IDH1

Chr 2

isocitrate dehydrogenase (NADP(+)) 1

Catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase (PubMed:10521434, PubMed:19935646). Plays a critical role in the generation of NADPH, an important cofactor in many biosynthesis pathways (PubMed:10521434). May act as a corneal epithelial crystallin and may be involved in maintaining corneal epithelial transparency (By similarity)

OMIMResearchGenerating clinical summary…
DNmechanismLOEUF 1.331 OMIM phenotype
Clinical SummaryIDH1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.33LOEUF
pLI 0.000
Z-score 0.40
OE 0.90 (0.631.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.60Z-score
OE missense 0.89 (0.791.00)
207 obs / 233.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.90 (0.631.33)
00.351.4
Missense OE?0.89 (0.791.00)
00.61.4
Synonymous OE?0.88
01.21.6
LoF obs/exp: 19 / 21.0Missense obs/exp: 207 / 233.0Syn Z: 0.87

This gene — mechanism propensity

DN
0.6549th %ile
GOF
0.5267th %ile
LOF
0.4038th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Acute Myeloid LeukemiaIDH1 Gene MutationIvosidenib

a New Treatment of Newly Diagnosed IDH1 Mutation Acute Myeloid Leukemia

RECRUITING
NCT07007949Phase PHASE2The First Affiliated Hospital of Soochow UniversityStarted 2025-06-01
Ivosidenib combined with venetoclax and azacitidineIvosidenib combined with venetoclax and azacitidine
AMLRefractoryRelapsed

Multicenter, Platform-type Clinical Study of Refractory/Recurrent Acute Myeloid Leukemia

RECRUITING
NCT06265545Phase NAInstitute of Hematology & Blood Diseases Hospital, ChinaStarted 2024-02-22
Ivosidenib,Venetoclax,gilteritinib,Selinexor
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies
Acute Myeloid Leukemia

Phase 1/1b Trial Of Olutasidenib And Ziftomenib For NPM1 And IDH1 Co-Mutated Acute Myeloid Leukemia

NOT YET RECRUITING
NCT07411586Phase PHASE1M.D. Anderson Cancer CenterStarted 2026-08-31
ZiftomenibOlutasidenib
Myeloproliferative Neoplasms

Ivosidenib and Ruxolitinib in Patients With Advanced Myeloproliferative Neoplasms (MPNs) That Have an IDH1 Gene Mutation

RECRUITING
NCT06291987Phase PHASE1University of ChicagoStarted 2024-09-19
IvosidenibRuxolitinib
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
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
Acute Myeloid Leukemia With Gene Mutations

Oral Decitabine Plus Ivosidenib as First Line for Older/Unfit Adult AML Patients

NOT YET RECRUITING
NCT07507760Phase PHASE2PETHEMA FoundationStarted 2026-04
Decitabine/Cedazuridine 35 Mg-100 Mg ORAL TABLETIvosidenib Oral TabletHydroxyurea
Glioma, MalignantComputer-Assisted

Radiomics-Based Visualization and Quantitative Validation of IDH1 Heterogeneity in Gliomas

ACTIVE NOT RECRUITING
NCT05969691Phase NAMingge LLCStarted 2019-03-15
Validation of IDH1 mutations from the radiomics model
Locally Advanced or Metastatic Conventional Chondrosarcoma With an IDH1 Mutation, Untreated or Previously Treated With 1 Systemic Treatment Regimen

Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen

RECRUITING
NCT06127407Phase PHASE3Servier Bio-Innovation LLCStarted 2024-07-09
Ivosidenib 500mgPlacebo
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
GliomaGlioblastomaHigh Grade Glioma

Nivolumab in Patients With IDH-Mutant Gliomas With and Without Hypermutator Phenotype

ACTIVE NOT RECRUITING
NCT03718767Phase PHASE2National Cancer Institute (NCI)Started 2019-03-27
Nivolumab