In the current study, we have profiled the dynamic active enhancers in the paired ccRCC tissues and identified 10 171 gain VELs in ccRCC, ≈2/3 are new enhancers compared with the previous study.[24] We then experimentally verified the oncogenic roles of the enhancers for FABP5, FABP6, LPCAT1, MET, SEMA5B, SH3GL1, SNX33, and RHBDF2 in ccRCC cells, and predicted IRX3, HSF4, RUNX1, and CEBPB as potential oncogenic TFs. This evidence concerns the gene SEMA5B and nonpapillary renal cell carcinoma.