CLDN4 (Claudin-4)

2005-10-01   Stefanie Ripka , Thomas M Gress 

Abteilung Innere Medizin I, Universitâtsklinikum Ulm, Robert Koch Str.8, 89081 Ulm, Germany

Identity

HGNC
LOCATION
7q11.23
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
CPE-R,CPER,CPETR,CPETR1,WBSCR8,hCPE-R
FUSION GENES

DNA/RNA

Description

intronless; one exon spanning 1.68 kb

Transcription

one transcript of 1.68kb with 630 bp of coding sequence

Proteins

Description

The CLDN4 protein contains 209 amino acids and has a molecular weight of 22.1 kDa with four putative transmembrane segments. It directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3.

Expression

Claudin-4 is expressed in many fetal and adult tissues, predominantly in lung, intestine and kidney. Overexpressed in pancreatic, breast, ovarian, and prostate cancer.

Localisation

Integral membrane protein. Tight junction component.

Function

CLDN4 plays a major role in tight junction-specific obliteration of the intercellular space.

Homology

Belongs to the claudin family.

Implicated in

Entity name
Williams-Beuren syndrom
Disease
Williams-Beuren syndrom (WBS) includes supravalvular aortic stenosis (SVAS), multiple peripheral pulmonary arterial stenoses, elfin face, mental and statural deficiency, characteristic dental malformation, and infantile hypercalcemia. It is associated with an autosomal dominant contiguous gene deletion involving genes from chromosome band 7q11.23, including CLDN4, elastin and LIM-kinase1. Haploinsufficiency for CLDN4 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the context of this disease.
Entity name
Gastric cancer
Oncogenesis
Downregulated in gastric cancer. Absence of CLDN4 may play a role in the disruption of cell-to-cell adhesion in diffuse type gastric cancer and in a loss of differentiation.
Entity name
pancreatic cancer
Disease
.
Oncogenesis
Overexpressed in pancreatic cancer. Overexpression is predominantly observed in well-differentiated tumors with decreased metastatic potential
Entity name
Breast cancer
Oncogenesis
Overexpressed in breast cancer and Pagets disease. Significance unclear.
Entity name
Ovarian cancer
Oncogenesis
CLDN4 is upregulated in ovarian tumors and cell lines and may represent a novel marker for this disease.
Entity name
Squamous cell carcinoma and Bowens disease
Oncogenesis
Expression of claudin-4 is associated with keratinization in SCC and BD.
Entity name
Prostate cancer
Oncogenesis
Overexpressed in prostate cancer ephitelium. Significance unclear

Bibliography

Pubmed IDLast YearTitleAuthors
156434982005Loss of the tight junction protein claudin 4 correlates with histological growth-pattern and differentiation in advanced gastric adenocarcinoma.Lee SK et al
116918072001Expression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium.Long H et al
145598132003Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer.Michl P et al
98926641999Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands.Morita K et al
153275392004Tight junction-associated proteins (occludin, ZO-1, claudin-1, claudin-4) in squamous cell carcinoma and Bowen's disease.Morita K et al
149839362004Claudin 4 protein expression in primary and metastatic pancreatic cancer: support for use as a therapeutic target.Nichols LS et al
98782481998Genes for the CPE receptor (CPETR1) and the human homolog of RVP1 (CPETR2) are localized within the Williams-Beuren syndrome deletion.Paperna T et al
156192132004Claudins 2, 3, 4, and 5 in Paget's disease and breast carcinoma.Soini Y et al
157435082005Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study.Tokés AM et al

Other Information

Locus ID:

NCBI: 1364
MIM: 602909
HGNC: 2046
Ensembl: ENSG00000189143

Variants:

dbSNP: 1364
ClinVar: 1364
TCGA: ENSG00000189143
COSMIC: CLDN4

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000189143ENST00000340958O14493
ENSG00000189143ENST00000340958Q75L80
ENSG00000189143ENST00000431918O14493
ENSG00000189143ENST00000431918Q75L80
ENSG00000189143ENST00000435050O14493
ENSG00000189143ENST00000435050Q75L80

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
Cell adhesion molecules (CAMs)KEGGko04514
Tight junctionKEGGko04530
Leukocyte transendothelial migrationKEGGko04670
Cell adhesion molecules (CAMs)KEGGhsa04514
Tight junctionKEGGhsa04530
Leukocyte transendothelial migrationKEGGhsa04670
Hepatitis CKEGGko05160
Hepatitis CKEGGhsa05160
Cell-Cell communicationREACTOMER-HSA-1500931
Cell junction organizationREACTOMER-HSA-446728
Cell-cell junction organizationREACTOMER-HSA-421270
Tight junction interactionsREACTOMER-HSA-420029

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
127001402003Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture.116
145598132003Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer.81
200861752010Smad signaling is required to maintain epigenetic silencing during breast cancer progression.74
157435082005Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study.69
194478952009Claudin-4 augments alveolar epithelial barrier function and is induced in acute lung injury.68
196193032009Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer.67
288190952017Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion.66
162367112005EphA2 phosphorylates the cytoplasmic tail of Claudin-4 and mediates paracellular permeability.62
167147632006Crucial roles of Sp1 and epigenetic modifications in the regulation of the CLDN4 promoter in ovarian cancer cells.46
250314282014Proinflammatory cytokine-induced tight junction remodeling through dynamic self-assembly of claudins.43

Citation

Stefanie Ripka ; Thomas M Gress

CLDN4 (Claudin-4)

Atlas Genet Cytogenet Oncol Haematol. 2005-10-01

Online version: http://atlasgeneticsoncology.org/gene/42975/cldn4