Activin receptor type-2B (ACTR-IIB), upon ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Defects in ACTR-IIB are the cause of visceral heterotaxy autosomal type 4 (HTX4), a form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. HTX4 results in an abnormal arrangement of visceral organs and a wide variety of congenital defects.