VHL and nonpapillary renal cell carcinoma: ccRCC has been considered a type of metabolic disease on the basis of the upregulation of several gene products e.g., VHL, MET, fumarate hydratase (FH), folliculin (FLCN), succinate dehydrogenase (SDH) and, TSC1/2 that regulate the mTOR pathway, PTEN, and other energy metabolism-related pathways [110].