Furthermore, it is known that HIFs function can be affected by mutations that have been observed in different carcinomas, brain gliomas, and skin melanomas [82]; in-depth analysis within the COSMIC database, performed in this work and by other Authors [19] indicated that many cancer-related missense mutations are located in the PAS-A-PAS-B regions at the HIF-2α:ARNT interface, thus offering a valid reference point to validate our hypotheses. This evidence concerns the gene EPAS1 and cancer.