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CLDN9 (claudin 9)

Written2012-12Erika Patricia Rendon-Huerta, Ana C Torres-Martínez, Luis Montaño
Departamento de Bioquimica, Facultad de Medicina, UNAM, 04510, Mexico City, Mexico

(Note : for Links provided by Atlas : click)

Identity

Other alias
HGNC (Hugo) CLDN9
LocusID (NCBI) 9080
Atlas_Id 51555
Location 16p13.3  [Link to chromosome band 16p13]
Location_base_pair Starts at 3012456 and ends at 3014505 bp from pter ( according to hg19-Feb_2009)  [Mapping CLDN9.png]

DNA/RNA

 
Description 2050 base-pairs DNA linear, starts at 30624573 and ends at 3064506 bp from pter with plus strand orientation. This gene contains 1 exon.
Transcription The transcription produces 1 spliced mRNA variant (NM_020982), 2139 bp.
Pseudogene Not found.

Protein

 
Description The transcription of this gene gives 1 spliced mRNA that encodes 1 protein isoform with 217 aa and 22848 Da of molecular weight.
 
Expression Pituitary gland (71,08%), lung (14,44%), intestine (6,87%), eye (6,56%), and brain (1,05%).
Localisation This is a multi-pass membrane protein localized in the tight junction, cell membrane, cytoplasm and nucleus.
 
Function Claudin-9 belongs to the claudin family. Claudins constitute integral membrane proteins responsible for solute and electrolyte permeability of the tight junction that serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets. Tight junctions also play a critical role in maintaining cell polarity and signal transductions. Claudin-9 creates charge specific channels in the paracellular space, plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity, is required to preserve sensory cells in the hearing organ because claudin-9-defective tight junctions fail to shield the basolateral side of hair cells from the K+-rich endolymph. Its ion barrier function is essential in the cochlea, but appears to be dispensable in other organs. Is one of the entry cofactors for hepatitis C virus; it enables HCV entry into target cells just as efficiently as CLDN1.
Homology The CLDN9 gene is conserved in chimpanzee, dog, cow, mouse, rat, dog, opossum, lizard and zebrafish.

Implicated in

Note
  
Entity Gastric adenocarcinoma
Note Abnormal claudin expression has been documented in several malignancies. Strong claudin-9 expression was associated with higher mortality rate (66%) in the diffuse- vs the intestinal-type (25%) gastric adenocarcinoma after a 2-year follow-up (Rendón-Huerta et al., 2010). Claudin-9 expression is closely related to gastric carcinogenesis, and their detection is a useful prognostic marker in gastric adenocarcinoma.
Claudin-9 overexpression in AGS cells enhanced their invasive potential (1,6-fold), cell migration and proliferation rate (13,3%); it also increased claudin-1 and zonula occludens-1 levels (Zavala et al., 2011). Increased expression of claudin-9 is sufficient to enhance tumorigenic properties of a gastric adenocarcinoma cell line.
  
  
Entity Hepatitis C virus infection
Note Claudin-9 mediates the entry of HCV into target cells. CLDN9 is expressed in the liver, the primary site of HCV replication, and peripheral blood mononuclear cells, an additional site of HCV replication. Sequence comparison and mutagenesis studies, showed that residues N38 and V45 in the first extracellular loop of CLDN9 are necessary for HCV entry (Zheng et al., 2007).
Claudin-9 expressed in CD81+ (tetraspanin) cells also enables the entry of HCV pseudoparticles. Claudin -1 and -9 function equally well as entry cofactors in endothelial cells but claudin-1 is more efficient in hepatoma cells (Meertens et al., 2008). This suggests that additional cellular factors modulate the ability of claudins to function as HCV entry cofactors.
  
  
Entity Hearing
Note Claudin-9 is required for the preservation of sensory cells in the hearing organ because its absence in a specific subdomain underneath more apical tight-junction strands formed by other claudins, fails to shield the basolateral side of hair cells from the K+-rich endolymph (Nakano et al., 2009). Claudin-9 mutant mice have shown that even the deeper (subapical) tight-junction strands have biologically important ion barrier function.
  
  
Entity Cornea
Note Epigenetic regulators such as TSA, 5-aza, and DMSO significantly enhance the expression of claudin-9 in corneal cells, changing transcriptional signals by demethylating CpG islands (Nishikiori et al., 2008); additionally, the epigenetic regulators increase transendothelial electrical resistance and suppress fluxes of corneal cells, thus enhancing the corneal barrier function, in murine experimental corneal trauma.
  
  
Entity Neonatal development
Note Claudins are the gatekeepers of the paracellular pathway, and claudin isoform expression determines the permeability characteristics of the paracellular pathway. Claudin-9 is not expressed or barely detectable in the adult mouse but it is expressed in the neonatal mouse kidney. Claudin-9 mRNA is present in 1-day-old proximal convoluted tubules (Abuazza et al., 2006). Expression of claudin-9 results in an increased transepithelial resistance, decreased chloride permeability, and decreased P(Na)/P(Cl) and P(HCO3)/P(Cl) (Sas et al. 2008). Claudin-9 may play a role in the maturational changes in kidney paracellular permeability.
  
  
Entity Pathway signalling
Note Transmembrane proteins of the claudin family are critical determinants of TJ permeability but little is known about the signaling pathways that control their expression. In mammary epithelial cells SP600125 (an inhibitor of Jun N-terminal kinase) increased claudin-9 expression whereas PD169316 (a p38 MAPK inhibitor) did not modify claudin-9 expression (Carrozzino et al., 2009). Claudin-9 expression is associated with cellular stress.
  

Bibliography

Claudins 6, 9, and 13 are developmentally expressed renal tight junction proteins.
Abuazza G, Becker A, Williams SS, Chakravarty S, Truong HT, Lin F, Baum M.
Am J Physiol Renal Physiol. 2006 Dec;291(6):F1132-41. Epub 2006 Jun 13.
PMID 16774906
 
Inhibition of basal p38 or JNK activity enhances epithelial barrier function through differential modulation of claudin expression.
Carrozzino F, Pugnale P, Feraille E, Montesano R.
Am J Physiol Cell Physiol. 2009 Sep;297(3):C775-87. doi: 10.1152/ajpcell.00084.2009. Epub 2009 Jul 15.
PMID 19605737
 
The tight junction proteins claudin-1, -6, and -9 are entry cofactors for hepatitis C virus.
Meertens L, Bertaux C, Cukierman L, Cormier E, Lavillette D, Cosset FL, Dragic T.
J Virol. 2008 Apr;82(7):3555-60. doi: 10.1128/JVI.01977-07. Epub 2008 Jan 30.
PMID 18234789
 
A claudin-9-based ion permeability barrier is essential for hearing.
Nakano Y, Kim SH, Kim HM, Sanneman JD, Zhang Y, Smith RJ, Marcus DC, Wangemann P, Nessler RA, Banfi B.
PLoS Genet. 2009 Aug;5(8):e1000610. doi: 10.1371/journal.pgen.1000610. Epub 2009 Aug 21.
PMID 19696885
 
Prevention of murine experimental corneal trauma by epigenetic events regulating claudin 6 and claudin 9.
Nishikiori N, Sawada N, Ohguro H.
Jpn J Ophthalmol. 2008 May-Jun;52(3):195-203. doi: 10.1007/s10384-008-0524-z. Epub 2008 Jul 27.
PMID 18661270
 
Distribution and expression pattern of claudins 6, 7, and 9 in diffuse- and intestinal-type gastric adenocarcinomas.
Rendon-Huerta E, Teresa F, Teresa GM, Xochitl GS, Georgina AF, Veronica ZZ, Montano LF.
J Gastrointest Cancer. 2010 Mar;41(1):52-9. doi: 10.1007/s12029-009-9110-y. Epub 2009 Dec 4.
PMID 19960275
 
Effect of claudins 6 and 9 on paracellular permeability in MDCK II cells.
Sas D, Hu M, Moe OW, Baum M.
Am J Physiol Regul Integr Comp Physiol. 2008 Nov;295(5):R1713-9. doi: 10.1152/ajpregu.90596.2008. Epub 2008 Sep 10.
PMID 18784328
 
Claudin-6, 7, or 9 overexpression in the human gastric adenocarcinoma cell line AGS increases its invasiveness, migration, and proliferation rate.
Zavala-Zendejas VE, Torres-Martinez AC, Salas-Morales B, Fortoul TI, Montano LF, Rendon-Huerta EP.
Cancer Invest. 2011 Jan;29(1):1-11. doi: 10.3109/07357907.2010.512594. Epub 2010 Sep 27.
PMID 20874001
 
Claudin-6 and claudin-9 function as additional coreceptors for hepatitis C virus.
Zheng A, Yuan F, Li Y, Zhu F, Hou P, Li J, Song X, Ding M, Deng H.
J Virol. 2007 Nov;81(22):12465-71. Epub 2007 Sep 5.
PMID 17804490
 

Citation

This paper should be referenced as such :
Rendon-Huerta, EP ; Torres-Martinez, AC ; Montao, L
CLDN9 (claudin 9)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(6):400-403.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CLDN9ID51555ch16p13.html


External links

Nomenclature
HGNC (Hugo)CLDN9   2051
Cards
AtlasCLDN9ID51555ch16p13
Entrez_Gene (NCBI)CLDN9  9080  claudin 9
Aliases
GeneCards (Weizmann)CLDN9
Ensembl hg19 (Hinxton)ENSG00000213937 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000213937 [Gene_View]  chr16:3012456-3014505 [Contig_View]  CLDN9 [Vega]
ICGC DataPortalENSG00000213937
TCGA cBioPortalCLDN9
AceView (NCBI)CLDN9
Genatlas (Paris)CLDN9
WikiGenes9080
SOURCE (Princeton)CLDN9
Genetics Home Reference (NIH)CLDN9
Genomic and cartography
GoldenPath hg38 (UCSC)CLDN9  -     chr16:3012456-3014505 +  16p13.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CLDN9  -     16p13.3   [Description]    (hg19-Feb_2009)
EnsemblCLDN9 - 16p13.3 [CytoView hg19]  CLDN9 - 16p13.3 [CytoView hg38]
Mapping of homologs : NCBICLDN9 [Mapview hg19]  CLDN9 [Mapview hg38]
OMIM615799   
Gene and transcription
Genbank (Entrez)AI791760 AK091002 AY390431 BC051870 BC065830
RefSeq transcript (Entrez)NM_020982
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CLDN9
Cluster EST : UnigeneHs.296949 [ NCBI ]
CGAP (NCI)Hs.296949
Alternative Splicing GalleryENSG00000213937
Gene ExpressionCLDN9 [ NCBI-GEO ]   CLDN9 [ EBI - ARRAY_EXPRESS ]   CLDN9 [ SEEK ]   CLDN9 [ MEM ]
Gene Expression Viewer (FireBrowse)CLDN9 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9080
GTEX Portal (Tissue expression)CLDN9
Protein : pattern, domain, 3D structure
UniProt/SwissProtO95484   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO95484  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO95484
Splice isoforms : SwissVarO95484
PhosPhoSitePlusO95484
Domaine pattern : Prosite (Expaxy)CLAUDIN (PS01346)   
Domains : Interpro (EBI)Claudin    Claudin9    Claudin_CS    PMP22/EMP/MP20/Claudin   
Domain families : Pfam (Sanger)PMP22_Claudin (PF00822)   
Domain families : Pfam (NCBI)pfam00822   
Conserved Domain (NCBI)CLDN9
DMDM Disease mutations9080
Blocks (Seattle)CLDN9
SuperfamilyO95484
Human Protein AtlasENSG00000213937
Peptide AtlasO95484
HPRD13071
IPIIPI00030843   IPI00422611   
Protein Interaction databases
DIP (DOE-UCLA)O95484
IntAct (EBI)O95484
FunCoupENSG00000213937
BioGRIDCLDN9
STRING (EMBL)CLDN9
ZODIACCLDN9
Ontologies - Pathways
QuickGOO95484
Ontology : AmiGOvirus receptor activity  structural molecule activity  protein binding  plasma membrane  bicellular tight junction  integral component of membrane  viral process  calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules  cell junction  identical protein binding  intracellular membrane-bounded organelle  cell-cell junction organization  
Ontology : EGO-EBIvirus receptor activity  structural molecule activity  protein binding  plasma membrane  bicellular tight junction  integral component of membrane  viral process  calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules  cell junction  identical protein binding  intracellular membrane-bounded organelle  cell-cell junction organization  
Pathways : KEGGCell adhesion molecules (CAMs)    Tight junction    Leukocyte transendothelial migration    Hepatitis C   
REACTOMEO95484 [protein]
REACTOME PathwaysR-HSA-420029 [pathway]   
NDEx NetworkCLDN9
Atlas of Cancer Signalling NetworkCLDN9
Wikipedia pathwaysCLDN9
Orthology - Evolution
OrthoDB9080
GeneTree (enSembl)ENSG00000213937
Phylogenetic Trees/Animal Genes : TreeFamCLDN9
HOVERGENO95484
HOGENOMO95484
Homologs : HomoloGeneCLDN9
Homology/Alignments : Family Browser (UCSC)CLDN9
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCLDN9 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CLDN9
dbVarCLDN9
ClinVarCLDN9
1000_GenomesCLDN9 
Exome Variant ServerCLDN9
ExAC (Exome Aggregation Consortium)CLDN9 (select the gene name)
Genetic variants : HAPMAP9080
Genomic Variants (DGV)CLDN9 [DGVbeta]
DECIPHERCLDN9 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCLDN9 
Mutations
ICGC Data PortalCLDN9 
TCGA Data PortalCLDN9 
Broad Tumor PortalCLDN9
OASIS PortalCLDN9 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCLDN9  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCLDN9
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 CLDN9
DgiDB (Drug Gene Interaction Database)CLDN9
DoCM (Curated mutations)CLDN9 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CLDN9 (select a term)
intoGenCLDN9
NCG5 (London)CLDN9
Cancer3DCLDN9(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM615799   
Orphanet
MedgenCLDN9
Genetic Testing Registry CLDN9
NextProtO95484 [Medical]
TSGene9080
GENETestsCLDN9
Target ValidationCLDN9
Huge Navigator CLDN9 [HugePedia]
snp3D : Map Gene to Disease9080
BioCentury BCIQCLDN9
ClinGenCLDN9
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9080
Chemical/Pharm GKB GenePA26577
Clinical trialCLDN9
Miscellaneous
canSAR (ICR)CLDN9 (select the gene name)
Probes
Litterature
PubMed26 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCLDN9
EVEXCLDN9
GoPubMedCLDN9
iHOPCLDN9
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Jun 30 11:03:42 CEST 2017

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