Calpains are ubiquitous, well-conserved family of calcium-dependent, cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large subunit possesses a cysteine protease domain, and both subunits possess calcium-binding domains. Calpains have been implicated in neurodegenerative processes, as their activ... See more...

Aliases for CAPN9 Gene

Aliases for CAPN9 Gene

  • Calpain 9 2 3 5
  • NCL-4 2 3 4
  • Digestive Tract-Specific Calpain 3 4
  • Novel Calpain Large Subunit-4 2 3
  • New Calpain 4 3 4
  • Calpain-9 3 4
  • GC36 2 3
  • Calpain 9 (NCL-4) 2
  • Protein CG36 4
  • EC 3.4.22.54 50
  • EC 3.4.22.- 4
  • EC 3.4.22 50
  • CAPN9 5
  • NCL4 4

External Ids for CAPN9 Gene

Previous GeneCards Identifiers for CAPN9 Gene

  • GC01P229360
  • GC01P226611
  • GC01P227356
  • GC01P227918
  • GC01P227189
  • GC01P228949
  • GC01P230883
  • GC01P201367

Summaries for CAPN9 Gene

Entrez Gene Summary for CAPN9 Gene

  • Calpains are ubiquitous, well-conserved family of calcium-dependent, cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large subunit possesses a cysteine protease domain, and both subunits possess calcium-binding domains. Calpains have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx and oxidative stress. The protein encoded by this gene is expressed predominantly in stomach and small intestine and may have specialized functions in the digestive tract. This gene is thought to be associated with gastric cancer. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for CAPN9 Gene

CAPN9 (Calpain 9) is a Protein Coding gene. Diseases associated with CAPN9 include D-Glyceric Aciduria and Gastric Cancer. Among its related pathways are Degradation of the extracellular matrix and Apoptosis Pathway. Gene Ontology (GO) annotations related to this gene include calcium ion binding and calcium-dependent cysteine-type endopeptidase activity. An important paralog of this gene is CAPN3.

UniProtKB/Swiss-Prot Summary for CAPN9 Gene

Tocris Summary for CAPN9 Gene

  • Calpains are a group of calcium-sensitive cysteine proteases that are ubiquitously expressed in mammals. Structurally, calpains contain two subunits; an 80 kDa catalytic subunit and a 28 kDa regulatory subunit that functions as a chaperone to stabilize the 80 kDa structure.

Gene Wiki entry for CAPN9 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CAPN9 Gene

Genomics for CAPN9 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CAPN9 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
GH01J230746 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE dbSUPER 264.4 +0.5 466 1.9 FOXA2 SMAD4 RARA KDM1A ZBTB40 FOXA1 TFAP4 ZMYM3 KLF1 ZNF24 CAPN9 AGT lnc-COG2-2 ENSG00000244137 C1orf198
GH01J230768 Enhancer 1.1 Ensembl ENCODE CraniofacialAtlas dbSUPER 30.4 +22.1 22137 1.2 ZNF217 CTBP1 SMAD4 TEAD3 SIN3A BCL6 FOXA1 DPF2 BHLHE40 NFIL3 CAPN9 ENSG00000223393 C1orf198 COG2 lnc-COG2-2 ENSG00000244137
GH01J230750 Enhancer 1.5 VISTA ENCODE CraniofacialAtlas dbSUPER 19.3 +5.5 5547 5.2 ZNF600 CEBPA POLR2A ZNF341 ZBTB7B FOXA2 KDM6A SP2 SMAD4 SAP130 CAPN9 COG2 AGT lnc-COG2-2 ENSG00000244137 C1orf198
GH01J230758 Enhancer 1.3 Ensembl ENCODE CraniofacialAtlas dbSUPER 19.8 +12.2 12212 3.4 CEBPA ZIC2 ZNF217 SAP130 MIER3 TAL1 RARA TEAD3 ZKSCAN1 BCL6 CAPN9 COG2 ENSG00000223393 lnc-COG2-2 ENSG00000244137 C1orf198
GH01J230779 Enhancer 0.5 Ensembl 29.8 +31.8 31812 0.6 NFATC3 JUND JUN ATF3 FOS ZNF24 CEBPB CAPN9 AGT COG2 lnc-COG2-2 LOC107985359 ENSG00000244137 C1orf198
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CAPN9 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CAPN9

Top Transcription factor binding sites by QIAGEN in the CAPN9 gene promoter:
  • AML1a
  • deltaCREB
  • PPAR-gamma1
  • PPAR-gamma2
  • Roaz

Genomic Locations for CAPN9 Gene

Latest Assembly
chr1:230,747,289-230,803,356
(GRCh38/hg38)
Size:
56,068 bases
Orientation:
Plus strand

Previous Assembly
chr1:230,883,134-230,937,735
(GRCh37/hg19 by Entrez Gene)
Size:
54,602 bases
Orientation:
Plus strand

chr1:230,883,130-230,937,749
(GRCh37/hg19 by Ensembl)
Size:
54,620 bases
Orientation:
Plus strand

Genomic View for CAPN9 Gene

Genes around CAPN9 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CAPN9 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CAPN9 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CAPN9 Gene

Proteins for CAPN9 Gene

  • Protein details for CAPN9 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O14815-CAN9_HUMAN
    Recommended name:
    Calpain-9
    Protein Accession:
    O14815
    Secondary Accessions:
    • B1APS1
    • B1AQI0
    • Q9NS74

    Protein attributes for CAPN9 Gene

    Size:
    690 amino acids
    Molecular mass:
    79097 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for CAPN9 Gene

    Alternative splice isoforms for CAPN9 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CAPN9 Gene

Selected DME Specific Peptides for CAPN9 Gene

O14815:
  • GATRTDI
  • LGDCWLLA
  • EAMEDFTGGV
  • TFWTNPQ
  • FINLREV
  • YAGIFHF
  • LLEKAYAK
  • RNPWGQVEW
  • WNGSWSD
  • EDFTGGV
  • TAGGCRN
  • RGSTAGGC
  • RTDICQG
  • PSTFEPH

Post-translational modifications for CAPN9 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for CAPN9 Gene

Gene Families for CAPN9 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for CAPN9 Gene

GenScript: Design optimal peptide antigens:
  • Protein CG36 (CAN9_HUMAN)
  • Calpain 9, isoform CRA_a (Q6PIV8_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O14815

UniProtKB/Swiss-Prot:

CAN9_HUMAN :
  • Belongs to the peptidase C2 family.
Family:
  • Belongs to the peptidase C2 family.
genes like me logo Genes that share domains with CAPN9: view

Function for CAPN9 Gene

Molecular function for CAPN9 Gene

UniProtKB/Swiss-Prot Function:
Calcium-regulated non-lysosomal thiol-protease.
UniProtKB/Swiss-Prot Induction:
Down-regulated in gastric cancer tissue and in gastric cell lines of differentiated and poorly differentiated types.

Enzyme Numbers (IUBMB) for CAPN9 Gene

Phenotypes From GWAS Catalog for CAPN9 Gene

Gene Ontology (GO) - Molecular Function for CAPN9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004198 calcium-dependent cysteine-type endopeptidase activity TAS,IBA 21873635
GO:0005509 calcium ion binding TAS,IEA --
GO:0008233 peptidase activity IEA --
GO:0008234 cysteine-type peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with CAPN9: view
genes like me logo Genes that share phenotypes with CAPN9: view

Animal Models for CAPN9 Gene

MGI Knock Outs for CAPN9:

miRNA for CAPN9 Gene

miRTarBase miRNAs that target CAPN9

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CAPN9

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CAPN9 Gene

Localization for CAPN9 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 CAPN9 gene
Compartment Confidence
cytosol 3
nucleus 2
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CAPN9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005575 cellular_component ND --
GO:0005737 cytoplasm IBA 21873635
genes like me logo Genes that share ontologies with CAPN9: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for CAPN9 Gene

Pathways & Interactions for CAPN9 Gene

PathCards logo

SuperPathways for CAPN9 Gene

SuperPathway Contained pathways
1 DREAM Repression and Dynorphin Expression
.37
.36
.31
2 Degradation of the extracellular matrix
3 Apoptosis Pathway
4 ERK Signaling
.61
5 Integrin Pathway
.67
genes like me logo Genes that share pathways with CAPN9: view

Pathways by source for CAPN9 Gene

1 BioSystems pathway for CAPN9 Gene
1 Tocris pathway for CAPN9 Gene
5 Qiagen pathways for CAPN9 Gene
  • Calpain Protease Regulates Cellular Mechanics
  • Caspase Cascade
  • ERK Signaling
  • FAK1 Signaling
  • nNOS Signaling in Skeletal Muscle

Gene Ontology (GO) - Biological Process for CAPN9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA,IBA 21873635
GO:0007586 digestion TAS,IEA --
GO:0045214 sarcomere organization IEA --
genes like me logo Genes that share ontologies with CAPN9: view

No data available for SIGNOR curated interactions for CAPN9 Gene

Drugs & Compounds for CAPN9 Gene

(3) Drugs for CAPN9 Gene - From: HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium Nutra 6959
Calpeptin Pharma Ca2+-dependent protease,calpain inhibitor, Calpain and cathepsin L inhibitor 0
MDL 28170 Pharma Calpain and cathepsin B inhibitor, selective, Potent, selective calpain and cathepsin B inhibitor 0

(2) Tocris Compounds for CAPN9 Gene

Compound Action Cas Number
Calpeptin Calpain and cathepsin L inhibitor 117591-20-5
MDL 28170 Potent, selective calpain and cathepsin B inhibitor 88191-84-8
genes like me logo Genes that share compounds with CAPN9: view

Transcripts for CAPN9 Gene

mRNA/cDNA for CAPN9 Gene

3 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CAPN9

Alternative Splicing Database (ASD) splice patterns (SP) for CAPN9 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^ 18a · 18b ^ 19 ^ 20 ^
SP1: - - -
SP2: - - - -
SP3: - - - - -
SP4: -
SP5: - -
SP6:
SP7:
SP8:

ExUns: 21a · 21b · 21c
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:

Relevant External Links for CAPN9 Gene

GeneLoc Exon Structure for
CAPN9

Expression for CAPN9 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CAPN9 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CAPN9 Gene

This gene is overexpressed in Stomach (x14.5), Colon - Transverse (x10.4), and Minor Salivary Gland (x6.5).

Protein differential expression in normal tissues from HIPED for CAPN9 Gene

This gene is overexpressed in Stomach (67.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CAPN9 Gene



Protein tissue co-expression partners for CAPN9 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CAPN9

SOURCE GeneReport for Unigene cluster for CAPN9 Gene:

Hs.498021

mRNA Expression by UniProt/SwissProt for CAPN9 Gene:

O14815-CAN9_HUMAN
Tissue specificity: Expressed predominantly in stomach.

Evidence on tissue expression from TISSUES for CAPN9 Gene

  • Stomach(4.7)
genes like me logo Genes that share expression patterns with CAPN9: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for CAPN9 Gene

Orthologs for CAPN9 Gene

This gene was present in the common ancestor of animals.

Orthologs for CAPN9 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CAPN9 29 30
  • 99.66 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CAPN9 29 30
  • 89.37 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Capn9 29 16 30
  • 83.24 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Capn9 29
  • 83.24 (n)
Oppossum
(Monodelphis domestica)
Mammalia CAPN9 30
  • 80 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CAPN9 30
  • 73 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CAPN9 29 30
  • 75.75 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CAPN9 30
  • 77 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia capn9 29
  • 69.28 (n)
Str.2459 29
Zebrafish
(Danio rerio)
Actinopterygii capn9 29 29 30
  • 64.83 (n)
OneToOne
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.2168 29
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP012068 29
  • 55.08 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta CalpA 29 31
  • 54.57 (n)
CalpB 31
  • 44 (a)
CalpC 31
  • 31 (a)
Worm
(Caenorhabditis elegans)
Secernentea clp-7 31
  • 47 (a)
clp-6 31
  • 42 (a)
clp-3 31
  • 39 (a)
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.4609 30
  • 46 (a)
OneToMany
Species where no ortholog for CAPN9 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • Cow (Bos Taurus)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • 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)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • 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)

Evolution for CAPN9 Gene

ENSEMBL:
Gene Tree for CAPN9 (if available)
TreeFam:
Gene Tree for CAPN9 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CAPN9: view image
Alliance of Genome Resources:
Additional Orthologs for CAPN9

Paralogs for CAPN9 Gene

(14) SIMAP similar genes for CAPN9 Gene using alignment to 3 proteins:

  • CAN9_HUMAN
  • E7ESS6_HUMAN
  • Q6PIV8_HUMAN
genes like me logo Genes that share paralogs with CAPN9: view

Variants for CAPN9 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CAPN9 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
rs12562749 -- p.Ala102Val
rs12731961 -- p.Arg522Trp
rs16852652 -- p.Glu342Lys
rs16852683 -- p.Met611Ile
rs1933631 -- p.Lys322Gln

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CAPN9 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for CAPN9 Gene

Variant ID Type Subtype PubMed ID
esv3589093 CNV gain 21293372
nsv1000488 CNV gain 25217958
nsv1010882 CNV gain 25217958
nsv549335 CNV gain 21841781
nsv832836 CNV loss 17160897

Variation tolerance for CAPN9 Gene

Residual Variation Intolerance Score: 96.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 13.26; 95.28% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CAPN9 Gene

Human Gene Mutation Database (HGMD)
CAPN9
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CAPN9
Leiden Open Variation Database (LOVD)
CAPN9

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CAPN9 Gene

Disorders for CAPN9 Gene

MalaCards: The human disease database

(4) MalaCards diseases for CAPN9 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
d-glyceric aciduria
  • d-glyceric acidemia
gastric cancer
  • gastric cancer, somatic
inflammatory bowel disease 15
  • ibd15
coffin-siris syndrome 1
  • css1
- elite association - COSMIC cancer census association via MalaCards
Search CAPN9 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CAPN9

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with CAPN9: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CAPN9 Gene

Publications for CAPN9 Gene

  1. Isolation of two novel genes, down-regulated in gastric cancer. (PMID: 10835488) Yoshikawa Y … Kato I (Japanese journal of cancer research : Gann 2000) 2 3 4 22
  2. The crystal structures of human calpains 1 and 9 imply diverse mechanisms of action and auto-inhibition. (PMID: 17157313) Davis TL … Dhe-Paganon S (Journal of molecular biology 2007) 3 4 22
  3. Molecular cloning and characterization of a novel tissue-specific calpain predominantly expressed in the digestive tract. (PMID: 9524069) Lee HJ … Suzuki K (Biological chemistry 1998) 2 3 4
  4. A Large-scale genetic association study of esophageal adenocarcinoma risk. (PMID: 20453000) Liu CY … Christiani DC (Carcinogenesis 2010) 3 40
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 40

Products for CAPN9 Gene

Sources for CAPN9 Gene