For example, congenital heart disease–linked Nkx2.5 mutations impaired sumoylation (Wang et al., 2008), and Nkx2.5 haplo-insufficient mice with the cardiac-specific expression of sumoylation-deficient Nkx2.5 mutant developed congenital heart defects (Kim et al., 2011), recapitulating the human cardiac phenotypes. Here, NKX2-5 is linked to congenital heart disease.