CLDN5 Gene

HGNC Family	Claudins (CLDN)
Name	claudin 5
Description	This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets. Mutations in this gene have been found in patients with velocardiofacial syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2018]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Claudin‐5 is a transmembrane tight junction protein that plays a critical role in barrier formation and permeability regulation in both endothelial and epithelial cells. In the blood–brain barrier (BBB), claudin‐5 is the predominant adhesion molecule; genetic ablation in mice produces a size‐selective opening of the BBB—allowing the passage of small molecules (<800 Da) without gross vascular disruption—which highlights its importance in maintaining CNS homeostasis and offers a potential strategy for drug delivery."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, claudin‐5 expression is subject to dynamic regulation; for example, exosomal microRNA (miR‐25‐3p) originating from tumor cells can down‐regulate claudin‐5 (together with other junctional proteins) via suppression of transcription factors such as KLF2/KLF4, thereby promoting vascular leakiness associated with metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, VEGF‐A signaling in brain endothelial cells leads to selective down‐regulation of claudin‐5 (and occludin), and the restoration of claudin‐5 protects against VEGF‐induced increases in paracellular permeability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " At the structural level, site‐directed mutagenesis and molecular modeling studies have identified key aromatic and hydrophilic residues within the extracellular loops of claudin‐5 that mediate trans‐interactions essential for tight junction strand formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Beyond its central role in the BBB, claudin‐5 also contributes to paracellular barrier function in epithelial tissues such as the colon, where its expression strengthens the tight junction seal and enhances transepithelial resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Collectively, these findings underscore the multifaceted functions of claudin‐5 in regulating barrier integrity, suggesting that its modulation may have important therapeutic implications in neurovascular disorders, metastatic disease, and other conditions characterized by barrier dysfunction.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Takehiro Nitta, Masaki Hata, Shimpei Gotoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200302070"}], "href": "https://doi.org/10.1083/jcb.200302070"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12743111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12743111"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Philipp Berndt, Lars Winkler, Jimmi Cording, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tight junction proteins at the blood-brain barrier: far more than claudin-5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-019-03030-7"}], "href": "https://doi.org/10.1007/s00018-019-03030-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30734065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30734065"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zhicheng Zeng, Yuling Li, Yangjian Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-07810-w"}], "href": "https://doi.org/10.1038/s41467-018-07810-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30568162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30568162"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Azeb Tadesse Argaw, Blake T Gurfein, Yueting Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0808698106"}], "href": "https://doi.org/10.1073/pnas.0808698106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19174516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19174516"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jörg Piontek, Lars Winkler, Hartwig Wolburg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Formation of tight junction: determinants of homophilic interaction between classic claudins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.07-8319com"}], "href": "https://doi.org/10.1096/fj.07-8319com"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17761522"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17761522"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Salah Amasheh, Thomas Schmidt, Michaela Mahn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Contribution of claudin-5 to barrier properties in tight junctions of epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Tissue Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00441-005-1101-0"}], "href": "https://doi.org/10.1007/s00441-005-1101-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16158492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16158492"}]}]}]}
Synonyms	BEC1, TMVCF, AWAL, TMDVCF, CPETRL1
Proteins	CLD5_HUMAN
NCBI Gene ID	7122
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CLDN5 has 6,618 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 111 datasets.

Click the + buttons to view associations for CLDN5 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CLDN5 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLDN5 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLDN5 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CLDN5 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CLDN5 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CLDN5 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLDN5 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CLDN5 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CLDN5 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CLDN5 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CLDN5 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLDN5 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CLDN5 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CLDN5 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CLDN5 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CLDN5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CLDN5 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CLDN5 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CLDN5 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CLDN5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CLDN5 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CLDN5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CLDN5 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLDN5 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CLDN5 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CLDN5 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CLDN5 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CLDN5 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CLDN5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CLDN5 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CLDN5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CLDN5 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CLDN5 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CLDN5 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CLDN5 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CLDN5 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CLDN5 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CLDN5 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CLDN5 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with CLDN5 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing CLDN5 from the GeneSigDB Published Gene Signatures dataset.