How are changes in the ACVR1 gene related to health conditions?
Now we all know that Fibrodysplasia Ossificans Progressiva (FOP) is caused by mutations in the ACVR1 gene. All individuals with a definite diagnosis of FOP 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 (FOP).