Atlas of Genetics and Cytogenetics in Oncology and Haematology

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CLDN4 (Claudin-4)

Written2005-10Stefanie Ripka, Thomas M Gress
Abteilung Innere Medizin I, Universitâtsklinikum Ulm, Robert Koch Str.8, 89081 Ulm, Germany

(Note : for Links provided by Atlas : click)


Alias_symbol (synonym)CPE-R
Other aliasCPETR,
WBSCR8 (Williams-Beuren syndrome chromosome region 8 protein)
hCPE-R, CPE-R (Clostridium perfringens enterotoxin receptor)
LocusID (NCBI) 1364
Atlas_Id 42975
Location 7q11.23  [Link to chromosome band 7q11]
Location_base_pair Starts at 73830863 and ends at 73832693 bp from pter ( according to hg19-Feb_2009)  [Mapping CLDN4.png]
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CLDN4 (7q11.23) / GLT8D1 (3p21.1)CLDN4 (7q11.23) / MUC4 (3q29)CLDN4 (7q11.23) / NEAT1 (11q13.1)
FAM129B (9q33.3) / CLDN4 (7q11.23)FAM129B (9q34.11) / CLDN4 (7q11.23)GPRC5C (17q25.1) / CLDN4 (7q11.23)
PPP1R16A (8q24.3) / CLDN4 (7q11.23)PTTG1IP (21q22.3) / CLDN4 (7q11.23)RPS3 (11q13.4) / CLDN4 (7q11.23)
TF (3q22.1) / CLDN4 (7q11.23)


Description intronless; one exon spanning 1.68 kb
Transcription one transcript of 1.68kb with 630 bp of coding sequence


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 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 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 pancreatic cancer
Disease .
Oncogenesis Overexpressed in pancreatic cancer. Overexpression is predominantly observed in well-differentiated tumors with decreased metastatic potential
Entity Breast cancer
Oncogenesis Overexpressed in breast cancer and Paget's disease. Significance unclear.
Entity Ovarian cancer
Oncogenesis CLDN4 is upregulated in ovarian tumors and cell lines and may represent a novel marker for this disease.
Entity Squamous cell carcinoma and Bowen's disease
Oncogenesis Expression of claudin-4 is associated with keratinization in SCC and BD.
Entity Prostate cancer
Oncogenesis Overexpressed in prostate cancer ephitelium. Significance unclear


Loss of the tight junction protein claudin 4 correlates with histological growth-pattern and differentiation in advanced gastric adenocarcinoma.
Lee SK, Moon J, Park SW, Song SY, Chung JB, Kang JK
Oncology reports. 2005 ; 13 (2) : 193-199.
PMID 15643498
Expression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium.
Long H, Crean CD, Lee WH, Cummings OW, Gabig TG
Cancer research. 2001 ; 61 (21) : 7878-7881.
PMID 11691807
Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer.
Michl P, Barth C, Buchholz M, Lerch MM, Rolke M, Holzmann KH, Menke A, Fensterer H, Giehl K, Löhr M, Leder G, Iwamura T, Adler G, Gress TM
Cancer research. 2003 ; 63 (19) : 6265-6271.
PMID 14559813
Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands.
Morita K, Furuse M, Fujimoto K, Tsukita S
Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 96 (2) : 511-516.
PMID 9892664
Tight junction-associated proteins (occludin, ZO-1, claudin-1, claudin-4) in squamous cell carcinoma and Bowen's disease.
Morita K, Tsukita S, Miyachi Y
The British journal of dermatology. 2004 ; 151 (2) : 328-334.
PMID 15327539
Claudin 4 protein expression in primary and metastatic pancreatic cancer: support for use as a therapeutic target.
Nichols LS, Ashfaq R, Iacobuzio-Donahue CA
American journal of clinical pathology. 2004 ; 121 (2) : 226-230.
PMID 14983936
Genes for the CPE receptor (CPETR1) and the human homolog of RVP1 (CPETR2) are localized within the Williams-Beuren syndrome deletion.
Paperna T, Peoples R, Wang YK, Kaplan P, Francke U
Genomics. 1998 ; 54 (3) : 453-459.
PMID 9878248
Claudins 2, 3, 4, and 5 in Paget's disease and breast carcinoma.
Soini Y
Human pathology. 2004 ; 35 (12) : 1531-1536.
PMID 15619213
Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions: a research study.
Tokés AM, Kulka J, Paku S, Szik A, P´ska C, Nov´k PK, Szil´k L, Kiss A, Bögi K, Schaff Z
Breast cancer research : BCR. 2005 ; 7 (2) : R296-R305.
PMID 15743508


This paper should be referenced as such :
Ripka, S ; Gress, TM
CLDN4 (claudin-4)
Atlas Genet Cytogenet Oncol Haematol. 2006;10(2):77-78.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)CLDN4   2046
Entrez_Gene (NCBI)CLDN4  1364  claudin 4
GeneCards (Weizmann)CLDN4
Ensembl hg19 (Hinxton)ENSG00000189143 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000189143 [Gene_View]  chr7:73830863-73832693 [Contig_View]  CLDN4 [Vega]
ICGC DataPortalENSG00000189143
TCGA cBioPortalCLDN4
Genatlas (Paris)CLDN4
SOURCE (Princeton)CLDN4
Genetics Home Reference (NIH)CLDN4
Genomic and cartography
GoldenPath hg38 (UCSC)CLDN4  -     chr7:73830863-73832693 +  7q11.23   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CLDN4  -     7q11.23   [Description]    (hg19-Feb_2009)
EnsemblCLDN4 - 7q11.23 [CytoView hg19]  CLDN4 - 7q11.23 [CytoView hg38]
Mapping of homologs : NCBICLDN4 [Mapview hg19]  CLDN4 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AB000712 AI560666 AK026651 AK124076 AK126315
RefSeq transcript (Entrez)NM_001305
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CLDN4
Cluster EST : UnigeneHs.729359 [ NCBI ]
CGAP (NCI)Hs.729359
Alternative Splicing GalleryENSG00000189143
Gene ExpressionCLDN4 [ NCBI-GEO ]   CLDN4 [ EBI - ARRAY_EXPRESS ]   CLDN4 [ SEEK ]   CLDN4 [ MEM ]
Gene Expression Viewer (FireBrowse)CLDN4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1364
GTEX Portal (Tissue expression)CLDN4
Human Protein AtlasENSG00000189143-CLDN4 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO14493   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO14493  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO14493
Splice isoforms : SwissVarO14493
Domaine pattern : Prosite (Expaxy)CLAUDIN (PS01346)   
Domains : Interpro (EBI)Claudin    Claudin4    Claudin_CS    PMP22/EMP/MP20/Claudin   
Domain families : Pfam (Sanger)PMP22_Claudin (PF00822)   
Domain families : Pfam (NCBI)pfam00822   
Conserved Domain (NCBI)CLDN4
DMDM Disease mutations1364
Blocks (Seattle)CLDN4
PDB (SRS)5B2G   
PDB (PDBSum)5B2G   
PDB (IMB)5B2G   
Structural Biology KnowledgeBase5B2G   
SCOP (Structural Classification of Proteins)5B2G   
CATH (Classification of proteins structures)5B2G   
Human Protein Atlas [tissue]ENSG00000189143-CLDN4 [tissue]
Peptide AtlasO14493
IPIIPI00021944   IPI01010878   
Protein Interaction databases
IntAct (EBI)O14493
Ontologies - Pathways
Ontology : AmiGOtransmembrane signaling receptor activity  structural molecule activity  plasma membrane  integral component of plasma membrane  bicellular tight junction  bicellular tight junction  signal transduction  female pregnancy  circadian rhythm  basal plasma membrane  apical plasma membrane  apicolateral plasma membrane  lateral plasma membrane  calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules  response to progesterone  identical protein binding  establishment of skin barrier  
Ontology : EGO-EBItransmembrane signaling receptor activity  structural molecule activity  plasma membrane  integral component of plasma membrane  bicellular tight junction  bicellular tight junction  signal transduction  female pregnancy  circadian rhythm  basal plasma membrane  apical plasma membrane  apicolateral plasma membrane  lateral plasma membrane  calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules  response to progesterone  identical protein binding  establishment of skin barrier  
Pathways : KEGGCell adhesion molecules (CAMs)    Tight junction    Leukocyte transendothelial migration    Hepatitis C   
REACTOMEO14493 [protein]
REACTOME PathwaysR-HSA-420029 [pathway]   
NDEx NetworkCLDN4
Atlas of Cancer Signalling NetworkCLDN4
Wikipedia pathwaysCLDN4
Orthology - Evolution
GeneTree (enSembl)ENSG00000189143
Phylogenetic Trees/Animal Genes : TreeFamCLDN4
Homologs : HomoloGeneCLDN4
Homology/Alignments : Family Browser (UCSC)CLDN4
Gene fusions - Rearrangements
Fusion : MitelmanFAM129B/CLDN4 [9q33.3/7q11.23]  [t(7;9)(q11;q34)]  
Fusion : MitelmanGPRC5C/CLDN4 [17q25.1/7q11.23]  [t(7;17)(q11;q25)]  
Fusion : MitelmanPPP1R16A/CLDN4 [8q24.3/7q11.23]  [t(7;8)(q11;q24)]  
Fusion : MitelmanPTTG1IP/CLDN4 [21q22.3/7q11.23]  [t(7;21)(q11;q22)]  
Fusion: TCGA_MDACCFAM129B 9q33.3 CLDN4 7q11.23 PRAD
Fusion: TCGA_MDACCGPRC5C 17q25.1 CLDN4 7q11.23 PRAD
Fusion: TCGA_MDACCPPP1R16A 8q24.3 CLDN4 7q11.23 PRAD
Fusion: TCGA_MDACCPTTG1IP 21q22.3 CLDN4 7q11.23 PRAD
Tumor Fusion PortalCLDN4
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCLDN4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CLDN4
Exome Variant ServerCLDN4
ExAC (Exome Aggregation Consortium)ENSG00000189143
GNOMAD BrowserENSG00000189143
Genetic variants : HAPMAP1364
Genomic Variants (DGV)CLDN4 [DGVbeta]
DECIPHERCLDN4 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCLDN4 
ICGC Data PortalCLDN4 
TCGA Data PortalCLDN4 
Broad Tumor PortalCLDN4
OASIS PortalCLDN4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCLDN4  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCLDN4
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CLDN4
DgiDB (Drug Gene Interaction Database)CLDN4
DoCM (Curated mutations)CLDN4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CLDN4 (select a term)
NCG5 (London)CLDN4
Cancer3DCLDN4(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry CLDN4
NextProtO14493 [Medical]
Target ValidationCLDN4
Huge Navigator CLDN4 [HugePedia]
snp3D : Map Gene to Disease1364
BioCentury BCIQCLDN4
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1364
Chemical/Pharm GKB GenePA26572
Clinical trialCLDN4
canSAR (ICR)CLDN4 (select the gene name)
PubMed127 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Nov 21 14:47:10 CET 2017

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