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CAPN3

calpain 3

The CAPN3 gene provides instructions for producing calpain-3, an enzyme essential for maintaining healthy muscle structure and function, particularly in skeletal muscles. CAPN3 is a gene that encodes the calpain-3 enzyme, which plays a vital role in the remodelling and repair of muscle fibres.

Chromosome 15q15.1 Autosomal recessive HGNC:1480 Tier C
CAPN3 15q15.1 p arm q arm 15

CAPN3 is located on the long (q) arm of chromosome 15, at band 15q15.1. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 15 in the library →

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
CAPN3 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The CAPN3 gene contains the genetic blueprint for calpain-3, a calcium-activated neutral protease found predominantly in muscle tissue. This enzyme is crucial for the ongoing maintenance and repair of muscle fibres. Dysfunctional calpain-3 can lead to the progressive weakening and wasting of muscles.

What the gene does

The calpain-3 enzyme, encoded by the CAPN3 gene, is primarily located within muscle fibre structures known as sarcomeres. Sarcomeres are the fundamental units responsible for muscle contraction. Calpain-3's main role involves cleaving damaged proteins into smaller segments, facilitating their removal from the sarcomere. This continuous process of breaking down old proteins and synthesising new ones, known as sarcomere remodelling, allows muscle cells to adapt to physiological demands. Additionally, calpain-3 interacts with other proteins to help regulate calcium transport within muscle fibres, which is critical for muscle contraction and relaxation.

Video: Genetics 101

Chromosome location

The CAPN3 gene is situated on the long arm of chromosome 15 at position 15.1, denoted as 15q15.1. This specific genomic location places it within a region that has been linked to several inherited conditions affecting muscle health.

Protein structure

The calpain-3 protein is composed of 821 amino acids and exhibits a complex domain architecture. Key regions include a Disordered region at amino acids 7-37, followed by the crucial Calpain catalytic domain from amino acids 74-417. A Domain III spans amino acids 418-586, leading into a Linker region (amino acids 587-649) which also overlaps with another Disordered region (amino acids 609-652). The protein further includes four EF-hand domains: EF-hand 1 (amino acids 649-683), EF-hand 2 (amino acids 692-725), EF-hand 3 (amino acids 722-757), and EF-hand 4 (amino acids 787-821). The final Domain IV covers amino acids 650-821.

Domain map · 821 amino acids
Calpain catalytic (74–417)Domain III (418–586)Linker (587–649)EF-hand 1 (649–683)Domain IV (650–821)EF-hand 2 (692–725)EF-hand 3 (722–757)EF-hand 4 (787–821)Calpain catalytic74–417Domain III418–586Domain IV650–8211~411821
Domain - independent functional unit
Region - functional region
🧬 Explore 3D structure on AlphaFold
UniProt:P20807Length:821 aaStructure:AlphaFold

Key variants

Variants in the CAPN3 gene can disrupt the normal production or function of the calpain-3 enzyme. These genetic changes can range from single nucleotide alterations to larger deletions or insertions, all of which may impair the enzyme's ability to maintain muscle integrity and repair damaged proteins.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for CAPN3.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1194-2del
Deletion
 - Pathogenic ★★★☆ Autosomal recessive limb-girdle muscular dystrophy
c.734dup
Duplication
 p.Pro245_Ser246insTer Pathogenic ★★★☆ Autosomal recessive limb-girdle muscular dystrophy
c.1030-1G>T
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Autosomal recessive limb-girdle muscular dystrophy type 2A
c.1193+2T>C
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Autosomal recessive limb-girdle muscular dystrophy type 2A
c.1507_1511del
Deletion
 p.Gly503fs Pathogenic ★★☆☆ Autosomal recessive limb-girdle muscular dystrophy type 2A
c.1936C>T
single nucleotide variant
 p.Gln646Ter Pathogenic/Likely pathogenic ★★☆☆ Autosomal recessive limb-girdle muscular dystrophy type 2A
c.2047A>T
single nucleotide variant
 p.Lys683Ter Pathogenic/Likely pathogenic ★★☆☆ Autosomal recessive limb-girdle muscular dystrophy type 2A
c.233del
Deletion
 p.Pro78fs Pathogenic/Likely pathogenic ★★☆☆ Autosomal recessive limb-girdle muscular dystrophy type 2A
c.633-2A>G
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Muscular dystrophy, limb-girdle, autosomal dominant 4
c.698G>T
single nucleotide variant
 p.Gly233Val Pathogenic/Likely pathogenic ★★☆☆ Autosomal recessive limb-girdle muscular dystrophy

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the CAPN3 gene are primarily associated with inherited muscle disorders, most notably limb-girdle muscular dystrophy type 2A. This condition is characterised by progressive weakness and wasting of muscles, particularly those around the shoulders, hips, and upper limbs.

Inheritance pattern

Conditions caused by pathogenic CAPN3 variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous CAPN3 carrier status across ancestry groups?

UK clinical status

CAPN3 is included in the UK National Health Service (NHS) Genomic Medicine Service's national test directory. It is listed on the 'Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies' panel (R82), indicating its relevance for diagnostic testing within the NHS.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies · R82 NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the function of the CAPN3 gene?

The CAPN3 gene provides instructions for making calpain-3, an enzyme primarily found in muscle fibres. This enzyme is vital for breaking down and removing damaged proteins, a process known as sarcomere remodelling, which maintains muscle health and function.

What condition is associated with CAPN3 gene variants?

Pathogenic variants in the CAPN3 gene are primarily associated with limb-girdle muscular dystrophy type 2A. This is a genetic muscle-wasting disorder that mainly affects the muscles around the hips and shoulders.

How is CAPN3 relevant to muscle health?

Calpain-3, encoded by CAPN3, helps muscle cells adapt and repair themselves by processing damaged proteins. This constant renewal ensures that muscle fibres can function correctly and respond to the body's needs.

References

  1. Broglio L, Tentorio M, Cotelli MS. Limb-girdle muscular dystrophy-associated protein diseases. The neurologist. 2010. PMID: 21150381
  2. Guglieri M, Straub V, Bushby K. Limb-girdle muscular dystrophies. Current opinion in neurology. 2008. PMID: 18769252
  3. Beckmann JS, Spencer M. Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance. Neuromuscular disorders : NMD. 2008. PMID: 18974005
  4. Kramerova I, Beckmann JS, Spencer MJ. Molecular and cellular basis of calpainopathy (limb girdle muscular dystrophy type 2A). Biochimica et biophysica acta. 2007. PMID: 16934440
  5. Duguez S, Bartoli M, Richard I. Calpain 3: a key regulator of the sarcomere? The FEBS journal. 2006. PMID: 16884488
  6. Straub V, Bushby K. The childhood limb-girdle muscular dystrophies. Seminars in pediatric neurology. 2006. PMID: 17027860
  7. Guglieri M, Magri F, Comi GP. Molecular etiopathogenesis of limb girdle muscular and congenital muscular dystrophies: boundaries and contiguities. Clinica chimica acta; international journal of clinical chemistry. 2005. PMID: 16002060
  8. Laval SH, Bushby KM. Limb-girdle muscular dystrophies--from genetics to molecular pathology. Neuropathology and applied neurobiology. 2004. PMID: 15043707
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 27 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .