Gene: CAPN3

Alternate names for this Gene: CANP3|CANPL3|LGMD2|LGMD2A|LGMDD4|LGMDR1|nCL-1|p94

Gene Summary: Calpain, 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.

Gene is located in Chromosome: 15

Location in Chromosome : 15q15.1

Description of this Gene: calpain 3

Type of Gene: protein-coding

rs56702977 in CAPN3 gene and Fibrinogen assay PMID 26561523 2016 A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.

PMID 28107422 2017 Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study.

rs1057524468 in CAPN3 gene and Limb-girdle muscular dystrophy type 2A PMID 15689361 2005 LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene.

PMID 10330340 1999 Calpainopathy-a survey of mutations and polymorphisms.

PMID 28915917 2017 Translocation of molecular chaperones to the titin springs is common in skeletal myopathy patients and affects sarcomere function.

PMID 16627476 2006 Suppressed disassembly of autolyzing p94/CAPN3 by N2A connectin/titin in a genetic reporter system.

PMID 21520333 2011 LOVD v.2.0: the next generation in gene variant databases.

PMID 10102422 1999 Calpain III mutation analysis of a heterogeneous limb-girdle muscular dystrophy population.

PMID 15221789 2004 Molecular diagnosis in LGMD2A: mutation analysis or protein testing?

PMID 16650086 2006 Screening of the CAPN3 gene in patients with possible LGMD2A.

PMID 8624690 1996 Juvenile limb-girdle muscular dystrophy. Clinical, histopathological and genetic data from a small community living in the Reunion Island.

PMID 9642272 1998 Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A.

PMID 9150160 1997 Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.

PMID 27708273 2017 The sensitivity of exome sequencing in identifying pathogenic mutations for LGMD in the United States.

PMID 7720071 1995 Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.

PMID 19156839 2009 Protein sequences encode safeguards against aggregation.

PMID 27066545 2015 Respiratory chain deficiency in nonmitochondrial disease.

PMID 18073330 2008 NF-kappaB-dependent expression of the antiapoptotic factor c-FLIP is regulated by calpain 3, the protein involved in limb-girdle muscular dystrophy type 2A.

PMID 17562833 2007 Limb-girdle muscular dystrophy in the Netherlands: gene defect identified in half the families.

PMID 16141003 2005 Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes.

PMID 18854869 2009 How to tackle the diagnosis of limb-girdle muscular dystrophy 2A.

PMID 19015733 2008 Gene expression profiling in limb-girdle muscular dystrophy 2A.

PMID 16411092 2006 Calpain-3 mutations in Turkey.

PMID 16372320 2006 Analysis of histopathologic and molecular pathologic findings in Czech LGMD2A patients.

PMID 16971480 2007 Screening of calpain-3 autolytic activity in LGMD muscle: a functional map of CAPN3 gene mutations.

PMID 18563459 2008 Characterization of novel CAPN3 isoforms in white blood cells: an alternative approach for limb-girdle muscular dystrophy 2A diagnosis.

PMID 14578192 2003 Loss of calpain-3 autocatalytic activity in LGMD2A patients with normal protein expression.

PMID 19226146 2009 Limb-girdle muscular dystrophy type 2A can result from accelerated autoproteolytic inactivation of calpain 3.

PMID 9266733 1997 A biochemical, genetic, and clinical survey of autosomal recessive limb girdle muscular dystrophies in Turkey.

PMID 25252031 2014 Muscle-specific calpain-3 is phosphorylated in its unique insertion region for enrichment in a myofibril fraction.

PMID 27055500 2016 Calpain 3 deficiency affects SERCA expression and function in the skeletal muscle.

PMID 26632398 2016 Clinical and Pathological Heterogeneity of Korean Patients with CAPN3 Mutations.

PMID 27431290 2017 Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.

PMID 21984748 2012 Patients with a phenotype consistent with facioscapulohumeral muscular dystrophy display genetic and epigenetic heterogeneity.

PMID 22378277 2012 Diagnosis by sequencing: correction of misdiagnosis from FSHD2 to LGMD2A by whole-exome analysis.

PMID 17157502 2007 Quantitative analysis of CAPN3 transcripts in LGMD2A patients: involvement of nonsense-mediated mRNA decay.

PMID 25135358 2014 Autosomal recessive limb-girdle muscular dystrophies in the Czech Republic.

PMID 27023906 2016 Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue.

PMID 15725583 2005 The frequency of limb girdle muscular dystrophy 2A in northeastern Italy.

PMID 21204801 2011 Eosinophilic infiltration related to CAPN3 mutations: a pathophysiological component of primary calpainopathy?

PMID 10567047 1999 Mutations of calpain 3 gene in patients with sporadic limb-girdle muscular dystrophy in Japan.

PMID 18337726 2008 cDNA analyses of CAPN3 enhance mutation detection and reveal a low prevalence of LGMD2A patients in Denmark.

PMID 11525884 2001 Calpain 3 gene mutations: genetic and clinico-pathologic findings in limb-girdle muscular dystrophy.

PMID 26404900 2015 ISPD mutations account for a small proportion of Italian Limb Girdle Muscular Dystrophy cases.

PMID 26060040 2016 Clinical applications of next-generation sequencing-based gene panel in patients with muscular dystrophy: Korean experience.

PMID 27066573 2015 Genetic profile for suspected dysferlinopathy identified by targeted next-generation sequencing.

PMID 20635405 2010 Transcriptional and translational effects of intronic CAPN3 gene mutations.

PMID 17258832 2007 Characterization of lobulated fibers in limb girdle muscular dystrophy type 2A by gene expression profiling.

PMID 15733273 2005 Novel mutations in the calpain 3 gene in Germany.

PMID 17994539 2008 Clinical, molecular, and protein correlations in a large sample of genetically diagnosed Italian limb girdle muscular dystrophy patients.

PMID 22006685 2011 Does the severity of the LGMD2A phenotype in compound heterozygotes depend on the combination of mutations?

PMID 9777948 1998 Characterization of monoclonal antibodies to calpain 3 and protein expression in muscle from patients with limb-girdle muscular dystrophy type 2A.

PMID 25512505 2014 The N- and C-terminal autolytic fragments of CAPN3/p94/calpain-3 restore proteolytic activity by intermolecular complementation.

PMID 9762961 1998 Limb-girdle muscular dystrophy in Guipúzcoa (Basque Country, Spain).

PMID 16542520 2006 Early onset calpainopathy with normal non-functional calpain 3 level.

PMID 26886200 2016 Utility of a next-generation sequencing-based gene panel investigation in German patients with genetically unclassified limb-girdle muscular dystrophy.

PMID 11371436 2001 Mutations in calpain 3 associated with limb girdle muscular dystrophy: analysis by molecular modeling and by mutation in m-calpain.

PMID 15351423 2004 Mutations in Czech LGMD2A patients revealed by analysis of calpain3 mRNA and their phenotypic outcome.

PMID 9655129 1998 Pseudometabolic expression and phenotypic variability of calpain deficiency in two siblings.

PMID 9771675 1998 Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.

PMID 18055493 2007 Analysis of the UK diagnostic strategy for limb girdle muscular dystrophy 2A.

PMID 9452114 1998 A small in-frame deletion within the protease domain of muscle-specific calpain, p94 causes early-onset limb-girdle muscular dystrophy 2A.

PMID 27234031 2017 Improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing in patients arising from a consanguineous population.

PMID 27020652 2017 Report of limb girdle muscular dystrophy type 2a in 6 Iranian patients, one with a novel deletion in CAPN3 gene.

PMID 20044116 2010 [Diagnostic procedure of limb girdle muscular dystrophies 2A or calpainopathies: French cohort from a neuromuscular center (Bordeaux)].

PMID 17897828 2008 Limb-girdle muscular dystrophy: diagnostic evaluation, frequency and clues to pathogenesis.

PMID 17318636 2007 A large deletion and novel point mutations in the calpain 3 gene (CAPN3) in Bulgarian LGMD2A patients.

PMID 23169433 2013 Resistance training in patients with limb-girdle and becker muscular dystrophies.

PMID 22443334 2012 Calpain 3 is important for muscle regeneration: evidence from patients with limb girdle muscular dystrophies.

PMID 19556129 2009 Immunohistochemical analysis of calpain 3: advantages and limitations in diagnosing LGMD2A.

PMID 11053681 2000 Secondary reduction in calpain 3 expression in patients with limb girdle muscular dystrophy type 2B and Miyoshi myopathy (primary dysferlinopathies).

PMID 27500519 2017 Cardiopulmonary dysfunction in patients with limb-girdle muscular dystrophy 2A.

PMID 25046369 2014 Exome sequencing as a second-tier diagnostic approach for clinically suspected dysferlinopathy patients.

PMID 25214167 2014 MotorPlex provides accurate variant detection across large muscle genes both in single myopathic patients and in pools of DNA samples.

PMID 12461690 2002 Clinical variability in calpainopathy: what makes the difference?

PMID 11731278 2002 Myopathy with lobulated muscle fibers: evidence for heterogeneous etiology and clinical presentation.

PMID 17702496 2007 Frequency of calpain-3 c.550delA mutation in limb girdle muscular dystrophy type 2 and isolated hyperCKemia in German patients.

PMID 26501342 2015 Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1).

PMID 17236769 2007 A third of LGMD2A biopsies have normal calpain 3 proteolytic activity as determined by an in vitro assay.

PMID 15843148 2005 Here we identified a sibling pair with LGMD2A-type muscular dystrophy caused by a homozygous Ser606Leu (S606L) substitution in the IS2 linker domain.

PMID 11245732 2001 Normal calpain expression in genetically confirmed limb-girdle muscular dystrophy type 2A.

PMID 25079074 2014 Redox state and mitochondrial respiratory chain function in skeletal muscle of LGMD2A patients.

PMID 20517216 2010 [Clinical-genetic characteristics of limb girdle-muscular dystrophy type 2A].

PMID 20694146 2010 Calpain 3 is a rapid-action, unidirectional proteolytic switch central to muscle remodeling.

PMID 11166169 2001 Strategy for mutation analysis in the autosomal recessive limb-girdle muscular dystrophies.

PMID 22158424 2012 CAPN3 mRNA processing alteration caused by splicing mutation associated with novel genomic rearrangement of Alu elements.

PMID 18334579 2008 Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle.

PMID 19048948 2008 [Case of LGMD2A (calpainopathy) clinically presenting as Miyoshi distal myopathy].

PMID 25326637 2014 Clinical exome sequencing for genetic identification of rare Mendelian disorders.

PMID 27854218 2016 Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases.

PMID 27363342 2017 Discovery of pathogenic variants in a large Korean cohort of inherited muscular disorders.

PMID 19364062 2008 Phenotypic variability in siblings with calpainopathy (LGMD2A).

PMID 23821418 2013 Muscle pathology in 31 patients with calpain 3 gene mutations..

PMID 15884399 2005 [Calpain-3 gene defect causing limb gird muscular dystrophy in a Hungarian family].

PMID 26677118 2015 Limb-girdle muscular dystrophy type 2A in Brazilian children.

PMID 27081656 2016 Natural history of LGMD2A for delineating outcome measures in clinical trials.

PMID 17979987 2007 Transcriptional explorations of CAPN3 identify novel splicing mutations, a large-sized genomic deletion and evidence for messenger RNA decay.

PMID 26301378 2015 Neuromuscular Pathology Case.

PMID 24803842 2013 Eosinophils in hereditary and inflammatory myopathies.

PMID 27447704 2017 Muscular dystrophies and myopathies: the spectrum of mutated genes in the Czech Republic.

PMID 26484845 2015 The Frequency of c.550delA Mutation of the CANP3 Gene in the Polish LGMD2A Population.

PMID 21624972 2011 Pathogenity of some limb girdle muscular dystrophy mutations can result from reduced anchorage to myofibrils and altered stability of calpain 3.

PMID 22926650 2012 Genetic variability and clinical spectrum of Chinese patients with limb-girdle muscular dystrophy type 2A.

PMID 27011640 2016 Limb-girdle muscular dystrophy in the Agarwals: Utility of founder mutations in CAPN3 gene.

PMID 23666804 2013 Ancestral founder mutations in calpain-3 in the Indian Agarwal community: historical, clinical, and molecular perspective.

PMID 24846670 2014 Crystal structure of calpain-3 penta-EF-hand (PEF) domain - a homodimerized PEF family member with calcium bound at the fifth EF-hand.

PMID 19285864 2009 Eosinophilic myositis in calpainopathy: could immunosuppression of the eosinophilic myositis alter the early natural course of the dystrophic disease?

PMID 15726252 2005 Diagnostic value of muscle MRI in differentiating LGMD2I from other LGMDs.

PMID 26810512 2016 Rhabdomyolysis featuring muscular dystrophies.

PMID 7795603 1995 Genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy in a genetic isolate (Amish) and evidence for a new locus.

PMID 7762565 1995 Preferential localization of the limb-girdle muscular dystrophy type 2A gene in the proximal part of a 1-cM 15q15.1-q15.3 interval.

PMID 9246005 1997 DNA studies of limb-girdle muscular dystrophy type 2A in the Amish exclude a modifying mitochondrial gene and show no evidence for a modifying nuclear gene.

PMID 14645990 2003 A homozygous R769Q mutation in the calpain-3 gene and absence of muscle calpain-3 protein confirmed a calpainopathy.

PMID 23677060 2013 Exome sequencing as a diagnostic tool to identify a causal mutation in genetically highly heterogeneous limb-girdle muscular dystrophy.

PMID 15138196 2004 Null mutation of calpain 3 (p94) in mice causes abnormal sarcomere formation in vivo and in vitro.

PMID 16100770 2005 Calpainopathy (LGMD2A) in Croatia: molecular and haplotype analysis.

PMID 14981715 2004 Prevalence of the 550delA mutation in calpainopathy (LGMD 2A) in Croatia.

PMID 28602176 2017 Calpainopathy with macrophage-rich, regional inflammatory infiltrates.

PMID 27259757 2016 A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.

PMID 22057634 2011 Ahnak1 abnormally localizes in muscular dystrophies and contributes to muscle vesicle release.

PMID 16607617 2006 CAPN3 mutations in patients with idiopathic eosinophilic myositis.

PMID 25987458 2015 A comprehensive genetic diagnosis of Chinese muscular dystrophy and congenital myopathy patients by targeted next-generation sequencing.

PMID 28403181 2017 Mutational spectrum of Chinese LGMD patients by targeted next-generation sequencing.

PMID 27066551 2015 Expanding genotype/phenotype of neuromuscular diseases by comprehensive target capture/NGS.

PMID 12890817 2003 This pattern was also seen in one patient with early stage LGMD2A who had a P82L missense mutation and a partial deficiency of calpain 3 in the muscle, but was not seen in early stage patients affected by other forms of LGMD.

PMID 27262448 2016 Linkage Study Revealed Complex Haplotypes in a Multifamily due to Different Mutations in CAPN3 Gene in an Iranian Ethnic Group.

rs149698681 in CAPN3 gene and Monocyte count procedure PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs149698681 in CAPN3 gene and Monocyte count result PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs2412710 in CAPN3 gene and Triglycerides measurement PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

PMID 24097068 2013 Discovery and refinement of loci associated with lipid levels.

PMID 20686565 2010 Biological, clinical and population relevance of 95 loci for blood lipids.