{"entity":{"id":"idh","kind":"target","name":"IDH1 / IDH2","aka":[],"tldr":"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.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Isocitrate_dehydrogenase","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Isocitrate_dehydrogenase"}],"tags":["driver","epigenetic"],"related":["idh1-r132","idh2-mutation"],"cancers":["glioblastoma","aml","cholangiocarcinoma","gallbladder","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["oncomine-dx-target-test","tqb3454","hmpl-306","safusidenib"],"companies":[],"institutions":[],"pathways":["glioma-signalling"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-javle-biliary-ngs-cancer-2016","paper-tcga-molecular-taxonomy-primary-prostate-cell-2015"],"journals":[],"dependsOn":[],"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."],"symbol":"IDH1, IDH2","role":[],"sources":[],"specificity":"tumour-specific","distribution":"few-types","specificityNote":"Tumour-specific alteration: 2 of 2 label readouts filed under it measure a sequence variant (IDH1 R132 mutation, IDH2 mutation (R140 and R172)) absent from normal cells. HPA IDH1: RNA tissue enhanced (liver 501 nTPM); high antibody staining in 10 normal tissues; highest cancer staining prostate cancer (6 of 11 high). HPA IDH2: RNA group enriched (heart muscle 462 nTPM, skeletal muscle 1,220 nTPM, tongue 1,504 nTPM); high antibody staining in 24 normal tissues; highest cancer staining colorectal cancer (7 of 12 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Brain and spinal cord tumours (all types), Leukaemia, Biliary tract cancer (all types)); approvals of single-target medicines aimed at it also list Nasal cavity and paranasal sinus cancers (including esthesioneuroblastoma), not counted; Open Targets associates it with 8 specific cancer types at or above 0.5 (acute myeloid leukemia, Ollier disease, glioblastoma, cholangiocarcinoma, glioma, Maffucci syndrome and more). (Rule 3 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"IDH1 R132 mutation label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=65d254c0-67ad-42c4-b972-ad463b755b2d","note":"Susceptible IDH1 mutation"},{"label":"IDH2 mutation (R140 and R172) label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a5b4cdf0-3fa8-4c6c-80f6-8d8a00e3a5b6","note":"IDH2 mutation"},{"label":"Human Protein Atlas IDH1 tissue","url":"https://www.proteinatlas.org/ENSG00000138413-IDH1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas IDH2 tissue","url":"https://www.proteinatlas.org/ENSG00000182054-IDH2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000138413 associations","url":"https://platform.opentargets.org/target/ENSG00000138413/associations","note":"cancer associations at or above 0.5 (CC0)"},{"label":"Open Targets ENSG00000182054 associations","url":"https://platform.opentargets.org/target/ENSG00000182054/associations","note":"cancer associations at or above 0.5 (CC0)"}],"biology":"Neomorphic enzyme activity; 2-HG inhibits TET and histone demethylases.","whereFound":["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"],"targetClass":"enzyme","prevalence":[{"cancerId":"glioblastoma","pct":"70-80","measure":"IDH1/2 mutation in grade 2-3 glioma","source":"https://www.cbioportal.org/study/summary?id=lgg_tcga_pan_can_atlas_2018","note":"<10% in primary glioblastoma"},{"cancerId":"aml","pct":"15-20","measure":"IDH1 or IDH2 mutation","source":"https://www.cbioportal.org/study/summary?id=laml_tcga_pan_can_atlas_2018"},{"cancerId":"cholangiocarcinoma","pct":"10-20","measure":"IDH1 mutation (intrahepatic)","source":"https://www.cbioportal.org/study/summary?id=chol_tcga_pan_can_atlas_2018"},{"cancerId":"gallbladder","pct":"0.4","measure":"Mutation","source":"https://www.cbioportal.org/study/summary?id=gbc_mskcc_2022","note":"IDH1 mutation in 1 of 244 samples, 0.4%, and no IDH2 mutation in cBioPortal gbc_mskcc_2022; 2 of 103 and 1 of 103 in gbc_msk_2018."},{"cancerId":"prostate","pct":"0.5-1","measure":"Hotspot mutation defining a methylator subtype","source":"https://www.cbioportal.org/study/summary?id=prad_tcga_pan_can_atlas_2018","note":"cBioPortal: 5 of 494, 1.0%, in prad_tcga_pan_can_atlas_2018 (2 R132C, 1 R132G, 1 R132H); 9 of 1,013, 0.9%, in prad_p1000; 14 of 2,260, 0.6%, in prostate_msk_2024; 3 of 477, 0.6%, in prad_cpcg_2017. The TCGA taxonomy put it at 1% of 333 primary tumours and showed the IDH1-mutant subset carried a methylator phenotype (Cancer Genome Atlas Research Network 2015)."}]},"route":"/targets/idh/","neighbours":{"biomarker":[{"id":"idh1-r132","kind":"biomarker","name":"IDH1 R132 mutation","route":"/biomarkers/idh1-r132/"},{"id":"idh2-mutation","kind":"biomarker","name":"IDH2 mutation (R140 and R172)","route":"/biomarkers/idh2-mutation/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"idh-mutant-astrocytoma","kind":"cancer","name":"Astrocytoma, IDH-mutant (grades 2 to 4)","route":"/cancers/idh-mutant-astrocytoma/"},{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"brain-tumours","kind":"cancer","name":"Brain and spinal cord tumours (all types)","route":"/cancers/brain-tumours/"},{"id":"chondrosarcoma","kind":"cancer","name":"Chondrosarcoma","route":"/cancers/chondrosarcoma/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"},{"id":"aml-idh","kind":"cancer","name":"IDH1- and IDH2-mutated acute myeloid leukaemia","route":"/cancers/aml-idh/"},{"id":"intrahepatic-cholangiocarcinoma","kind":"cancer","name":"Intrahepatic cholangiocarcinoma","route":"/cancers/intrahepatic-cholangiocarcinoma/"},{"id":"sinonasal","kind":"cancer","name":"Nasal cavity and paranasal sinus cancers (including esthesioneuroblastoma)","route":"/cancers/sinonasal/"},{"id":"oligodendroglioma","kind":"cancer","name":"Oligodendroglioma, IDH-mutant and 1p/19q-codeleted","route":"/cancers/oligodendroglioma/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"sinonasal-undifferentiated-carcinoma","kind":"cancer","name":"Sinonasal undifferentiated carcinoma (SNUC) and SWI/SNF-deficient sinonasal carcinoma","route":"/cancers/sinonasal-undifferentiated-carcinoma/"}],"drug":[{"id":"enasidenib","kind":"drug","name":"Enasidenib","route":"/drugs/enasidenib/"},{"id":"hmpl-306","kind":"drug","name":"HMPL-306","route":"/drugs/hmpl-306/"},{"id":"ivosidenib","kind":"drug","name":"Ivosidenib","route":"/drugs/ivosidenib/"},{"id":"olutasidenib","kind":"drug","name":"Olutasidenib","route":"/drugs/olutasidenib/"},{"id":"oncomine-dx-target-test","kind":"drug","name":"Oncomine Dx Target Test","route":"/drugs/oncomine-dx-target-test/"},{"id":"safusidenib","kind":"drug","name":"Safusidenib","route":"/drugs/safusidenib/"},{"id":"tqb3454","kind":"drug","name":"TQB3454","route":"/drugs/tqb3454/"},{"id":"vorasidenib","kind":"drug","name":"Vorasidenib","route":"/drugs/vorasidenib/"}],"pathway":[{"id":"cancer-metabolism","kind":"pathway","name":"Cancer metabolism","route":"/pathways/cancer-metabolism/"},{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"},{"id":"glioma-signalling","kind":"pathway","name":"Glioma (KEGG map)","route":"/pathways/glioma-signalling/"},{"id":"glutamine-metabolism","kind":"pathway","name":"Glutamine addiction","route":"/pathways/glutamine-metabolism/"},{"id":"idh-2hg","kind":"pathway","name":"Mutant IDH / 2-hydroxyglutarate","route":"/pathways/idh-2hg/"}],"paper":[{"id":"paper-javle-biliary-ngs-cancer-2016","kind":"paper","name":"Biliary cancer: utility of next-generation sequencing for clinical management","route":"/key-papers/paper-javle-biliary-ngs-cancer-2016/"},{"id":"paper-mody-biliary-ctdna-profiling-jco-po-2019","kind":"paper","name":"Circulating tumor DNA profiling of advanced biliary tract cancers","route":"/key-papers/paper-mody-biliary-ctdna-profiling-jco-po-2019/"},{"id":"paper-indigo-nejm-2023","kind":"paper","name":"INDIGO: vorasidenib, the first targeted drug for IDH-mutant low-grade glioma","route":"/key-papers/paper-indigo-nejm-2023/"},{"id":"paper-jo-idh2-r172-mutations-snuc-mod-pathol-2017","kind":"paper","name":"Recurrent IDH2 R172X mutations in sinonasal undifferentiated carcinoma","route":"/key-papers/paper-jo-idh2-r172-mutations-snuc-mod-pathol-2017/"},{"id":"paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","kind":"paper","name":"TCGA: the molecular taxonomy of primary prostate cancer","route":"/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/"}],"trial":[{"id":"agile","kind":"trial","name":"AGILE","route":"/trials/agile/"},{"id":"claridhy","kind":"trial","name":"ClarIDHy","route":"/trials/claridhy/"},{"id":"indigo","kind":"trial","name":"INDIGO","route":"/trials/indigo/"},{"id":"safir-abc10","kind":"trial","name":"SAFIR-ABC10","route":"/trials/safir-abc10/"}],"term":[{"id":"1p19q-codeletion","kind":"term","name":"1p/19q codeletion","route":"/terms/1p19q-codeletion/"},{"id":"differentiation-syndrome","kind":"term","name":"Differentiation syndrome","route":"/terms/differentiation-syndrome/"},{"id":"epigenetic-progenitor-theory","kind":"term","name":"Epigenetic progenitor theory: cancer without a first mutation","route":"/terms/epigenetic-progenitor-theory/"},{"id":"deregulating-cellular-energetics","kind":"term","name":"Hallmark: reprogramming cellular metabolism","route":"/terms/deregulating-cellular-energetics/"},{"id":"biliary-anatomy-subtypes","kind":"term","name":"Intrahepatic, perihilar, distal and gallbladder cancer","route":"/terms/biliary-anatomy-subtypes/"},{"id":"metabolic-theory-of-cancer","kind":"term","name":"Metabolic theory of cancer: from Warburg to oncometabolites","route":"/terms/metabolic-theory-of-cancer/"}],"technology":[{"id":"epigenetic-drugs","kind":"technology","name":"Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)","route":"/technologies/epigenetic-drugs/"}],"person":[{"id":"andreas-von-deimling","kind":"person","name":"Andreas von Deimling","route":"/people/andreas-von-deimling/"},{"id":"courtney-dinardo","kind":"person","name":"Courtney D. DiNardo","route":"/people/courtney-dinardo/"},{"id":"eytan-stein","kind":"person","name":"Eytan M. Stein","route":"/people/eytan-stein/"},{"id":"ghassan-abou-alfa","kind":"person","name":"Ghassan K. Abou-Alfa","route":"/people/ghassan-abou-alfa/"},{"id":"ingo-mellinghoff","kind":"person","name":"Ingo K. Mellinghoff","route":"/people/ingo-mellinghoff/"},{"id":"tak-mak","kind":"person","name":"Tak W. Mak","route":"/people/tak-mak/"},{"id":"timothy-ley","kind":"person","name":"Timothy J. Ley","route":"/people/timothy-ley/"}],"bottleneck":[{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"}],"idea":[{"id":"idea-bio2-mechanism-defined-baskets","kind":"idea","name":"Group trials by broken mechanism, not by organ or single mutation","route":"/ideas/idea-bio2-mechanism-defined-baskets/"}],"institution":[{"id":"duke-cancer-institute","kind":"institution","name":"Duke Cancer Institute","route":"/institutions/duke-cancer-institute/"},{"id":"nccs","kind":"institution","name":"National Cancer Centre Singapore","route":"/institutions/nccs/"}],"roadmap":[{"id":"epigenetics-roadmap","kind":"roadmap","name":"Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome","route":"/roadmaps/epigenetics-roadmap/"}],"target":[{"id":"tet2","kind":"target","name":"TET2","route":"/targets/tet2/"}]}}