{"entity":{"id":"kmt2c","kind":"target","name":"KMT2C","aka":["lysine methyltransferase 2C","Histone-lysine N-methyltransferase 2C","KIAA1506","MLL3"],"tldr":"KMT2C (Histone-lysine N-methyltransferase 2C) 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 Breast cancer, Prostate cancer, 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. Likely plays a redundant role with KMT2D in enriching H3K4me1 mark on primed and active enhancer elements.\n\nCIViC holds 9 clinical evidence items and 0 assertions across 3 variants, naming Immune Checkpoint Inhibitor, Gefitinib, Olaparib and Afatinib and others. Open Targets scores its association with cancer at 0.76 (direct and indirect evidence; datatypes literature 0.96, genetic association 0.00, somatic mutation 0.99). IntOGen calls it a driver in 79 cohorts (9 activating, 68 loss-of-function), covering Adrenocortical Carcinoma, Adenoid Cystic Carcinoma, Acute Myeloid Leukaemia, Anal Squamous Cell Carcinoma, Basal Cell Carcinoma, Bladder Urothelial Carcinoma and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:13726","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13726"},{"label":"UniProt Q8NEZ4","url":"https://www.uniprot.org/uniprotkb/Q8NEZ4/entry"},{"label":"NCBI Gene 58508","url":"https://www.ncbi.nlm.nih.gov/gene/58508"},{"label":"Ensembl ENSG00000055609","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000055609"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["breast-cancer","prostate","urothelial","pancreatic","lung-cancer","colorectal","leukaemia","rcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-grasso-mutational-landscape-lethal-crpc-nature-2012","paper-armenia-long-tail-oncogenic-drivers-prostate-nat-genet-2018"],"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 9 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 68 cohorts; CIViC holds 9 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: Skin Squamous Cell Carcinoma."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"KMT2C","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:13726","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13726","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q8NEZ4","url":"https://www.uniprot.org/uniprotkb/Q8NEZ4/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene KMT2C","url":"https://civicdb.org/features/14089","note":"9 evidence items, 0 assertions, 3 variants; diseases: Melanoma, Lung Non-small Cell Carcinoma, Bladder Carcinoma, Breast Cancer, Diffuse Large B-cell Lymphoma and 3 more (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000055609","url":"https://platform.opentargets.org/target/ENSG00000055609/associations","note":"association with cancer (MONDO_0004992) 0.76; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.56, colorectal cancer 0.63, gastric cancer 0.54, prostate cancer 0.65, urinary bladder cancer 0.63, renal cell carcinoma 0.53 (GraphQL API, CC0)"},{"label":"IntOGen KMT2C","url":"https://www.intogen.org/search?gene=KMT2C","note":"driver in 79 cohorts (Act 9, LoF 68); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA KMT2C: RNA low tissue specificity; no normal tissue stained high. Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Breast cancer (all types), Prostate cancer, Bladder & urothelial cancer, Pancreatic ductal adenocarcinoma, Lung cancer (all types), Colorectal cancer, Leukaemia and more); Open Targets associates it with 6 specific cancer types at or above 0.5 (prostate adenocarcinoma, medulloblastoma, cervical squamous cell carcinoma, breast adenocarcinoma, urinary bladder cancer, pancreatic adenocarcinoma). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt Q8NEZ4","url":"https://www.uniprot.org/uniprotkb/Q8NEZ4/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene KMT2C","url":"https://civicdb.org/features/14089","note":"9 evidence items, 0 assertions, 3 variants; diseases: Melanoma, Lung Non-small Cell Carcinoma, Bladder Carcinoma, Breast Cancer, Diffuse Large B-cell Lymphoma and 3 more (GraphQL API, CC0)"},{"label":"IntOGen KMT2C","url":"https://www.intogen.org/search?gene=KMT2C","note":"driver in 79 cohorts (Act 9, LoF 68); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas KMT2C tissue","url":"https://www.proteinatlas.org/ENSG00000055609-KMT2C/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000055609 associations","url":"https://platform.opentargets.org/target/ENSG00000055609/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:13726","ensembl":"ENSG00000055609","uniprot":"Q8NEZ4","entrez":"58508","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. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/10819331/","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. Likely plays a redundant role with KMT2D in enriching H3K4me1 mark on primed and active enhancer elements. Location: Nucleus (UniProt). Locus 7q36.1 (HGNC).","whereFound":["Breast cancer: Open Targets association 0.72 with breast cancer (MONDO_0007254); CIViC evidence names this disease","Prostate cancer: Open Targets association 0.65 with prostate cancer (MONDO_0008315); IntOGen driver in 10 cohorts (PRAD, PROSTATE)","Bladder & urothelial cancer: Open Targets association 0.63 with urinary bladder cancer (MONDO_0001187); CIViC evidence names this disease","Pancreatic ductal adenocarcinoma: IntOGen driver in 6 cohorts (PAAD, PANCREAS)","Lung cancer: Open Targets association 0.65 with lung cancer (MONDO_0008903)","Colorectal cancer: Open Targets association 0.63 with colorectal cancer (MONDO_0005575); IntOGen driver in 4 cohorts (COAD, COADREAD)","Prostate cancer: truncating mutation in chromatin and histone modifiers 4-15% depending on disease state"],"targetClass":"transcription","prevalence":[{"cancerId":"prostate","pct":"4-15","measure":"Truncating mutation in chromatin and histone modifiers","source":"https://www.cbioportal.org/study/summary?id=prostate_msk_2024","note":"cBioPortal mutation in prostate_msk_2024: KMT2C 156 of 2,260, 6.9%; KMT2D 152, 6.7%; KDM6A 81, 3.6%. In prad_su2c_2019: KMT2C 40 of 444, 9.0%; KMT2D 37, 8.3%; KDM6A 11, 2.5%. In prad_su2c_2015: KMT2C 23 of 150, 15.3%; KMT2D 18, 12.0%. KMT2D (then called MLL2) was mutated in 8.6% of the prostate cancers in the rapid-autopsy series, where the MLL complex was shown to interact with the androgen receptor and to be required for receptor-mediated signalling (Grasso 2012)."}]},"route":"/targets/kmt2c/","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":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"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":"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/"}],"paper":[{"id":"paper-sausen-ctdna-pancreatic-resection-nat-commun-2015","kind":"paper","name":"Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients","route":"/key-papers/paper-sausen-ctdna-pancreatic-resection-nat-commun-2015/"},{"id":"paper-armenia-long-tail-oncogenic-drivers-prostate-nat-genet-2018","kind":"paper","name":"The long tail of oncogenic drivers in prostate cancer","route":"/key-papers/paper-armenia-long-tail-oncogenic-drivers-prostate-nat-genet-2018/"},{"id":"paper-grasso-mutational-landscape-lethal-crpc-nature-2012","kind":"paper","name":"The mutational landscape of lethal castration-resistant prostate cancer","route":"/key-papers/paper-grasso-mutational-landscape-lethal-crpc-nature-2012/"},{"id":"paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018","kind":"paper","name":"Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis","route":"/key-papers/paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018/"}]}}