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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.
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.
CIViC 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.
In plain words · 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.
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.
Histone methyltransferase that catalyses methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4).
No product in this corpus aims at KMT2C yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
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.)
Sources: UniProt Q8NEZ4; CIViC gene KMT2C; IntOGen KMT2C; Human Protein Atlas KMT2C tissue; Open Targets ENSG00000055609 associations
First described 2000. 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". Source.
Sources: HGNC HGNC:13726 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q8NEZ4 (protein name, function text, keywords and locations (REST API)); CIViC gene KMT2C (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)); Open Targets ENSG00000055609 (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)); IntOGen KMT2C (driver in 79 cohorts (Act 9, LoF 68); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
RNA: low tissue specificity, detected in all normal tissues.
No normal tissue stained high.
No cancer sample stained medium or high.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Prostate cancer | 4-15% | Truncating mutation in chromatin and histone modifiers | 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). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It is the quantitative answer to why prostate cancer has so few targeted therapies. The common events are not druggable, the druggable ones are individually rare, and no trial can be powered on a driver present in 2% of men without an international basket.
This is the sourced bridge between expression subtype and mutation: it tells a clinician that a LAR tumour is the one to sequence for PIK3CA and AKT1, and that immunomodulatory biology is a favourable prognostic group before any immunotherapy.
The first demonstration that molecular residual disease can be read in pancreatic cancer and that it moves months ahead of the scan.
The explanation for why prostate cancer has so few targeted drugs outside the hormone axis and the DNA-repair genes: it is a quiet genome with structural rather than point-mutational damage, and the recurrent changes sit in the machinery that reads DNA rather than in kinases.
Query for this target: (TITLE:"KMT2C" OR ABSTRACT:"KMT2C" OR TITLE:"lysine methyltransferase 2C" OR ABSTRACT:"lysine methyltransferase 2C" OR TITLE:"Histone-lysine N-methyltransferase 2C" OR ABSTRACT:"Histone-lysine N-methyltransferase 2C" OR TITLE:"KIAA1506" OR ABSTRACT:"KIAA1506" OR TITLE:"MLL3" OR ABSTRACT:"MLL3") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about KMT2C, not a curated reading list.
Shares Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients, The long tail of oncogenic drivers in prostate cancer, The mutational landscape of lethal castration-resistant prostate cancer, Bladder & urothelial cancer.
Shares Leukaemia (all types), Bladder & urothelial cancer, CIViC, IntOGen.
Shares Leukaemia (all types), Renal cell carcinoma, Bladder & urothelial cancer, CIViC.
Shares Leukaemia (all types), Renal cell carcinoma, CIViC, IntOGen.
Shares Leukaemia (all types), Renal cell carcinoma, Bladder & urothelial cancer, CIViC.
Shares Leukaemia (all types), Bladder & urothelial cancer, CIViC, IntOGen.
Shares The long tail of oncogenic drivers in prostate cancer, The mutational landscape of lethal castration-resistant prostate cancer, CIViC, IntOGen.
Shares Leukaemia (all types), CIViC, IntOGen, Lung cancer (all types).