NKX2-5 and ventricular septal defect: On the other hand, it seems that the role of genes, such as GATA4, TBX5, NKX2-5, HOMEZ, PLAGL1, and CITED2, in heart development is significant, as numerous studies on knockout mice report that mutations in these genes are frequently associated with VSD or other congenital heart anomalies [43–45].