BMP signaling has been implicated in the cardiac specification and development of cardiac chambers, valves, septa, and outflow tract (Wang et al., 2011), and SMAD6 mutations in humans are associated with syndromic and non-syndromic congenital malformations, including cardiac outflow tract defects, as well as patent foramen ovale and atrial and ventricular septal defects (Calpena et al., 2020; Galvin et al., 2000; Tan et al., 2012). The gene discussed is SMAD6; the disease is Patent foramen ovale.