ACVR1

The ACVR1 gene provides instructions for making the activin receptor type I protein, which is a member of a protein family called bone morphogenetic protein (BMP) type I receptors. BMP receptors span the cell membrane, so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. This arrangement allows receptors to receive signals from outside the cell and transmit them inside to affect cell development and function.

Activin receptor type I is found in many tissues of the body including skeletal muscle and cartilage. It helps to control the growth and development of the bones and muscles, including the gradual replacement of cartilage by bone (ossification). This process occurs in normal skeletal maturation from birth to young adulthood.

Activin receptor type I is normally activated at appropriate times by molecules called ligands. Activation may occur when these ligands, such as BMPs, attach (bind) to the receptor or to other proteins with which it forms a complex. A protein called FKBP12 can inhibit activin receptor type I by binding to the receptor and preventing inappropriate (leaky) activation in the absence of ligand.

fibrodysplasia ossificans progressiva - caused by mutations in the ACVR1 gene

All individuals with a definite diagnosis of fibrodysplasia ossificans progressiva have a mutation in which the protein building block (amino acid) histidine is substituted for the amino acid arginine at position 206 of the ACVR1 protein (written as Arg206His or R206H). Researchers believe that under certain conditions this mutation may change the shape of the receptor. This shape change may disrupt the binding of an inhibitor protein such as FKBP12 or interfere with other mechanisms that control activation. As a result, the receptor may be constantly activated (constitutive activation), even in the absence of ligands. Constitutive activation of the receptor causes overgrowth of bone and cartilage and fusion of joints, resulting in the signs and symptoms of fibrodysplasia ossificans progressiva.