These mutations led to a significant loss in the HIF1A transcriptional repressive capacity of CITED2 and significantly diminished TFAP2C (a gene involved in early development, specifically morphogenesis) coactivation, providing evidence that CITED2 is a disease-causing gene for congenital heart malformations in humans, particularly septal defects and malrotations of the great arteries [148]. This evidence concerns the gene CITED2 and congenital heart malformation.