We observed that Pfam interaction domains were more abundant in the two sets of cancer‐associated proteins, than in the background human proteins (P < 10−4 and P < 10−13, respectively, chi‐squared test), whereas no significant difference between the first two sets was observed, Fig 4A. Hence, this underlined that forming interactions with other proteins was often an essential part for the function of proteins with hotspots. This evidence concerns the gene PROS1 and cancer.