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CAPN3 gene
URL of this page: https://medlineplus.gov/genetics/gene/capn3/

CAPN3 gene

calpain 3

Normal Function

The CAPN3 gene provides instructions for making an enzyme called calpain-3, which is found within muscle fiber structures called sarcomeres. Sarcomeres are needed for the tensing of muscle fibers (contraction). When linked together, sarcomeres form myofibrils, which are the basic units of muscle fibers. 

Calpain-3 cuts (cleaves) damaged proteins into shorter segments so that they can be easily removed from the sarcomere. The process of making new proteins and breaking down older proteins within the sarcomere is known as sarcomere remodeling. This process enables the muscle cells to adapt to the body's needs. 

In addition to maintaining the sarcomeres, calpain-3 also interacts with other proteins to help regulate calcium transport within muscle fibers. 

Health Conditions Related to Genetic Changes

Limb-girdle muscular dystrophy

Variants (also called mutations) in the CAPN3 gene can cause two types of limb-girdle muscular dystrophy called LGMD R1 and LGMD D4. LGMD R1 is much more common than LGMD D4. Limb-girdle muscular dystrophies are characterized by muscle weakness (myopathy) and wasting (atrophy), particularly in the muscles of the shoulders, hips, and upper limbs. Individuals with LGMD R1 are more likely to have problems with their shoulders than people with other forms of limb-girdle muscular dystrophy. 

Variants in the CAPN3 gene are the most common cause of limb-girdle muscular dystrophy. Many of the CAPN3 gene variants that cause limb-girdle muscular dystrophy lead to the substitution of one protein building block (amino acid) for another in the calpain-3 enzyme, which causes cells to produce a version of the enzyme that does not function properly. This interferes with the cell's ability to remove waste from the sarcomere, which impairs muscle function. These changes lead to the myopathy and atrophy seen in people with limb-girdle muscular dystrophy. 

More About This Health Condition

Other Names for This Gene

  • calcium-activated neutral protease 3, muscle-specific, large subunit
  • calpain
  • calpain, large polypeptide L3
  • CANP3
  • CANPL3
  • nCL-1
  • p94

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Angelini C. Calpainopathy. 2005 May 10 [updated 2025 May 1]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1313/ Citation on PubMed
  • Beckmann JS, Spencer M. Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance. Neuromuscul Disord. 2008 Dec;18(12):913-21. doi: 10.1016/j.nmd.2008.08.005. Epub 2008 Oct 29. Citation on PubMed or Free article on PubMed Central
  • Broglio L, Tentorio M, Cotelli MS, Mancuso M, Vielmi V, Gregorelli V, Padovani A, Filosto M. Limb-girdle muscular dystrophy-associated protein diseases. Neurologist. 2010 Nov;16(6):340-52. doi: 10.1097/NRL.0b013e3181d35b39. Citation on PubMed
  • Chen L, Tang F, Gao H, Zhang X, Li X, Xiao D. CAPN3: A muscle‑specific calpain with an important role in the pathogenesis of diseases (Review). Int J Mol Med. 2021 Nov;48(5):203. doi: 10.3892/ijmm.2021.5036. Epub 2021 Sep 22. Citation on PubMed
  • Duguez S, Bartoli M, Richard I. Calpain 3: a key regulator of the sarcomere? FEBS J. 2006 Aug;273(15):3427-36. doi: 10.1111/j.1742-4658.2006.05351.x. Citation on PubMed
  • Ermolova N, Kudryashova E, DiFranco M, Vergara J, Kramerova I, Spencer MJ. Pathogenity of some limb girdle muscular dystrophy mutations can result from reduced anchorage to myofibrils and altered stability of calpain 3. Hum Mol Genet. 2011 Sep 1;20(17):3331-45. doi: 10.1093/hmg/ddr239. Epub 2011 May 30. Citation on PubMed
  • Guglieri M, Magri F, Comi GP. Molecular etiopathogenesis of limb girdle muscular and congenital muscular dystrophies: boundaries and contiguities. Clin Chim Acta. 2005 Nov;361(1-2):54-79. doi: 10.1016/j.cccn.2005.05.020. Citation on PubMed
  • Guglieri M, Straub V, Bushby K, Lochmuller H. Limb-girdle muscular dystrophies. Curr Opin Neurol. 2008 Oct;21(5):576-84. doi: 10.1097/WCO.0b013e32830efdc2. Citation on PubMed
  • Kramerova I, Beckmann JS, Spencer MJ. Molecular and cellular basis of calpainopathy (limb girdle muscular dystrophy type 2A). Biochim Biophys Acta. 2007 Feb;1772(2):128-44. doi: 10.1016/j.bbadis.2006.07.002. Epub 2006 Jul 15. Citation on PubMed
  • Laval SH, Bushby KM. Limb-girdle muscular dystrophies--from genetics to molecular pathology. Neuropathol Appl Neurobiol. 2004 Apr;30(2):91-105. doi: 10.1111/j.1365-2990.2004.00555.x. Citation on PubMed
  • Straub V, Bushby K. The childhood limb-girdle muscular dystrophies. Semin Pediatr Neurol. 2006 Jun;13(2):104-14. doi: 10.1016/j.spen.2006.06.006. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.