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FLASH GENE
Symbol CLDN4 contributors: mct - updated : 21-01-2015
HGNC name claudin 4
HGNC id 2046
Location 7q11.23      Physical location : 73.245.192 - 73.247.014
Synonym name
  • clostridium perfringens enterotoxin receptor 4
  • Williams-Beuren syndrome chromosomal region 8 protein
  • Synonym symbol(s) CPETR1, CPE-R, WBSCR8, CPETR
    DNA
    TYPE functioning gene
    STRUCTURE 1.83 kb     1 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • TWIST1 binds to an E-box site of the CLDN4 promoter
  • MAPPING cloned Y linked N status provisional
    Physical map
    LOC389515 7 similar to Shwachman-Bodian-Diamond syndrome protein (CGI-97) POM121 7q11.23 POM121 membrane glycoprotein (rat) WBSCR20C 7q11.23 POM121 membrane glycoprotein (rat) TRIM50C 7 tripartite motif-containing 50C LOC389516 7 hypothetical gene supported by BC002581; NM_012447 LOC389517 7 similar to Williams Beuren syndrome chromosome region 19 GTF2IP1 7q11.23 general transcription factor II, i, pseudogene 1 LOC389518 7 similar to Neutrophil cytosolic factor 1 LOC389519 7 similar to transcription factor GTF2IRD2 LOC389520 7 similar to Nuclear envelope pore membrane protein POM 121 (Pore membrane protein of 121 kDa) (P145) WBSCR20A 7q11.23 Williams Beuren syndrome chromosome region 20A TRIM50A 7q11.23 tripartite motif-containing 50A FKBP6 7q11.23 FK506 binding protein 6, 36kDa FZD9 7q11.23 frizzled homolog 9 (Drosophila) BAZ1B 7q11.23 bromodomain adjacent to zinc finger domain, 1B BCL7B 7q11.23 B-cell CLL/lymphoma 7B TBL2 7q11.23 transducin (beta)-like 2 WBSCR14 7q11.23 Williams Beuren syndrome chromosome region 14 WBSCR24 7q11.23 Williams Beuren syndrome chromosome region 24 STX1A 7q11.23 syntaxin 1A (brain) WBSCR18 7q11.23 Williams Beuren syndrome chromosome region 18 WBSCR22 7q11.23 Williams Beuren syndrome chromosome region 22 WBSCR21 7q11.23 Williams Beuren syndrome chromosome region 21 CLDN3 7q11.23 claudin 3 CLDN4 7q11.23 claudin 4 WBSCR27 7q11.23 claudin 4 WBSCR28 7q11.23 Williams-Beuren syndrome critical region 28 ELN 7q11.23 elastin (supravalvular aortic stenosis, Williams-Beuren syndrome) LIMK1 7q11.23 LIM domain kinase 1 WBSCR1 7q11.23 Williams-Beuren syndrome chromosome region 1 WBSCR5 7q11.23 Williams-Beuren syndrome chromosome region 5 RFC2 7q11.23 replication factor C (activator 1) 2, 40kDa CYLN2 7q11.23 cytoplasmic linker 2 GTF2IRD1 7q11.23 GTF2I repeat domain containing 1 LOC389521 7 LOC389521 WBSCR23 7q11.23 Williams-Beuren syndrome chromosome region 23 GTF2I 7q11.23 general transcription factor II, i
    regionally located situated in the Williams-Beuren critical region
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 1846 22 209 - 1999 10366445
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunethymus   highly Homo sapiens
    Reproductivemale systemmale genital tractepididymis   Homo sapiens
    Respiratorylung     Homo sapiens
    Urinarykidneytubulecollecting duct   Homo sapiens
     kidneynephronrenal capsule   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte Homo sapiens
    Respiratoryalveolar cell type 1 Homo sapiens
    Respiratoryepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period neonatal
    Text infant brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four putative transmembrane segments
  • a cytoplasmic region, which has important roles in the formation and function of tight junctions, but dispensable for the TCR costimulatory activity
  • mono polymer monomer
    HOMOLOGY
    Homologene
    FAMILY
  • claudin family
  • CATEGORY adhesion , structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
    text integral membrane protein
    basic FUNCTION
  • tight junction specific obliteration of the intercelular space
  • creating charge specific channels in the paracellular space
  • forms a paracellular chloride channel in the collecting duct
  • essential role in the formation and maintenance of tight junctions
  • integral membrane cell-junction protein
  • act as molecular mediator of embryo implantation
  • interaction with CLDN8 are required for the anion-selective paracellular channel in the collecting duct
  • forms a paracellular chloride channel in the collecting duct
  • with CLDN8 are required for paracellular reabsorption of Cl–, interacted in cell membranes
  • roles for CLDN3 and CLDN4 in alveolar epithelial barrier function
  • potentially promotes the recruitment of free CD4/LCK to the TCR proximity on antigen engagement directly or indirectly
  • both CLDN3 and CLDN4 mediate interactions with other cells that restrain growth and metastatic potential by sustaining expression of E-cadherin and limiting CTNNB1 signaling
  • plays an important role in maintaining the homeostatic integrity of normal urothelium
  • tight junction protein regulating the paracellular permeability of cell layers
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • major structural components of tight junction (TJ) strands
  • CLDN4 and CLDN16 may participate not in homodimers but in obligate heterodimers with selected other claudins
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with LIF (are associated with assisted reproduction outcome)
  • in the collecting duct cells, the assembly of CLDN4 into tight junctions strands required its interaction with CLDN8
  • accumulates CLDN1 and CLDN3 in TJs to enhance cell-cell contact in renal tubular epithelial cells
  • GRHL2 regulates epithelial morphogenesis through transcriptional up-regulation of CLDN3 and CLDN4, as well as of RAB25, which increases the CLDN4 protein and its localization at TJs
  • EGF controls the levels of CLDN2 and CLDN4 proteins and mRNAs through SRC and STAT3 activity
  • CLDN4 serves to restrain pro-oncogenic signaling from EPHA2 by limiting the activity of CTNNB1 and PI3K and preventing phosphorylation of EPHA2 on S897 by AKT1 0)
  • GRHL2/OVOL2 network controlling CLDN4 and RAB25 expression that facilitates lumen expansion and barrier formation in subtypes of renal epithelia
  • cell & other
    REGULATION
    induced by E-protein activity in the later stages of DP thymocytes before positive selection, suggesting that it increases the efficiency of positive selection through unique TCR costimulatory activity
    repressed by TWIST1 (up-regulation of TWIST1 decreased both gene and protein expression levels of endogenous CLDN4 and the suppression was mediated by direct binding of TWIST1 to the canonical E-box in the promoter region of CLDN4)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colorectal cancer
    tumoral     --over  
    in ovarian carcinoma
    tumoral     --over  
    in intestinal-type gastric cancer ( lower in diffuse-type gasric cancer)
    tumoral     --over  
    in prostate cancer, highly expressed in lower grade lesions than in higher grade
    tumoral     --low  
    in highly aggressive esophageal cancer and the reduction of CLDN4 leads to the resultant disruption of tight junctions that may be associated with EMT
    constitutional     --over  
    in the placentas of diabetic mothers and in toxaemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • very useful marker for distinguishing mesothelioma and adenocarcinoma, even if histological specimens are small, as in biopsies that contain limited numbers of tumor cells
  • highly specific and sensitive immunohistochemical marker for assisting in distinguishing epithelioid mesotheliomas from metastatic carcinomas to the serosal membranes (pMID: 23596113)
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    anti-claudin-3 and -4 bispecific monoclonal antibody shows promise in the development of a diagnostic and therapeutic antibody for cancers
    cancerdigestivecolon
    potential markers and therapy target in colorectal cancer
    cancerreproductiveprostate
    useful as a potential marker and therapeutic target for prostate cancer metastases
    ANIMAL & CELL MODELS
  • progressive hydronephrosis in Cldn4(-/-) mice arises from urinary tract obstruction due to urothelial hyperplasia