IGFBP3 and neoplasm: For example, in bladder cancer, which has one of the highest frequencies of KDM6A mutations, KDM6 inactivation leads to increased H3K27 methylation at regulatory elements that control the tumour suppressor genes such as IGFBP3. IGFBP3 is a known pro-apoptotic factor and its suppression leads to aberrant cell cycle progression and tumourigenesis [50].