What effect does the mutation in ACVR1 cause in FOP?

The mutation in ACVR1 that leads to Fibrodysplasia Ossificans Progressiva (FOP) results in a gain-of-function effect that demonstrates agonist activity. In FOP, the mutated ACVR1 gene produces a receptor that becomes constitutively active, meaning it signals continuously without the need for its normal activator, BMP (Bone Morphogenetic Protein). This continuous signaling causes the inappropriate formation of bone in soft tissues, leading to the hallmark symptom of FOP, which is progressive ossification and loss of mobility.

This gain-of-function mutation is characterized by the receptor’s altered behavior, driving excess bone formation even in the absence of external stimuli or signals that typically would promote such activity. Consequently, the agonist activity is reflected in the exaggerated response of the signaling pathway associated with ACVR1 due to its mutation, rather than a reduction in activity or an antagonistic effect. Understanding this mechanism is crucial for grasping the pathology behind FOP and highlights the importance of receptor signaling in tissue development and regeneration.