Reassuringly, the most enriched pathways were HIF-1 signaling (4.5-fold enrichment, p = 3.18E−17) and renal cell carcinoma (4-fold enrichment, p = 5.65E−09), the latter a disease where the HIF transcriptional response is active due to VHL inactivation by mutation.118. This evidence concerns the gene VHL and hereditary clear cell renal cell carcinoma.