KDM6A is a histone demethylase that belongs to the KDM6 family, specifically targeting di- and tri-methylated histone H3 lysine 27 (H3K27) to remove these modifications, thereby affecting gene expression and transcriptional regulation. KDM6A is frequently mutated in various cancers and functions as a tumor suppressor. Its loss of function or mutations have been implicated in the development and progression of cancers such as multiple myeloma, esophageal squamous cell carcinoma, clear cell renal cell carcinoma, medulloblastoma, adenoid cystic carcinoma, urothelial bladder cancer, T-cell acute lymphoblastic leukemia, and pancreatic cancer. In prostate cancer, KDM6A mutations are associated with the progression to lethal castration-resistant disease. KDM6A is important for the differentiation of embryonic stem cells and the development of various tissues. Its mutations are known to cause Kabuki syndrome, which is characterized by distinct facial features, skeletal anomalies, and intellectual disability. Apart from its demethylase activity, KDM6A also modulates chromatin reprogramming and mediates transcriptional activation/repression in a ligand protein-dependent manner, affecting various physiological and pathological processes.
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