CAPN3
Calpain 3
Gene Summary
RefSeq / NCBICalpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene encodes a muscle-specific member of the calpain large subunit family that specifically binds to titin. Mutations in this gene are associated with limb-girdle muscular dystrophies type 2A. Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed. [provided by RefSeq, Jul 2008]
Clinical Phenotype
Limb-girdle muscular dystrophy R1 (LGMD2A/R1): the most common LGMD worldwide. Proximal weakness with scapular winging, toe walking, and lordosis. CK is markedly elevated. Cardiac involvement is rare.
Molecular Mechanism
Calpain-3 is a calcium-dependent cysteine protease found in skeletal muscle. It cleaves titin and is involved in myofibrillar remodeling. Loss of calpain-3 leads to impaired sarcomere maintenance and progressive muscle fiber degeneration.
Clinical Hallmarks & Key Evidence
LGMD R1 is the most prevalent LGMD globally, particularly in the Basque Country (Spain) and Reunion Island — populations used to first define the disease.
Richard I et al. Cell. 1995;81(1):27-40.
Scapular winging is a prominent early sign and may precede significant limb weakness, helping distinguish LGMD2A from Duchenne or Emery-Dreifuss MD.
Fardeau M et al. C R Acad Sci III. 1996;319(3):257-64.
Calpain-3 Western blot on muscle biopsy shows absent or reduced band at 94 kDa — complementing genetic testing in resource-limited settings.
Anderson LV et al. Am J Pathol. 1998;153(4):1169-79.
External Resources
Gene data compiled from the Washington University Neuromuscular Disease Center, NCBI Gene, and OMIM. For clinical use, always refer to primary sources.