Details for: CARD10

Gene ID: 29775

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: CARD10

Ensembl ID: ENSG00000100065

Description: caspase recruitment domain family member 10

Cell Significance Landscape

Associated with

Significant Cells

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

  • tuft cell of colon CL0009041
    CSI 4.06
    rCSI 9.45%
    PRS 95.02
  • cerebral cortex endothelial cell CL1001602
    CSI 3.06
    rCSI 5.29%
    PRS 90.66
  • goblet cell CL0000160
    CSI 2.88
    rCSI 2.72%
    PRS 92.27
  • BEST4+ enteroycte CL4030026
    CSI 2.53
    rCSI 3.15%
    PRS 93.53
  • enterocyte CL0000584
    CSI 2.44
    rCSI 3.94%
    PRS 91.4
  • colon epithelial cell CL0011108
    CSI 2.32
    rCSI 2.43%
    PRS 92.25
  • intestine goblet cell CL0019031
    CSI 2.27
    rCSI 2.02%
    PRS 92.38
  • brush cell CL0002204
    CSI 2.24
    rCSI 4.44%
    PRS 95.55
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.2
    rCSI 3.51%
    PRS 95.67
  • colonocyte CL1000347
    CSI 2.15
    rCSI 3.08%
    PRS 92.46
  • basal cell CL0000646
    CSI 2.11
    rCSI 2.82%
    PRS 91.78
  • stem cell CL0000034
    CSI 2.01
    rCSI 1.94%
    PRS 91.54
  • intestinal tuft cell CL0019032
    CSI 1.96
    rCSI 2.99%
    PRS 95.03
  • cardiac endothelial cell CL0010008
    CSI 1.54
    rCSI 6.19%
    PRS 94.76
  • small intestine goblet cell CL1000495
    CSI 1.49
    rCSI 3.27%
    PRS 95.41
  • melanocyte of skin CL1000458
    CSI 1.49
    rCSI 2.03%
    PRS 69.2
  • colon goblet cell CL0009039
    CSI 1.31
    rCSI 3.12%
    PRS 95.08
  • type EC enteroendocrine cell CL0000577
    CSI 1.19
    rCSI 4.22%
    PRS 94.74
  • suprabasal keratinocyte CL4033013
    CSI 1.02
    rCSI 1.66%
    PRS 69.72
  • podocyte CL0000653
    CSI 0.74
    rCSI 3.3%
    PRS 94.19

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 [CARD10](/details-gene/29775) (Caspase Recruitment Domain Family Member 10) is a protein-coding gene located on chromosome 22q13.1. It encodes a scaffolding protein that is a member of the membrane-associated guanylate kinase (MAGUK) family. Functionally, [CARD10](/details-gene/29775) is a crucial adaptor protein in signal transduction pathways, most notably in the positive regulation of canonical NF-kappaB signaling. This is achieved through its interaction with BCL10 and MALT1 to form the CBM signalosome complex [Link](https://doi.org/10.1074/jbc.m102488200). Expression data indicates that **Overall**, [CARD10](/details-gene/29775) is a significant marker for various epithelial and endothelial cell types, particularly those forming barrier tissues, such as [tuft cell of colon](/details-cell/CL0009041), [cerebral cortex endothelial cell](/details-cell/CL1001602), and [goblet cell](/details-cell/CL0000160). Its function is implicated in the regulation of the immune response and apoptosis, with mutations linked to immunodeficiency and autoimmunity [Link](https://doi.org/10.1038/s41423-020-0423-x). ## Cellular Roles and Expression Landscape The expression profile of [CARD10](/details-gene/29775) highlights its importance in epithelial and endothelial lineages, suggesting a primary role in barrier integrity, environmental sensing, and localized immune surveillance. **Overall**, the gene shows the highest significance in specialized cells of the intestinal epithelium. It is a top marker for [tuft cell of colon](/details-cell/CL0009041) (CSI: 4.06), a chemosensory cell type involved in initiating type 2 immune responses. High significance is also observed in secretory cells like [goblet cell](/details-cell/CL0000160) (CSI: 2.88) and absorptive cells such as [BEST4+ enteroycte](/details-cell/CL4030026) (CSI: 2.53) and [enterocyte](/details-cell/CL0000584) (CSI: 2.44). This strong and consistent signal across various intestinal cell types, including [colon epithelial cell](/details-cell/CL0011108) and [stem cell](/details-cell/CL0000034), underscores its fundamental role in gut homeostasis and signaling. Beyond the gastrointestinal tract, [CARD10](/details-gene/29775) is also a significant marker for endothelial cells from diverse vascular beds, including [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 3.06), [retinal blood vessel endothelial cell](/details-cell/CL0002585) (CSI: 2.20), and [cardiac endothelial cell](/details-cell/CL0010008) (CSI: 1.54). This pattern suggests a conserved function in regulating endothelial cell response to inflammatory or metabolic cues across different organs. ## Pathways and Molecular Function [CARD10](/details-gene/29775) functions as a critical signaling adaptor protein, primarily mediating the activation of the NF-kappaB pathway. This role is supported by multiple functional annotations and publications. Its molecular function is defined as a [signaling receptor complex adaptor activity](/details-go/GO:0030159), enabling it to participate in [protein-containing complex assembly](/details-go/GO:0065003). Specifically, it is a core component of the [CBM complex](/details-go/GO:0032449), where it binds BCL10 to initiate downstream signaling cascades [Link](https://doi.org/10.1016/s0014-5793(01)02414-0). This activity directly leads to the [activation of nf-kappab-inducing kinase activity](/details-go/GO:0007250) and the [positive regulation of canonical nf-kappab signal transduction](/details-go/GO:0043123). Consistent with its expression in barrier tissues and its NF-kappaB-related function, [CARD10](/details-gene/29775) is implicated in the [regulation of immune response](/details-go/GO:0050776) and the [regulation of apoptotic process](/details-go/GO:0042981). Its localization to the [cytoplasm](/details-go/GO:0005737) is expected for a scaffold protein, while its noted presence in the [immunological synapse](/details-go/GO:0001772) highlights its role in facilitating structured cell-cell communication, a function that may be relevant not only in lymphocytes but also in the context of epithelial-immune cell crosstalk. The gene is also involved in the [negative regulation of cell migration involved in sprouting angiogenesis](/details-go/GO:0090051), a process highly relevant to its expression in endothelial cells. ## Research Directions The widespread expression of [CARD10](/details-gene/29775) in barrier tissues and its central role in NF-kappaB signaling present several avenues for future research, particularly concerning inflammatory diseases and cancer. ### Proposed Hypotheses: 1. **[CARD10](/details-gene/29775) acts as a critical mediator of intestinal epithelial cell responses to microbial-associated molecular patterns (MAMPs).** Given its high expression in gut epithelial cells ([tuft cell of colon](/details-cell/CL0009041), [goblet cell](/details-cell/CL0000160)) and its function in NF-kappaB activation, it is hypothesized that [CARD10](/details-gene/29775) dysfunction could alter the threshold for inflammatory responses, contributing to the pathogenesis of inflammatory bowel disease (IBD). 2. **In endothelial cells, [CARD10](/details-gene/29775) integrates angiogenic and inflammatory signals to regulate vascular homeostasis.** Its role in both NF-kappaB signaling and angiogenesis regulation suggests it may be a key node in pathological processes like tumor angiogenesis or vascular inflammation in atherosclerosis, where these pathways are intertwined. ### Experimental Approach: To test the first hypothesis regarding its role in the gut epithelium, a robust experimental model would involve CRISPR-Cas9-mediated knockout of [CARD10](/details-gene/29775) in human intestinal stem cells. These cells would then be used to generate 3D intestinal organoids. The [CARD10](/details-gene/29775)-knockout and wild-type organoids would be challenged with various stimuli, such as the bacterial component lipopolysaccharide (LPS) or specific commensal and pathogenic bacteria. The resulting inflammatory response could be quantified by measuring NF-kappaB p65 nuclear translocation via immunofluorescence microscopy and the secretion of key cytokines (e.g., IL-8, TNF-alpha) into the culture medium using ELISA. RNA-sequencing could further provide a global view of the transcriptional programs dependent on [CARD10](/details-gene/29775) signaling. ### Therapeutic Potential: The therapeutic potential of targeting [CARD10](/details-gene/29775) is bivalent and context-dependent. The report of immunodeficiency and autoimmunity resulting from a mutant form of the gene suggests that loss-of-function is pathological [Link](https://doi.org/10.1038/s41423-020-0423-x). In such cases, therapeutic strategies could focus on gene therapy or pharmacological **activation** to restore proper immune function. Conversely, the NF-kappaB pathway, which [CARD10](/details-gene/29775) activates, is a well-established pro-survival pathway frequently hijacked by cancer cells. Therefore, in epithelial or endothelial-derived malignancies where [CARD10](/details-gene/29775) is overexpressed or constitutively active, it represents a potential target for **inhibition** to suppress tumor growth and survival.

Genular Protein ID: 2017633575

Symbol: CAR10_HUMAN

Name: Caspase recruitment domain-containing protein 10

UniProtKB Accession Codes:

Q9BWT7 Q14CQ8 Q5TFG6 Q8NC81 Q9UGR5 Q9UGR6 Q9Y3H0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 3 ExpressionAtlas 1 GO 9 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11259443

Title: CARD10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with Bcl10 and activates NF-kappa B.

PubMed ID: 11259443

DOI: 10.1074/jbc.m102488200

PubMed ID: 11356195

Title: Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-kappaB activation.

PubMed ID: 11356195

DOI: 10.1016/s0014-5793(01)02414-0

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 10591208

Title: The DNA sequence of human chromosome 22.

PubMed ID: 10591208

DOI: 10.1038/990031

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: 27991920

Title: TMEM43/LUMA is a key signaling component mediating EGFR-induced NF-kappaB activation and tumor progression.

PubMed ID: 27991920

DOI: 10.1038/onc.2016.430

PubMed ID: 32238915

Title: Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity.

PubMed ID: 32238915

DOI: 10.1038/s41423-020-0423-x

Sequence Information:

  • Length: 1032
  • Mass: 115931
  • Checksum: 298AAC132778376A
  • Sequence:
    • MPGRAEAGEA EEEAGAGSGS EAEEDALWER IEGVRHRLAR ALNPAKLTPY LRQCRVIDEQ 
DEEEVLSTYR FPCRVNRTGR LMDILRCRGK RGYEAFLEAL EFYYPEHFTL LTGQEPAQRC 
SMILDEEGPE GLTQFLMTEV RRLREARKSQ LQREQQLQAR GRVLEEERAG LEQRLRDQQQ 
AQERCQRLRE DWEAGSLELL RLKDENYMIA MRLAQLSEEK NSAVLRSRDL QLAVDQLKLK 
VSRLEEECAL LRRARGPPPG AEEKEKEKEK EKEPDNVDLV SELRAENQRL TASLRELQEG 
LQQEASRPGA PGSERILLDI LEHDWREAQD SRQELCQKLH AVQGELQWAE ELRDQYLQEM 
EDLRLKHRTL QKDCDLYKHR MATVLAQLEE IEKERDQAIQ SRDRIQLQYS QSLIEKDQYR 
KQVRGLEAER DELLTTLTSL EGTKALLEVQ LQRAQGGTCL KACASSHSLC SNLSSTWSLS 
EFPSPLGGPE ATGEAAVMGG PEPHNSEEAT DSEKEINRLS ILPFPPSAGS ILRRQREEDP 
APPKRSFSSM SDITGSVTLK PWSPGLSSSS SSDSVWPLGK PEGLLARGCG LDFLNRSLAI 
RVSGRSPPGG PEPQDKGPDG LSFYGDRWSG AVVRRVLSGP GSARMEPREQ RVEAAGLEGA 
CLEAEAQQRT LLWNQGSTLP SLMDSKACQS FHEALEAWAK GPGAEPFYIR ANLTLPERAD 
PHALCVKAQE ILRLVDSAYK RRQEWFCTRV DPLTLRDLDR GTVPNYQRAQ QLLEVQEKCL 
PSSRHRGPRS NLKKRALDQL RLVRPKPVGA PAGDSPDQLL LEPCAEPERS LRPYSLVRPL 
LVSALRPVVL LPECLAPRLI RNLLDLPSSR LDFQVCPAES LSGEELCPSS APGAPKAQPA 
TPGLGSRIRA IQESVGKKHC LLELGARGVR ELVQNEIYPI VIHVEVTEKN VREVRGLLGR 
PGWRDSELLR QCRGSEQVLW GLPCSWVQVP AHEWGHAEEL AKVVRGRILQ EQARLVWVEC 
GSSRGCPSSS EA