 Gain-of-function mutations in the gene ACVR1/ALK2 is responsible for the genetic disease fibrodysplasia ossificans progressiva.The typical FOP patient has the amino acid arginine substituted for the amino acid histidine at position 206 in this protein.This causes a change in the critical glycine-serine activation domain of the protein which will cause the protein to bind its inhibitory ligand (FKBP12) less tightly, and thus over-activate the BMP/SMAD pathway.