In this study, combining chromatin activation and transcriptomic data from multiple ccRCC model systems and clinical samples, we find that one of the strongest super enhancers in ccRCC cells, partially activated by the ccRCC-initiating VHL-HIF2A pathway, is associated with the KLF6 locus, a gene encoding a zinc finger DNA-binding transcription factor of the Kruppel-like family. Here, VHL is linked to nonpapillary renal cell carcinoma.