CLDN9 (claudin 9)

2012-12-01   Erika Patricia Rendon-Huerta  , Ana C Torres-Martínez  , Luis Montaño  

Departamento de Bioquimica, Facultad de Medicina, UNAM, 04510, Mexico City, Mexico

Identity

HGNC
LOCATION
16p13.3
LOCUSID
ALIAS
DFNB116

DNA/RNA

Atlas Image

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.

Proteins

Atlas Image

Description

The transcription of this gene gives 1 spliced mRNA that encodes 1 protein isoform with 217 aa and 22848 Da of molecular weight.
Atlas Image

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.
Atlas Image

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 name
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 name
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 name
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 name
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 name
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 name
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.

Article Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 9080
MIM: 615799
HGNC: 2051
Ensembl: ENSG00000213937

Variants:

dbSNP: 9080
ClinVar: 9080
TCGA: ENSG00000213937
COSMIC: CLDN9

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000213937ENST00000445369O95484

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45
50

Pathways

PathwaySourceExternal ID
Cell adhesion molecules (CAMs)KEGGko04514
Tight junctionKEGGko04530
Leukocyte transendothelial migrationKEGGko04670
Cell adhesion molecules (CAMs)KEGGhsa04514
Tight junctionKEGGhsa04530
Leukocyte transendothelial migrationKEGGhsa04670
Hepatitis CKEGGko05160
Hepatitis CKEGGhsa05160
Cell-Cell communicationREACTOMER-HSA-1500931
Cell junction organizationREACTOMER-HSA-446728
Cell-cell junction organizationREACTOMER-HSA-421270
Tight junction interactionsREACTOMER-HSA-420029

References

Pubmed IDYearTitleCitations
377193612023Pharmacological Activity of Matrine in Inhibiting Colon Cancer Cells VM Formation, Proliferation, and Invasion by Downregulating Claudin-9 Mediated EMT Process and MAPK Signaling Pathway.1
377193612023Pharmacological Activity of Matrine in Inhibiting Colon Cancer Cells VM Formation, Proliferation, and Invasion by Downregulating Claudin-9 Mediated EMT Process and MAPK Signaling Pathway.1
361291462022Claudin‑9 is a novel prognostic biomarker for endometrial cancer.5
361291462022Claudin‑9 is a novel prognostic biomarker for endometrial cancer.5
311754262019A truncating CLDN9 variant is associated with autosomal recessive nonsyndromic hearing loss.11
311754262019A truncating CLDN9 variant is associated with autosomal recessive nonsyndromic hearing loss.11
290314212018TLR2 activation induced by H. pylori LPS promotes the differential expression of claudin-4, -6, -7 and -9 via either STAT3 and ERK1/2 in AGS cells.19
290314212018TLR2 activation induced by H. pylori LPS promotes the differential expression of claudin-4, -6, -7 and -9 via either STAT3 and ERK1/2 in AGS cells.19
264647082015Expression of claudin-5, -7, -8 and -9 in cervical carcinoma tissues and adjacent non-neoplastic tissues.10
264647082015Expression of claudin-5, -7, -8 and -9 in cervical carcinoma tissues and adjacent non-neoplastic tissues.10
252810282014Overexpression of the cell adhesion molecule claudin-9 is associated with invasion in pituitary oncocytomas.9
252810282014Overexpression of the cell adhesion molecule claudin-9 is associated with invasion in pituitary oncocytomas.9
238646332013Functional analysis of claudin-6 and claudin-9 as entry factors for hepatitis C virus infection of human hepatocytes by using monoclonal antibodies.16
238646332013Functional analysis of claudin-6 and claudin-9 as entry factors for hepatitis C virus infection of human hepatocytes by using monoclonal antibodies.16
208740012011Claudin-6, 7, or 9 overexpression in the human gastric adenocarcinoma cell line AGS increases its invasiveness, migration, and proliferation rate.53

Citation

Erika Patricia Rendon-Huerta ; Ana C Torres-Martínez ; Luis Montaño

CLDN9 (claudin 9)

Atlas Genet Cytogenet Oncol Haematol. 2012-12-01

Online version: http://atlasgeneticsoncology.org/gene/51555/favicon/cancer-prone-explorer/gene-explorer/