Data from studies using paired isogenic renal cell carcinomas with non-functional (VHL null; HIF-1α/2αhigh) and functional VHL protein (VHL restored; HIF-1α/2αlow), along with siRNA of HIF, allowed us to firmly implicate the role of HIF in downregulating MHC class I expression. This evidence concerns the gene VHL and hereditary clear cell renal cell carcinoma.