Several recent studies have shown that, in cc RCC, in addition to inactivating mutations in VHL tumor suppressor genes, genes such as BAP1, PBRM1, SETD2, and KDM5C play a role in tumor development, for example, causing mutations in the ubiquitin-mediated protein hydrolysis pathway (UMPP) in cc RCC; recent sequencing studies of cc RCC sequencing studies have recently identified chromatin modification genes such as PBRM1, KDM6A/UTX, KDM5C/JARID1C, SETD2, MLL2, and BAP1 that are highly associated with inactivating point mutations in their progression and poor prognosis. The gene discussed is VHL; the disease is neoplasm.