CLDN1 (Claudin 1): Tight Junction Protein in Barrier Function and Disease
A comprehensive biomedical overview of CLDN1, its genomic context, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | CLDN1 |
|---|---|
| Full Name | Claudin 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q28 |
| NCBI Gene ID | 9076 ncbi.nlm.nih.gov/gene/9076 |
| Ensembl ID | ENSG00000163347 |
| UniProt ID | O95832 |
| OMIM ID | 603718 |
| HGNC ID | 2048 |
| Aliases | SEMP1, ILVASC, CLD1 |
Description
CLDN1 encodes claudin-1, a major integral membrane protein of tight junctions. It is essential for paracellular barrier function in epithelial and endothelial cells, contributing to tissue integrity and selective ion transport. CLDN1 also serves as a receptor for hepatitis C virus (HCV) entry into hepatocytes. Mutations in CLDN1 cause neonatal ichthyosis-sclerosing cholangitis syndrome (NISCH), and altered expression is linked to various cancers and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neonatal ichthyosis-sclerosing cholangitis syndrome (NISCH) | Loss-of-function mutations (e.g., frameshift, nonsense) lead to defective tight junctions in skin and bile ducts, causing ichthyosis and cholangitis. | OMIM #607626; ClinVar; PMID: 15108291 |
| Hepatitis C virus (HCV) infection | CLDN1 acts as a co-receptor for HCV entry; genetic variants may influence susceptibility or treatment response. | PMID: 17981119; PMID: 22080952 |
| Hepatocellular carcinoma (HCC) | Downregulation of CLDN1 is associated with epithelial-mesenchymal transition (EMT) and poor prognosis; loss of tight junction integrity promotes invasion. | PMID: 21516114; PMID: 26014203 |
| Colorectal cancer | Reduced CLDN1 expression correlates with tumor progression and metastasis; aberrant localization (cytoplasmic/nuclear) is observed. | PMID: 19116627; PMID: 23563179 |
| Inflammatory bowel disease (IBD) | Altered CLDN1 expression disrupts intestinal barrier, contributing to inflammation and disease severity. | PMID: 19052199; PMID: 23349065 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Skin | 8.9 | Low |
| Kidney | 7.2 | Low |
| Colon | 6.8 | Low |
| Lung | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.3 | High expression; used in HCV entry studies |
| Caco-2 (colon) | 12.1 | High expression; intestinal barrier model |
| A549 (lung) | 3.2 | Low expression |
| MCF7 (breast) | 1.5 | Very low expression |
| HeLa (cervix) | 0.8 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.354delC (p.Pro118LeufsTer24) | Frameshift | Rare (NISCH) | Loss of function; truncated protein |
| c.200C>T (p.Pro67Leu) | Missense | Rare (NISCH) | Loss of function; impaired trafficking |
| c.1A>G (p.Met1Val) | Start codon loss | Rare (NISCH) | Loss of function; no protein synthesis |
| c.487C>T (p.Arg163Ter) | Nonsense | Rare (NISCH) | Loss of function; truncated protein |
| c.53C>T (p.Ser18Phe) | Missense | Rare (NISCH) | Loss of function; altered localization |
Mutation functional classification
Loss of Function (LOF)
Most CLDN1 mutations are loss-of-function, leading to defective tight junctions and NISCH syndrome. These include frameshift, nonsense, and missense variants that impair protein synthesis, trafficking, or assembly.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for CLDN1. Overexpression in some cancers may be considered a gain-of-function at the expression level, but not due to specific mutations.
Dominant Negative (DN)
No dominant-negative mutations have been documented. CLDN1 mutations are typically autosomal recessive, requiring biallelic loss.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • identical protein binding |
| • structural molecule activity | • cell-cell junction |
| • tight junction | • plasma membrane |
| • apicolateral plasma membrane | • bicellular tight junction |
| • cell-cell adhesion | • calcium-independent cell-cell adhesion |
| • establishment of skin barrier | • response to virus |
| • hepatitis C virus entry into host cell |
Pathways
• Tight junction pathway (KEGG: hsa04530)
• Adherens junction (related)
• Hepatitis C virus entry pathway (KEGG: hsa05160)
• Epithelial cell signaling in Helicobacter pylori infection (related)
Protein Summary
Claudin-1 is a 211-amino-acid protein with four transmembrane domains, two extracellular loops, and cytoplasmic N- and C-termini. It forms the backbone of tight junction strands, interacting with other claudins and scaffolding proteins like ZO-1. The extracellular loops mediate cell-cell adhesion and serve as a binding site for HCV envelope glycoproteins. Post-translational modifications include phosphorylation, which regulates tight junction assembly. Claudin-1 is critical for epidermal barrier function and hepatic bile duct integrity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLDN1 Knockout HEK293 Cell Line | EDJ-KQ3729 | Human | 9076 | Details Get a Quote |
| CLDN12 Knockout HEK293 Cell Line | EDJ-KQ5771 | Human | 9069 | Details Get a Quote |
| CLDN10 Knockout HEK293 Cell Line | EDJ-KQ6453 | Human | 9071 | Details Get a Quote |
| CLDN16 Knockout HEK293 Cell Line | EDJ-KQ7130 | Human | 10686 | Details Get a Quote |
| CLDN15 Knockout HEK293 Cell Line | EDJ-KQ7473 | Human | 24146 | Details Get a Quote |
| CLDN14 Knockout HEK293 Cell Line | EDJ-KQ8073 | Human | 23562 | Details Get a Quote |
| CLDN17 Knockout HEK293 Cell Line | EDJ-KQ8504 | Human | 26285 | Details Get a Quote |
| CLDN19 Knockout HEK293 Cell Line | EDJ-KQ11118 | Human | 149461 | Details Get a Quote |
| CLDN18 Knockout HEK293 Cell Line | EDJ-KQ17692 | Human | 51208 | Details Get a Quote |
| CLDN15 Knockout A-549 Cell Line | EDJ-KQ34035 | Human | 24146 | Details Get a Quote |
| CLDN15 Knockout HCT 116 Cell Line | EDJ-KQ34037 | Human | 24146 | Details Get a Quote |
| CLDN15 Knockout HeLa Cell Line | EDJ-KQ34038 | Human | 24146 | Details Get a Quote |
| CLDN1 Knockout A-549 Cell Line | EDJ-KQ25778 | Human | 9076 | Details Get a Quote |
| CLDN1 Knockout HeLa Cell Line | EDJ-KQ25779 | Human | 9076 | Details Get a Quote |
| CLDN12 Knockout A-549 Cell Line | EDJ-KQ30518 | Human | 9069 | Details Get a Quote |
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