Furthermore, we showed that Activin A ligand binding is conserved in medaka Acvr2 receptors and that the GS-box destabilizing R206H-equivalent mutations R379H in medaka olaAcvr1, and R239H in olaAcvr1l, respectively, resulted in elevated SMAD1/5/8 signaling, which is a hallmark of FOP. Here, SMAD1 is linked to fibrodysplasia ossificans progressiva.