Human calmodulin missense mutations in the CALM1, CALM2, and CALM3 genes cause severe cardiac arrhythmias, including CPVT and LQTS, by impairing the regulation of CaV1.2 and RyR2 calcium channels.
Human calmodulin mutations (calmodulinopathies) are a recently identified cause of severe, often early-onset cardiac arrhythmias driven by dysregulation of critical cardiac calcium channels.
release channel, ryanodine receptor isoform 2, RyR2. Currently, no non-cardiac phenotypes have been described for CaM variant carriers. However, sequencing of large human cohorts reveals a cumulative frequency of additional rare CaM mutations that raise the possibility of CaM variants not exclusively causing severe cardiac arrhythmias. Here, we provide an overview of the identified CaM variants and their known consequences for target regulation and cardiac disease phenotype. We discuss experimental data, patient genotypes and phenotypes as well as which questions remain open to understand this complexity.
Jensen et al. (Tue,) conducted a review in Cardiac arrhythmias (CPVT, LQTS, IVF). Calmodulin (CaM) mutations was evaluated. Human calmodulin missense mutations in the CALM1, CALM2, and CALM3 genes cause severe cardiac arrhythmias, including CPVT and LQTS, by impairing the regulation of CaV1.2 and RyR2 calcium channels.