Heterozygous loss- or gain of function variants in TBX5 can cause Holt-Oram syndrome in humans, characterized by congenital heart defects and cardiac conduction anomalies, as a result of profound changes in the gene regulatory networks controlling heart development and function (Basson et al., 1997; Bruneau et al., 1999; Kathiriya et al., 2021; Li et al., 1997; Mori et al., 2006; Moskowitz et al., 2004). The gene discussed is TBX5; the disease is Holt-Oram syndrome.