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CAST calpastatin [ Homo sapiens (human) ]

Gene ID: 831, updated on 9-Apr-2023

Summary

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Official Symbol
CASTprovided by HGNC
Official Full Name
calpastatinprovided by HGNC
Primary source
HGNC:HGNC:1515
See related
Ensembl:ENSG00000153113 MIM:114090; AllianceGenome:HGNC:1515
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
BS-17; PLACK
Summary
The protein encoded by this gene is an endogenous calpain (calcium-dependent cysteine protease) inhibitor. It consists of an N-terminal domain L and four repetitive calpain-inhibition domains (domains 1-4), and it is involved in the proteolysis of amyloid precursor protein. The calpain/calpastatin system is involved in numerous membrane fusion events, such as neural vesicle exocytosis and platelet and red-cell aggregation. The encoded protein is also thought to affect the expression levels of genes encoding structural or regulatory proteins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2010]
Expression
Ubiquitous expression in esophagus (RPKM 82.1), heart (RPKM 55.7) and 24 other tissues See more
Orthologs
mouse all
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Genomic context

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See CAST in Genome Data Viewer
Location:
5q15
Exon count:
36
Annotation release Status Assembly Chr Location
RS_2023_03 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (96662037..96774683)
RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (97162871..97275514)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (95997741..96110387)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101929710 Neighboring gene NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5-like Neighboring gene Sharpr-MPRA regulatory region 11450 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:95992448-95993647 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:95997733-95998234 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:96038749-96039248 Neighboring gene uncharacterized LOC107986363 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:96069728-96070260 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:96116076-96117275 Neighboring gene uncharacterized LOC124901031 Neighboring gene endoplasmic reticulum aminopeptidase 1

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
  • 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. A novel homozygous nonsense mutation in CAST associated with PLACK syndrome. Temel ŞG, et al. Cell Tissue Res, 2019 Nov. PMID 31392520
  2. Evaluating the association between calpastatin (CAST) gene and keratoconus in the Han Chinese population. Zhang J, et al. Gene, 2018 May 5. PMID 29428799
  3. Loss-of-function mutations in CAST cause peeling skin, leukonychia, acral punctate keratoses, cheilitis, and knuckle pads. Lin Z, et al. Am J Hum Genet, 2015 Mar 5. PMID 25683118, Free PMC Article
  4. The Ca(2+)-dependent interaction of calpastatin domain L with the C-terminal tail of the Cav1.2 channel. Sun W, et al. FEBS Lett, 2014 Mar 3. PMID 24462690
  5. Calpastatin gene (CAST) is not associated with late onset sporadic Parkinson's disease in the Han Chinese population. Zhang L, et al. PLoS One, 2013. PMID 23951044, Free PMC Article

See all (139) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Variants in Genes of Calpain System as Modifiers of Spinocerebellar Ataxia Type 3 Phenotype.
    Title: Variants in Genes of Calpain System as Modifiers of Spinocerebellar Ataxia Type 3 Phenotype.
  2. Critical Roles of Calpastatin in Ischemia/Reperfusion Injury in Aged Livers.
    Title: Critical Roles of Calpastatin in Ischemia/Reperfusion Injury in Aged Livers.
  3. A new recessive form of genetic peeling skin syndrome with peeling skin, leukonychia, acral punctate keratoses, cheilitis and knuckle pads (termed PLACK syndrome) shown associated with the loss of function mutations in the CAST gene encoding calpastatin.
    Title: A novel homozygous nonsense mutation in CAST associated with PLACK syndrome.
  4. new human calpastatin skipped of the inhibitory region protects calpain-1 from inactivation and degradation.
    Title: A new human calpastatin skipped of the inhibitory region protects calpain-1 from inactivation and degradation.
  5. Low CAST expression is associated with ovarian cancer.
    Title: Calpain system protein expression and activity in ovarian cancer.
  6. Unexpected role of the L-domain of calpastatin during the autoproteolytic activation of human erythrocyte calpain.
    Title: Unexpected role of the L-domain of calpastatin during the autoproteolytic activation of human erythrocyte calpain.
  7. single nucleotide polymorphisms in CAST gene confer risk for keratoconus susceptibility in Han Chinese population
    Title: Evaluating the association between calpastatin (CAST) gene and keratoconus in the Han Chinese population.
  8. Kaposi sarcoma-associated herpesvirus reduces CAST (calpastatin) and consequently decreases ATG5 expression in both THP-1 monocytoid cells and primary monocytes.
    Title: KSHV reduces autophagy in THP-1 cells and in differentiating monocytes by decreasing CAST/calpastatin and ATG5 expression.
  9. calpains and calpastatin in patients with idiopathic pulmonary arterial hypertension (PAH) and mice with hypoxic or spontaneous (SM22-5HTT(+) strain) PH, were investigated.
    Title: Extracellular Calpain/Calpastatin Balance Is Involved in the Progression of Pulmonary Hypertension.
  10. Loss of CAST in angiogenic ECs facilitates mu-calpain-induced SOCS3 degradation, which amplifies pathological angiogenesis through interleukin-6/STAT3/VEGF-C axis.
    Title: Calpastatin counteracts pathological angiogenesis by inhibiting suppressor of cytokine signaling 3 degradation in vascular endothelial cells.
Submit: New GeneRIF Correction See all GeneRIFs (49)

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
Peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome
MedGen: C4225381 OMIM: 616295 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.
EBI GWAS Catalog
Genome-wide association study of alcohol dependence.
EBI GWAS Catalog
Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups.
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

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

Homology

Clone Names

  • MGC9402

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding HDA PubMed 
enables cadherin binding HDA PubMed 
enables calcium-dependent cysteine-type endopeptidase inhibitor activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables calcium-dependent cysteine-type endopeptidase inhibitor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables endopeptidase inhibitor activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in inhibition of cysteine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in inhibition of cysteine-type endopeptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of type B pancreatic cell apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in presynaptic active zone organization TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
  
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
calpastatin
Names
calpain inhibitor
sperm BS-17 component

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

  1. NG_029490.2 RefSeqGene

    Range
    5340..117647
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001042440.5 → NP_001035905.1  calpastatin isoform f

    See identical proteins and their annotated locations for NP_001035905.1

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    Consensus CDS
    CCDS54882.1
    UniProtKB/Swiss-Prot
    P20810
    Related
    ENSP00000379157.2, ENST00000395812.6
    Conserved Domains (1) summary
    pfam00748
    Location:412 → 542
    Calpain_inhib; Calpain inhibitor

  2. NM_001042441.3 → NP_001035906.1  calpastatin isoform g

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    UniProtKB/Swiss-Prot
    P20810
    Conserved Domains (1) summary
    pfam00748
    Location:434 → 564
    Calpain_inhib; Calpain inhibitor

  3. NM_001042442.3 → NP_001035907.1  calpastatin isoform h

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    Consensus CDS
    CCDS43344.1
    UniProtKB/Swiss-Prot
    P20810
    Related
    ENSP00000501713.1, ENST00000674984.1
    Conserved Domains (1) summary
    pfam00748
    Location:431 → 561
    Calpain_inhib; Calpain inhibitor

  4. NM_001042443.3 → NP_001035908.1  calpastatin isoform i

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    UniProtKB/Swiss-Prot
    P20810, Q9H1Z5
    Related
    ENSP00000379158.2, ENST00000395813.5
    Conserved Domains (1) summary
    pfam00748
    Location:370 → 500
    Calpain_inhib; Calpain inhibitor

  5. NM_001042444.3 → NP_001035909.1  calpastatin isoform j

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    Consensus CDS
    CCDS93750.1
    UniProtKB/Swiss-Prot
    P20810
    Related
    ENSP00000501659.1, ENST00000675033.1
    Conserved Domains (1) summary
    pfam00748
    Location:329 → 459
    Calpain_inhib; Calpain inhibitor

  6. NM_001042445.3 → NP_001035910.1  calpastatin isoform k

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    Consensus CDS
    CCDS83017.1
    UniProtKB/TrEMBL
    E9PCH5
    Related
    ENSP00000426946.1, ENST00000509903.5
    Conserved Domains (1) summary
    pfam00748
    Location:335 → 465
    Calpain_inhib; Calpain inhibitor

  7. NM_001042446.3 → NP_001035911.1  calpastatin isoform l

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    Conserved Domains (1) summary
    pfam00748
    Location:316 → 446
    Calpain_inhib; Calpain inhibitor

  8. NM_001190442.2 → NP_001177371.1  calpastatin isoform m

    See identical proteins and their annotated locations for NP_001177371.1

    Status: REVIEWED

    Source sequence(s)
    AB208816, AC008906, AC020900, AL832349, AY189741, DB450697
    Consensus CDS
    CCDS54883.1
    UniProtKB/TrEMBL
    Q59HE3, Q86YM9
    Related
    ENSP00000343421.3, ENST00000338252.7
    Conserved Domains (1) summary
    pfam00748
    Location:357 → 487
    Calpain_inhib; Calpain inhibitor

  9. NM_001284212.4 → NP_001271141.1  calpastatin isoform n

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, BX648397, U31345
    UniProtKB/Swiss-Prot
    P20810
    Related
    ENSP00000502345.1, ENST00000674702.1
    Conserved Domains (1) summary
    pfam00748
    Location:329 → 459
    Calpain_inhib; Calpain inhibitor

  10. NM_001284213.4 → NP_001271142.1  calpastatin isoform o

    Status: REVIEWED

    Source sequence(s)
    AC020900, AK300624, BM676369, BQ940454, CA775469, KC877037
    Consensus CDS
    CCDS75279.1
    UniProtKB/TrEMBL
    B7Z6N0, E9PDE4
    Related
    ENSP00000425670.1, ENST00000504465.5
    Conserved Domains (1) summary
    pfam00748
    Location:298 → 428
    Calpain_inhib; Calpain inhibitor

  11. NM_001330626.2 → NP_001317555.1  calpastatin isoform p

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037

  12. NM_001330627.2 → NP_001317556.1  calpastatin isoform q

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    Conserved Domains (1) summary
    pfam00748
    Location:412 → 542
    Calpain_inhib; Calpain inhibitor

  13. NM_001330628.2 → NP_001317557.1  calpastatin isoform r

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    Conserved Domains (1) summary
    pfam00748
    Location:397 → 527
    Calpain_inhib; Calpain inhibitor

  14. NM_001330629.2 → NP_001317558.1  calpastatin isoform s

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037

  15. NM_001330630.2 → NP_001317559.1  calpastatin isoform t

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    Related
    ENSP00000501797.1, ENST00000674587.1

  16. NM_001330631.2 → NP_001317560.1  calpastatin isoform m

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    Consensus CDS
    CCDS54883.1
    UniProtKB/Swiss-Prot
    P20810
    Related
    ENSP00000502136.1, ENST00000675614.1

  17. NM_001330632.2 → NP_001317561.1  calpastatin isoform u

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037

  18. NM_001330633.2 → NP_001317562.1  calpastatin isoform v

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    Conserved Domains (1) summary
    pfam00748
    Location:351 → 481
    Calpain_inhib; Calpain inhibitor

  19. NM_001330634.2 → NP_001317563.1  calpastatin isoform w

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    Related
    ENSP00000502244.1, ENST00000675479.1

  20. NM_001375317.1 → NP_001362246.1  calpastatin isoform x

    Status: REVIEWED

    Source sequence(s)
    AC008906, AC020900, KC877037
    Consensus CDS
    CCDS93749.1
    UniProtKB/TrEMBL
    A0A6Q8PH20
    Related
    ENSP00000502449.1, ENST00000675663.1
    Conserved Domains (1) summary
    pfam00748
    Location:416 → 546
    Calpain_inhib; Calpain inhibitor

  21. NM_001750.7 → NP_001741.4  calpastatin isoform a

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
    Source sequence(s)
    AC008906, AC020900, KC877037
    UniProtKB/Swiss-Prot
    P20810
    Related
    ENSP00000501872.1, ENST00000675179.1
    Conserved Domains (1) summary
    pfam00748
    Location:453 → 583
    Calpain_inhib; Calpain inhibitor

  22. NM_173060.5 → NP_775083.1  calpastatin isoform b

    See identical proteins and their annotated locations for NP_775083.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) represents use of an alternate promoter compared to variant 1.
    Source sequence(s)
    AC008906, AL832174, AL832349, AY189741
    Consensus CDS
    CCDS4082.1
    UniProtKB/Swiss-Prot
    P20810
    UniProtKB/TrEMBL
    Q86YM9
    Related
    ENSP00000312523.5, ENST00000309190.9
    Conserved Domains (1) summary
    pfam00748
    Location:348 → 478
    Calpain_inhib; Calpain inhibitor

RNA

  1. NR_104285.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (15) has multiple differences compared to variant 6. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AL045308, DB033043, U58996
    Related
    ENST00000484552.6

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_03

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    96662037..96774683
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    97162871..97275514
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_173061.2: Suppressed sequence

    Description
    NM_173061.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.

  2. NM_173062.1: Suppressed sequence

    Description
    NM_173062.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

  3. NM_173063.1: Suppressed sequence

    Description
    NM_173063.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.

  4. NR_033798.1: Suppressed sequence

    Description
    NR_033798.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P20810.4 GenPept UniProtKB/Swiss-Prot:P20810

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