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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.
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.
In plain words · 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.
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.
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'.
No product in this corpus aims at KDM6A yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
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 KDM6A: RNA low tissue specificity; high antibody staining in 12 normal tissues; highest cancer staining lymphoma (4 of 10 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Bladder & urothelial cancer, Prostate cancer, Pancreatic ductal adenocarcinoma, Lung cancer (all types), Oesophageal cancer, Breast cancer (all types), Hepatocellular carcinoma and more); Open Targets associates it with 3 specific cancer types at or above 0.5 (urinary bladder cancer, urinary bladder carcinoma, prostate adenocarcinoma). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt O15550; CIViC gene KDM6A; IntOGen KDM6A; Human Protein Atlas KDM6A tissue; Open Targets ENSG00000147050 associations
First described 1997. Earliest sequence paper UniProt cites for the protein: Lahn B.T. et al, Science, 1997, "Functional coherence of the human Y chromosome". Source.
Sources: HGNC HGNC:12637 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt O15550 (protein name, function text, keywords and locations (REST API)); CIViC gene KDM6A (7 evidence items, 0 assertions, 3 variants; diseases: Acute Myeloid Leukaemia, Urinary Bladder Cancer, Pancreatic Cancer (GraphQL API, CC0)); Open Targets ENSG00000147050 (association with cancer (MONDO_0004992) 0.81; per-cancer scores at or above 0.5: gastric cancer 0.54, prostate cancer 0.62, urinary bladder cancer 0.76, neuroendocrine neoplasm 0.55, skin cancer 0.55, breast cancer 0.59 (GraphQL API, CC0)); IntOGen KDM6A (driver in 45 cohorts (Act 11, LoF 34); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adipose tissue, Cerebellum, Cerebral cortex, Endometrium, Esophagus, Hippocampus, Lung, Nasopharynx.
Medium only: carcinoid, head and neck cancer, liver cancer, pancreatic 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.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Pancreatic ductal adenocarcinoma | 3-4% | Inactivating mutation or structural disruption | cBioPortal: 91 of 2,336, 3.9%, in pdac_msk_2024; 12 of 383, 3.1%, in paad_qcmg_uq_2016; 7 of 179, 3.9%, in paad_tcga_pan_can_atlas_2018; 12 of 395, 3.0%, in pancreas_msk_2024. Named a new candidate driver by structural variation in 100 whole genomes (Waddell 2015); the squamous subtype is enriched for KDM6A mutation (Bailey 2016); KDM6A loss induced squamous-like, metastatic tumours through super-enhancer activation of TP63, MYC and RUNX3 and conferred BET inhibitor sensitivity in mice (Andricovich 2018). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It joins the pathology (adenosquamous), the transcriptome (basal-like) and the genome (KDM6A, MYC) into one account of the chemotherapy-resistant subtype, and shows a single biopsy can miss it.
It gives the 3 to 4% of KDM6A-mutant, squamous-programme tumours a mechanism and a candidate drug class.
With Moffitt's classical and basal-like split (the squamous and basal-like groups overlap) this fixed the molecular vocabulary of the disease and gave Precision-Panc and the UK's Glasgow group their trial framework.
The genomic case for platinum in BRCA-type pancreatic cancer, four years before POLO built a maintenance strategy on top of it.
Query for this target: (TITLE:"KDM6A" OR ABSTRACT:"KDM6A" OR TITLE:"lysine demethylase 6A" OR ABSTRACT:"lysine demethylase 6A" OR TITLE:"Lysine-specific demethylase 6A" OR ABSTRACT:"Lysine-specific demethylase 6A") 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 KDM6A, not a curated reading list.
Shares Genomic analyses identify molecular subtypes of pancreatic cancer, Bladder & urothelial cancer, Hepatocellular carcinoma, CIViC.
Shares Genomic analyses identify molecular subtypes of pancreatic cancer, Oesophageal cancer, IntOGen, Gastric & gastro-oesophageal junction cancer.
Shares Whole genomes redefine the mutational landscape of pancreatic cancer, CIViC, IntOGen, Gastric & gastro-oesophageal junction cancer.
Shares Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors, A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma, Oesophageal cancer, Bladder & urothelial cancer.
Shares Whole genomes redefine the mutational landscape of pancreatic cancer, Genomic analyses identify molecular subtypes of pancreatic cancer, Oesophageal cancer, CIViC.
Shares Whole genomes redefine the mutational landscape of pancreatic cancer, Genomic analyses identify molecular subtypes of pancreatic cancer, Pancreatic ductal adenocarcinoma, Prostate cancer.
Shares Genomic analyses identify molecular subtypes of pancreatic cancer, Pancreatic ductal adenocarcinoma.
Shares Whole genomes redefine the mutational landscape of pancreatic cancer, Genomic analyses identify molecular subtypes of pancreatic cancer, Oesophageal cancer, Bladder & urothelial cancer.