# KMT2D

Source: https://onco.cc/targets/kmt2d/  
OnCo record `kmt2d` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: lysine methyltransferase 2D; Histone-lysine N-methyltransferase 2D; MLL4; CAGL114; TNRC21; MLL2
- Tags: cancer-genes-wave
- Symbol: KMT2D
- Class: transcription
- 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).
- Where found: 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

- 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.

## Sources

- HGNC HGNC:7133: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7133
- UniProt O14686: https://www.uniprot.org/uniprotkb/O14686/entry
- NCBI Gene 8085: https://www.ncbi.nlm.nih.gov/gene/8085
- Ensembl ENSG00000167548: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000167548

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Neuroendocrine tumours](https://onco.cc/cancers/neuroendocrine/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Prostate cancer](https://onco.cc/cancers/prostate/)

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JSON: https://onco.cc/api/v1/entities/kmt2d.json