RPS6KA4 and craniosynostosis: Lastly, protein altering de novo mutations were also identified in other regulators and mediators of MAP kinase signaling, including RASAL2, DUSP5, MAP3K8, KSR2, RPS6KA4, and RGS3. 5 of 6 occurred in probands with sagittal craniosynostosis (Table 1—source data 1).