TJP1 Gene - Tight Junction Protein ZO-1: Structure, Function, and Clinical Significance
Comprehensive resource on TJP1 (ZO-1), a key scaffold protein in tight junctions, its role in cell polarity, barrier function, and disease associations.
Gene Information Card
| Symbol | TJP1 |
|---|---|
| Full Name | Tight Junction Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q13.1 |
| NCBI Gene ID | 7082 ncbi.nlm.nih.gov/gene/7082 |
| Ensembl ID | ENSG00000104067 |
| UniProt ID | Q07157 |
| OMIM ID | 601009 |
| HGNC ID | 11827 |
| Aliases | ZO-1, Zona Occludens 1, DKFZp686M05161, FLJ33883 |
Description
The TJP1 gene encodes tight junction protein 1 (ZO-1), a peripheral membrane protein that scaffolds tight junctions in epithelial and endothelial cells. ZO-1 links transmembrane tight junction proteins (e.g., claudins, occludin) to the actin cytoskeleton, regulating paracellular permeability, cell polarity, and signal transduction. It contains PDZ, SH3, and guanylate kinase domains, and is involved in cell proliferation, migration, and gene expression. Mutations and altered expression of TJP1 are associated with various cancers and genetic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Altered TJP1 expression disrupts tight junction integrity, promoting epithelial-mesenchymal transition (EMT) and metastasis. | COSMIC; multiple studies |
| Hepatocellular carcinoma | Downregulation of ZO-1 leads to loss of cell polarity and increased invasiveness. | COSMIC; literature |
| Breast cancer | Aberrant ZO-1 localization or expression correlates with tumor progression and poor prognosis. | COSMIC; literature |
| Inflammatory bowel disease (IBD) | TJP1 variants may affect intestinal barrier function, increasing susceptibility to IBD. | ClinVar; GWAS |
| Hereditary hearing loss | Rare TJP1 mutations have been reported in patients with non-syndromic hearing loss, though evidence is limited. | ClinVar; case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Liver | 8.7 | Low |
| Colon | 15.3 | High |
| Heart | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (colon epithelial) | 18.2 | High expression; used as model for intestinal barrier |
| HepG2 (liver) | 9.8 | Moderate expression |
| A549 (lung epithelial) | 14.5 | High expression |
| MCF7 (breast epithelial) | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Ter) | Nonsense | Rare (<0.01%) | Predicted loss of function; may cause truncated protein |
| c.1567G>A (p.Val523Met) | Missense | 0.02% (gnomAD) | Uncertain significance; may affect protein stability |
| c.2101delA (p.Ser701ValfsTer3) | Frameshift | Not reported | Loss of function; likely pathogenic in hearing loss |
| c.3456T>G (p.Ile1152Ser) | Missense | 0.01% | Uncertain; possibly damaging |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated ZO-1 protein are likely loss-of-function, impairing tight junction assembly and barrier integrity.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; overexpression of wild-type TJP1 may contribute to cancer progression.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with protein-protein interactions, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Tight junction pathway (KEGG: hsa04530)
• Adherens junction pathway (KEGG: hsa04520)
• Epithelial cell signaling in Helicobacter pylori infection (KEGG: hsa05120)
• Leukocyte transendothelial migration (KEGG: hsa04670)
• Wnt signaling pathway (KEGG: hsa04310)
Protein Summary
ZO-1 is a 220 kDa scaffold protein with three PDZ domains, an SH3 domain, and a guanylate kinase (GUK) domain. It localizes at tight junctions and interacts with claudins, occludin, and actin. ZO-1 also shuttles to the nucleus to regulate gene expression. It is essential for maintaining epithelial polarity and barrier function. Post-translational modifications include phosphorylation, which modulates its localization and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TJP1 Knockout HEK293 Cell Line | EDJ-KQ2052 | Human | 7082 | Details Get a Quote |
| TJP1 Knockout A-549 Cell Line | EDJ-KQ22111 | Human | 7082 | Details Get a Quote |
| TJP1 Knockout HCT 116 Cell Line | EDJ-KQ22112 | Human | 7082 | Details Get a Quote |
| TJP1 Knockout HeLa Cell Line | EDJ-KQ22113 | Human | 7082 | Details Get a Quote |
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