KDM6A

Overview

KDM6A (UTX) is an H3K27 histone demethylase and chromatin-modifying tumor suppressor that is one of the most frequently mutated genes in urothelial carcinoma.

Alterations observed in the corpus

  • KDM6A was among the genes frequently co-altered with FGFR3 in urothelial carcinoma in the MSK bladder_msk_2023 cohort, alongside CDKN2A and CDKN2B PMID:37682528.
  • KDM6A was identified as a novel recurrent driver mutation (chromatin remodeling) enriched in MG3 and MG4 meningioma molecular groups in a clinically applicable integrative molecular classification of 201 meningiomas PMID:34433969.
  • KDM6A deep deletion detected in neuroendocrine prostate cancer (NEPC) PDX pair 144 in a multi-omic characterization of 44 PDXs from 38 patients in the MDA PCa PDX series PMID:38488813.
  • KDM6A was among the liquid biopsy-associated genes analyzed in ctDNA-based VTE risk prediction across cancer types in a MSK cohort (n=5,765) PMID:39147831.
  • KDM6A detected in 18% of pretreatment cfDNA samples from 201 metastatic urothelial carcinoma patients in the CALGB 90601 trial (MSK-ACCESS, 129-gene panel); no statistically significant survival association was reported for KDM6A alone but it is among the most common alterations in the mUC cfDNA landscape. PMID:40256659
  • Chromatin modifier commonly mutated in bladder cancer; shared trunk mutation in phylogenetic analyses of primary-metastasis pairs PMID:36543146
  • KDM6A is a chromatin-modifying gene with high prevalence of non-silent variants in metastatic UC (UC-GENOME cohort), consistent with TCGA-BLCA PMID:36333289
  • KDM6A (UTX) identified as mutated in medulloblastoma WGS cohort (PCGP, 37 tumors); mutations implicate histone H3K27 demethylation pathway disruption in pediatric brain cancer PMID:22722829
  • KDM6A alterations detected in prostate cancer WES cohort (Michigan, 112 tumors); loss of KDM6A histone demethylase activity may synergize with EZH2 gain in prostate cancer progression PMID:22722839
  • Somatic mutations detected in medulloblastoma WES cohort (Broad, 92 tumors) PMID:22820256
  • Somatic mutations identified in medulloblastoma WGS/WES cohort (ICGC, 76 tumors) PMID:22832583
  • Chromatin-modifying gene recurrently altered in AML; part of the epigenetic modifier category alongside EZH2, KMT2A, and KMT2C in the TCGA AML cohort PMID:23634996
  • Missense mutation in 7% of ACC samples; loss of H3K27me3 demethylase activity confirmed in vitro; identified as a CHASM driver in ACC PMID:23685749
  • Mutated in adenoid cystic carcinoma (ACC); part of a cluster of chromatin-remodeling genes collectively mutated in 12/24 ACC cases PMID:23778141
  • Histone demethylase KDM6A/UTY mutated in 30% of transitional cell carcinoma (BLCA) bladder tumors, the highest-frequency chromatin-remodeler alteration in the 99-tumor Chinese TCC cohort PMID:24121792
  • KDM6A mutated in 2/21 (9%) of sinonasal adenoid cystic carcinoma cases with frameshift and splice-site variants (c.2172_2173del + c.618-619+2del in one case; c.64del in a second case) PMID:24418857
  • KDM6A (H3K27 demethylase) mutated in 24% of muscle-invasive bladder cancers; mutually exclusive with KMT2D; part of the chromatin regulator mutation landscape affecting 76% of bladder tumors PMID:24476821
  • KDM6A (histone demethylase) is recurrently mutated in ESCC, contributing to epigenetic dysregulation as part of the chromatin-remodeling alteration pathway PMID:24686850
  • Truncating mutations in 41% of muscle-invasive bladder cancer tumours (MSKCC cohort, n=109); not independently associated with recurrence-free or cancer-specific survival in this cohort PMID:25092538
  • Significantly mutated across muscle-invasive urothelial carcinoma cohort by MutSigCV; not differentially enriched between cisplatin responders and non-responders PMID:25096233
  • Chromatin-modifying gene mutated in upper tract urothelial carcinoma (UTUC); mutations common in both low- and high-grade UTUC and concordant across spatial tumor components, suggesting early/clonal events PMID:26278805
  • Truncating chromatin-modifier mutations in primary prostate cancer; enriched in the 26% unclassified genomic subset with high SCNA burden PMID:26544944
  • Added to the significantly-mutated gene list in periampullary tumors by an inactivation-bias statistical test (alongside PBRM1 and RECQL4); recurrently inactivated across ampullary, duodenal, and distal bile-duct adenocarcinoma cohort (n=160) PMID:26804919
  • Recurrent chromatin-regulator mutation in adenoid cystic carcinoma (ACC; n=25 WGS); co-occurs with KMT2C, KMT2D, and SMARCA2/SMARCC1 mutations, consistent with a broader chromatin-remodeling axis in ACC pathogenesis PMID:26862087
  • Significantly mutated in lung SqCC but not other cancer types (excluding HNSC, BLCA) in the TCGA pan-lung cohort PMID:27158780
  • Mut-driver in breast cancer; well-known driver in other cancer types suggesting cross-cancer drug repurposing potential PMID:27161491
  • KDM6A M997fs frameshift identified in pediatric medulloblastoma (MBL) as a prognostic marker for risk-stratification into group 4 PMID:28007021.
  • KDM6A (UTX) histone-modifier alterations frequent in esophageal squamous cell carcinoma (ESCC), especially in the ESCC2 molecular subtype; co-altered with KMT2D and KMT2C PMID:28052061.
  • Q1037 missense mutation in 1/19 sequenced 1p/19q-codeleted oligodendroglioma cases PMID:28472509
  • Most commonly altered chromatin-modifying gene in non-muscle-invasive bladder cancer (NMIBC), mutated in 38% of cases PMID:28583311
  • Recurrent histone-methylation-modifier mutations in medulloblastoma; KDM6A especially enriched in methylation subtype VIII alongside ZMYM3 PMID:28726821
  • Histone demethylase SMG in MIBC (n=412); recurrent inactivating mutations plus 4.9% focal deletions; loss implicates BRD4-EZH2 signaling dependence and sensitivity to JQ1 and EZH2 inhibition; also a MutCN cluster definer. PMID:28988769

Cancer types (linked)

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • Not directly linked to therapy response in the corpus.

Open questions

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:36543146

This page was processed by crosslinker on 2026-05-14. - PMID:36333289

This page was processed by crosslinker on 2026-05-14. - PMID:22722829

This page was processed by crosslinker on 2026-05-14. - PMID:22722839

This page was processed by crosslinker on 2026-05-14. - PMID:22820256

This page was processed by crosslinker on 2026-05-14. - PMID:22832583

This page was processed by crosslinker on 2026-05-14. - PMID:23634996

This page was processed by crosslinker on 2026-05-14. - PMID:23685749

This page was processed by crosslinker on 2026-05-14. - PMID:23778141

This page was processed by crosslinker on 2026-05-14. - PMID:24121792

This page was processed by crosslinker on 2026-05-14. - PMID:24418857

This page was processed by crosslinker on 2026-05-14. - PMID:24476821

This page was processed by crosslinker on 2026-05-14. - PMID:24686850

This page was processed by crosslinker on 2026-05-14. - PMID:25092538

This page was processed by crosslinker on 2026-05-14. - PMID:25096233

This page was processed by crosslinker on 2026-05-14. - PMID:26278805

This page was processed by crosslinker on 2026-05-14. - PMID:26544944

This page was processed by entity-page-writer on 2026-05-15. - PMID:26804919

This page was processed by entity-page-writer on 2026-05-15. - PMID:26862087

This page was processed by entity-page-writer on 2026-05-15. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:27161491

This page was processed by entity-page-writer on 2026-05-15. - PMID:28007021

This page was processed by entity-page-writer on 2026-05-15. - PMID:28052061

This page was processed by entity-page-writer on 2026-05-15. - PMID:28472509

This page was processed by entity-page-writer on 2026-05-15. - PMID:28583311

This page was processed by entity-page-writer on 2026-05-15. - PMID:28726821

This page was processed by wiki-cli on 2026-05-15. - PMID:28988769

This page was processed by entity-page-writer on 2026-05-15.