CLDN5 Gene: Claudin-5 in Blood-Brain Barrier Integrity
Essential tight junction protein for endothelial barrier function and neurovascular health
Gene Information Card
| Symbol | CLDN5 |
|---|---|
| Full Name | Claudin 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q11.21 |
| NCBI Gene ID | 7122 ncbi.nlm.nih.gov/gene/7122 |
| Ensembl ID | ENSG00000184113 |
| UniProt ID | O00501 |
| OMIM ID | 602101 |
| HGNC ID | 2051 |
| Aliases | TMVCF, BEC1, CPETR1 |
Description
CLDN5 encodes claudin-5, a transmembrane protein that is a major component of tight junctions in endothelial cells. It is essential for maintaining the blood-brain barrier (BBB) and regulating paracellular permeability. Loss of claudin-5 leads to increased BBB leakage and is implicated in neurological disorders, stroke, and cerebral edema.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Velocardiofacial syndrome (VCFS) | CLDN5 is located in the 22q11.2 deletion region; haploinsufficiency may contribute to BBB dysfunction in VCFS patients. | OMIM #192430; NCBI Gene |
| Cerebral small vessel disease | Reduced CLDN5 expression disrupts tight junctions, leading to microvascular leakage and white matter damage. | ClinVar; PubMed studies |
| Stroke/ischemia | Ischemic conditions downregulate CLDN5, increasing BBB permeability and exacerbating edema. | NCBI Gene; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Lung | 8.3 | Medium |
| Heart | 6.1 | Medium |
| Kidney | 4.7 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| hCMEC/D3 (brain endothelial) | 15.2 | High expression; model for BBB studies |
| HUVEC (umbilical vein endothelial) | 9.8 | Moderate expression |
| HEK293 | 0.5 | Very low; not endogenous |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.200C>T (p.Pro67Leu) | Missense | Rare | Alters tight junction assembly; associated with VCFS |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of protein expression; likely pathogenic |
| c.478G>A (p.Gly160Ser) | Missense | Rare | Disrupts extracellular loop; reduced barrier function |
Mutation functional classification
Loss of Function (LOF)
Most CLDN5 mutations lead to loss of function by impairing protein folding, trafficking, or tight junction incorporation, resulting in increased paracellular permeability.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CLDN5.
Dominant Negative (DN)
Some missense mutations (e.g., p.Pro67Leu) may exert dominant-negative effects by interfering with wild-type claudin-5 polymerization in tight junctions.
View complete mutation data：
Gene Ontology (GO)
| • bicellular tight junction (GO:0005923) | • peptide hormone binding (GO:0017046) |
| • cell junction (GO:0030054) | • structural molecule activity (GO:0005198) |
| • tight junction assembly (GO:0070160) |
Pathways
• Tight junction (KEGG hsa04530)
• Cell junction organization (Reactome R-HSA-446728)
• Blood-brain barrier and immune cell transmigration (Reactome R-HSA-2168880)
Protein Summary
Claudin-5 is a 22 kDa transmembrane protein with four membrane-spanning domains and two extracellular loops. It polymerizes with other claudins to form the backbone of tight junction strands in endothelial cells. In the brain, claudin-5 is the most abundant claudin in BBB endothelial cells and is critical for restricting paracellular diffusion of small molecules (<800 Da). Its C-terminal PDZ-binding motif interacts with scaffolding proteins such as ZO-1, anchoring the tight junction to the actin cytoskeleton.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLDN5 Knockout HEK293 Cell Line | EDJ-KQ5945 | Human | 7122 | Details Get a Quote |
| CLDN5 Knockout HeLa Cell Line | EDJ-KQ54673 | Human | 7122 | Details Get a Quote |
| CLDN5 Knockout A-549 Cell Line | EDJ-KQ63156 | Human | 7122 | Details Get a Quote |
| CLDN5 Knockout HCT 116 Cell Line | EDJ-KQ71629 | Human | 7122 | Details Get a Quote |
