Mechanistic work revealed that Tbx5 and Nk2.5 synergistically interact to promote the expression of the gap junction protein Cx40 (Gja5), reduction of which is assumed to contribute to the cardiac anomalies in Holt-Oram syndrome (Bruneau et al., 2001; Zhou et al., 2005). The gene discussed is GJA5; the disease is Holt-Oram syndrome.