Details for: CAPN5

Gene ID: 726

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CAPN5

Ensembl ID: ENSG00000149260

Description: calpain 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • nasal mucosa goblet cell CL0002480
    CSI 6.47
    rCSI 7.51%
    PRS 96.28
  • multi-ciliated epithelial cell CL0005012
    CSI 6.02
    rCSI 6%
    PRS 93.84
  • secretory cell CL0000151
    CSI 5.96
    rCSI 6.22%
    PRS 96.47
  • M cell of gut CL0000682
    CSI 5.6
    rCSI 5.95%
    PRS 97.19
  • foveolar cell of stomach CL0002179
    CSI 4.58
    rCSI 9.75%
    PRS 97.21
  • ciliated cell CL0000064
    CSI 3.81
    rCSI 6.17%
    PRS 92.93
  • neural crest cell CL0011012
    CSI 3.76
    rCSI 2.97%
    PRS 94.52
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.75
    rCSI 4.48%
    PRS 91.22
  • colon epithelial cell CL0011108
    CSI 3.72
    rCSI 3.89%
    PRS 95.78
  • colonocyte CL1000347
    CSI 3.51
    rCSI 5.03%
    PRS 95.62
  • goblet cell CL0000160
    CSI 3.34
    rCSI 3.15%
    PRS 95.64
  • duct epithelial cell CL0000068
    CSI 3.22
    rCSI 4.71%
    PRS 98.28
  • enteroendocrine cell CL0000164
    CSI 3.21
    rCSI 4.39%
    PRS 95.2
  • bronchial goblet cell CL1000312
    CSI 2.92
    rCSI 11.67%
    PRS 98.07
  • intestine goblet cell CL0019031
    CSI 2.86
    rCSI 2.54%
    PRS 95.68
  • stem cell CL0000034
    CSI 2.75
    rCSI 2.65%
    PRS 95.63
  • mucous neck cell CL0000651
    CSI 2.73
    rCSI 3.93%
    PRS 97.46
  • intestinal epithelial cell CL0002563
    CSI 2.6
    rCSI 2.72%
    PRS 95.78
  • BEST4+ enteroycte CL4030026
    CSI 2.53
    rCSI 3.14%
    PRS 96.23
  • transit amplifying cell of colon CL0009011
    CSI 2.36
    rCSI 2.77%
    PRS 97.39
  • enteroendocrine cell of small intestine CL0009006
    CSI 2.35
    rCSI 5.16%
    PRS 97.03
  • transit amplifying cell CL0009010
    CSI 2.33
    rCSI 3.56%
    PRS 97.94
  • ependymal cell CL0000065
    CSI 2.22
    rCSI 4.51%
    PRS 86.46
  • enterocyte CL0000584
    CSI 2.19
    rCSI 3.53%
    PRS 94.58
  • small intestine goblet cell CL1000495
    CSI 2.14
    rCSI 4.69%
    PRS 97.34
  • colon goblet cell CL0009039
    CSI 2.1
    rCSI 4.98%
    PRS 97.11
  • squamous epithelial cell CL0000076
    CSI 2.05
    rCSI 4.86%
    PRS 93.59
  • club cell CL0000158
    CSI 1.95
    rCSI 2.86%
    PRS 95.39
  • enterocyte of epithelium of large intestine CL0002071
    CSI 1.93
    rCSI 10.13%
    PRS 97.35
  • intestinal tuft cell CL0019032
    CSI 1.92
    rCSI 2.93%
    PRS 96.83
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.74
    rCSI 3.06%
    PRS 90.99
  • paneth cell CL0000510
    CSI 1.7
    rCSI 2.5%
    PRS 98.34
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.6
    rCSI 2.68%
    PRS 91.36
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.45
    rCSI 3.9%
    PRS 97.59
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.75
    rCSI 2.35%
    PRS 92.85
  • paneth cell of colon CL0009009
    CSI 0.46
    rCSI 4.51%
    PRS 97.47

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CAPN5](/details-gene/726) encodes calpain-5, a calcium-dependent cysteine protease. **Overall**, expression data reveals that [CAPN5](/details-gene/726) is a highly significant gene in various secretory and ciliated epithelial cell types, particularly those forming mucosal barriers in the respiratory and gastrointestinal tracts. Its primary functions are linked to [proteolysis](/details-go/GO:0006508) and the organization of the extracellular matrix, suggesting a role in tissue homeostasis, remodeling, and mucosal defense. Clinically, mutations in [CAPN5](/details-gene/726) have been directly associated with autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a form of autoimmune uveitis characterized by retinal neovascularization and photoreceptor degeneration [Link](https://doi.org/10.1371/journal.pgen.1003001), highlighting its critical and specific role in ocular immune privilege and retinal health. ## Cellular Roles and Expression Landscape The expression profile of [CAPN5](/details-gene/726) indicates a specialized function in epithelial tissues, particularly at mucosal surfaces. **Overall**, it exhibits the highest significance scores in cells responsible for secretion and ciliary action. Top marker cells include [nasal mucosa goblet cell](/details-cell/CL0002480) (CSI: 6.47), [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 6.02), and [secretory cell](/details-cell/CL0000151) (CSI: 5.96). This strong signature extends to various specialized epithelial populations throughout the body, such as [M cell of gut](/details-cell/CL0000682), [foveolar cell of stomach](/details-cell/CL0002179), and [bronchial goblet cell](/details-cell/CL1000312). This consistent high expression across functionally related cell types suggests a conserved role for [CAPN5](/details-gene/726) in processes common to these cells, such as mucus production, mucociliary clearance, and the maintenance of the epithelial barrier. A secondary, more specialized expression pattern is observed in the nervous system, with notable significance in [VIP GABAergic cortical interneuron](/details-cell/CL4023016) and [neural crest cell](/details-cell/CL0011012), which aligns with its annotated presence in the [synapse](/details-go/GO:0045202). ## Pathways and Molecular Function The molecular function of [CAPN5](/details-gene/726) is defined by its [calcium-dependent cysteine-type endopeptidase activity](/details-go/GO:0004198), enabling it to perform targeted [proteolysis](/details-go/GO:0006508). This activity is integral to its involvement in pathways that modulate the cellular microenvironment. Functional annotation implicates [CAPN5](/details-gene/726) in the [Degradation of the extracellular matrix](/details-pathway/R-HSA-1474228) and broader [Extracellular matrix organization](/details-pathway/R-HSA-1474244). These functions are consistent with its high expression in mucosal epithelial layers, which undergo constant renewal and remodeling. Cellular component analysis localizes the protein to the [cytoplasm](/details-go/GO:0005737), [cell surface](/details-go/GO:0009986), [focal adhesion](/details-go/GO:0005925), and [extracellular exosome](/details-go/GO:0070062). This distribution suggests that [CAPN5](/details-gene/726) can act both intracellularly and extracellularly, potentially processing substrates within the cell, at the cell-matrix interface, or after being secreted via exosomes to modify the surrounding environment. ## Research Directions The established link between [CAPN5](/details-gene/726) mutations and autoimmune uveitis provides a strong foundation for further investigation into its pathological mechanisms [Link](https://doi.org/10.1371/journal.pgen.1003001). While the provided expression data highlights its role in mucosal epithelia, its critical function in the eye suggests a highly context-specific role that warrants deeper exploration. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** In mucosal tissues, [CAPN5](/details-gene/726) is essential for maintaining mucociliary clearance by proteolytically processing mucin proteins or other components of the mucus layer, thereby ensuring proper viscosity and transport. Its dysregulation could contribute to diseases characterized by mucus obstruction, such as chronic obstructive pulmonary disease (COPD) or cystic fibrosis. 2. **Hypothesis 2:** The gain-of-function mutations in [CAPN5](/details-gene/726) that cause uveitis lead to aberrant proteolytic activity within retinal cells, cleaving novel substrates that are either structurally essential or generate neoantigens. These neoantigens subsequently break local immune tolerance and trigger the autoimmune cascade that leads to photoreceptor destruction. To test the role of [CAPN5](/details-gene/726) in retinal pathology (Hypothesis 2), a key experiment would be to generate a knock-in mouse model expressing a human disease-causing mutation (e.g., L244P). Proteomic analysis of the retinas from these mice compared to wild-type controls could identify novel cleavage products or protein interaction partners of the mutant calpain-5. This could be followed by immunological studies to determine if these novel protein fragments are antigenic and can induce an autoimmune response when presented to T-cells. Given that uveitis-associated mutations appear to confer a toxic gain-of-function, [CAPN5](/details-gene/726) represents a compelling therapeutic target. The development of a highly specific small-molecule inhibitor targeting the protease activity of [CAPN5](/details-gene/726) would be a promising strategy. Such an inhibitor could potentially halt the aberrant proteolysis in the retina and prevent the progression of autoimmune damage. The primary challenge would be achieving specificity for [CAPN5](/details-gene/726) over other members of the calpain family to minimize off-target effects.

Genular Protein ID: 1447427887

Symbol: CAN5_HUMAN

Name: Calpain-5

UniProtKB Accession Codes:

O15484 O00263

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 3 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 1 EMBL 3 Ensembl 3 ExpressionAtlas 1 GO 8 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 12 KEGG 1 MANE-Select 1 MEROPS 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 SMART 3 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9367857

Title: Identification of a novel, tissue-specific calpain htra-3; a human homologue of the Caenorhabditis elegans sex determination gene.

PubMed ID: 9367857

DOI: 10.1006/bbrc.1997.7571

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9339374

Title: A new subfamily of vertebrate calpains lacking a calmodulin-like domain: implications for calpain regulation and evolution.

PubMed ID: 9339374

DOI: 10.1006/geno.1997.4870

PubMed ID: 23055945

Title: Calpain-5 mutations cause autoimmune uveitis, retinal neovascularization, and photoreceptor degeneration.

PubMed ID: 23055945

DOI: 10.1371/journal.pgen.1003001

Sequence Information:

  • Length: 640
  • Mass: 73169
  • Checksum: 7A3A9A1A920410BC
  • Sequence:
    • MFSCVKPYED QNYSALRRDC RRRKVLFEDP LFPATDDSLY YKGTPGPAVR WKRPKGICED 
PRLFVDGISS HDLHQGQVGN CWFVAACSSL ASRESLWQKV IPDWKEQEWD PEKPNAYAGI 
FHFHFWRFGE WVDVVIDDRL PTVNNQLIYC HSNSRNEFWC ALVEKAYAKL AGCYQALDGG 
NTADALVDFT GGVSEPIDLT EGDFANDETK RNQLFERMLK VHSRGGLISA SIKAVTAADM 
EARLACGLVK GHAYAVTDVR KVRLGHGLLA FFKSEKLDMI RLRNPWGERE WNGPWSDTSE 
EWQKVSKSER EKMGVTVQDD GEFWMTFEDV CRYFTDIIKC RVINTSHLSI HKTWEEARLH 
GAWTLHEDPR QNRGGGCINH KDTFFQNPQY IFEVKKPEDE VLICIQQRPK RSTRREGKGE 
NLAIGFDIYK VEENRQYRMH SLQHKAASSI YINSRSVFLR TDQPEGRYVI IPTTFEPGHT 
GEFLLRVFTD VPSNCRELRL DEPPHTCWSS LCGYPQLVTQ VHVLGAAGLK DSPTGANSYV 
IIKCEGDKVR SAVQKGTSTP EYNVKGIFYR KKLSQPITVQ VWNHRVLKDE FLGQVHLKAD 
PDNLQALHTL HLRDRNSRQP SNLPGTVAVH ILSSTSLMAV