Figure 4. Genes associated with arrhythmogenic cardiomyopathy (ACM).

Pathogenic variants in desmosomal genes (shown in yellow) are very frequent among patients with ACM. Less frequently, pathogenic variants in ACM patients are found in genes encoding proteins that interact with the desmosome (CDH2, CTNNA3, and DES), in the genes potentially involved in expression of proteins (LMNA, TFGB3, and TMEM43), in the genes related to sarcoplasmic reticulum calcium homeostasis (PLN), or in the sarcomeric gene TTN (less frequently involved genes are shown in blue). Pathogenic variants in the SCN5A gene have been associated with defects in cadherin 2 (encoded by CDH2) at the intercalated disc, which might underlie the mechanism of ACM (although a direct interaction between these molecules has yet to be demonstrated). SERCA, sarcoplasmic/endoplasmic reticulum calcium ATPase 2; TGFβ, transforming growth factor-β.