Finally, we could identify 40 cancer mutations in addition to the PKD1 D665N mutation perturbing the αD1 site, eight of which containing the same amino acid substitution D to N (PKCb D427N, TSSK1 D97N, TTBK1 D116N, CDK11b D507N, CDK8 D103N, PFTAIRE1 D198N, PDGFRa D681N, and STYK1 D201N) and thereby constituting high-confidence downstream rewiring mutants (Figure S4; Table S1). The gene discussed is CDK8; the disease is cancer.