KDM5A

Overview

KDM5A (Lysine Demethylase 5A, also known as JARID1A or RBP2) is a histone H3K4 demethylase involved in transcriptional regulation and chromatin remodeling. KDM5A demethylates H3K4me2/3 marks associated with active transcription. It has been identified as a chromatin modifier with roles in cell differentiation and drug resistance in multiple cancer types. In adenoid cystic carcinoma (ACC), KDM5A is part of a cluster of chromatin-remodeling genes recurrently mutated across the tumor cohort.

Alterations observed in the corpus

  • Mutated in adenoid cystic carcinoma (ACC); part of a cluster of chromatin-remodeling genes (including ARID1A, ARID1B, ARID5B, KMT2C, KDM6A, CREBBP, EP300, SMARCA2, CHD2, BRD2) collectively mutated in 12/24 ACC cases PMID:23778141
  • Somatic mutation as part of the histone demethylase KDM5A/KDM5B gene group, altered in 6% of transitional cell carcinoma (BLCA) bladder tumors; contributes to the 58% overall chromatin-remodeler mutation rate in the 99-tumor TCC cohort PMID:24121792
  • KDM5A mismatch-repair and chromatin-remodeling defect detected in hypermutated gastric adenocarcinoma (Pt1); co-occurs with MSH6, TGFBR2, and KMT2D in the hypermutated subclone PMID:25583476
  • Novel amplification target gene in lung SqCC identified in the TCGA pan-lung cancer cohort PMID:27158780
  • Identified as an epigenetic regulator with truncal/subclonal events in matched-tumor phylogenetic analysis of prostate cancer PMID:28825054

Cancer types (linked)

  • ACC (adenoid cystic carcinoma): somatic mutation in whole-genome sequencing study; part of pervasive chromatin-remodeling gene disruption in this tumor type.

Co-occurrence and mutual exclusivity

  • Co-occurs with other chromatin-remodeling gene mutations in ACC; 12/24 cases carried at least one alteration in this gene cluster PMID:23778141

Therapeutic relevance

  • Not directly targeted in the corpus; chromatin-remodeling gene mutations in ACC collectively implicate epigenetic therapeutic approaches.

Open questions

  • Functional consequence of KDM5A mutation in ACC and its relationship to the dominant MYB-NFIB fusion driver has not been characterized PMID:23778141

Sources

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

This page was processed by crosslinker on 2026-05-14. - PMID:25583476

This page was processed by crosslinker on 2026-05-14. - PMID:27158780

This page was processed by wiki-cli on 2026-05-14. - PMID:28825054

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