KDM6A是抑癌基因，编码蛋白（赖氨酸特异去甲基化酶6A）是一种染色质修饰酶，其介导转录辅激活，其功能是作为二甲基化和三甲基化组蛋白H3赖氨酸27（H3K27）去甲基化酶。KDM6A的胚系缺失和点突变引起Kabuki综合征。在大量的人类恶性肿瘤中发现了KDM6A的失活突变，包括多发性骨髓瘤和食管鳞状细胞癌。后来的研究发现KDM6A突变也存在于透明细胞肾细胞癌、髓母细胞瘤、腺样囊性癌、尿路上皮性膀胱癌、马兜铃酸相关的上尿路上皮癌、T细胞急性淋巴细胞白血病和胰腺癌中。在前列腺癌中，KDM6A基因突变认为是可发展为致命的去势抗性疾病。

KDM6A (lysine-specific demethylase 6A) encodes a chromatin-modifying enzyme that mediates transcriptional co-activation by functioning as a di- and tri-methylated histone H3 lysine 27 (H3K27) demethylase. KDM6A is part of the larger ASC-2 complex (ASCOM) that also contains lysine-specific methyltransferase 2D (KMT2D) and lysine-specific methyltransferase 2C (KMT2C). KDM6A is located on Xp11.2, but it escapes X inactivation, resulting in bi-allelic expression in females. Association of KDM6A with KMT2D and KMT2C couples H3K27 demethylation to H3K4 methylation. Germline deletions and point mutations in KDM6A cause Kabuki syndrome, which is characterized by typical facial features, skeletal anomalies, dermatoglyphic abnormalities, mild-to-moderate intellectual disability and postnatal short stature. Early sequencing efforts led to the discovery of inactivating KDM6A mutations in a number of human malignancies including multiple myeloma and esophageal squamous cell carcinoma. Later studies found KDM6A mutations in clear cell renal cell carcinoma, medulloblastoma, adenoid cystic carcinoma, urothelial bladder cancer, aristolochic acid-associated upper tract urothelial carcinoma, T-cell acute lymphoblastic leukemia, and pancreatic cancer. In prostate cancer, KDM6A mutations are seen in progression to lethal castration-resistant disease. Loss of KDM6A may confer sensitivity to EZH2 inhibitors.

GeneCards OncoKB My Cancer Genome