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CAPN3 calpain 3 [ Homo sapiens (human) ]

Gene ID: 825, updated on 3-Nov-2024

Summary

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Official Symbol
CAPN3provided by HGNC
Official Full Name
calpain 3provided by HGNC
Primary source
HGNC:HGNC:1480
See related
Ensembl:ENSG00000092529 MIM:114240; AllianceGenome:HGNC:1480
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
p94; CANP3; LGMD2; nCL-1; CANPL3; LGMD2A; LGMDD4; LGMDR1
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. [provided by RefSeq, Jul 2008]
Expression
Broad expression in bone marrow (RPKM 19.1), kidney (RPKM 13.9) and 24 other tissues See more
Orthologs
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Genomic context

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See CAPN3 in Genome Data Viewer
Location:
15q15.1
Exon count:
26
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (42359501..42412317)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (40165536..40218365)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (42651699..42704515)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene VPS39 divergent transcript Neighboring gene transmembrane protein 87A Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9297 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9298 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr15:42565593-42566792 Neighboring gene glucosidase alpha, neutral C Neighboring gene BCL2 interacting protein 3 pseudogene 5 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:42652107-42652607 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:42655654-42656620 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr15:42676684-42677239 Neighboring gene uncharacterized LOC105370794 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr15:42677734-42678933 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9299 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9300 Neighboring gene zinc finger protein 106 Neighboring gene RNA, U6 small nuclear 188, pseudogene Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr15:42749529-42750361 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:42750362-42751193 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9301 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9302 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9303 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:42787505-42788048 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:42788049-42788592 Neighboring gene MPRA-validated peak2311 silencer Neighboring gene synaptosome associated protein 23 Neighboring gene leucine rich repeat containing 57

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. CAPN3 mRNA processing alteration caused by splicing mutation associated with novel genomic rearrangement of Alu elements. Salem IH, et al. J Hum Genet, 2012 Feb. PMID 22158424
  2. Clinical variability in calpainopathy: what makes the difference? de Paula F, et al. Eur J Hum Genet, 2002 Dec. PMID 12461690
  3. Calpainopathy. Adam MP, et al. , 1993. PMID 20301490
  4. Calpain 3 gene expression in skeletal muscle is associated with body fat content and measures of insulin resistance. Walder K, et al. Int J Obes Relat Metab Disord, 2002 Apr. PMID 12075569
  5. [Clinical-genetic characteristics of limb girdle-muscular dystrophy type 2A]. Dadali EL, et al. Zh Nevrol Psikhiatr Im S S Korsakova, 2010. PMID 20517216

See all (158) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Two Novel Variants of the CAPN3 Gene in Chinese Patients with Limb-Girdle Muscular Dystrophy Recessive 1.
    Title: Two Novel Variants of the CAPN3 Gene in Chinese Patients with Limb-Girdle Muscular Dystrophy Recessive 1.
  2. Identification of novel pathogenic variants of Calpain-3 gene in limb girdle muscular dystrophy R1.
    Title: Identification of novel pathogenic variants of Calpain-3 gene in limb girdle muscular dystrophy R1.
  3. The CAPN3 p.Lys 254del variant is not always associated with dominant CAPN3-related muscular dystrophy.
    Title: The CAPN3 p.Lys 254del variant is not always associated with dominant CAPN3-related muscular dystrophy.
  4. Family and literature analysis demonstrates phenotypic effect of two variants in the calpain-3 gene.
    Title: Family and literature analysis demonstrates phenotypic effect of two variants in the calpain-3 gene.
  5. Calpain-3 Is Not a Sodium Dependent Protease and Simply Requires Calcium for Activation.
    Title: Calpain-3 Is Not a Sodium Dependent Protease and Simply Requires Calcium for Activation.
  6. CAPN3 c.1746-20C>G variant is hypomorphic for LGMD R1 calpain 3-related.
    Title: CAPN3 c.1746-20C>G variant is hypomorphic for LGMD R1 calpain 3-related.
  7. An 86 amino acids motif in CAPN3 is essential for formation of the nucleolus-localized Def-CAPN3 complex.
    Title: An 86 amino acids motif in CAPN3 is essential for formation of the nucleolus-localized Def-CAPN3 complex.
  8. A recurrent rare intronic variant in CAPN3 alters mRNA splicing and causes autosomal recessive limb-girdle muscular dystrophy-1 in three Pakistani pedigrees.
    Title: A recurrent rare intronic variant in CAPN3 alters mRNA splicing and causes autosomal recessive limb-girdle muscular dystrophy-1 in three Pakistani pedigrees.
  9. Splicing impact of deep exonic missense variants in CAPN3 explored systematically by minigene functional assay.
    Title: Splicing impact of deep exonic missense variants in CAPN3 explored systematically by minigene functional assay.
  10. Clinical and genetic features of Calpainopathies in Saudi Arabia - a descriptive cross-sectional study.
    Title: Clinical and genetic features of Calpainopathies in Saudi Arabia - a descriptive cross-sectional study.
Submit: New GeneRIF Correction See all GeneRIFs (99)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Biological, clinical and population relevance of 95 loci for blood lipids.
EBI GWAS Catalog
Discovery and refinement of loci associated with lipid levels.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of calpain 3 (CAPN3; p94) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Activation of the Ca(2+)-dependent protease, calpain, is involved in cytotoxic effects mediated by HIV-1 gp120 in neuroblastoma cultures PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Potential readthrough

Included gene: GANC

Homology

Clone Names

  • MGC4403, MGC10767, MGC11121, MGC14344

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables calcium ion binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables calcium-dependent cysteine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables calcium-dependent cysteine-type endopeptidase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables calcium-dependent cysteine-type endopeptidase activity TAS
Traceable Author Statement
more info
 PubMed 
enables catalytic activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables cysteine-type peptidase activity TAS
Traceable Author Statement
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ligase regulator activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables molecular adaptor activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables peptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables sodium ion binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables structural constituent of muscle ISS
Inferred from Sequence or Structural Similarity
more info
  
enables titin binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in G1 to G0 transition involved in cell differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in apoptotic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in calcium-dependent self proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to calcium ion ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to salt stress ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in muscle cell cellular homeostasis TAS
Traceable Author Statement
more info
 PubMed 
involved_in muscle organ development TAS
Traceable Author Statement
more info
 PubMed 
involved_in muscle structure development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in myofibril assembly ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in myofibril assembly TAS
Traceable Author Statement
more info
 PubMed 
involved_in negative regulation of DNA-templated transcription ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of protein sumoylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of DNA-templated transcription IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of NF-kappaB transcription factor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of proteolysis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of release of sequestered calcium ion into cytosol ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of satellite cell activation involved in skeletal muscle regeneration ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein destabilization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein localization to membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in protein-containing complex assembly ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in proteolysis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of canonical NF-kappaB signal transduction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of catalytic activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of myoblast differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in response to calcium ion ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in response to muscle activity ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in sarcomere organization ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in self proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in T-tubule ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in Z disc ISS
Inferred from Sequence or Structural Similarity
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in myofibril ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in nucleolus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
part_of protein-containing complex ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
calpain-3
Names
calpain p94, large [catalytic] subunit
calpain, large polypeptide L3
muscle-specific calcium-activated neutral protease 3 large subunit
new calpain 1
NP_000061.1
NP_077320.1
NP_775110.1
NP_775111.1
NP_775112.1
NP_775113.1

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008660.1 RefSeqGene

    Range
    16399..69215
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_849

mRNA and Protein(s)

  1. NM_000070.3 → NP_000061.1  calpain-3 isoform a

    See identical proteins and their annotated locations for NP_000061.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a).
    Source sequence(s)
    AC012651
    Consensus CDS
    CCDS45245.1
    UniProtKB/Swiss-Prot
    A6H8K6, P20807, Q7L4R0, Q9BQC8, Q9BTU4, Q9Y5S6, Q9Y5S7
    UniProtKB/TrEMBL
    F8W8F5
    Related
    ENSP00000380349.3, ENST00000397163.8
    Conserved Domains (6) summary
    cd00051
    Location:697 → 751
    EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
    pfam00648
    Location:75 → 415
    Peptidase_C2; Calpain family cysteine protease
    pfam01067
    Location:429 → 579
    Calpain_III; Calpain large subunit, domain III
    pfam13499
    Location:728 → 784
    EF-hand_7; EF-hand domain pair
    pfam16648
    Location:583 → 653
    Calpain_u2; Unstructured region on Calpain-3
    cl08302
    Location:728 → 817
    EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

  2. NM_024344.2 → NP_077320.1  calpain-3 isoform b

    See identical proteins and their annotated locations for NP_077320.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, compared to variant 1. It encodes isoform b, which is slightly shorter than isoform a.
    Source sequence(s)
    AC012651
    Consensus CDS
    CCDS32207.1
    UniProtKB/TrEMBL
    F8W8F5
    Related
    ENSP00000350181.3, ENST00000357568.8
    Conserved Domains (6) summary
    cd00051
    Location:691 → 745
    EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
    pfam00648
    Location:75 → 415
    Peptidase_C2; Calpain family cysteine protease
    pfam01067
    Location:429 → 579
    Calpain_III; Calpain large subunit, domain III
    pfam13499
    Location:722 → 778
    EF-hand_7; EF-hand domain pair
    pfam16648
    Location:583 → 647
    Calpain_u2; Unstructured region on Calpain-3
    cl08302
    Location:722 → 811
    EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

  3. NM_173087.2 → NP_775110.1  calpain-3 isoform c

    See identical proteins and their annotated locations for NP_775110.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks three in-frame exons in the coding region, compared to variant 1. It encodes isoform c, which is shorter than isoform a.
    Source sequence(s)
    AC012651
    Consensus CDS
    CCDS10085.1
    UniProtKB/TrEMBL
    F8W8F5
    Related
    ENSP00000183936.4, ENST00000349748.8
    Conserved Domains (4) summary
    cd00051
    Location:605 → 659
    EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
    pfam00648
    Location:75 → 367
    Peptidase_C2; Calpain family cysteine protease
    pfam01067
    Location:381 → 531
    Calpain_III; Calpain large subunit, domain III
    pfam13499
    Location:636 → 692
    EF-hand_7; EF-hand domain pair

  4. NM_173088.2 → NP_775111.1  calpain-3 isoform d

    See identical proteins and their annotated locations for NP_775111.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and 5' coding region, and uses a downstream start codon, compared to variant 1. It encodes isoform d, which has a shorter N-terminus compared to isoform a.
    Source sequence(s)
    AC012651
    Consensus CDS
    CCDS45246.1
    UniProtKB/TrEMBL
    A0A0S2Z3E1, H3BMH1
    Related
    ENSP00000380384.4, ENST00000397200.8
    Conserved Domains (3) summary
    pfam01067
    Location:1 → 67
    Calpain_III; Calpain large subunit, domain III
    pfam16648
    Location:71 → 141
    Calpain_u2; Unstructured region on Calpain-3
    cd16190
    Location:141 → 309
    EFh_PEF_CAPN3; Calcium-activated neutral

  5. NM_173089.2 → NP_775112.1  calpain-3 isoform e

    See identical proteins and their annotated locations for NP_775112.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR and uses a downstream start codon, compared to variant 1. It encodes isoform e, which has a shorter N-terminus compared to isoform a.
    Source sequence(s)
    AC012651
    Consensus CDS
    CCDS10086.1
    UniProtKB/TrEMBL
    Q496N2
    Related
    ENSP00000501303.1, ENST00000674093.1
    Conserved Domains (2) summary
    cd15897
    Location:31 → 60
    EFh_PEF; EF-hand motif [structural motif]
    cl25352
    Location:1 → 156
    EFh_PEF; The penta-EF hand (PEF) family

  6. NM_173090.2 → NP_775113.1  calpain-3 isoform e

    See identical proteins and their annotated locations for NP_775113.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) differs in the 5' UTR and uses a downstream start codon, compared to variant 1. It encodes isoform e, which has a shorter N-terminus compared to isoform a.
    Source sequence(s)
    AC012651
    Consensus CDS
    CCDS10086.1
    UniProtKB/TrEMBL
    Q496N2
    Related
    ENSP00000380387.4, ENST00000397204.9
    Conserved Domains (2) summary
    cd15897
    Location:31 → 60
    EFh_PEF; EF-hand motif [structural motif]
    cl25352
    Location:1 → 156
    EFh_PEF; The penta-EF hand (PEF) family

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

    Range
    42359501..42412317
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060939.1 Alternate T2T-CHM13v2.0

    Range
    40165536..40218365
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_212465.2: Suppressed sequence

    Description
    NM_212465.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

  2. NR_027911.1: Suppressed sequence

    Description
    NR_027911.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

  3. NR_027912.1: Suppressed sequence

    Description
    NR_027912.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P20807.2 GenPept UniProtKB/Swiss-Prot:P20807

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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