Details for: CLDN2

Gene ID: 9075

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: CLDN2

Ensembl ID: ENSG00000165376

Description: claudin 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • pancreatic ductal cell CL0002079
    CSI 6.63
    rCSI 12.89%
    PRS 95.62
  • intestinal epithelial cell CL0002563
    CSI 4.87
    rCSI 5.09%
    PRS 93.19
  • epithelial cell CL0000066
    CSI 3.25
    rCSI 4.99%
    PRS 85.19
  • colonocyte CL1000347
    CSI 3.16
    rCSI 4.54%
    PRS 93.37
  • mucous neck cell CL0000651
    CSI 2.91
    rCSI 4.19%
    PRS 96.41
  • stem cell CL0000034
    CSI 2.77
    rCSI 2.67%
    PRS 92.64
  • choroid plexus epithelial cell CL0000706
    CSI 2.73
    rCSI 4.48%
    PRS 90.33
  • goblet cell CL0000160
    CSI 2.65
    rCSI 2.51%
    PRS 93.18
  • epithelial cell of proximal tubule CL0002306
    CSI 2.48
    rCSI 6.07%
    PRS 90.35
  • M cell of gut CL0000682
    CSI 1.97
    rCSI 2.09%
    PRS 95.8
  • enterocyte CL0000584
    CSI 1.91
    rCSI 3.08%
    PRS 92.34

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):
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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 [CLDN2](/details-gene/9075) encodes claudin-2, a 22 kDa integral membrane protein that is a critical component of tight junctions. As a member of the claudin family, it plays a central role in forming paracellular barriers and pores that control the passage of ions, solutes, and water between cells. Expression data indicate that [CLDN2](/details-gene/9075) is a highly significant gene in various epithelial tissues, particularly those involved in secretion and absorption. Its function is primarily associated with creating cation- and water-selective channels, which contributes to processes like intestinal nutrient absorption and fluid balance in exocrine glands. Mutations in [CLDN2](/details-gene/9075) have been linked to clinical conditions, including obstructive azoospermia ([301060](https://omim.org/entry/301060)). ## Cellular Roles and Expression Landscape The expression profile of [CLDN2](/details-gene/9075) firmly establishes its identity as a key structural and functional protein in specialized epithelial cell populations. **Overall**, the gene shows the highest significance in cells responsible for forming linings of ducts and absorptive surfaces. Its most prominent role is in the pancreas, where it is the top marker for [pancreatic ductal cell](/details-cell/CL0002079) (CSI: 6.63). This suggests a critical function in maintaining the unique ionic and fluid environment of pancreatic ducts. Following this, [CLDN2](/details-gene/9075) is highly significant in the gastrointestinal tract, with high CSI scores in [intestinal epithelial cell](/details-cell/CL0002563), [colonocyte](/details-cell/CL1000347), [goblet cell](/details-cell/CL0000160), [M cell of gut](/details-cell/CL0000682), and [enterocyte](/details-cell/CL0000584). This pattern underscores its involvement in regulating paracellular transport, a function essential for nutrient and water absorption in the gut. Beyond the digestive system, [CLDN2](/details-gene/9075) is also a significant marker in other secretory and barrier-forming epithelia, including [choroid plexus epithelial cell](/details-cell/CL0000706), which is responsible for producing cerebrospinal fluid, and [epithelial cell of proximal tubule](/details-cell/CL0002306) in the kidney, which is vital for reabsorption. The consistent high expression across these diverse epithelial types highlights its fundamental role in establishing selective paracellular permeability. ## Pathways and Molecular Function The functional annotations for [CLDN2](/details-gene/9075) are highly consistent with its expression pattern and established role as a tight junction protein. Its molecular function is defined by its '[Structural molecule activity](/details-cell/GO:0005198)' within the '[Bicellular tight junction](/details-cell/GO:0005923)', where it engages in '[Identical protein binding](/details-cell/GO:0042802)' to form pores. This is further detailed by its involvement in '[Paracellular tight junction channel activity](/details-cell/GO:0160187)', which directly enables '[Paracellular transport](/details-cell/GO:0160184)'. Research has confirmed that [CLDN2](/details-gene/9075) specifically forms a paracellular water channel, facilitating fluid movement across epithelial sheets ([Link](https://doi.org/10.1242/jcs.060665)). At a higher biological level, these molecular functions contribute to key processes such as '[Cell-cell adhesion](/details-cell/GO:0098609)' and '[Bicellular tight junction assembly](/details-cell/GO:0070830)', which are fundamental to epithelial integrity. These processes are part of broader pathways like '[Cell junction organization](/details-cell/R-HSA-446728)' and '[Tight junction interactions](/details-cell/R-HSA-420029)' as annotated by Reactome. The gene's role extends to specific physiological functions tied to its cellular locations, including the '[Regulation of intestinal d-glucose absorption](/details-cell/GO:1903985)', '[Regulation of intestinal lipid absorption](/details-cell/GO:1904729)', and '[Regulation of bile acid secretion](/details-cell/GO:0120188)', aligning perfectly with its high expression in intestinal and pancreatic ductal epithelia. ## Research Directions The specific role of [CLDN2](/details-gene/9075) in forming "leaky" or pore-forming tight junctions, rather than barrier-forming ones, presents several avenues for investigation into its contribution to both homeostasis and disease. **Testable Hypotheses:** 1. Given its role in regulating intestinal absorption of glucose and lipids, dysregulation of [CLDN2](/details-gene/9075) expression or function in [intestinal epithelial cell](/details-cell/CL0002563) may contribute to the pathophysiology of metabolic syndrome by altering gut permeability and nutrient influx. 2. Based on its association with obstructive azoospermia ([Link](https://doi.org/10.1038/s10038-019-0642-0)), [CLDN2](/details-gene/9075) may be essential for maintaining the specific luminal fluid composition required for sperm maturation and transport within the male reproductive tract, such as in the efferent ductules. **Proposed Experiment:** To test the first hypothesis regarding its role in metabolic disease, a compelling approach would be to utilize human intestinal organoids. CRISPR-Cas9 could be used to knock down or knock out [CLDN2](/details-gene/9075) in these organoids. The functional consequences could be assessed by measuring changes in transepithelial electrical resistance (TEER) to quantify barrier leakiness and by using fluorescently-labeled glucose and fatty acid analogs to directly measure paracellular flux. This system would allow for a precise determination of how [CLDN2](/details-gene/9075) contributes to nutrient transport across the gut epithelium. **Therapeutic Potential:** As a transmembrane protein, [CLDN2](/details-gene/9075) is a potentially druggable target. In pathological conditions characterized by excessive gut permeability, such as inflammatory bowel disease (IBD) where its expression is often upregulated, [CLDN2](/details-gene/9075) represents a target for **inhibition**. Developing small molecules or monoclonal antibodies that specifically block the [CLDN2](/details-gene/9075) paracellular channel could help restore barrier function, reduce inflammation, and alleviate symptoms. Its tissue-restricted expression profile suggests that systemic inhibition might have a manageable side-effect profile.

Genular Protein ID: 956519914

Symbol: CLD2_HUMAN

Name: SP82

UniProtKB Accession Codes:

P57739 B2R6B9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 9 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 11 Ensembl 3 EvolutionaryTrace 1 GO 16 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 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 PDB 1 PDBsum 1 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 3 Rhea 9 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11934881

Title: Cloning of the human claudin-2 5'-flanking region revealed a TATA-less promoter with conserved binding sites in mouse and human for caudal-related homeodomain proteins and hepatocyte nuclear factor-1alpha.

PubMed ID: 11934881

DOI: 10.1074/jbc.m110261200

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15498874

Title: Large-scale cDNA transfection screening for genes related to cancer development and progression.

PubMed ID: 15498874

DOI: 10.1073/pnas.0404089101

PubMed ID: 16303743

Title: Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.

PubMed ID: 16303743

DOI: 10.1093/dnares/12.2.117

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 20460438

Title: Claudin-2, a component of the tight junction, forms a paracellular water channel.

PubMed ID: 20460438

DOI: 10.1242/jcs.060665

PubMed ID: 22731716

Title: SUMOylation of claudin-2.

PubMed ID: 22731716

DOI: 10.1111/j.1749-6632.2012.06541.x

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

PubMed ID: 31320686

Title: Identification of a missense variant in CLDN2 in obstructive azoospermia.

PubMed ID: 31320686

DOI: 10.1038/s10038-019-0642-0

Sequence Information:

  • Length: 230
  • Mass: 24549
  • Checksum: 52CA642D4A62B70D
  • Sequence:
    • MASLGLQLVG YILGLLGLLG TLVAMLLPSW KTSSYVGASI VTAVGFSKGL WMECATHSTG 
ITQCDIYSTL LGLPADIQAA QAMMVTSSAI SSLACIISVV GMRCTVFCQE SRAKDRVAVA 
GGVFFILGGL LGFIPVAWNL HGILRDFYSP LVPDSMKFEI GEALYLGIIS SLFSLIAGII 
LCFSCSSQRN RSNYYDAYQA QPLATRSSPR PGQPPKVKSE FNSYSLTGYV