CLDN4 (Claudin-4)

2005-10-01 Stefanie Ripka , Thomas M Gress Affiliation

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

Identity

HGNC

CLDN4

LOCATION

7q11.23

IMAGE

LEGEND

Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

LOCUSID

1364

ALIAS

CPE-R,CPER,CPETR,CPETR1,WBSCR8,hCPE-R

FUSION GENES

Show Gene Fusions

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

Article Bibliography

Pubmed ID	Last Year	Title	Authors
15643498	2005	Loss of the tight junction protein claudin 4 correlates with histological growth-pattern and differentiation in advanced gastric adenocarcinoma.	Lee SK et al
11691807	2001	Expression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium.	Long H et al
14559813	2003	Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer.	Michl P et al
9892664	1999	Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands.	Morita K et al
15327539	2004	Tight junction-associated proteins (occludin, ZO-1, claudin-1, claudin-4) in squamous cell carcinoma and Bowen's disease.	Morita K et al
14983936	2004	Claudin 4 protein expression in primary and metastatic pancreatic cancer: support for use as a therapeutic target.	Nichols LS et al
9878248	1998	Genes for the CPE receptor (CPETR1) and the human homolog of RVP1 (CPETR2) are localized within the Williams-Beuren syndrome deletion.	Paperna T et al
15619213	2004	Claudins 2, 3, 4, and 5 in Paget's disease and breast carcinoma.	Soini Y et al
15743508	2005	Claudin-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 ID	Transcript ID	Uniprot
ENSG00000189143	ENST00000340958	O14493
ENSG00000189143	ENST00000340958	Q75L80
ENSG00000189143	ENST00000431918	O14493
ENSG00000189143	ENST00000431918	Q75L80
ENSG00000189143	ENST00000435050	O14493
ENSG00000189143	ENST00000435050	Q75L80

Expression (GTEx)

100

150

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Cell adhesion molecules (CAMs)	KEGG	ko04514
Tight junction	KEGG	ko04530
Leukocyte transendothelial migration	KEGG	ko04670
Cell adhesion molecules (CAMs)	KEGG	hsa04514
Tight junction	KEGG	hsa04530
Leukocyte transendothelial migration	KEGG	hsa04670
Hepatitis C	KEGG	ko05160
Hepatitis C	KEGG	hsa05160
Cell-Cell communication	REACTOME	R-HSA-1500931
Cell junction organization	REACTOME	R-HSA-446728
Cell-cell junction organization	REACTOME	R-HSA-421270
Tight junction interactions	REACTOME	R-HSA-420029

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
38415551	2024	Immunohistochemical Expression of Claudin-1 and Claudin-4 in Urothelial Carcinoma of the Urinary Bladder.	0
38415551	2024	Immunohistochemical Expression of Claudin-1 and Claudin-4 in Urothelial Carcinoma of the Urinary Bladder.	0
35512220	2023	BAP1 and Claudin-4, But Not MTAP, Reliably Distinguish Borderline and Low-grade Serous Ovarian Tumors From Peritoneal Mesothelioma.	2
37057131	2023	CLDN4 as a Novel Diagnostic and Prognostic Biomarker and Its Association with Immune Infiltrates in Ovarian Cancer.	2
37153991	2023	[Effects of Fusobacterium nucleus derived outer membrane vesicles on claudin-4 expression in oral epithelial cells].	0
37331346	2023	Diagnostic Utility of Claudin4 and Comparison with BerEp4 as a Marker for Metastatic Adenocarcinoma in Serous Effusions.	0
38384059	2023	Expression of Claudin-4 and D2-40 and their significance in prostatic adenocarcinoma.	0
35512220	2023	BAP1 and Claudin-4, But Not MTAP, Reliably Distinguish Borderline and Low-grade Serous Ovarian Tumors From Peritoneal Mesothelioma.	2
37057131	2023	CLDN4 as a Novel Diagnostic and Prognostic Biomarker and Its Association with Immune Infiltrates in Ovarian Cancer.	2
37153991	2023	[Effects of Fusobacterium nucleus derived outer membrane vesicles on claudin-4 expression in oral epithelial cells].	0
37331346	2023	Diagnostic Utility of Claudin4 and Comparison with BerEp4 as a Marker for Metastatic Adenocarcinoma in Serous Effusions.	0
38384059	2023	Expression of Claudin-4 and D2-40 and their significance in prostatic adenocarcinoma.	0
35418179	2022	TGF-β induces GBM mesenchymal transition through upregulation of CLDN4 and nuclear translocation to activate TNF-α/NF-κB signal pathway.	24
35760010	2022	CLDN4 promotes growth of acute myeloid leukemia cells via regulating AKT and ERK1/2 signaling.	3
35811406	2022	Computational study of ion permeation through claudin-4 paracellular channels.	8

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