SH3 and cysteine-rich domain-containing protein 3 (STAC3)

SH3 and cysteine-rich domain-containing protein 3 (STAC3) is a muscle-specific adaptor protein essential for skeletal muscle excitation–contraction coupling, where it facilitates communication between the dihydropyridine receptor (voltage-gated calcium channel CaV1.1) and the ryanodine receptor 1, thereby enabling membrane depolarization to trigger calcium release and muscle contraction[1][2][4][6]. STAC3 contains a cysteine-rich domain and two SH3 domains, and is specifically expressed in skeletal muscle tissue[6][8]. Mutations in STAC3 disrupt this coupling process, causing congenital myopathies such as Native American myopathy, characterized by muscle weakness, joint contractures, and a high risk of malignant hyperthermia during anesthesia exposure[1][6][4]. There are currently no direct pharmacological agents targeting STAC3, but its gene status is a clinical indicator for safe anesthetic management[1].

Other names

STAC3SH3 and cysteine rich domain 3SH3 and cysteine-rich domain-containing protein 3MGC2793CMYO13CMYP13MYPBBNAM (Native American myopathy protein)

Mutations affect excitation–contraction coupling, increasing risk to malignant hyperthermia on exposure to volatile anesthetics and/or depolarizing muscle relaxants (e.g., succinylcholine), rather than through direct drug interaction