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STAC3 gene

Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

STAC3 gene

The STAC3 gene provides instructions for making a protein essential for skeletal muscle contraction and is linked to a specific muscle disorder.

Normal Function

The STAC3 gene provides instructions for making a protein whose function is not completely understood. It plays a role in muscles used for movement (skeletal muscles). For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by changes in the concentration of certain charged atoms (ions) in muscle cells. The STAC3 protein aids in the process that triggers the release of calcium ions within muscle cells to start (initiate) muscle contraction.

The STAC3 protein interacts with two structures in muscle cells that are critical for calcium ion flow, dihydropyridine receptor (DHPR) and ryanodine receptor 1 (RYR1). However, STAC3's role in this formation is unknown. RYR1 forms a channel (the RYR1 channel) through which calcium ions can flow. In response to certain signals, DHPR turns on (activates) the RYR1 channel, and the activated RYR1 channel releases calcium ions stored in structures inside muscle cells. The resulting increase in the calcium ion concentration within muscle cells stimulates muscles to contract, allowing the body to move. The process by which certain chemical signals trigger muscle contraction is called excitation-contraction (E-C) coupling.

Health Conditions Related to Genetic Changes

STAC3 disorder

At least five mutations in the STAC3 gene have been found to cause STAC3 disorder (formerly known as Native American myopathy). This condition is a muscle disorder characterized by:

  • Weakness
  • Droopy eyelids (ptosis) and other distinctive facial features
  • Joint deformities (contractures)
  • Increased risk of a condition known as malignant hyperthermia, which is a severe reaction to particular anesthetic drugs that are often used during surgery and other invasive procedures.

Mutations in the STAC3 gene reduce the amount or impair the function of the STAC3 protein. Although the mechanism is unclear, studies show that a shortage of working STAC3 protein affects the function of DHPR and prevents the release of calcium ions by RYR1 channels, resulting in a buildup of calcium in storage. A disruption in calcium ion release prevents muscles from contracting normally, leading to the muscle weakness characteristic of STAC3 disorder.

It is unclear how these STAC3 gene mutations lead to malignant hyperthermia in susceptible individuals. Mutations in other genes related to malignant hyperthermia activate the RYR1 channel improperly in response to certain drugs. As a result, large amounts of calcium ions are released from storage within muscle cells. An overabundance of available calcium ions causes skeletal muscles to contract abnormally, which leads to muscle rigidity. An increase in calcium ion concentration also activates processes that generate heat (leading to increased body temperature) and produce excess acid (leading to acidosis). It is unknown if STAC3 gene mutations have a similar effect on RYR1 channel activity.

Other Names for This Gene

  • SH3 AND CYSTEINE-RICH DOMAINS 3
  • STAC3 gene

Frequently Asked Questions

Diagnosis typically begins with a clinical evaluation by a geneticist or neurologist who assesses for characteristic signs such as muscle weakness, droopy eyelids (ptosis), and joint contractures. Definitive diagnosis requires genetic testing, specifically sequencing of the STAC3 gene, to identify pathogenic mutations. In some cases, a muscle biopsy may be performed to rule out other myopathies, though genetic confirmation is the gold standard. It is important to note that standard muscle enzyme panels like creatine kinase may be normal or only mildly elevated, so a high clinical suspicion is necessary to order the specific genetic test.
Malignant hyperthermia is a life-threatening emergency triggered by certain anesthetic agents or muscle relaxants. Warning signs include a rapid and unexplained rise in body temperature, severe muscle rigidity, rapid heart rate, and confusion. If these symptoms occur during surgery or after exposure to triggers, it is a medical emergency requiring immediate administration of dantrolene, a medication that relaxes muscles, and aggressive cooling measures. Patients with STAC3 disorder must inform all healthcare providers about their condition before any procedure involving anesthesia to ensure safe alternatives are used.
Yes, consistent physical therapy is a cornerstone of management for STAC3 disorder. Stretching exercises and range-of-motion activities are critical to prevent or slow the progression of joint contractures, which can limit mobility and cause pain. Occupational therapy may also be beneficial to help patients maintain independence in daily activities. While these interventions do not cure the underlying genetic defect, they significantly improve quality of life by preserving function and reducing the risk of secondary complications like skin breakdown or difficulty with hygiene. Early and regular engagement with a multidisciplinary rehabilitation team is recommended.
STAC3 disorder is typically inherited in an autosomal recessive pattern, meaning an individual must inherit two mutated copies of the gene, one from each parent, to develop the condition. Parents are usually carriers who do not show symptoms. If a couple has one child with STAC3 disorder, there is a 25% chance with each subsequent pregnancy that the child will also be affected. Genetic counseling is strongly recommended for families to understand the inheritance pattern, assess the risk for future children, and discuss options such as prenatal diagnosis or preimplantation genetic testing for assisted reproduction.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.