Mutations in genes encoding different Z-disc proteins such as integrin-linked kinase (ILK) and nexilin have recently been shown to cause heart failure by distinct mechanisms such as disturbed mechanosensing, altered mechanotransduction or mechanical Z-disc destabilization.
Expression in zebrafish of nexilin proteins encoded by NEXN mutant alleles induced Z-disk damage and heart failure, demonstrating a dominant-negative effect and confirming the disease-causing nature of these mutations.