{"entity":{"id":"setd2","kind":"target","name":"SETD2","aka":["SET domain containing 2, histone lysine methyltransferase","Histone-lysine N-methyltransferase SETD2","HIF-1","KIAA1732","FLJ23184","KMT3A"],"tldr":"SETD2 (Histone-lysine N-methyltransferase SETD2) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Renal cell carcinoma, Leukaemia, Non-Hodgkin lymphoma and 5 more.","summary":"Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate. It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro. Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation.\n\nCIViC holds 3 clinical evidence items and 0 assertions across 2 variants, naming Akt Inhibitor MK2206, PI3Kbeta Inhibitor AZD8186, Samotolisib and Anti-PD1 Monoclonal Antibody and others. Open Targets scores its association with cancer at 0.81 (direct and indirect evidence; datatypes genetic literature 0.38, affected pathway 0.76, literature 0.99, genetic association 0.36, somatic mutation 0.94). IntOGen calls it a driver in 34 cohorts (1 activating, 33 loss-of-function), covering Acute Lymphoblastic Leukaemia, Renal Clear Cell Carcinoma, Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma, Oesophagogastric Adenocarcinoma, Ewing Sarcoma, Glioblastoma and others. In OnCo, 1 product record names it (Temsirolimus).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:18420","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:18420"},{"label":"UniProt Q9BYW2","url":"https://www.uniprot.org/uniprotkb/Q9BYW2/entry"},{"label":"NCBI Gene 29072","url":"https://www.ncbi.nlm.nih.gov/gene/29072"},{"label":"Ensembl ENSG00000181555","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000181555"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["rcc","leukaemia","non-hodgkin-lymphoma","pancreatic","mesothelioma","skin-cancer","lung-cancer","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["temsirolimus"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 6 therapies; IntOGen calls it an activating (Act) driver in 1 cohort; IntOGen calls it a loss-of-function (LoF) driver in 33 cohorts; CIViC holds 3 clinical evidence items on its variants; UniProt keyword \"DNA repair\". Evidence tier \"approved-drug\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Malignant Mesothelioma; Low-Grade Glioma, NOS."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"SETD2","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker","dna-repair"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:18420","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:18420","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9BYW2","url":"https://www.uniprot.org/uniprotkb/Q9BYW2/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene SETD2","url":"https://civicdb.org/features/11289","note":"3 evidence items, 0 assertions, 2 variants; diseases: Clear Cell Renal Cell Carcinoma, Malignant Mesothelioma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000181555","url":"https://platform.opentargets.org/target/ENSG00000181555/associations","note":"association with cancer (MONDO_0004992) 0.81; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.59, renal cell carcinoma 0.70, melanoma 0.64, neuroendocrine neoplasm 0.52, acute lymphoblastic leukaemia 0.64, B-cell chronic lymphocytic leukaemia 0.51 (GraphQL API, CC0)"},{"label":"IntOGen SETD2","url":"https://www.intogen.org/search?gene=SETD2","note":"driver in 34 cohorts (Act 1, LoF 33); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:18420","ensembl":"ENSG00000181555","uniprot":"Q9BYW2","entrez":"29072","biology":"Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate. It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro. Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation. Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A. Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction. Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR). Location: Nucleus; Chromosome (UniProt). Locus 3p21.31 (HGNC).","whereFound":["Renal cell carcinoma: Open Targets association 0.70 with renal cell carcinoma (MONDO_0005086); IntOGen driver in 5 cohorts (CCRCC, PRCC, RCC)","Leukaemia: Open Targets association 0.66 with leukaemia (MONDO_0005059)","Non-Hodgkin lymphoma: Open Targets association 0.64 with non-Hodgkin lymphoma (MONDO_0018908)","Pancreatic ductal adenocarcinoma: IntOGen driver in 3 cohorts (PAAD, PANCREAS)","Mesothelioma: IntOGen driver in 3 cohorts (PLMESO)","Skin cancer: Open Targets association 0.61 with skin cancer (MONDO_0002898)"],"targetClass":"transcription","prevalence":[]},"route":"/targets/setd2/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"drug":[{"id":"temsirolimus","kind":"drug","name":"Temsirolimus","route":"/drugs/temsirolimus/"}]}}