TJP2 (Tight Junction Protein 2): Structure, Function, and Clinical Significance
A comprehensive overview of the TJP2 gene, its protein product, associated diseases, expression patterns, and mutational landscape.
Gene Information Card
| Symbol | TJP2 |
|---|---|
| Full Name | Tight junction protein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q21.12 |
| NCBI Gene ID | 9414 ncbi.nlm.nih.gov/gene/9414 |
| Ensembl ID | ENSG00000119139 |
| UniProt ID | Q9UDY2 |
| OMIM ID | 607709 |
| HGNC ID | 11826 |
| Aliases | ZO-2, ZO2, DKFZp686M0613, MGC26269 |
Description
TJP2 encodes tight junction protein 2 (also known as ZO-2), a peripheral membrane protein that is a member of the membrane-associated guanylate kinase (MAGUK) family. It is a scaffolding protein that links tight junction transmembrane proteins to the actin cytoskeleton, playing a critical role in cell polarity, barrier function, and signal transduction. Mutations in TJP2 are associated with progressive familial intrahepatic cholestasis type 4 (PFIC4) and some forms of hearing loss.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Progressive familial intrahepatic cholestasis type 4 (PFIC4) | Biallelic loss-of-function mutations in TJP2 lead to disruption of tight junctions in hepatocytes, impairing bile salt transport and causing cholestasis. | ClinVar, OMIM |
| Non-syndromic hearing loss (autosomal recessive) | Mutations in TJP2 can affect tight junctions in the inner ear, leading to sensorineural hearing loss. | ClinVar, OMIM |
| Hepatocellular carcinoma | Somatic mutations and altered expression of TJP2 have been observed in liver cancer, potentially contributing to tumor progression. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High | High |
| Kidney | High | High |
| Small intestine | High | High |
| Colon | High | High |
| Lung | Medium | Medium |
| Brain | Medium | Medium |
| Heart | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | High | Hepatocyte cell line |
| Caco-2 (colon) | High | Intestinal epithelial cell line |
| MDCK (kidney) | High | Canine kidney epithelial cell line |
| A549 (lung) | Medium | Lung carcinoma cell line |
| SH-SY5Y (neuroblastoma) | Low | Neuronal cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.949_950del (p.Leu317ValfsTer3) | Frameshift | Rare | Loss of function; associated with PFIC4 |
| c.1126C>T (p.Arg376Ter) | Nonsense | Rare | Loss of function; associated with PFIC4 |
| c.2086G>A (p.Gly696Arg) | Missense | Rare | Likely loss of function; associated with hearing loss |
| c.2668C>T (p.Arg890Trp) | Missense | Rare | Uncertain significance; reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations in TJP2 are loss-of-function (frameshift, nonsense, splice-site) leading to truncated or absent protein, causing PFIC4 or hearing loss.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for TJP2.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by disrupting protein-protein interactions, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • cell-cell adherens junction (GO:0005913) | • bicellular tight junction (GO:0005923) |
| • protein binding (GO:0005515) | • cytoplasm (GO:0005737) |
| • plasma membrane (GO:0005886) | • cell-cell junction (GO:0005911) |
| • cytoskeletal protein binding (GO:0008092) | • signaling receptor binding (GO:0005102) |
Pathways
• Tight junction pathway (KEGG: hsa04530)
• Adherens junction pathway (KEGG: hsa04520)
• Epithelial cell signaling in Helicobacter pylori infection (KEGG: hsa05120)
Protein Summary
TJP2 encodes ZO-2, a 160 kDa scaffolding protein with three PDZ domains, one SH3 domain, and a guanylate kinase (GUK) domain. It localizes to tight junctions and interacts with claudins, occludin, and actin. ZO-2 also shuttles to the nucleus and may regulate gene expression. It is essential for maintaining epithelial barrier integrity and cell polarity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TJP2 Knockout HEK293 Cell Line | EDJ-KQ6580 | Human | 9414 | Details Get a Quote |
| TJP2 Knockout HeLa Cell Line | EDJ-KQ29451 | Human | 9414 | Details Get a Quote |
| TJP2 Knockout A-549 Cell Line | EDJ-KQ30796 | Human | 9414 | Details Get a Quote |
| TJP2 Knockout HCT 116 Cell Line | EDJ-KQ30797 | Human | 9414 | Details Get a Quote |
