Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

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)


LocusID (NCBI) 9080
Atlas_Id 51555
Location 16p13.3  [Link to chromosome band 16p13]
Location_base_pair Starts at 3012923 and ends at 3014505 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping CLDN9.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)


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.


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

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.


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


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 ]

External links

HGNC (Hugo)CLDN9   2051
Entrez_Gene (NCBI)CLDN9    claudin 9
GeneCards (Weizmann)CLDN9
Ensembl hg19 (Hinxton)ENSG00000213937 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000213937 [Gene_View]  ENSG00000213937 [Sequence]  chr16:3012923-3014505 [Contig_View]  CLDN9 [Vega]
ICGC DataPortalENSG00000213937
TCGA cBioPortalCLDN9
Genatlas (Paris)CLDN9
SOURCE (Princeton)CLDN9
Genetics Home Reference (NIH)CLDN9
Genomic and cartography
GoldenPath hg38 (UCSC)CLDN9  -     chr16:3012923-3014505 +  16p13.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CLDN9  -     16p13.3   [Description]    (hg19-Feb_2009)
GoldenPathCLDN9 - 16p13.3 [CytoView hg19]  CLDN9 - 16p13.3 [CytoView hg38]
genome Data Viewer NCBICLDN9 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AI791760 AK091002 AY390431 BC051870 BC065830
RefSeq transcript (Entrez)NM_020982
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CLDN9
Alternative Splicing GalleryENSG00000213937
Gene ExpressionCLDN9 [ NCBI-GEO ]   CLDN9 [ EBI - ARRAY_EXPRESS ]   CLDN9 [ SEEK ]   CLDN9 [ MEM ]
Gene Expression Viewer (FireBrowse)CLDN9 [ Firebrowse - Broad ]
GenevisibleExpression of CLDN9 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9080
GTEX Portal (Tissue expression)CLDN9
Human Protein AtlasENSG00000213937-CLDN9 [pathology]   [cell]   [tissue]
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
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
Blocks (Seattle)CLDN9
PDB (RSDB)6OV2    6OV3   
PDB Europe6OV2    6OV3   
PDB (PDBSum)6OV2    6OV3   
PDB (IMB)6OV2    6OV3   
Structural Biology KnowledgeBase6OV2    6OV3   
SCOP (Structural Classification of Proteins)6OV2    6OV3   
CATH (Classification of proteins structures)6OV2    6OV3   
Human Protein Atlas [tissue]ENSG00000213937-CLDN9 [tissue]
Peptide AtlasO95484
IPIIPI00030843   IPI00422611   
Protein Interaction databases
IntAct (EBI)O95484
Ontologies - Pathways
Ontology : AmiGOvirus receptor activity  structural molecule activity  protein binding  plasma membrane  plasma membrane  bicellular tight junction  bicellular tight junction  cell adhesion  integral component of membrane  calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules  cell junction  identical protein binding  intracellular membrane-bounded organelle  viral entry into host cell  bicellular tight junction assembly  
Ontology : EGO-EBIvirus receptor activity  structural molecule activity  protein binding  plasma membrane  plasma membrane  bicellular tight junction  bicellular tight junction  cell adhesion  integral component of membrane  calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules  cell junction  identical protein binding  intracellular membrane-bounded organelle  viral entry into host cell  bicellular tight junction assembly  
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
GeneTree (enSembl)ENSG00000213937
Phylogenetic Trees/Animal Genes : TreeFamCLDN9
Homologs : HomoloGeneCLDN9
Homology/Alignments : Family Browser (UCSC)CLDN9
Gene fusions - Rearrangements
Fusion : Fusion_HubCLDN9--HCFC1R1    CLDN9--THOC6   
Fusion : QuiverCLDN9
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCLDN9 [hg38]
Exome Variant ServerCLDN9
GNOMAD BrowserENSG00000213937
Varsome BrowserCLDN9
Genomic Variants (DGV)CLDN9 [DGVbeta]
DECIPHERCLDN9 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCLDN9 
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]  
Somatic Mutations in Cancer : COSMIC3DCLDN9
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)
NCG6 (London) select CLDN9
Cancer3DCLDN9(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry CLDN9
NextProtO95484 [Medical]
Target ValidationCLDN9
Huge Navigator CLDN9 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA26577
Clinical trialCLDN9
canSAR (ICR)CLDN9 (select the gene name)
DataMed IndexCLDN9
PubMed30 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Feb 19 17:48:08 CET 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us