Loss of Rap, specifically of the Rap1b isoform, in Prkar1a KO thyroids in the setting of overactivation of the PKA pathway, resulted in reduced risk of developing thyroid cancer by 65%; this occurred independently of Epac1 as its deletion did not have any effect in PKA-Rap1 associated thyroid tumorigenesis, underlying the essential role of PKA-Rap1 signaling in the development of FTC [68]. The gene discussed is RAPGEF3; the disease is thyroid gland carcinoma.