IDH2

Chr 15

isocitrate dehydrogenase (NADP(+)) 2

Also known as: D2HGA2, ICD-M, IDH, IDH-2, IDHM, IDP, IDPM, mNADP-IDH

NCBI Gene: 3418 ENSG00000182054 UniProt: P48735 OMIM: 147650

The protein is a mitochondrial NADP(+)-dependent isocitrate dehydrogenase that catalyzes the oxidative decarboxylation of isocitrate to 2-oxoglutarate in intermediary metabolism and energy production. Mutations cause D-2-hydroxyglutaric aciduria 2, a metabolic disorder with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variation (pLI 0.88, LOEUF 0.38), indicating that functional copies are critical for normal cellular metabolism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

LOEUF 0.381 OMIM phenotype

Clinical Summary— IDH2

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.88) — some intolerance to loss-of-function variants.

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Clinical Trials

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

Explore recent and relevant literature in Research Assistant →

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint

0.38LOEUF

pLI 0.883

Z-score 3.54

OE 0.15 (0.07–0.38)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint

1.34Z-score

OE missense 0.76 (0.68–0.86)

191 obs / 250.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios

LoF OE0.15 (0.07–0.38)

0≤0.351.4

Missense OE0.76 (0.68–0.86)

0≤0.61.4

Synonymous OE1.27

0≤1.21.6

LoF obs/exp: 3 / 20.2Missense obs/exp: 191 / 250.8Syn Z: -2.17

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

IDH2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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

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

Astrocytoma, IDH-Mutant, Grade 3

Testing Addition of an Anti-cancer Drug, Vorasidenib to Temozolomide, After Radiation for Advanced Brain Cancer

NOT YET RECRUITING

NCT07215910Phase PHASE3Alliance for Clinical Trials in OncologyStarted 2025-10-20

Intensity-Modulated Radiation TherapyVolume Modulated Arc TherapyPencil Beam Scanning

Myeloproliferative Neoplasms

Registry of Patients With MPNs in Taiwan

ACTIVE NOT RECRUITING

NCT03618485Chang Gung Memorial HospitalStarted 2017-04-01

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

AML, Adult

MRD-positive AML Clinical Study

RECRUITING

NCT07131059Phase NAInstitute of Hematology & Blood Diseases Hospital, ChinaStarted 2024-05-11

IvosidenibGilteritinibVenetoclax

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

Peripheral T-Cell Lymphoma

Real-world Outcomes of Peripheral T-cell Lymphoma: A Multicenter Retrospective and Prospective Cohort Study

RECRUITING

NCT07270861Fudan UniversityStarted 2025-11-15

Observational

Acute Myeloid LeukemiaBlasts 20-30 Percent of Bone Marrow Nucleated CellsChronic Myelomonocytic Leukemia

Azacitidine and Enasidenib in Treating Patients With IDH2-Mutant Myelodysplastic Syndrome

RECRUITING

NCT03383575Phase PHASE2M.D. Anderson Cancer CenterStarted 2018-01-17