Our study found ATP5O, DYRK1A, MRAP and OLIG2 have high burden in AVSD, especially DYRK1A that is highly and dynamically expressed in the developing heart, and the gain of function rather loss of function of it will leads to AVSD and Down’s syndrome phenotype. This evidence concerns the gene DYRK1A and familial atrioventricular septal defect.