In addition, loss of SMAD4 is associated with disease progression and poor prognosis in many tumorigenic diseases (Ogawa et al., 2019; Liang et al., 2020; Ezrova et al., 2021), and loss of SMAD4 causes cardiac dysfunction and dilated cardiomyopathy (Umbarkar et al., 2019). This evidence concerns the gene SMAD4 and dilated cardiomyopathy.