KDM6A
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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'.
- 3 · How drugs use it
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.
External identifiers
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)
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).
- 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)
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 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.
Latest papers
topQuery 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.
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