidenib, Venetoclax, Azacitidine
AML, Adult

OBServatory of Compassionate Use of IVOsidenib in France for Patients With Acute Myeloid Leukemia

RECRUITING
NCT06377579French Innovative Leukemia OrganisationStarted 2024-07-31
Myeloproliferative Neoplasms

Registry of Patients With MPNs in Taiwan

ACTIVE NOT RECRUITING
NCT03618485Chang Gung Memorial HospitalStarted 2017-04-01
Acute Myeloid LeukemiaMyelodysplastic Syndrome

Testing the Use of an IDH1 Inhibitor, Olutasidenib, in Acute Myeloid Leukemia Added to ASTX727 and Venetoclax; in High-Risk MDS Added to ASTX727; and Alone in Low Risk MDS (A MyeloMATCH Treatment Substudy)

NOT YET RECRUITING
NCT07153497Phase PHASE2National Cancer Institute (NCI)Started 2026-05-27
Biospecimen CollectionBone Marrow AspirationBone Marrow Biopsy
Low-grade GliomaIDH2 Gene MutationRecurrent Glioma

Niraparib In Recurrent IDH 1/2 Gliomas

ACTIVE NOT RECRUITING
NCT05406700Phase EARLY_PHASE1Massachusetts General HospitalStarted 2023-05-18
NiraparibResection/Treatment with Niraparib
Acute Myeloid Leukemia (AML)

A Study of Gilteritinib in Combination With Ivosidenib or Enasidenib in People With Acute Myeloid Leukemia (AML)

RECRUITING
NCT05756777Phase PHASE1Memorial Sloan Kettering Cancer CenterStarted 2023-06-26
GilteritinibIvosidenibEnasidenib
Acute Myeloid Leukemia

IDH Targeted/Non- Targeted vs Non-targeted/IDH-targeted Approaches in the Treatment of Newly Diagnosed IDH Mutated AML Patients Not Candidates for Intensive Induction Therapy (I- DATA Study)

RECRUITING
NCT05401097Phase PHASE2Alice MimsStarted 2022-09-13
AzacitidineBiopsyEnasidenib

External Resources

Links to major genomics databases and tools