KMT2D
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
Histone methyltransferase that catalyses methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4).
- 3 · How drugs use it
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.
External identifiers
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)
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).
- 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
Notes
top- 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.
Latest papers
topQuery 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.
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