CLDN7 (claudin 7)
2011-08-01 Ana Carolina de Carvalho , Andre Vettore AffiliationLaboratory of Cancer Molecular Biology, Department of Biological Sciences, Federal University of Sao Paulo, Diadema, SP, Brazil
Identity
HGNC
LOCATION
17p13.1
IMAGE
LEGEND
Figure 1. Schematic representation of the claudin 7 chromosome location, transcript variants and protein isoforms.
LOCUSID
ALIAS
CEPTRL2,CLDN-7,CPETRL2,Hs.84359,claudin-1
FUSION GENES
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.
- 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.
Proteins
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
Entity name
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 name
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 name
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 name
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 name
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 name
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 name
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.
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 21310043 | 2011 | The level of claudin-7 is reduced as an early event in colorectal carcinogenesis. | Bornholdt J et al |
| 21134740 | 2011 | High claudin-7 expression is associated with a poor response to platinum-based chemotherapy in epithelial ovarian carcinoma. | Kim CJ et al |
| 12673207 | 2003 | 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 et al |
| 15790437 | 2005 | Increased expressions of claudin-1 and claudin-7 during the progression of cervical neoplasia. | Lee JW et al |
| 21083599 | 2010 | Claudin-7 down-regulation is an important feature in oral squamous cell carcinoma. | Lourenço SV et al |
| 18357381 | 2008 | Reduced expression of the claudin-7 gene correlates with venous invasion and liver metastasis in colorectal cancer. | Oshima T et al |
| 16048505 | 2005 | Reduced expression of Claudin-7 in fine needle aspirates from breast carcinomas correlate with grading and metastatic disease. | Sauer T et al |
| 17306334 | 2007 | Loss of claudins-1 and -7 and expression of claudins-3 and -4 correlate with prognostic variables in prostatic adenocarcinomas. | Sheehan GM et al |
| 18298564 | 2008 | Claudin-7 expression in human epithelial ovarian cancer. | Tassi RA et al |
| 16647955 | 2006 | Reduced expression of claudin-7 correlates with invasion and metastasis in squamous cell carcinoma of the esophagus. | Usami Y et al |
Other Information
Locus ID:
NCBI: 1366
MIM: 609131
HGNC: 2049
Ensembl: ENSG00000181885
Variants:
dbSNP: 1366
ClinVar: 1366
TCGA: ENSG00000181885
COSMIC: CLDN7
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38050671 | 2024 | Hypoxia-inducible microRNA-155 negatively regulates epithelial barrier in eosinophilic esophagitis by suppressing tight junction claudin-7. | 0 |
| 38050671 | 2024 | Hypoxia-inducible microRNA-155 negatively regulates epithelial barrier in eosinophilic esophagitis by suppressing tight junction claudin-7. | 0 |
| 36275703 | 2022 | Matrix metalloproteinase 7 contributes to intestinal barrier dysfunction by degrading tight junction protein Claudin-7. | 12 |
| 36275703 | 2022 | Matrix metalloproteinase 7 contributes to intestinal barrier dysfunction by degrading tight junction protein Claudin-7. | 12 |
| 33441633 | 2021 | Reduced occludin and claudin-7 expression is associated with urban locations and exposure to second-hand smoke in allergic rhinitis patients. | 12 |
| 33483086 | 2021 | Titanium dioxide particles modulate epithelial barrier protein, Claudin 7 in asthma. | 5 |
| 34281572 | 2021 | Claudin-7 deficiency promotes stemness properties in colorectal cancer through Sox9-mediated Wnt/β-catenin signalling. | 13 |
| 34571860 | 2021 | A Claudin-Based Molecular Signature Identifies High-Risk, Chemoresistant Colorectal Cancer Patients. | 8 |
| 34763991 | 2021 | Claudin-7 in keratinocytes is downregulated by the inhibition of HMG-CoA reductase and is highly expressed in the stratum granulosum of the psoriatic epidermis. | 0 |
| 34774484 | 2021 | N-glycosylation status of Trop2 impacts its surface density, interaction with claudin-7 and exosomal release. | 2 |
| 33441633 | 2021 | Reduced occludin and claudin-7 expression is associated with urban locations and exposure to second-hand smoke in allergic rhinitis patients. | 12 |
| 33483086 | 2021 | Titanium dioxide particles modulate epithelial barrier protein, Claudin 7 in asthma. | 5 |
| 34281572 | 2021 | Claudin-7 deficiency promotes stemness properties in colorectal cancer through Sox9-mediated Wnt/β-catenin signalling. | 13 |
| 34571860 | 2021 | A Claudin-Based Molecular Signature Identifies High-Risk, Chemoresistant Colorectal Cancer Patients. | 8 |
| 34763991 | 2021 | Claudin-7 in keratinocytes is downregulated by the inhibition of HMG-CoA reductase and is highly expressed in the stratum granulosum of the psoriatic epidermis. | 0 |
Citation
Ana Carolina de Carvalho ; Andre Vettore
CLDN7 (claudin 7)
Atlas Genet Cytogenet Oncol Haematol. 2011-08-01
Online version: http://atlasgeneticsoncology.org/gene/40099/cldn7
