VHL and nonpapillary renal cell carcinoma: As another example, ccRCC is closely associated with VHL gene alterations that lead to stabilization and resulting accumulation of HIF-1α and HIF-2α; the increased HIF levels lead to both alterations in glutamine metabolism, and sensitivity to glutamine deprivation [28], as well as increased transcription of a number of downstream genes such as GLUT1, which enables transport of glucose for ATP production [24].