Details for: CLDN6

Gene ID: 9074

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: CLDN6

Ensembl ID: ENSG00000184697

Description: claudin 6

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • epithelial cell of lung CL0000082
    CSI 6.99
    rCSI 5.8%
    PRS 99.17
  • stem cell CL0000034
    CSI 4.17
    rCSI 4.02%
    PRS 98.33
  • intestinal epithelial cell CL0002563
    CSI 3.97
    rCSI 4.15%
    PRS 98
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.51
    rCSI 3.38%
    PRS 98.12
  • placental villous trophoblast CL2000060
    CSI 3.46
    rCSI 5.34%
    PRS 98.03
  • extravillous trophoblast CL0008036
    CSI 3.37
    rCSI 4.17%
    PRS 97.98
  • enterocyte CL0000584
    CSI 2.97
    rCSI 4.79%
    PRS 97.33
  • progenitor cell CL0011026
    CSI 2.75
    rCSI 5.85%
    PRS 96.43
  • transit amplifying cell CL0009010
    CSI 2.41
    rCSI 3.69%
    PRS 99.16
  • pancreatic ductal cell CL0002079
    CSI 1.73
    rCSI 3.37%
    PRS 98.53

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 [CLDN6](/details-gene/9074) (claudin 6) is a protein-coding gene located on chromosome 16p13.3. It is a member of the claudin family of transmembrane proteins, which are essential components of tight junctions. These structures regulate the paracellular transport of solutes and maintain cell polarity in epithelial and endothelial cell sheets. Functionally, [CLDN6](/details-gene/9074) is integral to [bicellular tight junction assembly](/details-go/GO:0070830) and [calcium-independent cell-cell adhesion](/details-go/GO:0016338). Expression data highlights its significant role in various epithelial tissues, with the highest significance observed in [epithelial cell of lung](/details-cell/CL0000082). Its notable presence in [stem cell](/details-cell/CL0000034) and trophoblast populations also suggests a role in developmental processes and placental function. Additionally, research has identified [CLDN6](/details-gene/9074) as a co-receptor for the hepatitis C virus, implicating it in viral pathogenesis ([Link](https://doi.org/10.1128/jvi.01457-07)). ## Cellular Roles and Expression Landscape The expression profile of [CLDN6](/details-gene/9074) reveals a highly specific pattern centered on epithelial barrier tissues and developmental cell populations. **Overall**, the gene shows its most significant expression in [epithelial cell of lung](/details-cell/CL0000082) (CSI: 6.99), followed by other epithelial cell types such as [intestinal epithelial cell](/details-cell/CL0002563) (CSI: 3.97), [fallopian tube secretory epithelial cell](/details-cell/CL4030006) (CSI: 3.51), and [pancreatic ductal cell](/details-cell/CL0002079) (CSI: 1.73). This pattern strongly supports its primary role in forming and maintaining tight junction barriers in diverse organs. Concurrently, [CLDN6](/details-gene/9074) is a significant marker for cells associated with development and proliferation. It is highly expressed in [stem cell](/details-cell/CL0000034) (CSI: 4.17), [progenitor cell](/details-cell/CL0011026) (CSI: 2.75), and [transit amplifying cell](/details-cell/CL0009010) (CSI: 2.41). Its prominence in placental tissues, including [placental villous trophoblast](/details-cell/CL2000060) (CSI: 3.46) and [extravillous trophoblast](/details-cell/CL0008036) (CSI: 3.37), further underscores its importance during embryogenesis and feto-maternal interface maintenance. The combined expression signature suggests that [CLDN6](/details-gene/9074) is crucial for both establishing barriers in developing tissues and maintaining them in specific adult epithelia. The lack of significant expression in major immune or neuronal cell lineages implies a highly specialized function restricted to these contexts. ## Pathways and Molecular Function The molecular functions of [CLDN6](/details-gene/9074) are tightly linked to its role in cell adhesion and barrier formation. Gene Ontology annotations confirm its involvement in [bicellular tight junction assembly](/details-go/GO:0070830) and its localization to the [apicolateral plasma membrane](/details-go/GO:0016327), the primary site of tight junctions in polarized epithelial cells. Reactome pathway analysis reinforces this, placing [CLDN6](/details-gene/9074) within critical processes such as [Cell junction organization](/details-pathway/R-HSA-446728) and specifically [Tight junction interactions](/details-pathway/R-HSA-420029). These functions are consistent with its high expression in barrier-forming cells like [enterocyte](/details-cell/CL0000584) and lung epithelia. Beyond its structural role, [CLDN6](/details-gene/9074) also participates in signaling and host-pathogen interactions. Its annotation for [virus receptor activity](/details-go/GO:0001618) is experimentally supported by studies demonstrating it acts as a coreceptor, along with CD81, for hepatitis C virus entry into host cells ([Link](https://doi.org/10.1128/jvi.01457-07); [Link](https://doi.org/10.1074/jbc.m110.104836)). This dual functionality as both a structural protein and a viral entry point highlights its multifaceted biological importance. ## Research Directions While [CLDN6](/details-gene/9074) is primarily expressed during embryonic development and in specific adult epithelia, its re-expression is a hallmark of several cancers, including ovarian, lung, and testicular carcinomas. This oncofetal expression pattern presents both research opportunities and therapeutic potential. **Proposed Hypotheses:** 1. The aberrant re-expression of [CLDN6](/details-gene/9074) in non-small cell lung cancer disrupts the integrity of native epithelial tight junctions, contributing to a loss of cell polarity and an increase in cellular motility, thereby promoting local invasion and metastasis. 2. Given its high expression in trophoblasts and progenitor cells, [CLDN6](/details-gene/9074) may play a regulatory role in cell fate decisions and differentiation programs. Its forced expression in adult somatic cells could potentially induce a more plastic, progenitor-like state. **Experimental Approach:** To test the first hypothesis, a compelling experiment would involve using CRISPR-Cas9 to knock out [CLDN6](/details-gene/9074) in a human lung adenocarcinoma cell line (e.g., A549) that endogenously expresses it. The resulting knockout cells and wild-type controls could be cultured on transwell inserts to form monolayers. The impact on barrier integrity would be quantified by measuring transepithelial electrical resistance (TEER). Simultaneously, metastatic potential could be assessed using a Boyden chamber invasion assay, measuring the ability of cells to migrate through a basement membrane matrix. A significant increase in TEER and a decrease in invasion in the knockout cells would support the hypothesis that [CLDN6](/details-gene/9074) contributes to a malignant phenotype by disrupting epithelial barrier function. **Therapeutic Potential:** The highly restricted expression of [CLDN6](/details-gene/9074) in healthy adult tissues, combined with its frequent and high-level re-expression on the surface of tumor cells, makes it an exceptionally attractive target for cancer immunotherapy. Its nature as a transmembrane protein is ideal for targeting with antibody-based therapies. Indeed, [CLDN6](/details-gene/9074) is currently being investigated as a target for both CAR-T cell therapies and antibody-drug conjugates (ADCs). The therapeutic strategy would be inhibitory or cytotoxic, aiming to specifically eliminate cancer cells that display this oncofetal antigen, while sparing healthy tissues.

Genular Protein ID: 1562924084

Symbol: CLD6_HUMAN

Name: Claudin-6

UniProtKB Accession Codes:

P56747 B3KQP9 D3DUA5

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 2 ExpressionAtlas 1 GO 9 Gene3D 1 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 1 MINT 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 Pumba 1 RNAct 1 Reactome 1 RefSeq 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: 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: 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: 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: 17804490

Title: Claudin-6 and claudin-9 function as additional coreceptors for hepatitis C virus.

PubMed ID: 17804490

DOI: 10.1128/jvi.01457-07

PubMed ID: 20375010

Title: Claudin association with CD81 defines hepatitis C virus entry.

PubMed ID: 20375010

DOI: 10.1074/jbc.m110.104836

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

Sequence Information:

  • Length: 220
  • Mass: 23292
  • Checksum: D80AECB5681502AA
  • Sequence:
    • MASAGMQILG VVLTLLGWVN GLVSCALPMW KVTAFIGNSI VVAQVVWEGL WMSCVVQSTG 
QMQCKVYDSL LALPQDLQAA RALCVIALLV ALFGLLVYLA GAKCTTCVEE KDSKARLVLT 
SGIVFVISGV LTLIPVCWTA HAIIRDFYNP LVAEAQKREL GASLYLGWAA SGLLLLGGGL 
LCCTCPSGGS QGPSHYMARY STSAPAISRG PSEYPTKNYV