# KDM6A

Source: https://onco.cc/targets/kdm6a/  
OnCo record `kdm6a` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

KDM6A (Lysine-specific demethylase 6A) is an enzyme. 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 Bladder & urothelial cancer, Prostate cancer, Pancreatic ductal adenocarcinoma and 5 more.

## Summary

Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression.

CIViC holds 7 clinical evidence items and 0 assertions across 3 variants, naming Olaparib, Venetoclax, BET Inhibitor and EZH2 Inhibitor. Open Targets scores its association with cancer at 0.81 (direct and indirect evidence; datatypes literature 0.99, genetic association 0.00, somatic mutation 0.97). IntOGen calls it a driver in 45 cohorts (11 activating, 34 loss-of-function), covering Acute Lymphoblastic Leukaemia, Bladder/Urinary Tract, Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Oesophageal Adenocarcinoma, Oesophageal Squamous Cell Carcinoma and others.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: lysine demethylase 6A; Lysine-specific demethylase 6A
- Tags: cancer-genes-wave
- Symbol: KDM6A
- Class: enzyme
- Biology: Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A. Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression. Location: Nucleus (UniProt). Locus Xp11.3 (HGNC).
- Where found: Bladder & urothelial cancer: Open Targets association 0.76 with urinary bladder cancer (MONDO_0001187); IntOGen driver in 9 cohorts (BLADDER, BLCA); Prostate cancer: Open Targets association 0.62 with prostate cancer (MONDO_0008315); IntOGen driver in 9 cohorts (PRAD, PROSTATE); Pancreatic ductal adenocarcinoma: CIViC evidence names this disease; IntOGen driver in 4 cohorts (PAAD); Lung cancer: Open Targets association 0.63 with lung cancer (MONDO_0008903); Oesophageal cancer: IntOGen driver in 3 cohorts (ESCA, ESCC); Breast cancer: Open Targets association 0.59 with breast cancer (MONDO_0007254); IntOGen driver in 2 cohorts (BRCA); Pancreatic ductal adenocarcinoma: inactivating mutation or structural disruption 3-4%

## 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 4 therapies; IntOGen calls it an activating (Act) driver in 11 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 34 cohorts; CIViC holds 7 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: Urinary Bladder Cancer.
- Pancreatic ductal adenocarcinoma: inactivating mutations or structural disruption in 3 to 4% (cBioPortal), first proposed as a driver from whole-genome rearrangements (Waddell 2015) and enriched in the squamous subtype (Bailey 2016). KDM6A loss induced squamous-like, metastatic tumours through super-enhancers at delta-Np63, MYC and RUNX3, selectively in females, and conferred BET inhibitor sensitivity in mice (Andricovich 2018).

## Sources

- HGNC HGNC:12637: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12637
- UniProt O15550: https://www.uniprot.org/uniprotkb/O15550/entry
- NCBI Gene 7403: https://www.ncbi.nlm.nih.gov/gene/7403
- Ensembl ENSG00000147050: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000147050

## 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/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- key papers: [A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-hayashi-squamous-basal-like-pancreatic-nat-cancer-2020/), [Genomic analyses identify molecular subtypes of pancreatic cancer](https://onco.cc/key-papers/paper-bailey-molecular-subtypes-pancreatic-nature-2016/), [Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors](https://onco.cc/key-papers/paper-andricovich-kdm6a-squamous-pancreatic-cancer-cell-2018/), [Whole genomes redefine the mutational landscape of pancreatic cancer](https://onco.cc/key-papers/paper-waddell-whole-genomes-pancreatic-nature-2015/)

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