In addition, mutations in the Apc2 zebrafish ortholog apc result in heart looping defects reminiscent of those in Foxa2 and Foxo1 knockouts in mice [3,6,14,119], mutations in the neb human ortholog KIF14 are linked with congenital heart defects associated with the Meckel-Gruber syndrome [120], the pav zebrafish ortholog kif20a is essential for heart development while mutations in the human KIF20A cause familial restrictive cardiomyopathy-6 [116,121], and mutations in the SMC2 human ortholog SMC3 are associated with high rates of congenital heart disease [122]. This evidence concerns the gene FOXO1 and Meckel syndrome.