{"entity":{"id":"tet2","kind":"target","name":"TET2","aka":["KIAA1546","tet methylcytosine dioxygenase 2"],"tldr":"TET2 is an enzyme that helps erase methyl marks from DNA so genes can be switched back on. Losing it is one of the commonest first steps toward blood cancer; mutant IDH blocks it indirectly, which is part of how ivosidenib works when it restores normal maturation.","summary":"TET2 (chromosome 4q24) is a dioxygenase that converts 5-methylcytosine to 5-hydroxymethylcytosine and on to 5-formylcytosine and 5-carboxylcytosine, the first steps of active DNA demethylation, and also recruits the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes (UniProt Q6N021). The clonal-haematopoiesis pathway record lists TET2 with DNMT3A and ASXL1 among the mutations of clonal haematopoiesis of indeterminate potential, present in more than a tenth of people over 70 and progressing to myeloid neoplasm at about 0.5 to 1% a year. In OnCo it appears as the enzyme that 2-hydroxyglutarate from mutant IDH1 inhibits, so that ivosidenib restores TET2-dependent demethylation and differentiation, and as a mutation of the follicular helper T-cell lymphomas in which romidepsin is active.","asOf":"2026-09-22","links":[{"label":"HGNC HGNC:25941","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:25941"},{"label":"UniProt Q6N021","url":"https://www.uniprot.org/uniprotkb/Q6N021/entry"},{"label":"NCBI Gene 54790","url":"https://www.ncbi.nlm.nih.gov/gene/54790"},{"label":"Sakata-Yanagimoto et al., Nat Genet 2014: somatic RHOA G17V in angioimmunoblastic T-cell lymphoma","url":"https://doi.org/10.1038/ng.2872"},{"label":"Palomero et al., Nat Genet 2014: recurrent mutations in epigenetic regulators, RHOA and FYN in peripheral T-cell lymphoma","url":"https://doi.org/10.1038/ng.2873"}],"tags":["wave5-target"],"related":["ivosidenib","romidepsin","idh","dnmt3a"],"cancers":["aml","aml-idh","peripheral-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":[],"technologies":["epigenetic-drugs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["epigenetic-reprogramming","clonal-haematopoiesis","idh-2hg"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.","Lymphoma, RHOA G17V and the epigenetic mutations of T-follicular-helper lymphoma: A single substitution, G17V, in the small GTPase RHOA produces a protein that does not bind GTP and that blocks the wild-type protein as well. It is specific to the tumour cell, whereas the TET2 mutations that accompany it are found in non-tumour haematopoietic cells too, which places the TET2 lesion earlier, in the stem cell, and makes this lymphoma a disease that grows out of clonal haematopoiesis. Frequency: RHOA G17V in 68% of angioimmunoblastic T-cell lymphoma samples, with every G17V case also carrying a TET2 mutation (Sakata-Yanagimoto 2014); independently, in 22 of 35 angioimmunoblastic cases, 67%, and 8 of 44 peripheral T-cell lymphoma not otherwise specified, 18%, alongside recurrent TET2, DNMT3A and IDH2 mutations and less frequent FYN, ATM, B2M and CD58 lesions (Palomero 2014). What it changes about treatment: Not through an approved test. The hypomethylating agents are used in this disease on the strength of the TET2 and DNMT3A biology rather than on a mutation result, and azacitidine-containing regimens have shown activity in T-follicular-helper histology specifically."],"provenance":{"editedBy":"OnCo content wave 5 (HGNC REST, UniProt REST, corpus drug and pathway records)","editedOn":"2026-09-22"},"symbol":"TET2","role":[],"sources":[],"specificitySources":[],"hgnc":"HGNC:25941","ensembl":"ENSG00000168769","uniprot":"Q6N021","entrez":"54790","firstDescribed":2000,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Nagase et al, DNA Res, 2000, \"Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/10997877/","biology":"Mutant IDH1 converts alpha-ketoglutarate to the oncometabolite 2-hydroxyglutarate, TET2 and histone demethylases lose activity, and blasts stop maturing; ivosidenib shuts off 2-HG production and TET2 regains activity (ivosidenib mechanism steps). TET2 itself has no drug in the corpus.","whereFound":["Clonal haematopoiesis of indeterminate potential","IDH-mutant AML (TET2 inhibited by 2-hydroxyglutarate)","Follicular helper T-cell lymphomas with TET2 and DNMT3A mutations"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/tet2/","neighbours":{"drug":[{"id":"ivosidenib","kind":"drug","name":"Ivosidenib","route":"/drugs/ivosidenib/"},{"id":"romidepsin","kind":"drug","name":"Romidepsin","route":"/drugs/romidepsin/"}],"target":[{"id":"dnmt3a","kind":"target","name":"DNA methyltransferase 3A (DNMT3A)","route":"/targets/dnmt3a/"},{"id":"idh","kind":"target","name":"IDH1 / IDH2","route":"/targets/idh/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-idh","kind":"cancer","name":"IDH1- and IDH2-mutated acute myeloid leukaemia","route":"/cancers/aml-idh/"},{"id":"angioimmunoblastic-t-cell-lymphoma","kind":"cancer","name":"Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma)","route":"/cancers/angioimmunoblastic-t-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"}],"technology":[{"id":"epigenetic-drugs","kind":"technology","name":"Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)","route":"/technologies/epigenetic-drugs/"}],"pathway":[{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"},{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"},{"id":"idh-2hg","kind":"pathway","name":"Mutant IDH / 2-hydroxyglutarate","route":"/pathways/idh-2hg/"}],"biomarker":[{"id":"rhoa-g17v","kind":"biomarker","name":"RHOA G17V","route":"/biomarkers/rhoa-g17v/"}]}}