In particular, we decided to directly test whether the pbx4 p.A131V variant functions as a genetic modifier and enhances the phenotype caused by loss of a known CHD gene, hand2. hand2 encodes a basic helix-loop-helix factor that has critical requirements for embryonic heart development in zebrafish and mice (Srivastava et al., 1997; Yelon et al., 2000), and mutations in the human HAND2 gene have been associated with CHD (Lu et al., 2016; Shen et al., 2010; Sun et al., 2016; Töpf et al., 2014). This evidence concerns the gene HAND2 and coronary artery disorder.