Details for: CLDN8

Gene ID: 9073

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: CLDN8

Ensembl ID: ENSG00000156284

Description: claudin 8

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • intestine goblet cell CL0019031
    CSI 7.25
    rCSI 6.43%
    PRS 94.14
  • renal beta-intercalated cell CL0002201
    CSI 7.01
    rCSI 16.71%
    PRS 95.69
  • epithelial cell CL0000066
    CSI 6.54
    rCSI 10.05%
    PRS 86.35
  • renal alpha-intercalated cell CL0005011
    CSI 5.09
    rCSI 6.81%
    PRS 97.06
  • lung ciliated cell CL1000271
    CSI 3.17
    rCSI 3.67%
    PRS 92.16
  • colon epithelial cell CL0011108
    CSI 2.81
    rCSI 2.95%
    PRS 94.09
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.39
    rCSI 3.38%
    PRS 94.6
  • renal principal cell CL0005009
    CSI 2.22
    rCSI 5.77%
    PRS 95.07
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.73
    rCSI 4.47%
    PRS 94.3
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.58
    rCSI 3.6%
    PRS 90.29
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.57
    rCSI 3.99%
    PRS 92.47
  • kidney connecting tubule principal cell CL4030018
    CSI 1.31
    rCSI 9.49%
    PRS 94.88
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.94
    rCSI 9.95%
    PRS 92.67

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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  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
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    • 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 [CLDN8](/details-gene/9073) is a protein-coding gene that encodes claudin-8, a member of the claudin family of transmembrane proteins. These proteins are integral components of tight junctions, which are specialized cell-cell adhesion complexes critical for regulating the passage of ions and solutes through the paracellular pathway in epithelial and endothelial cell sheets. The expression profile of [CLDN8](/details-gene/9073) indicates a highly specialized role in forming selective barriers, with its most significant expression observed in epithelial cells of the kidney and intestine. Its function is essential for maintaining tissue integrity and regulating ion homeostasis in these organs. ## Cellular Roles and Expression Landscape The **Overall** expression pattern of [CLDN8](/details-gene/9073) highlights its role as a key structural component in barrier-forming epithelia. The gene's significance is most pronounced in cell types responsible for regulated transport and secretion. - **Renal System:** [CLDN8](/details-gene/9073) demonstrates exceptionally high significance in multiple segments of the kidney nephron. It is a top marker for [renal beta-intercalated cell](/details-cell/CL0002201) (CSI: 7.01), [epithelial cell](/details-cell/CL0000066) (CSI: 6.54), and [renal alpha-intercalated cell](/details-cell/CL0005011) (CSI: 5.09). Its substantial expression extends to [renal principal cell](/details-cell/CL0005009), various [kidney loop of Henle](/details-cell/CL1001111) segments, and [kidney distal convoluted tubule epithelial cell](/details-cell/CL1000849). This widespread and high expression throughout the distal nephron suggests a critical function in establishing the tight junction barrier that controls the selective reabsorption of ions and water, which is fundamental to renal physiology. - **Gastrointestinal Tract:** The gene is also highly significant in the intestinal epithelium, particularly in [intestine goblet cell](/details-cell/CL0019031) (CSI: 7.25) and [colon epithelial cell](/details-cell/CL0011108). This points to a crucial role in maintaining the intestinal barrier, which segregates luminal contents from the underlying tissue and is vital for immune homeostasis and nutrient absorption. - **Other Epithelial Tissues:** Significant expression is also noted in other mucosal surfaces, such as [lung ciliated cell](/details-cell/CL1000271), indicating a broader role in epithelial barrier function across different organ systems. The consistent localization to epithelial lineages underscores its specialized function in cell-cell adhesion and paracellular transport regulation. ## Pathways and Molecular Function The molecular functions of [CLDN8](/details-gene/9073) are intrinsically linked to its role as a structural protein within tight junctions. Functional annotation data corroborates its localization and cellular roles. - **Tight Junction Assembly:** [CLDN8](/details-gene/9073) is directly involved in '[Bicellular tight junction assembly](/details-go/GO:0070830)' ([GO:0070830](https://www.ebi.ac.uk/QuickGO/term/GO:0070830)) and is a key component of the '[Bicellular tight junction](/details-go/GO:0005923)' ([GO:0005923](https://www.ebi.ac.uk/QuickGO/term/GO:0005923)). Reactome pathway analysis further confirms its participation in '[Tight junction interactions](/details-reactome/R-HSA-420029)' ([R-HSA-420029](https://reactome.org/content/detail/R-HSA-420029)) and the broader process of '[Cell junction organization](/details-reactome/R-HSA-446728)' ([R-HSA-446728](https://reactome.org/content/detail/R-HSA-446728)). - **Paracellular Permeability:** As a claudin, it is thought to form paracellular pores that selectively allow the passage of specific ions. Research suggests that the nanoscale arrangement of different claudin proteins within tight junction strands dictates the charge and size selectivity of the paracellular pathway ([Link](https://doi.org/10.1038/s41467-022-32533-4)). The high expression of [CLDN8](/details-gene/9073) in the distal nephron, a region critical for fine-tuning ion transport, is consistent with a role in regulating cation permeability. - **Molecular Interactions:** Its function relies on '[Identical protein binding](/details-go/GO:0042802)' ([GO:0042802](https://www.ebi.ac.uk/QuickGO/term/GO:0042802)) to form homodimers and interactions with other claudins and scaffolding proteins at the '[Apicolateral plasma membrane](/details-go/GO:0016327)' ([GO:0016327](https://www.ebi.ac.uk/QuickGO/term/GO:0016327)). ## Research Directions The specific and high expression of [CLDN8](/details-gene/9073) in ion-transporting epithelia suggests its dysregulation could be central to the pathophysiology of certain renal and intestinal disorders. **Proposed Hypotheses:** 1. **Role in Renal Ion Homeostasis:** Given its prominent expression in the distal nephron, it is hypothesized that [CLDN8](/details-gene/9073) is a primary determinant of paracellular calcium and magnesium reabsorption. Genetic variants or acquired downregulation of [CLDN8](/details-gene/9073) may underlie certain forms of familial or idiopathic hypomagnesemia by disrupting the integrity of the tight junction barrier in the distal convoluted tubule. 2. **Involvement in Inflammatory Bowel Disease (IBD):** Based on its high expression in the colonic epithelium, it is hypothesized that proinflammatory cytokines (e.g., TNF-alpha) present in the IBD microenvironment lead to the downregulation and mislocalization of [CLDN8](/details-gene/9073). This loss of [CLDN8](/details-gene/9073) from the tight junction contributes to the 'leaky gut' phenotype, increasing intestinal permeability and exacerbating the inflammatory cycle. **Experimental Approach:** To test the second hypothesis regarding the role of [CLDN8](/details-gene/9073) in IBD, a robust experimental plan could involve the use of an intestinal epithelial cell-specific conditional knockout mouse model (`Cldn8` fl/fl; Vil1-Cre). These mice and their wild-type littermates would be subjected to a model of experimental colitis, such as dextran sulfate sodium (DSS) administration in drinking water. Barrier function could be assessed *in vivo* by oral gavage of FITC-dextran and measuring its concentration in the serum. Disease progression would be monitored via weight loss, colon length, and histological scoring. It would be expected that the `Cldn8`-deficient mice would exhibit more severe colitis and higher intestinal permeability compared to controls, directly linking the loss of [CLDN8](/details-gene/9073) to compromised barrier integrity and increased susceptibility to inflammation. **Therapeutic Potential:** [CLDN8](/details-gene/9073) is unlikely to be a conventional drug target for inhibition, as its function is primarily structural. However, in diseases characterized by a compromised epithelial barrier, such as IBD or certain kidney diseases, [CLDN8](/details-gene/9073) represents a potential therapeutic target for *functional restoration*. The goal would be to enhance or stabilize its expression and localization at the tight junction. Strategies could include the development of small molecules that promote [CLDN8](/details-gene/9073) gene transcription or protein stability. Such an approach could help restore barrier integrity, reduce pathological leakage, and ameliorate disease symptoms, representing a novel host-directed therapy.

Genular Protein ID: 33343325

Symbol: CLD8_HUMAN

Name: Claudin-8

UniProtKB Accession Codes:

P56748 D3DSE3 Q53EX7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 4 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 1 ExpressionAtlas 1 GO 10 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 4 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 10830953

Title: The DNA sequence of human chromosome 21.

PubMed ID: 10830953

DOI: 10.1038/35012518

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: 17287494

Title: Gene expression profiling and its relevance to the blood-epididymal barrier in the human epididymis.

PubMed ID: 17287494

DOI: 10.1095/biolreprod.106.059246

PubMed ID: 36008380

Title: Nanoscale segregation of channel and barrier claudins enables paracellular ion flux.

PubMed ID: 36008380

DOI: 10.1038/s41467-022-32533-4

Sequence Information:

  • Length: 225
  • Mass: 24845
  • Checksum: F7920E8E71682473
  • Sequence:
    • MATHALEIAG LFLGGVGMVG TVAVTVMPQW RVSAFIENNI VVFENFWEGL WMNCVRQANI 
RMQCKIYDSL LALSPDLQAA RGLMCAASVM SFLAFMMAIL GMKCTRCTGD NEKVKAHILL 
TAGIIFIITG MVVLIPVSWV ANAIIRDFYN SIVNVAQKRE LGEALYLGWT TALVLIVGGA 
LFCCVFCCNE KSSSYRYSIP SHRTTQKSYH TGKKSPSVYS RSQYV