CALM1

Calmodulin-1 is a ubiquitous calcium-binding messenger protein that serves as the primary intracellular calcium sensor in eukaryotic cells. Through its four EF-hand domains, CALM1 binds calcium ions and undergoes conformational changes that enable it to interact with and regulate over 100 different target proteins including kinases, phosphatases, ion channels, and cytoskeletal proteins. It plays essential roles in muscle contraction, neurotransmitter release, cell cycle progression, and calcium homeostasis. Mutations in CALM1 cause severe cardiac arrhythmias including catecholaminergic polymorphic ventricular tachycardia (CPVT) and long QT syndrome (LQTS), which can lead to sudden cardiac death. The protein is also exploited by bacterial pathogens such as Shigella flexneri whose effector proteins bind the apo form of calmodulin to disrupt calcium signaling during infection.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

• cardiac_ion_channel_repolarization via RYR2 CPVT