Maynard et al. found that HIF-3α4, an alternatively spliced variant of human HIF-3α, prevented the engagement of HIF-2 to the hypoxia-responsive elements located in the promoter/ enhancer regions of hypoxia-inducible genes, thus suppressed the tumor growth of VHL-null renal cell carcinoma (34). This evidence concerns the gene SESN2 and hereditary clear cell renal cell carcinoma.