Calmodulin 2 (CALM2) mRNA (CALM2)

Calmodulin 2 (CALM2) mRNA is the transcript of one of three genes (CALM1, CALM2, CALM3) that encode the identical, ubiquitous calcium-sensing protein calmodulin (UniProt: P62158; NCBI Gene: 805). Calmodulin is essential for the regulation of numerous proteins, including cardiac ion channels like the L-type calcium channel (Cav1.2) and the ryanodine receptor (RyR2), which are critical for maintaining a stable heart rhythm (Limpitikul et al., 2017; Yamamoto et al., 2017). Mutations in the CALM2 gene are linked to severe, early-onset cardiac arrhythmias known as calmodulinopathies, including Long QT Syndrome (LQTS) and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) (Crotti et al., 2013). These mutations typically act in a dominant-negative fashion, where the presence of a small amount of mutant protein significantly disrupts cardiac electrical activity (Limpitikul et al., 2017). Consequently, CALM2 mRNA has become a target for precision medicine strategies, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), designed to selectively silence the mutant allele (Yamamoto et al., 2017). By reducing the expression of the pathogenic mRNA, these therapies aim to restore normal calcium signaling and prevent life-threatening ventricular arrhythmias (Limpitikul et al., 2017; Yamamoto et al., 2017).

Other names

CAM2CAMBCAMIIPHKD2Calmodulin-2

Allele-specific mRNA degradation via RNA interference or antisense-mediated RNase H cleavage (Limpitikul et al., 2017; Yamamoto et al., 2017)