IDH1

Chr 2

isocitrate dehydrogenase (NADP(+)) 1

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

NCBI Gene: 3417 ENSG00000138413 UniProt: O75874 OMIM: 147700

The enzyme catalyzes the NADP-dependent oxidative decarboxylation of isocitrate to 2-oxoglutarate and plays a critical role in generating NADPH, an important cofactor in biosynthesis pathways. Mutations cause autosomal recessive retinal dystrophy with early childhood onset, primarily affecting vision and retinal function. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.331 OMIM phenotype

Clinical Summary— IDH1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 276 VUS of 489 total submissions

💊

Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.60Z-score

OE missense 0.89 (0.79–1.00)

207 obs / 233.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.90 (0.63–1.33)

0≤0.351.4

Missense OE?0.89 (0.79–1.00)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 19 / 21.0Missense obs/exp: 207 / 233.0Syn Z: 0.87

This gene — mechanism propensity

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

489 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic4

VUS276

Likely Benign164

Benign21

Pathogenic

Likely Pathogenic

276

VUS

164

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	2
Likely Pathogenic	4	0	0	4
VUS	276	0	0	276
Likely Benign	6	0	158	164
Benign	3	17	1	21
Total	291	17	159	467

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap IDH1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

IDH1 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions