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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.
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.
CIViC 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.
In plain words · 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.
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.
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 KMT2D 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 KMT2D: RNA low tissue specificity; high antibody staining in 4 normal tissues. Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lung cancer (all types), Lymphoma, Bladder & urothelial cancer, Head and neck squamous cell carcinoma, Colorectal cancer, Prostate cancer, Neuroendocrine tumours and more); Open Targets associates it with 7 specific cancer types at or above 0.5 (diffuse large B-cell lymphoma, head and neck squamous cell carcinoma, prostate adenocarcinoma, squamous cell lung carcinoma, medulloblastoma, urinary bladder cancer and more). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt O14686; CIViC gene KMT2D; IntOGen KMT2D; Human Protein Atlas KMT2D tissue; Open Targets ENSG00000167548 associations
First described 1997. Earliest sequence paper UniProt cites for the protein: Prasad et al, Oncogene, 1997, "Structure and expression pattern of human ALR, a novel gene with strong homology to ALL-1 involved in acute leukemia and to Drosophila trithorax". Source.
Sources: HGNC HGNC:7133 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt O14686 (protein name, function text, keywords and locations (REST API)); CIViC gene KMT2D (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)); Open Targets ENSG00000167548 (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)); IntOGen KMT2D (driver in 91 cohorts (Act 14, LoF 77); 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. Acts as a coactivator for oestrogen receptor by being recruited by ESR1, thereby activating transcription. Location: Nucleus (UniProt). Locus 12q13.12 (HGNC).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Bone marrow, Caudate, Colon, Endometrium, Pancreas, Parathyroid gland, Placenta, Thyroid gland.
No cancer stained high; medium in breast cancer, carcinoid, colorectal cancer, endometrial cancer.
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.
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.
It is the empirical basis for treating the two histologies as separate diseases for targeted therapy and as one disease for immunotherapy, which is exactly how they are treated.
The first demonstration that molecular residual disease can be read in pancreatic cancer and that it moves months ahead of the scan.
Why small-cell lung cancer has no targeted therapy in the conventional sense: it is built from the loss of TP53 and RB1, and the drugs that transformed non-small-cell disease inhibit gains rather than restore losses. The NOTCH result pointed at DLL3 and, eventually, at tarlatamab.
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:"KMT2D" OR ABSTRACT:"KMT2D" OR TITLE:"lysine methyltransferase 2D" OR ABSTRACT:"lysine methyltransferase 2D" OR TITLE:"Histone-lysine N-methyltransferase 2D" OR ABSTRACT:"Histone-lysine N-methyltransferase 2D" OR TITLE:"MLL4" OR ABSTRACT:"MLL4" OR TITLE:"CAGL114" OR ABSTRACT:"CAGL114" OR TITLE:"TNRC21" OR ABSTRACT:"TNRC21") 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 KMT2D, not a curated reading list.
Shares Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas, The germinal centre reaction, Comprehensive genomic profiles of small cell lung cancer, Epigenetic reprogramming.
Shares Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas, The germinal centre reaction, Comprehensive genomic profiles of small cell lung cancer, Epigenetic reprogramming.
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 Epigenetic reprogramming, Mantle cell lymphoma, CIViC, IntOGen.
Shares Epigenetic reprogramming, Bladder & urothelial cancer, CIViC, IntOGen.
Shares The long tail of oncogenic drivers in prostate cancer, The mutational landscape of lethal castration-resistant prostate cancer, Neuroendocrine tumours, CIViC.
Shares Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients, Bladder & urothelial cancer, CIViC, IntOGen.
Shares The germinal centre reaction, Epigenetic reprogramming, CIViC, IntOGen.