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CLDN7 (claudin 7)

Written2011-08Ana Carolina de Carvalho, Andre Vettore
Laboratory of Cancer Molecular Biology, Department of Biological Sciences, Federal University of Sao Paulo, Diadema, SP, Brazil

(Note : for Links provided by Atlas : click)

Identity

Alias_namesCEPTRL2
CPETRL2
Alias_symbol (synonym)Hs.84359
Other aliasCLDN-7
claudin-1
HGNC (Hugo) CLDN7
LocusID (NCBI) 1366
Atlas_Id 40099
Location 17p13.1  [Link to chromosome band 17p13]
Location_base_pair Starts at 7259903 and ends at 7263193 bp from pter ( according to hg19-Feb_2009)  [Mapping CLDN7.png]
 
  Figure 1. Schematic representation of the claudin 7 chromosome location, transcript variants and protein isoforms.
Fusion genes
(updated 2016)
APOD (3q29) / CLDN7 (17p13.1)BPIFA1 (20q11.21) / CLDN7 (17p13.1)SLC34A2 (4p15.2) / CLDN7 (17p13.1)

DNA/RNA

Description 2573 base-pairs, starts at 7163223 and ends at 7165795 bp from pter with minus strand orientation.
Transcription This gene contains 4 exons and 3 introns. The transcription produces 3 alternatively spliced mRNA variants:
- variant 1 (NM_001307.5) encodes the longer isoform;
- variant 2 (NM_001185022.1) has an alternate 5' UTR sequence;
- variant 3 (NM_001185023.1) lacks an exon in the 3' CDS.
Pseudogene The sequence named LOC100129851 claudin 7 pseudogene is a pseudogene of Claudin 7 located at Xp11.4.

Protein

 
  Figure 2. Schematic representation of the claudin 7 protein showing the extracellular loops (EL1 and EL2), the transmembrane domains (TM1 to TM4) and its amino- and carboxy-terminal tails extending into the cytoplasm.
Description The transcription of this gene gives 3 alternatively spliced mRNA variants that encode 2 different protein isoforms (variants 1 and 2 encode the same isoform):

- Isoform 1 is the canonical sequence with 211 amino acids and it weighs 22418 Da.

MANSGLQLLGFSMALLGWVGLVACTAIPQWQMSSYAGDNIITAQAMYKGLWMDCVTQSTGMMSCKMYDSVLALSA
ALQATRALMVVSLVLGFLAMFVATMGMKCTRCGGDDKVKKARIAMGGGIIFIVAGLAALVACSWYGHQIVTDFYNPLI
PTNIKYEFGPAIFIGWAGSALVILGGALLSCSCPGNESKAGYRVPRSYPKSNSSKEYV

- Isoform 2 contains 145 amino acids, with a shorter C-terminus, lacking amino acids 159 to 211 in comparison to isoform 1. It weighs 15156 Da.

MANSGLQLLGFSMALLGWVGLVACTAIPQWQMSSYAGDNIITAQAMYKGLWMDCVTQSTGMMSCKMYDSVLALSA
ALQATRALMVVSLVLGFLAMFVATMGMKCTRCGGDDKVKKARIAMGGGIIFIVAGMSLALPSLLAGQGLP

CLDN-7 is an integral membrane protein with four hydrophobic transmembrane domains and two extracellular loops which appear to be implicated in tight junction formation and with their amino- and carboxy-terminal tails extending into the cytoplasm (figure 2).

Localisation The protein is localized in the cell membrane as a constituent of tight junctions.
Function CLDN-7 encodes a member of the claudin family of integral transmembrane proteins that are components of tight junction strands. Claudins regulate the paracellular transport being essential in maintaining a functional epithelial barrier, and also play critical roles in maintaining cell polarity and signal transductions. Studies have shown that altered levels of the different claudins may be related to invasion and progression of carcinoma cells in several primary neoplasms.

Mutations

Somatic In the catalogue of Somatic Mutations in Cancer (Sanger) reports only a heterozygous silent substitution (339G/T; V113V) in ovarian serous cystadenocarcinoma is present.

Polymorphisms
According to the Ensembl database 12 variations could be present in the transcripts (variants 1/2) of CLDN-7:
Position 963/396 of mRNA a synonymous G/A polymorphism at position 61 of the amino acid sequence.
Position 979/412 of mRNA a non-synonymous G/T polymorphism at position 77 of the amino acid sequence. Switching an Ala for an Asp residue. SIFT deleterious.
Position 1299/732 of mRNA a non-synonymous C/T polymorphism at position 397 of the amino acid sequence. Switching an Ala for an Thr residue. SIFT tolerated.
Position 1425/858 of mRNA a non-synonymous C/A polymorphism at position 523 of the amino acid sequence. Switching an Val for an Phe residue. SIFT deleterious.
Position 1492/925 of mRNA a non-synonymous A/G polymorphism at position 590 of the amino acid sequence. Switching an Val for an Ala residue. SIFT tolerated.
Position 1508/941 of mRNA a synonymous A/C polymorphism at position 606 of the amino acid sequence.

Implicated in

Note
  
Entity Colorectal carcinoma
Prognosis Oshima et al. (2008) studied surgical specimens of cancer tissue and adjacent normal mucosa from patients with untreated colorectal carcinoma. The reduced expression of Claudin 7 correlated with venous invasion and liver metastasis, thus suggesting that the reduced expression of the Claudin 7 gene may be a useful predictor of liver metastasis in patients with colorectal cancer.
Oncogenesis Bornholdt et al. (2011) observed that Claudin 7 gene was downregulated both at mRNA and protein levels in biopsies of colorectal tissue from mild/moderate dysplasia, severe dysplasia and carcinomas when comparing to biopsies from healthy individuals. These results suggest that Claudin 7 downregulation is as an early event in colorectal carcinogenesis, probably contributing to the compromised epithelial barrier in adenomas.
  
  
Entity Esophageal cancer
Prognosis Usami et al. (2006) found that reduced expression of Claudin 7 at the invasive front of the esophageal cancer was significantly associated with the depth of invasion, lymphatic vessel invasion, and lymph node metastasis. Reduced Claudin 7 expression was also found in the metastatic lymph nodes. They suggest that the reduced expression of Claudin 7 at the invasive front of esophageal squamous cell carcinoma may lead to tumor progression and subsequent metastatic events.
  
  
Entity Epithelial ovarian carcinoma
Prognosis Kim et al. (2011) described the up-regulation of Claudin 7 transcripts in patients with epithelial ovarian carcinoma (EOCs) in comparison to normal ovarian tissues. The protein Claudin 7 was observed in the majority of the EOCs but not in normal ovarian tissues. High Claudin 7 expression in primary tumor correlated with shorter progression-free survival and poor sensitivity to platinum-based chemotherapy. Claudin 7 inhibition in 2774 and HeyA8 human ovarian cancer cells by siRNA significantly enhanced the sensitivity of these cells to cisplatin treatment. These findings suggest Claudin 7 expression as an independent prognostic factor for progression-free survival in EOCs patients and that it may play a role in regulating response to platinum-based chemotherapy in the treatment of these tumors.
Oncogenesis Tassi et al. (2008) found Claudin 7 transcript and protein significantly overexpressed in both primary and metastatic EOCs compared to normal ovaries. Moreover, a strong immunoreactivity for Claudin 7 was detected in EOC cells present in ascites fluids, whereas ascites-derived inflammatory cells, histiocytes, and reactive mesothelial cells were negative. Claudin 7 is significantly overexpressed in all main histologic types of EOC and in single neoplastic cells disseminated in peritoneal cavity and pleural effusions, suggesting its potential role as novel diagnostic marker in ovarian cancer.
  
  
Entity Prostatic carcinoma
Prognosis Sheehan et al. (2007) reported the pattern of claudin expression in prostatic adenocarcinomas (PACs) and found that the decreased expression of Claudin 7 was correlated with high tumor grade.
  
  
Entity Oral squamous cell carcinoma
Prognosis Lourenço et al. (2010) showed that Claudin 7 expression was mostly negative or weakly expressed in oral squamous cell carcinoma samples. According their results, the loss of Claudin 7 expression was associated with tumor size, clinical stage and a worse disease-free survival.
  
  
Entity Uterine cervical neoplasia
Oncogenesis Lee et al. (2005) showed that Claudin 7 expressions is associated with the progression of uterine cervical neoplasia since its expression was undetectable in normal cervical squamous epithelium and gradually increase in accordance with the progression from LSIL (low-grade squamous intraepithelial lesion) to HSIL (high-grade squamous intraepithelial lesion) and ISCC (invasive squamous cell carcinoma). Claudin 7 were detected in all cases of ISCC. These authors suggested that Claudin 7 may play a significant role in tumor progression of cervical neoplasia.
  
  
Entity Breast cancer
Prognosis Kominsky et al. (2003) conducted RT-PCR and Western Blot analysis and reported that Claudin 7 expression is lower in breast invasive ductal carcinomas (IDC) than in normal breast epithelium. They also reported immunohistochemical (IHC) analysis of ductal carcinoma in situ (DCIS) and IDC and showed that the loss of Claudin 7 expression is correlated with histological grade, occurring predominantly in high-grade lesions. According to their results, Claudin 7 expression was lost in the vast majority of in situ lobular carcinoma cases. In summary, this study provides insight into the potential role of Claudin 7 in the breast tumor progression and in the ability of breast cancer cells to disseminate.
Sauer et al. (2005) evaluated the immunocytochemical expression of Claudin 7 in fine needle aspirates of breast carcinomas and found that reduced Claudin 7 expression was correlated with grading, locoregional and distant metastases, nodal involvement and cellular cohesion in invasive carcinomas.
  

Bibliography

The level of claudin-7 is reduced as an early event in colorectal carcinogenesis.
Bornholdt J, Friis S, Godiksen S, Poulsen SS, Santoni-Rugiu E, Bisgaard HC, Lothe IM, Ikdahl T, Tveit KM, Johnson E, Kure EH, Vogel LK.
BMC Cancer. 2011 Feb 10;11:65.
PMID 21310043
 
High claudin-7 expression is associated with a poor response to platinum-based chemotherapy in epithelial ovarian carcinoma.
Kim CJ, Lee JW, Choi JJ, Choi HY, Park YA, Jeon HK, Sung CO, Song SY, Lee YY, Choi CH, Kim TJ, Lee JH, Kim BG, Bae DS.
Eur J Cancer. 2011 Apr;47(6):918-25. Epub 2010 Dec 4.
PMID 21134740
 
Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast.
Kominsky SL, Argani P, Korz D, Evron E, Raman V, Garrett E, Rein A, Sauter G, Kallioniemi OP, Sukumar S.
Oncogene. 2003 Apr 3;22(13):2021-33.
PMID 12673207
 
Increased expressions of claudin-1 and claudin-7 during the progression of cervical neoplasia.
Lee JW, Lee SJ, Seo J, Song SY, Ahn G, Park CS, Lee JH, Kim BG, Bae DS.
Gynecol Oncol. 2005 Apr;97(1):53-9.
PMID 15790437
 
Claudin-7 down-regulation is an important feature in oral squamous cell carcinoma.
Lourenco SV, Coutinho-Camillo CM, Buim ME, de Carvalho AC, Lessa RC, Pereira CM, Vettore AL, Carvalho AL, Fregnani JH, Kowalski LP, Soares FA.
Histopathology. 2010 Nov;57(5):689-98. doi: 10.1111/j.1365-2559.2010.03685.x.
PMID 21083599
 
Reduced expression of the claudin-7 gene correlates with venous invasion and liver metastasis in colorectal cancer.
Oshima T, Kunisaki C, Yoshihara K, Yamada R, Yamamoto N, Sato T, Makino H, Yamagishi S, Nagano Y, Fujii S, Shiozawa M, Akaike M, Wada N, Rino Y, Masuda M, Tanaka K, Imada T.
Oncol Rep. 2008 Apr;19(4):953-9.
PMID 18357381
 
Reduced expression of Claudin-7 in fine needle aspirates from breast carcinomas correlate with grading and metastatic disease.
Sauer T, Pedersen MK, Ebeltoft K, Naess O.
Cytopathology. 2005 Aug;16(4):193-8.
PMID 16048505
 
Loss of claudins-1 and -7 and expression of claudins-3 and -4 correlate with prognostic variables in prostatic adenocarcinomas.
Sheehan GM, Kallakury BV, Sheehan CE, Fisher HA, Kaufman RP Jr, Ross JS.
Hum Pathol. 2007 Apr;38(4):564-9. Epub 2007 Feb 15.
PMID 17306334
 
Claudin-7 expression in human epithelial ovarian cancer.
Tassi RA, Bignotti E, Falchetti M, Ravanini M, Calza S, Ravaggi A, Bandiera E, Facchetti F, Pecorelli S, Santin AD.
Int J Gynecol Cancer. 2008 Nov-Dec;18(6):1262-71. Epub 2008 Feb 19.
PMID 18298564
 
Reduced expression of claudin-7 correlates with invasion and metastasis in squamous cell carcinoma of the esophagus.
Usami Y, Chiba H, Nakayama F, Ueda J, Matsuda Y, Sawada N, Komori T, Ito A, Yokozaki H.
Hum Pathol. 2006 May;37(5):569-77.
PMID 16647955
 

Citation

This paper should be referenced as such :
de, Carvalho AC ; Vettore, A
CLDN7 (claudin 7)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(1):37-40.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CLDN7ID40099ch17p13.html


External links

Nomenclature
HGNC (Hugo)CLDN7   2049
Cards
AtlasCLDN7ID40099ch17p13
Entrez_Gene (NCBI)CLDN7  1366  claudin 7
AliasesCEPTRL2; CLDN-7; CPETRL2; Hs.84359; 
claudin-1
GeneCards (Weizmann)CLDN7
Ensembl hg19 (Hinxton)ENSG00000181885 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000181885 [Gene_View]  chr17:7259903-7263193 [Contig_View]  CLDN7 [Vega]
ICGC DataPortalENSG00000181885
TCGA cBioPortalCLDN7
AceView (NCBI)CLDN7
Genatlas (Paris)CLDN7
WikiGenes1366
SOURCE (Princeton)CLDN7
Genetics Home Reference (NIH)CLDN7
Genomic and cartography
GoldenPath hg38 (UCSC)CLDN7  -     chr17:7259903-7263193 -  17p13.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CLDN7  -     17p13.1   [Description]    (hg19-Feb_2009)
EnsemblCLDN7 - 17p13.1 [CytoView hg19]  CLDN7 - 17p13.1 [CytoView hg38]
Mapping of homologs : NCBICLDN7 [Mapview hg19]  CLDN7 [Mapview hg38]
OMIM609131   
Gene and transcription
Genbank (Entrez)AF093823 AJ011497 AK225418 AK313958 BC001055
RefSeq transcript (Entrez)NM_001185022 NM_001185023 NM_001307
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CLDN7
Cluster EST : UnigeneHs.513915 [ NCBI ]
CGAP (NCI)Hs.513915
Alternative Splicing GalleryENSG00000181885
Gene ExpressionCLDN7 [ NCBI-GEO ]   CLDN7 [ EBI - ARRAY_EXPRESS ]   CLDN7 [ SEEK ]   CLDN7 [ MEM ]
Gene Expression Viewer (FireBrowse)CLDN7 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1366
GTEX Portal (Tissue expression)CLDN7
Protein : pattern, domain, 3D structure
UniProt/SwissProtO95471   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO95471  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO95471
Splice isoforms : SwissVarO95471
PhosPhoSitePlusO95471
Domaine pattern : Prosite (Expaxy)CLAUDIN (PS01346)   
Domains : Interpro (EBI)Claudin    Claudin7    Claudin_CS    PMP22/EMP/MP20/Claudin   
Domain families : Pfam (Sanger)PMP22_Claudin (PF00822)   
Domain families : Pfam (NCBI)pfam00822   
Conserved Domain (NCBI)CLDN7
DMDM Disease mutations1366
Blocks (Seattle)CLDN7
SuperfamilyO95471
Human Protein AtlasENSG00000181885
Peptide AtlasO95471
HPRD07633
IPIIPI00294755   IPI00794537   IPI00983469   
Protein Interaction databases
DIP (DOE-UCLA)O95471
IntAct (EBI)O95471
FunCoupENSG00000181885
BioGRIDCLDN7
STRING (EMBL)CLDN7
ZODIACCLDN7
Ontologies - Pathways
QuickGOO95471
Ontology : AmiGOstructural molecule activity  protein binding  plasma membrane  bicellular tight junction  negative regulation of cell adhesion  positive regulation of cell proliferation  integral component of membrane  basolateral plasma membrane  apicolateral plasma membrane  lateral plasma membrane  calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules  negative regulation of protein homooligomerization  identical protein binding  negative regulation of apoptotic process  response to ethanol  cell adhesion molecule binding  positive regulation of cell motility  
Ontology : EGO-EBIstructural molecule activity  protein binding  plasma membrane  bicellular tight junction  negative regulation of cell adhesion  positive regulation of cell proliferation  integral component of membrane  basolateral plasma membrane  apicolateral plasma membrane  lateral plasma membrane  calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules  negative regulation of protein homooligomerization  identical protein binding  negative regulation of apoptotic process  response to ethanol  cell adhesion molecule binding  positive regulation of cell motility  
Pathways : KEGGCell adhesion molecules (CAMs)    Tight junction    Leukocyte transendothelial migration    Hepatitis C   
REACTOMEO95471 [protein]
REACTOME PathwaysR-HSA-420029 [pathway]   
NDEx NetworkCLDN7
Atlas of Cancer Signalling NetworkCLDN7
Wikipedia pathwaysCLDN7
Orthology - Evolution
OrthoDB1366
GeneTree (enSembl)ENSG00000181885
Phylogenetic Trees/Animal Genes : TreeFamCLDN7
HOVERGENO95471
HOGENOMO95471
Homologs : HomoloGeneCLDN7
Homology/Alignments : Family Browser (UCSC)CLDN7
Gene fusions - Rearrangements
Fusion : MitelmanAPOD/CLDN7 [3q29/17p13.1]  [t(3;17)(q29;p13)]  
Fusion : MitelmanBPIFA1/CLDN7 [20q11.21/17p13.1]  [t(17;20)(p13;q11)]  
Fusion : MitelmanSLC34A2/CLDN7 [4p15.2/17p13.1]  [t(4;17)(p15;p13)]  
Fusion: TCGAAPOD 3q29 CLDN7 17p13.1 BRCA
Fusion: TCGABPIFA1 20q11.21 CLDN7 17p13.1 LUAD
Fusion: TCGASLC34A2 4p15.2 CLDN7 17p13.1 THCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCLDN7 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CLDN7
dbVarCLDN7
ClinVarCLDN7
1000_GenomesCLDN7 
Exome Variant ServerCLDN7
ExAC (Exome Aggregation Consortium)CLDN7 (select the gene name)
Genetic variants : HAPMAP1366
Genomic Variants (DGV)CLDN7 [DGVbeta]
DECIPHERCLDN7 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCLDN7 
Mutations
ICGC Data PortalCLDN7 
TCGA Data PortalCLDN7 
Broad Tumor PortalCLDN7
OASIS PortalCLDN7 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCLDN7  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCLDN7
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 CLDN7
DgiDB (Drug Gene Interaction Database)CLDN7
DoCM (Curated mutations)CLDN7 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CLDN7 (select a term)
intoGenCLDN7
NCG5 (London)CLDN7
Cancer3DCLDN7(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM609131   
Orphanet
MedgenCLDN7
Genetic Testing Registry CLDN7
NextProtO95471 [Medical]
TSGene1366
GENETestsCLDN7
Target ValidationCLDN7
Huge Navigator CLDN7 [HugePedia]
snp3D : Map Gene to Disease1366
BioCentury BCIQCLDN7
ClinGenCLDN7
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1366
Chemical/Pharm GKB GenePA26575
Clinical trialCLDN7
Miscellaneous
canSAR (ICR)CLDN7 (select the gene name)
Probes
Litterature
PubMed92 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCLDN7
EVEXCLDN7
GoPubMedCLDN7
iHOPCLDN7
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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