{"entity":{"id":"kmt2d","kind":"target","name":"KMT2D","aka":["lysine methyltransferase 2D","Histone-lysine N-methyltransferase 2D","MLL4","CAGL114","TNRC21","MLL2"],"tldr":"KMT2D (Histone-lysine N-methyltransferase 2D) 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 and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Lung cancer, Non-Hodgkin lymphoma, Bladder & urothelial cancer and 5 more.","summary":"Histone methyltransferase that catalyses methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place. Acts as a coactivator for oestrogen receptor by being recruited by ESR1, thereby activating transcription.\n\nCIViC holds 15 clinical evidence items and 0 assertions across 3 variants, naming Immune Checkpoint Inhibitor, Afatinib, Gefitinib and Olaparib and others. Open Targets scores its association with cancer at 0.81 (direct and indirect evidence; datatypes affected pathway 0.54, literature 0.97, genetic association 0.18, somatic mutation 0.95, animal model 0.27). IntOGen calls it a driver in 91 cohorts (14 activating, 77 loss-of-function), covering Adenoid Cystic Carcinoma, Acute Lymphoblastic Leukaemia, Anal Squamous Cell Carcinoma, Basal Cell Carcinoma, Burkitt Lymphoma, Bladder/Urinary Tract and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:7133","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7133"},{"label":"UniProt O14686","url":"https://www.uniprot.org/uniprotkb/O14686/entry"},{"label":"NCBI Gene 8085","url":"https://www.ncbi.nlm.nih.gov/gene/8085"},{"label":"Ensembl ENSG00000167548","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000167548"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["lung-cancer","non-hodgkin-lymphoma","urothelial","head-and-neck","colorectal","prostate","neuroendocrine","gastric"],"sections":[],"technologies":[],"targets":[],"drugs":[],"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 11 therapies; IntOGen calls it an activating (Act) driver in 14 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 77 cohorts; CIViC holds 15 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" 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: Kabuki Syndrome; High-Grade Glioma, NOS."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"KMT2D","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:7133","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7133","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt O14686","url":"https://www.uniprot.org/uniprotkb/O14686/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene KMT2D","url":"https://civicdb.org/features/64","note":"15 evidence items, 0 assertions, 3 variants; diseases: Mantle Cell Lymphoma, Colorectal Adenocarcinoma, Melanoma, Lung Non-small Cell Carcinoma, Lung Adenocarcinoma and 7 more (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000167548","url":"https://platform.opentargets.org/target/ENSG00000167548/associations","note":"association with cancer (MONDO_0004992) 0.81; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.57, colorectal cancer 0.65, gastric cancer 0.60, oesophageal cancer 0.59, prostate cancer 0.65, urinary bladder cancer 0.68 (GraphQL API, CC0)"},{"label":"IntOGen KMT2D","url":"https://www.intogen.org/search?gene=KMT2D","note":"driver in 91 cohorts (Act 14, LoF 77); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:7133","ensembl":"ENSG00000167548","uniprot":"O14686","entrez":"8085","biology":"Histone methyltransferase that catalyses methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place. Acts as a coactivator for oestrogen receptor by being recruited by ESR1, thereby activating transcription. Location: Nucleus (UniProt). Locus 12q13.12 (HGNC).","whereFound":["Lung cancer: Open Targets association 0.75 with lung cancer (MONDO_0008903)","Non-Hodgkin lymphoma: Open Targets association 0.71 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 3 cohorts (LNM, MLYM, NHL)","Bladder & urothelial cancer: Open Targets association 0.68 with urinary bladder cancer (MONDO_0001187); CIViC evidence names this disease","Head and neck squamous cell carcinoma: Open Targets association 0.66 with head and neck squamous cell carcinoma (MONDO_0010150); IntOGen driver in 6 cohorts (HNSC)","Colorectal cancer: Open Targets association 0.65 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease","Prostate cancer: Open Targets association 0.65 with prostate cancer (MONDO_0008315); CIViC evidence names this disease"],"targetClass":"transcription","prevalence":[]},"route":"/targets/kmt2d/","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":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}]}}