Details for: CAPN10

Gene ID: 11132

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: CAPN10

Ensembl ID: ENSG00000142330

Description: calpain 10

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • myeloid leukocyte CL0000766
    CSI 4.39
    rCSI 4.05%
    PRS 97.89
  • mucosal invariant T cell CL0000940
    CSI 3.87
    rCSI 3.12%
    PRS 98.83
  • group 3 innate lymphoid cell CL0001071
    CSI 3.52
    rCSI 2.65%
    PRS 98.06
  • ciliated epithelial cell CL0000067
    CSI 3.03
    rCSI 2.67%
    PRS 92.35
  • lung ciliated cell CL1000271
    CSI 2.4
    rCSI 2.77%
    PRS 94.13
  • cerebral cortex endothelial cell CL1001602
    CSI 2.28
    rCSI 3.94%
    PRS 94.9
  • peripheral nervous system neuron CL2000032
    CSI 2.1
    rCSI 2.86%
    PRS 93.98
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2
    rCSI 3.36%
    PRS 91.54
  • astrocyte of the cerebral cortex CL0002605
    CSI 2
    rCSI 4.48%
    PRS 91.67
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.7
    rCSI 3.01%
    PRS 91.2
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.08
    rCSI 2.62%
    PRS 89.85

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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  • 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 [CAPN10](/details-gene/11132) encodes calpain-10, a non-lysosomal, calcium-activated cysteine protease. Functionally, it is implicated in a variety of cellular processes, including proteolysis, apoptosis, and the regulation of the actin cytoskeleton. Clinically, genetic variants in [CAPN10](/details-gene/11132) have been significantly associated with an increased risk for type 2 diabetes mellitus ([Link](https://doi.org/10.1038/79876), OMIM: [601283](https://omim.org/entry/601283)). Expression analysis reveals its importance across diverse cell lineages, showing high significance in immune cells such as [myeloid leukocytes](/details-cell/CL0000766) and [mucosal invariant T cells](/details-cell/CL0000940), as well as in non-immune cells including [ciliated epithelial cells](/details-cell/CL0000067) and various neuronal subtypes. This broad but distinct expression pattern suggests multifaceted roles in both metabolic regulation and tissue-specific functions. ## Cellular Roles and Expression Landscape The expression profile of [CAPN10](/details-gene/11132) highlights its significant role in a wide range of cell types, suggesting it is a multifunctional protease rather than a lineage-specific marker. **Overall**, the gene shows the highest significance in cells of the immune system. It is a top marker for [myeloid leukocytes](/details-cell/CL0000766) (CSI: 4.39), as well as for specific lymphocyte populations like [mucosal invariant T cells](/details-cell/CL0000940) (CSI: 3.87) and [group 3 innate lymphoid cells](/details-cell/CL0001071) (CSI: 3.52). This pattern suggests a potential role in immune cell function, such as migration, activation, or effector responses at barrier tissues. Beyond the immune system, [CAPN10](/details-gene/11132) is also highly significant in specialized epithelial and neuronal cells. It is prominently expressed in [ciliated epithelial cells](/details-cell/CL0000067) and [lung ciliated cells](/details-cell/CL1000271), which may relate to its function in cytoskeletal organization. Furthermore, its notable significance in various central nervous system cells, including [cerebral cortex endothelial cells](/details-cell/CL1001602), [peripheral nervous system neurons](/details-cell/CL2000032), and specific cortical interneurons like [lamp5 GABAergic cortical interneurons](/details-cell/CL4023011), indicates a previously underappreciated role in neural biology. This diverse expression landscape underscores its involvement in fundamental cellular processes that are common across multiple tissues. ## Pathways and Molecular Function The molecular functions of [CAPN10](/details-gene/11132) are centered on its enzymatic activity as a calcium-dependent protease. Its core molecular function is defined as 'calcium-dependent cysteine-type endopeptidase activity' ([GO:0004198](https://www.ebi.ac.uk/QuickGO/term/GO:0004198)), enabling it to cleave specific protein substrates. Consistent with its established link to type 2 diabetes, [CAPN10](/details-gene/11132) is involved in biological processes related to metabolic control, including 'cellular response to insulin stimulus' ([GO:0032869](https://www.ebi.ac.uk/QuickGO/term/GO:0032869)), 'positive regulation of d-glucose import' ([GO:0046326](https://www.ebi.ac.uk/QuickGO/term/GO:0046326)), and 'positive regulation of insulin secretion' ([GO:0032024](https://www.ebi.ac.uk/QuickGO/term/GO:0032024)). Studies have demonstrated that suppressing its expression impairs insulin-stimulated glucose uptake in human skeletal muscle cells ([Link](https://doi.org/10.1016/j.ymgme.2007.05.001)). Additionally, [CAPN10](/details-gene/11132) participates in pathways related to cellular structure and survival, such as 'regulation of actin cytoskeleton organization' ([GO:0032956](https://www.ebi.ac.uk/QuickGO/term/GO:0032956)) and 'cellular component disassembly involved in execution phase of apoptosis' ([GO:0006921](https://www.ebi.ac.uk/QuickGO/term/GO:0006921)). Its annotation in Reactome pathways like 'Degradation of the extracellular matrix' ([R-HSA-1474228](https://reactome.org/content/detail/R-HSA-1474228)) and 'Extracellular matrix organization' ([R-HSA-1474244](https://reactome.org/content/detail/R-HSA-1474244)) aligns with a potential role in tissue remodeling, which could be relevant for the immune and neuronal cells where it is highly expressed. ## Research Directions The widespread yet specific expression of [CAPN10](/details-gene/11132) beyond its known metabolic context opens several avenues for future investigation, particularly concerning its role in immunology and neurobiology. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** Given its high significance in [myeloid leukocytes](/details-cell/CL0000766) and its function in extracellular matrix degradation and cytoskeletal organization, [CAPN10](/details-gene/11132) may be a critical regulator of macrophage and neutrophil migration and invasion during inflammatory responses. 2. **Hypothesis 2:** The high expression of [CAPN10](/details-gene/11132) in diverse neuronal subtypes, combined with its role in regulating apoptosis and cytoskeletal dynamics, suggests it may play a role in synaptic pruning, axonal guidance, or neuronal survival, potentially linking the cell's metabolic state to its structural integrity. To test the role of [CAPN10](/details-gene/11132) in myeloid cell migration (Hypothesis 1), a key experiment would be to use a myeloid-specific conditional knockout mouse model (e.g., *Lyz2-Cre;Capn10fl/fl*). These mice, along with floxed littermate controls, could be subjected to a sterile peritonitis model (e.g., thioglycollate injection). The recruitment of neutrophils and macrophages to the peritoneal cavity could then be quantified at various time points using flow cytometry, and tissue infiltration could be assessed histologically, providing direct evidence for its role in immune cell trafficking. **Therapeutic Potential:** The primary therapeutic relevance of [CAPN10](/details-gene/11132) lies in its association with type 2 diabetes. Because loss-of-function variants are linked to disease risk and its suppression impairs glucose uptake, a therapeutic strategy would likely focus on **activation** or potentiation of its enzymatic activity. The development of small molecule activators that specifically target calpain-10 could represent a novel approach to improve insulin sensitivity. However, designing specific activators for a protease without causing off-target effects on other calpains or cellular substrates presents a significant pharmacological challenge.

Genular Protein ID: 515550804

Symbol: CAN10_HUMAN

Name: Calpain-10

UniProtKB Accession Codes:

Q9HC96 A8MVS7 Q4ZFV1 Q8NCD4 Q96IG4 Q96JI2 Q9HC89 Q9HC90 Q9HC91 Q9HC92 Q9HC93 Q9HC94 Q9HC95

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 13 Ensembl 8 ExpressionAtlas 1 GO 16 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MEROPS 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 RNAct 1 Reactome 1 RefSeq 2 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11017071

Title: Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus.

PubMed ID: 11017071

DOI: 10.1038/79876

PubMed ID: 11347906

Title: Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.

PubMed ID: 11347906

DOI: 10.1093/dnares/8.2.85

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 14759258

Title: An unappreciated role for RNA surveillance.

PubMed ID: 14759258

DOI: 10.1186/gb-2004-5-2-r8

PubMed ID: 16721485

Title: A novel 111/121 diplotype in the Calpain-10 gene is associated with type 2 diabetes.

PubMed ID: 16721485

DOI: 10.1007/s10038-006-0410-9

PubMed ID: 17572128

Title: Targeted suppression of calpain-10 expression impairs insulin-stimulated glucose uptake in cultured primary human skeletal muscle cells.

PubMed ID: 17572128

DOI: 10.1016/j.ymgme.2007.05.001

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 672
  • Mass: 74952
  • Checksum: 74A48D879E896C71
  • Sequence:
    • MRAGRGATPA RELFRDAAFP AADSSLFCDL STPLAQFRED ITWRRPQEIC ATPRLFPDDP 
REGQVKQGLL GDCWFLCACA ALQKSRHLLD QVIPPGQPSW ADQEYRGSFT CRIWQFGRWV 
EVTTDDRLPC LAGRLCFSRC QREDVFWLPL LEKVYAKVHG SYEHLWAGQV ADALVDLTGG 
LAERWNLKGV AGSGGQQDRP GRWEHRTCRQ LLHLKDQCLI SCCVLSPRAG ARELGEFHAF 
IVSDLRELQG QAGQCILLLR IQNPWGRRCW QGLWREGGEG WSQVDAAVAS ELLSQLQEGE 
FWVEEEEFLR EFDELTVGYP VTEAGHLQSL YTERLLCHTR ALPGAWVKGQ SAGGCRNNSG 
FPSNPKFWLR VSEPSEVYIA VLQRSRLHAA DWAGRARALV GDSHTSWSPA SIPGKHYQAV 
GLHLWKVEKR RVNLPRVLSM PPVAGTACHA YDREVHLRCE LSPGYYLAVP STFLKDAPGE 
FLLRVFSTGR VSLSAIRAVA KNTTPGAALP AGEWGTVQLR GSWRVGQTAG GSRNFASYPT 
NPCFPFSVPE GPGPRCVRIT LHQHCRPSDT EFHPIGFHIF QVPEGGRSQD APPLLLQEPL 
LSCVPHRYAQ EVSRLCLLPA GTYKVVPSTY LPDTEGAFTV TIATRIDRPS IHSQEMLGQF 
LQEVSIMAVM KT