The mechanism of how VHL-C162F increases ZHX2 expression is not well established, although earlier, a genome-wide screen identified ZHX2 as a hydroxylation-dependent VHL substrate that promotes NF-κB activity and ccRCC tumorigenesis [13] The same authors have demonstrated that ZHX2 is regulated by VHL through prolyl hydroxylation and proteasomal degradation. This evidence concerns the gene VHL and nonpapillary renal cell carcinoma.