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 exo... See more...

Aliases for CAST Gene

Aliases for CAST Gene

  • Calpastatin 2 3 4 5
  • Sperm BS-17 Component 3 4
  • Calpain Inhibitor 3 4
  • BS-17 3
  • PLACK 3

External Ids for CAST Gene

Previous GeneCards Identifiers for CAST Gene

  • GC05P095228
  • GC05P096462
  • GC05P096026
  • GC05P096085
  • GC05P096105
  • GC05P096036
  • GC05P095865
  • GC05P091188

Summaries for CAST Gene

Entrez Gene Summary for CAST Gene

  • 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]

GeneCards Summary for CAST Gene

CAST (Calpastatin) is a Protein Coding gene. Diseases associated with CAST include Peeling Skin With Leukonychia, Acral Punctate Keratoses, Cheilitis, And Knuckle Pads and Cheilitis. Among its related pathways are Degradation of the extracellular matrix and DREAM Repression and Dynorphin Expression. Gene Ontology (GO) annotations related to this gene include cysteine-type endopeptidase inhibitor activity.

UniProtKB/Swiss-Prot Summary for CAST Gene

  • Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue.

Gene Wiki entry for CAST Gene

Additional gene information for CAST Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CAST Gene

Genomics for CAST Gene

GeneHancer (GH) Regulatory Elements for CAST Gene

Promoters and enhancers for CAST Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH05J095957 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 500 -564.7 -564683 8 ZBTB40 CTCF ZSCAN5C SIN3A TCF12 POLR2G SP1 GTF2E2 PHF8 JUND ELL2 LOC101929710 lnc-GLRX-5 CAST PCSK1 AB372744
GH05J096699 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 518.4 +179.9 179940 12 ZBTB40 ZNF217 EP300 ZSCAN5C SIN3A NRF1 POLR2G USF1 RBAK GTF2E2 CAST ERAP1 ENSG00000248734 RIOK2 ENSG00000249180 LOC101929710 lnc-ERAP2-8 RF00017-4799
GH05J096659 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 551.2 +136.8 136751 4.8 ZNF217 EP300 ZSCAN5C SIN3A TCF12 POLR2G PHF8 ZFX ZNF10 ZIC2 CAST ENSG00000248734 piR-43106-166 piR-57461-185
GH05J096743 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE dbSUPER 500.1 +217.5 217457 3 NRF1 ZIC2 DNMT1 MYC CTBP1 NFRKB OSR2 LEF1 NCOR1 KDM5B ENSG00000249180 CAST ERAP1 ENSG00000248734 LIX1 ERAP2 LOC105379094 lnc-ERAP2-8
GH05J096048 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE dbSUPER 500 -475.7 -475667 4.4 ATF2 ZBTB17 CEBPG EHMT2 GATA3 TAL1 ZBTB48 POLR2A ZNF664 ATF4 MIR583HG CAST LOC101929710 LOC105379096 piR-43107-247
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CAST on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CAST

Top Transcription factor binding sites by QIAGEN in the CAST gene promoter:
  • MyoD
  • p53
  • PPAR-gamma1
  • SREBP-1a
  • SREBP-1b
  • SREBP-1c
  • YY1

Genomic Locations for CAST Gene

Genomic Locations for CAST Gene
chr5:96,525,267-96,779,595
(GRCh38/hg38)
Size:
254,329 bases
Orientation:
Plus strand
chr5:95,860,971-96,115,299
(GRCh37/hg19)
Size:
254,329 bases
Orientation:
Plus strand

Genomic View for CAST Gene

Genes around CAST on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CAST Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CAST Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CAST Gene

Proteins for CAST Gene

  • Protein details for CAST Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P20810-ICAL_HUMAN
    Recommended name:
    Calpastatin
    Protein Accession:
    P20810
    Secondary Accessions:
    • B7Z468
    • G5E946
    • G5E9D3
    • O95360
    • Q05DE8
    • Q7Z4K0
    • Q96D08
    • Q9H1Z5

    Protein attributes for CAST Gene

    Size:
    708 amino acids
    Molecular mass:
    76573 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAH16066.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};

    Alternative splice isoforms for CAST Gene

neXtProt entry for CAST Gene

Post-translational modifications for CAST Gene

No data available for DME Specific Peptides for CAST Gene

Domains & Families for CAST Gene

Gene Families for CAST Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for CAST Gene

Blocks:
  • Calpain inhibitor repeat
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CAST Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ56102, highly similar to Homo sapiens calpastatin (CAST), transcript variant 8, mRNA (B7Z468_HUMAN)
  • cDNA FLJ56123, highly similar to Calpastatin (B7Z574_HUMAN)
  • Sperm BS-17 component (ICAL_HUMAN)
  • Calpastatin (Q13940_HUMAN)
  • CAST protein (Q6AZE3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P20810

UniProtKB/Swiss-Prot:

ICAL_HUMAN :
  • Each of the four flexible inhibitory domains can inhibit one calcium-bound calpain molecule by occupying both sides of the active site.
  • Belongs to the protease inhibitor I27 (calpastatin) family.
Domain:
  • Each of the four flexible inhibitory domains can inhibit one calcium-bound calpain molecule by occupying both sides of the active site.
Family:
  • Belongs to the protease inhibitor I27 (calpastatin) family.
genes like me logo Genes that share domains with CAST: view

Function for CAST Gene

Molecular function for CAST Gene

UniProtKB/Swiss-Prot Function:
Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue.
GENATLAS Biochemistry:
calpastatin,calcium dependent cysteine endopeptidase,calpain inhibitor

Phenotypes From GWAS Catalog for CAST Gene

Gene Ontology (GO) - Molecular Function for CAST Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IBA 21873635
GO:0003723 RNA binding HDA 22658674
GO:0004866 endopeptidase inhibitor activity TAS 7638179
GO:0004869 cysteine-type endopeptidase inhibitor activity IEA --
GO:0005515 protein binding IPI 17474147
genes like me logo Genes that share ontologies with CAST: view
genes like me logo Genes that share phenotypes with CAST: view

Human Phenotype Ontology for CAST Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CAST Gene

MGI Knock Outs for CAST:
  • Cast Cast<tm1Tcs>
  • Cast Cast<tm1.1(KOMP)Vlcg>

Animal Model Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CAST Gene

Localization for CAST Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CAST gene
Compartment Confidence
cytosol 5
nucleus 4
endoplasmic reticulum 4
plasma membrane 3
cytoskeleton 3
extracellular 2
mitochondrion 2
lysosome 2
peroxisome 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (4)
  • Endoplasmic reticulum (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CAST Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IDA,IBA --
GO:0005829 cytosol TAS --
GO:0016020 membrane IDA 14559243
genes like me logo Genes that share ontologies with CAST: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for CAST Gene

Pathways & Interactions for CAST Gene

genes like me logo Genes that share pathways with CAST: view

Pathways by source for CAST Gene

1 Qiagen pathway for CAST Gene
  • Calpain Protease Regulates Cellular Mechanics
1 Cell Signaling Technology pathway for CAST Gene

SIGNOR curated interactions for CAST Gene

Inactivates:

Gene Ontology (GO) - Biological Process for CAST Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0010466 negative regulation of peptidase activity IEA --
GO:0097340 inhibition of cysteine-type endopeptidase activity IMP 2407243
GO:1990709 presynaptic active zone organization TAS 27626661
GO:2000675 negative regulation of type B pancreatic cell apoptotic process IDA 15044459
genes like me logo Genes that share ontologies with CAST: view

Drugs & Compounds for CAST Gene

(16) Drugs for CAST Gene - From: DrugBank, ClinicalTrials, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium Approved Nutra Target 7884
Dihydroartemisinin Experimental, Investigational Pharma Target, ligand 113
Cola Pharma 2389
Gotu Kola Pharma 19

(16) Additional Compounds for CAST Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CAST: view

Transcripts for CAST Gene

mRNA/cDNA for CAST Gene

25 REFSEQ mRNAs :
51 NCBI additional mRNA sequence :
44 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for CAST Gene

No ASD Table

Relevant External Links for CAST Gene

GeneLoc Exon Structure for
CAST

Expression for CAST Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CAST Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CAST Gene

This gene is overexpressed in Muscle - Skeletal (x4.0).

Protein differential expression in normal tissues from HIPED for CAST Gene

This gene is overexpressed in Nasal epithelium (13.7), Peripheral blood mononuclear cells (8.4), and Lavage (6.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CAST Gene



Protein tissue co-expression partners for CAST Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CAST

SOURCE GeneReport for Unigene cluster for CAST Gene:

Hs.436186

Evidence on tissue expression from TISSUES for CAST Gene

  • Liver(4.7)
  • Lung(4.7)
  • Skin(4.7)
  • Nervous system(3.9)
  • Muscle(3.7)
  • Heart(3.3)
  • Kidney(3)
  • Blood(2.5)
  • Eye(2.5)
  • Adrenal gland(2.2)
  • Intestine(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CAST Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • immune
  • integumentary
Regions:
Head and neck:
  • mouth
Limb:
  • foot
  • hand
  • lower limb
  • upper limb
General:
  • blood
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with CAST: view

No data available for mRNA Expression by UniProt/SwissProt for CAST Gene

Orthologs for CAST Gene

This gene was present in the common ancestor of chordates.

Orthologs for CAST Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CAST 31 30
  • 98.93 (n)
OneToOne
dog
(Canis familiaris)
Mammalia CAST 31 30
  • 84.5 (n)
OneToOne
cow
(Bos Taurus)
Mammalia CAST 31 30
  • 82.4 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Cast 17 31 30
  • 78.85 (n)
rat
(Rattus norvegicus)
Mammalia Cast 30
  • 75.37 (n)
oppossum
(Monodelphis domestica)
Mammalia CAST 31
  • 57 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CAST 31
  • 54 (a)
OneToOne
chicken
(Gallus gallus)
Aves CAST 31 30
  • 61.17 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CAST 31
  • 43 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia cast 30
  • 56.49 (n)
Str.96 30
African clawed frog
(Xenopus laevis)
Amphibia calp3 30
zebrafish
(Danio rerio)
Actinopterygii cast 31
  • 22 (a)
OneToOne
Species where no ortholog for CAST was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CAST Gene

ENSEMBL:
Gene Tree for CAST (if available)
TreeFam:
Gene Tree for CAST (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CAST: view image

Paralogs for CAST Gene

No data available for Paralogs for CAST Gene

Variants for CAST Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CAST Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
708906 Benign: not provided 96,767,912(+) T/G NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT,INTRON_VARIANT
709742 Benign: not provided 96,762,275(+) A/G MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,THREE_PRIME_UTR_VARIANT
711433 Benign: not provided 96,746,383(+) T/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
715715 Benign: not provided 96,736,234(+) G/A SYNONYMOUS_VARIANT,INTRON_VARIANT
716343 Benign: not provided 96,765,218(+) C/T INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for CAST Gene

Structural Variations from Database of Genomic Variants (DGV) for CAST Gene

Variant ID Type Subtype PubMed ID
nsv1021263 CNV loss 25217958
nsv1028741 CNV gain 25217958
nsv1142440 CNV tandem duplication 24896259
nsv436983 CNV loss 16327808
nsv509982 OTHER sequence alteration 20534489
nsv516293 CNV gain+loss 19592680
nsv598962 CNV gain 21841781
nsv598963 CNV gain 21841781
nsv819693 CNV loss 19587683
nsv830411 CNV loss 17160897

Variation tolerance for CAST Gene

Residual Variation Intolerance Score: 87.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.59; 72.38% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CAST Gene

Human Gene Mutation Database (HGMD)
CAST
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CAST

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CAST Gene

Disorders for CAST Gene

MalaCards: The human disease database

(17) MalaCards diseases for CAST Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search CAST in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

ICAL_HUMAN
  • Peeling skin with leukonychia, acral punctate keratoses, cheilitis, and knuckle pads (PLACK) [MIM:616295]: An autosomal recessive disease characterized by generalized, continuous shedding of the outer layers of the epidermis, leukonychia, acral punctate keratosis, cheilitis, knuckle pads with multiple hyperkeratotic micropapules involving the interphalangeal joints, and palmoplantar keratoderma. {ECO:0000269 PubMed:25683118}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for CAST

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CAST: view

No data available for Genatlas for CAST Gene

Publications for CAST Gene

  1. SNPs in CAST are associated with Parkinson disease: a confirmation study. (PMID: 20127884) Allen AS … Satten GA (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2010) 3 23 41 54
  2. Sex differences in environmental and genetic factors for hypertension. (PMID: 18724972) Ruixing Y … Yuming C (The American journal of medicine 2008) 3 23 41 54
  3. Four promoters direct expression of the calpastatin gene. (PMID: 15820218) Raynaud P … Amarger V (Archives of biochemistry and biophysics 2005) 2 3 23 54
  4. Changes in calpastatin localization and expression during calpain activation: a new mechanism for the regulation of intracellular Ca(2+)-dependent proteolysis. (PMID: 14685690) Averna M … Melloni E (Cellular and molecular life sciences : CMLS 2003) 2 3 23 54
  5. Mutation analysis of the calpastatin gene (CAST) in patients with Alzheimer's disease. (PMID: 11849768) Nakayama J … Arinami T (Neuroscience letters 2002) 3 23 41 54

Products for CAST Gene

  • Boster Bio Antibodies for CAST