CLDN4 Gene: Claudin-4 in Tight Junctions and Cancer
A comprehensive overview of CLDN4, encoding claudin-4, a tight junction protein implicated in epithelial barrier function and tumor progression.
Gene Information Card
| Symbol | CLDN4 |
|---|---|
| Full Name | Claudin 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q11.23 |
| NCBI Gene ID | 1364 ncbi.nlm.nih.gov/gene/1364 |
| Ensembl ID | ENSG00000189143 |
| UniProt ID | O14493 |
| OMIM ID | 602909 |
| HGNC ID | 2047 |
| Aliases | CPE-R, CPER, WBSCR8, claudin-4 |
Description
CLDN4 encodes claudin-4, a member of the claudin family of integral membrane proteins that form tight junction strands. Claudin-4 is a major structural component of tight junctions, regulating paracellular ion flux and maintaining epithelial barrier integrity. It is expressed in various epithelial tissues and is frequently overexpressed in several cancers, contributing to tumor progression and metastasis. CLDN4 also serves as a receptor for Clostridium perfringens enterotoxin (CPE), which has implications for targeted cancer therapy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pancreatic cancer | Overexpression of claudin-4 enhances tumor cell survival, invasion, and chemoresistance; CPE-based therapy targets claudin-4. | Multiple studies (e.g., Michl et al., 2003; Neesse et al., 2013) show high CLDN4 expression in pancreatic ductal adenocarcinoma. |
| Ovarian cancer | Claudin-4 overexpression promotes peritoneal metastasis and correlates with poor prognosis; CPE-mediated cytotoxicity is being explored. | Evidence from clinical samples and functional studies (e.g., Rangel et al., 2003; Santin et al., 2004). |
| Breast cancer | Elevated claudin-4 expression is associated with invasive phenotypes and poor survival; potential therapeutic target. | Studies indicate upregulation in breast cancer tissues (e.g., Kominsky et al., 2003). |
| Gastric cancer | Claudin-4 overexpression contributes to tumor progression and may serve as a biomarker. | Immunohistochemistry and mRNA analyses show increased CLDN4 in gastric tumors (e.g., Kuo et al., 2006). |
| Inflammatory bowel disease (IBD) | Altered claudin-4 expression disrupts tight junction barrier, contributing to intestinal inflammation. | Studies report decreased claudin-4 in ulcerative colitis and Crohn's disease (e.g., Prasad et al., 2005). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | High | High expression in renal tubules |
| Pancreas | High | High in ductal cells |
| Liver | Low | Low in hepatocytes |
| Lung | Medium | Moderate in bronchial epithelium |
| Colon | High | High in intestinal epithelium |
| Breast | Medium | Variable in mammary epithelium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 | High | Colorectal adenocarcinoma cell line; used as intestinal barrier model |
| MCF-7 | Medium | Breast cancer cell line; moderate expression |
| PANC-1 | High | Pancreatic cancer cell line; high expression |
| OVCAR-3 | High | Ovarian cancer cell line; high expression |
| HCT116 | Low | Colorectal carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.157C>T (p.Arg53Cys) | Missense | Rare | Potential impact on tight junction function; not well characterized |
| c.206A>G (p.Asn69Ser) | Missense | Rare | Reported in cancer samples; functional significance unknown |
| c.340G>A (p.Gly114Arg) | Missense | Rare | Observed in COSMIC; may affect protein stability |
| c.448C>T (p.Arg150Trp) | Missense | Rare | Found in ClinVar; uncertain pathogenicity |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CLDN4 are rare and not well documented. They may impair tight junction integrity, but no specific pathogenic variants have been confirmed.
Gain of Function (GOF)
Gain-of-function alterations are primarily due to gene amplification or transcriptional upregulation, leading to protein overexpression in cancers, which enhances tumor aggressiveness.
Dominant Negative (DN)
No dominant-negative mutations have been reported for CLDN4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Tight junction pathway (KEGG hsa04530)
• Adherens junction (KEGG hsa04520) - indirect
• Claudin family pathway (Reactome: R-HSA-420029)
Protein Summary
Claudin-4 is a 209-amino acid protein with four transmembrane domains, two extracellular loops, and intracellular N- and C-termini. It forms tight junction strands by homophilic and heterophilic interactions with other claudins. The first extracellular loop is involved in ion selectivity and serves as the binding site for Clostridium perfringens enterotoxin (CPE). Claudin-4 is critical for maintaining the paracellular barrier, particularly in epithelial tissues. In cancer, overexpression of claudin-4 disrupts normal tight junction architecture, leading to increased cell motility and invasion. Its role as a CPE receptor makes it a promising target for cancer therapy, as CPE can selectively kill claudin-4-expressing tumor cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLDN4 Knockout HEK293 Cell Line | EDJ-KQ4327 | Human | 1364 | Details Get a Quote |
| CLDN4 Knockout HCT 116 Cell Line | EDJ-KQ25536 | Human | 1364 | Details Get a Quote |
| CLDN4 Knockout A-549 Cell Line | EDJ-KQ26825 | Human | 1364 | Details Get a Quote |
| CLDN4 Knockout HeLa Cell Line | EDJ-KQ26826 | Human | 1364 | Details Get a Quote |
