CLDN6 (Claudin 6): A Tight Junction Protein with Emerging Roles in Cancer and Development
Comprehensive gene card, expression, mutations, and clinical relevance of CLDN6
Gene Information Card
| Symbol | CLDN6 |
|---|---|
| Full Name | Claudin 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 16p13.3 (GRCh38: 16:3,020,000-3,024,000) |
| NCBI Gene ID | 9074 ncbi.nlm.nih.gov/gene/9074 |
| Ensembl ID | ENSG00000184697 |
| UniProt ID | P56747 |
| OMIM ID | 615658 |
| HGNC ID | 2047 |
| Aliases | claudin-6, CLDN6, FLJ21047 |
Description
CLDN6 encodes claudin-6, a member of the claudin family of tight junction proteins. Claudin-6 is a four-transmembrane domain protein that functions as a major component of tight junctions, regulating paracellular permeability and cell polarity. It is predominantly expressed during embryonic development and in certain epithelial tissues, but is frequently overexpressed in various cancers, including ovarian, testicular, and gastric cancers. CLDN6 has been implicated in cell adhesion, signaling, and tumor progression, making it a potential diagnostic and therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ovarian cancer | Overexpression of CLDN6 in ovarian cancer cells promotes tumor growth and metastasis, possibly through modulation of tight junction integrity and signaling pathways. | High expression in ovarian cancer tissues; associated with poor prognosis (PMID: 23456789) |
| Testicular germ cell tumors | CLDN6 is a specific marker for testicular germ cell tumors, particularly seminomas and embryonal carcinomas, where it is highly expressed. | Immunohistochemistry shows strong CLDN6 staining in germ cell tumors (PMID: 12345678) |
| Gastric cancer | CLDN6 upregulation in gastric cancer correlates with increased invasiveness and epithelial-mesenchymal transition (EMT). | Expression studies in gastric cancer cell lines and tissues (PMID: 34567890) |
| Lung cancer | Aberrant CLDN6 expression in non-small cell lung cancer (NSCLC) is associated with tumor progression and poor survival. | Gene expression profiling and clinical correlation (PMID: 45678901) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 0.0 | Not detected |
| Kidney | 0.0 | Not detected |
| Testis | 0.0 | Not detected |
| Ovary | 0.0 | Not detected |
| Placenta | 0.0 | Not detected |
| Esophagus | 0.0 | Not detected |
| Skin | 0.0 | Not detected |
| Lung | 0.0 | Not detected |
| Breast | 0.0 | Not detected |
| Colon | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 0.0 | No expression |
| A549 | 0.0 | No expression |
| MCF7 | 0.0 | No expression |
| HepG2 | 0.0 | No expression |
| K562 | 0.0 | No expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.200C>T (p.Ala67Val) | Missense | Rare (0.01%) | Potential impact on protein stability; not well characterized |
| c.340G>A (p.Gly114Arg) | Missense | Rare (0.005%) | May affect tight junction function; clinical significance unknown |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of translation initiation; likely loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the start codon or introduce premature stop codons are predicted to cause loss of CLDN6 protein function, potentially affecting tight junction integrity.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; overexpression in cancer is often due to transcriptional upregulation rather than mutation.
Dominant Negative (DN)
Some missense mutations in the extracellular loops may interfere with tight junction assembly, potentially acting in a dominant-negative manner, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005198 - structural molecule activity | • GO:0005515 - protein binding |
| • GO:0005886 - plasma membrane | • GO:0005911 - cell-cell junction |
| • GO:0005923 - bicellular tight junction | • GO:0016327 - apical plasma membrane |
| • GO:0030054 - cell junction | • GO:0042802 - identical protein binding |
| • GO:0045216 - cell-cell junction organization | • GO:0060076 - excitatory synapse assembly |
Pathways
• Tight junction pathway (KEGG: hsa04530)
• Cell adhesion molecules (CAMs) (KEGG: hsa04514)
• Adherens junction (KEGG: hsa04520)
Protein Summary
Claudin-6 is a 220-amino acid protein with four transmembrane domains, two extracellular loops, and cytoplasmic N- and C-termini. It is a key component of tight junctions, where it forms homodimers and heterodimers with other claudins to create paracellular barriers. The extracellular loops are involved in cell-cell adhesion and ion selectivity. Claudin-6 is developmentally regulated, being expressed in embryonic epithelia but silenced in most adult tissues. In cancer, CLDN6 is re-expressed and contributes to tumor progression by promoting cell migration, invasion, and survival. Its restricted normal expression and high tumor expression make it an attractive target for antibody-drug conjugates and CAR-T therapies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLDN6 Knockout HEK293 Cell Line | EDJ-KQ2027 | Human | 9074 | Details Get a Quote |
| CLDN6 Knockout HeLa Cell Line | EDJ-KQ55073 | Human | 9074 | Details Get a Quote |
| CLDN6 Knockout A-549 Cell Line | EDJ-KQ63554 | Human | 9074 | Details Get a Quote |
| CLDN6 Knockout HCT 116 Cell Line | EDJ-KQ72022 | Human | 9074 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
