TBX5 and familial atrioventricular septal defect: In addition, Garg reported [14] that the G296S mutation disrupts the DNA-binding and transactivation activity of GATA4 and destroys the synergy in transcriptional activation between GATA4 and its cofactor TBX5, resulting in heart anomalies such as pulmonary stenosis, atrioventricular septal defect, and ASD.