# IDH1 / IDH2

Source: https://onco.cc/targets/idh/  
OnCo record `idh` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A metabolic enzyme whose mutant form produces a molecule that scrambles how genes are read; blocking it slows brain tumours and leukaemias.

## Summary

IDH1 and IDH2 are metabolic enzymes whose mutant forms produce the oncometabolite 2-hydroxyglutarate, which inhibits TET and histone demethylases and scrambles how genes are read; inhibitors of the mutant enzyme lower 2-HG and let cells differentiate. Ivosidenib (IDH1) and enasidenib (IDH2) are approved in AML, ivosidenib in cholangiocarcinoma, and vorasidenib (Voranigo, dual IDH1/2) in grade 2 IDH-mutant glioma after INDIGO (2024), the first targeted therapy for low-grade glioma. IDH mutations occur in roughly 70 to 80 percent of grade 2 to 3 gliomas but under 10 percent of primary glioblastoma, in 15 to 20 percent of AML and 10 to 20 percent of intrahepatic cholangiocarcinoma, and in chondrosarcoma. Differentiation syndrome in AML and the durability of glioma control are open questions. Blocking a mutant metabolic enzyme slows brain tumours and leukaemias.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Tags: driver; epigenetic
- Symbol: IDH1, IDH2
- Class: enzyme
- Biology: Neomorphic enzyme activity; 2-HG inhibits TET and histone demethylases.
- Where found: Low-grade glioma (~80%); AML (~20%); Cholangiocarcinoma (~15%); Chondrosarcoma; Gallbladder cancer: mutation 0.4%; Prostate cancer: hotspot mutation defining a methylator subtype 0.5-1% depending on disease state

## Notes

- Gallbladder cancer: IDH1 mutation is rare (1 of 244 samples in cBioPortal gbc_mskcc_2022) against 16% of intrahepatic cholangiocarcinomas (Javle 2016); ivosidenib eligibility is effectively an intrahepatic question.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Isocitrate_dehydrogenase
- Wikipedia: https://en.wikipedia.org/wiki/Isocitrate_dehydrogenase

## Connected records

- biomarkers: [IDH1 R132 mutation](https://onco.cc/biomarkers/idh1-r132/), [IDH2 mutation (R140 and R172)](https://onco.cc/biomarkers/idh2-mutation/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Astrocytoma, IDH-mutant (grades 2 to 4)](https://onco.cc/cancers/idh-mutant-astrocytoma/), [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Brain and spinal cord tumours (all types)](https://onco.cc/cancers/brain-tumours/), [Chondrosarcoma](https://onco.cc/cancers/chondrosarcoma/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [IDH1- and IDH2-mutated acute myeloid leukaemia](https://onco.cc/cancers/aml-idh/), [Intrahepatic cholangiocarcinoma](https://onco.cc/cancers/intrahepatic-cholangiocarcinoma/), [Nasal cavity and paranasal sinus cancers (including esthesioneuroblastoma)](https://onco.cc/cancers/sinonasal/), [Oligodendroglioma, IDH-mutant and 1p/19q-codeleted](https://onco.cc/cancers/oligodendroglioma/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Sinonasal undifferentiated carcinoma (SNUC) and SWI/SNF-deficient sinonasal carcinoma](https://onco.cc/cancers/sinonasal-undifferentiated-carcinoma/)
- drugs: [Enasidenib](https://onco.cc/drugs/enasidenib/), [HMPL-306](https://onco.cc/drugs/hmpl-306/), [Ivosidenib](https://onco.cc/drugs/ivosidenib/), [Olutasidenib](https://onco.cc/drugs/olutasidenib/), [Oncomine Dx Target Test](https://onco.cc/drugs/oncomine-dx-target-test/), [Safusidenib](https://onco.cc/drugs/safusidenib/), [TQB3454](https://onco.cc/drugs/tqb3454/), [Vorasidenib](https://onco.cc/drugs/vorasidenib/)
- pathways: [Cancer metabolism](https://onco.cc/pathways/cancer-metabolism/), [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/), [Glioma (KEGG map)](https://onco.cc/pathways/glioma-signalling/), [Glutamine addiction](https://onco.cc/pathways/glutamine-metabolism/), [Mutant IDH / 2-hydroxyglutarate](https://onco.cc/pathways/idh-2hg/)
- key papers: [Biliary cancer: utility of next-generation sequencing for clinical management](https://onco.cc/key-papers/paper-javle-biliary-ngs-cancer-2016/), [Circulating tumor DNA profiling of advanced biliary tract cancers](https://onco.cc/key-papers/paper-mody-biliary-ctdna-profiling-jco-po-2019/), [INDIGO: vorasidenib, the first targeted drug for IDH-mutant low-grade glioma](https://onco.cc/key-papers/paper-indigo-nejm-2023/), [Recurrent IDH2 R172X mutations in sinonasal undifferentiated carcinoma](https://onco.cc/key-papers/paper-jo-idh2-r172-mutations-snuc-mod-pathol-2017/), [TCGA: the molecular taxonomy of primary prostate cancer](https://onco.cc/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/)
- trials: [AGILE](https://onco.cc/trials/agile/), [ClarIDHy](https://onco.cc/trials/claridhy/), [INDIGO](https://onco.cc/trials/indigo/), [SAFIR-ABC10](https://onco.cc/trials/safir-abc10/)
- terms: [1p/19q codeletion](https://onco.cc/terms/1p19q-codeletion/), [Differentiation syndrome](https://onco.cc/terms/differentiation-syndrome/), [Epigenetic progenitor theory: cancer without a first mutation](https://onco.cc/terms/epigenetic-progenitor-theory/), [Hallmark: reprogramming cellular metabolism](https://onco.cc/terms/deregulating-cellular-energetics/), [Intrahepatic, perihilar, distal and gallbladder cancer](https://onco.cc/terms/biliary-anatomy-subtypes/), [Metabolic theory of cancer: from Warburg to oncometabolites](https://onco.cc/terms/metabolic-theory-of-cancer/)
- technologies: [Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)](https://onco.cc/technologies/epigenetic-drugs/)
- people: [Andreas von Deimling](https://onco.cc/people/andreas-von-deimling/), [Courtney D. DiNardo](https://onco.cc/people/courtney-dinardo/), [Eytan M. Stein](https://onco.cc/people/eytan-stein/), [Ghassan K. Abou-Alfa](https://onco.cc/people/ghassan-abou-alfa/), [Ingo K. Mellinghoff](https://onco.cc/people/ingo-mellinghoff/), [Tak W. Mak](https://onco.cc/people/tak-mak/), [Timothy J. Ley](https://onco.cc/people/timothy-ley/)
- bottlenecks: [The brain: barrier and sanctuary](https://onco.cc/bottlenecks/b-brain-delivery/)
- ideas: [Group trials by broken mechanism, not by organ or single mutation](https://onco.cc/ideas/idea-bio2-mechanism-defined-baskets/)
- institutions: [Duke Cancer Institute](https://onco.cc/institutions/duke-cancer-institute/), [National Cancer Centre Singapore](https://onco.cc/institutions/nccs/)
- roadmaps: [Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome](https://onco.cc/roadmaps/epigenetics-roadmap/)
- targets: [TET2](https://onco.cc/targets/tet2/)

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JSON: https://onco.cc/api/v1/entities/idh.json