CAPN3 calpain 3 [Homo sapiens (human)] - Gene

Summary

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: mouse all
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Genomic context

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_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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

Associated conditions

Description	Tests
Autosomal recessive limb-girdle muscular dystrophy type 2A MedGen: C1869123 OMIM: 253600 GeneReviews: Calpainopathy	Compare labs
Muscular dystrophy, limb-girdle, autosomal dominant 4 MedGen: C4748295 OMIM: 618129 GeneReviews: Calpainopathy	Compare labs

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC104364P1 (e-PCR)
- UniSTS:270108

Capn3 (e-PCR), detects polymorphism
- UniSTS:507941

Capn3 (e-PCR), detects polymorphism
- UniSTS:507942

GDB:595491 (e-PCR)
- UniSTS:158019

GDB:595502 (e-PCR)
- UniSTS:158020

GDB:595506 (e-PCR)
- UniSTS:158021

GDB:595511 (e-PCR)
- UniSTS:158022

GDB:595521 (e-PCR)
- UniSTS:158023

GDB:595526 (e-PCR)
- UniSTS:158024

GDB:595530 (e-PCR)
- UniSTS:158025

GDB:595532 (e-PCR)
- UniSTS:158027

NoName (e-PCR)
- UniSTS:482904

GDB:596044 (e-PCR)
- UniSTS:158043

GDB:596046 (e-PCR)
- UniSTS:158045

GDB:596049 (e-PCR)
- UniSTS:158046

GDB:596085 (e-PCR)
- UniSTS:158047

GDB:596146 (e-PCR)
- UniSTS:158048

GDB:596192 (e-PCR)
- UniSTS:158049

GDB:596194 (e-PCR)
- UniSTS:158051

GDB:596196 (e-PCR)
- UniSTS:158052

EST160846 (e-PCR)
- UniSTS:5733

GDB:596199 (e-PCR)
- UniSTS:158054

GDB:596200 (e-PCR)
- UniSTS:158055

GDB:596203 (e-PCR)
- UniSTS:158056

GDB:596205 (e-PCR)
- UniSTS:158058

GDB:596208 (e-PCR)
- UniSTS:158059

GDB:596213 (e-PCR)
- UniSTS:158062

GDB:596223 (e-PCR)
- UniSTS:158066

GDB:596226 (e-PCR)
- UniSTS:158068

GDB:596229 (e-PCR)
- UniSTS:158069

GDB:596230 (e-PCR)
- UniSTS:158070

GDB:596235 (e-PCR)
- UniSTS:158073

GDB:596238 (e-PCR)
- UniSTS:158074

MARC_26098-26099:1032551724:1 (e-PCR)
- UniSTS:268938

RH17562 (e-PCR)
- UniSTS:8846

Capn3 (e-PCR), detects polymorphism
- UniSTS:141225

SHGC-35143 (e-PCR)
- UniSTS:682

D15S1208 (e-PCR)
- UniSTS:57520

D15S741 (e-PCR)
- UniSTS:151733

D15S756 (e-PCR)
- UniSTS:151748

D15S882E (e-PCR)
- UniSTS:153796

WI-17962 (e-PCR)
- UniSTS:79573

D15S774 (e-PCR)
- UniSTS:151766

SKM-CALPOV (e-PCR)
- UniSTS:251621

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

EC 3.4.22.54

NP_077320.1

EC 3.4.22.54

NP_775110.1

EC 3.4.22.54

NP_775111.1

EC 3.4.22.54

NP_775112.1

EC 3.4.22.54

NP_775113.1

EC 3.4.22.54

NCBI Reference Sequences (RefSeq)

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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

NG_008660.1 RefSeqGene

Range

16399..69215

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_849

mRNA and Protein(s)

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 ...
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 ...
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
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
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
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

NC_000015.10 Reference GRCh38.p14 Primary Assembly

Range

42359501..42412317

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

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

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.
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.
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.