Activin A receptor type 1 (ACVR1 (also known as ALK2))

Activin A receptor type 1 (ACVR1), also known as activin receptor-like kinase-2 (ALK2), is a type I serine/threonine protein kinase receptor in the TGF-β superfamily, with a central role in transducing signals from bone morphogenetic proteins (BMPs) and activins[7][9]. It is a single-pass transmembrane receptor with an extracellular ligand-binding domain and an intracellular kinase domain. Ligand binding induces complex formation with type II receptors, activating its kinase domain through phosphorylation of a regulatory GS domain. The receptor is essential for normal bone and tissue development; pathogenic gain-of-function mutations (notably R206H) cause fibrodysplasia ossificans progressiva (FOP), a disorder of progressive soft tissue ossification[7][5][9]. ACVR1/ALK2 is an important target in developmental biology, oncology, and rare disease therapeutics, and several small molecule kinase inhibitors have been developed for modulating its function in disease contexts[5][7].

Other names

Activin receptor-like kinase-2ALK2ACVR1Activin A receptor, type IActivin receptor type IActRIA

Drugs targeting ACVR1 typically work through competitive inhibition of the ATP-binding site of the kinase domain, leading to stabilization of the inactive state of the receptor kinase. This action blocks receptor-mediated SMAD phosphorylation and downstream transcription, thereby disrupting ligand (BMP/activin) induced signaling through ALK2/ACVR1.