{"entity":{"id":"kdm6a","kind":"target","name":"KDM6A","aka":["lysine demethylase 6A","Lysine-specific demethylase 6A"],"tldr":"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.\n\nCIViC 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:12637","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12637"},{"label":"UniProt O15550","url":"https://www.uniprot.org/uniprotkb/O15550/entry"},{"label":"NCBI Gene 7403","url":"https://www.ncbi.nlm.nih.gov/gene/7403"},{"label":"Ensembl ENSG00000147050","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000147050"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["urothelial","prostate","pancreatic","lung-cancer","esophageal","breast-cancer","hcc","gastric"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-waddell-whole-genomes-pancreatic-nature-2015","paper-bailey-molecular-subtypes-pancreatic-nature-2016","paper-andricovich-kdm6a-squamous-pancreatic-cancer-cell-2018"],"journals":[],"dependsOn":[],"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)."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"KDM6A","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:12637","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12637","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt O15550","url":"https://www.uniprot.org/uniprotkb/O15550/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene KDM6A","url":"https://civicdb.org/features/6054","note":"7 evidence items, 0 assertions, 3 variants; diseases: Acute Myeloid Leukaemia, Urinary Bladder Cancer, Pancreatic Cancer (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000147050","url":"https://platform.opentargets.org/target/ENSG00000147050/associations","note":"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)"},{"label":"IntOGen KDM6A","url":"https://www.intogen.org/search?gene=KDM6A","note":"driver in 45 cohorts (Act 11, LoF 34); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"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.)","specificitySources":[{"label":"UniProt O15550","url":"https://www.uniprot.org/uniprotkb/O15550/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene KDM6A","url":"https://civicdb.org/features/6054","note":"7 evidence items, 0 assertions, 3 variants; diseases: Acute Myeloid Leukaemia, Urinary Bladder Cancer, Pancreatic Cancer (GraphQL API, CC0)"},{"label":"IntOGen KDM6A","url":"https://www.intogen.org/search?gene=KDM6A","note":"driver in 45 cohorts (Act 11, LoF 34); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas KDM6A tissue","url":"https://www.proteinatlas.org/ENSG00000147050-KDM6A/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000147050 associations","url":"https://platform.opentargets.org/target/ENSG00000147050/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:12637","ensembl":"ENSG00000147050","uniprot":"O15550","entrez":"7403","firstDescribed":1997,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Lahn B.T. et al, Science, 1997, \"Functional coherence of the human Y chromosome\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9381176/","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).","whereFound":["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%"],"targetClass":"enzyme","prevalence":[{"cancerId":"pancreatic","pct":"3-4","measure":"Inactivating mutation or structural disruption","source":"https://www.cbioportal.org/study/summary?id=pdac_msk_2024","note":"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)."}]},"route":"/targets/kdm6a/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"paper":[{"id":"paper-hayashi-squamous-basal-like-pancreatic-nat-cancer-2020","kind":"paper","name":"A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma","route":"/key-papers/paper-hayashi-squamous-basal-like-pancreatic-nat-cancer-2020/"},{"id":"paper-bailey-molecular-subtypes-pancreatic-nature-2016","kind":"paper","name":"Genomic analyses identify molecular subtypes of pancreatic cancer","route":"/key-papers/paper-bailey-molecular-subtypes-pancreatic-nature-2016/"},{"id":"paper-andricovich-kdm6a-squamous-pancreatic-cancer-cell-2018","kind":"paper","name":"Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors","route":"/key-papers/paper-andricovich-kdm6a-squamous-pancreatic-cancer-cell-2018/"},{"id":"paper-waddell-whole-genomes-pancreatic-nature-2015","kind":"paper","name":"Whole genomes redefine the mutational landscape of pancreatic cancer","route":"/key-papers/paper-waddell-whole-genomes-pancreatic-nature-2015/"}]}}