CLDN18
Claudin 18: A Tight Junction Protein with Key Roles in Gastric Cancer and Targeted Therapy
Gene Information Card
| Symbol | CLDN18 |
|---|---|
| Full Name | Claudin 18 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q22.3 |
| NCBI Gene ID | 51208 ncbi.nlm.nih.gov/gene/51208 |
| Ensembl ID | ENSG00000166473 |
| UniProt ID | P56856 |
| OMIM ID | 609210 |
| HGNC ID | 2039 |
| Aliases | CLDN18.1, CLDN18.2, SFTA5 |
Description
CLDN18 encodes claudin 18, a member of the claudin family of tight junction proteins. It has two major splice variants: claudin 18.1 (expressed in lung) and claudin 18.2 (expressed in gastric epithelium). CLDN18 is frequently altered in cancers, particularly gastric adenocarcinoma, where CLDN18-ARHGAP fusions and CLDN18.2 overexpression are clinically actionable targets.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gastric Adenocarcinoma | CLDN18-ARHGAP fusion leads to loss of tight junction integrity and activation of RhoA signaling; CLDN18.2 overexpression provides a therapeutic target for monoclonal antibodies. | PMID: 25686104; PMID: 31570863 |
| Pancreatic Ductal Adenocarcinoma | CLDN18.2 is aberrantly expressed in a subset of pancreatic cancers, enabling targeted therapy with zolbetuximab. | PMID: 31570863 |
| Lung Adenocarcinoma | CLDN18.1 downregulation may contribute to epithelial-mesenchymal transition and invasion. | PMID: 29293986 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Stomach | 48.2 | High |
| Lung | 12.5 | Medium |
| Pancreas | 3.1 | Low |
| Esophagus | 2.8 | Low |
| Colon | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SNU-1 (gastric cancer) | 62.3 | High CLDN18.2 expression |
| KATO III (gastric cancer) | 45.1 | High CLDN18.2 expression |
| A549 (lung cancer) | 8.7 | CLDN18.1 predominant |
| PANC-1 (pancreatic cancer) | 15.4 | Moderate CLDN18.2 expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| CLDN18-ARHGAP26 fusion | Gene fusion | ~8% in diffuse-type gastric cancer | Loss of claudin 18 function; gain of ARHGAP26 RhoGAP activity |
| CLDN18-ARHGAP6 fusion | Gene fusion | Rare | Similar mechanism to ARHGAP26 fusion |
| R81H | Missense | <1% | Unknown functional effect |
| S130L | Missense | <1% | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
CLDN18-ARHGAP fusions disrupt tight junction assembly, leading to loss of cell-cell adhesion.
Gain of Function (GOF)
CLDN18.2 overexpression in cancer cells provides a selective advantage for immune evasion and proliferation.
Dominant Negative (DN)
Not reported for CLDN18.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Tight junction pathway (KEGG: hsa04530)
• Cell adhesion molecules (CAMs) (KEGG: hsa04514)
Protein Summary
Claudin 18 is a 261-amino acid transmembrane protein with four transmembrane domains, two extracellular loops, and intracellular N- and C-termini. The two splice variants (CLDN18.1 and CLDN18.2) differ in the first extracellular loop, which determines tissue specificity and antibody binding. CLDN18.2 is a validated target for the monoclonal antibody zolbetuximab in CLDN18.2-positive gastric and gastroesophageal junction adenocarcinomas.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLDN18 Knockout HEK293 Cell Line | EDJ-KQ17692 | Human | 51208 | Details Get a Quote |
| CLDN18 Knockout HeLa Cell Line | EDJ-KQ56251 | Human | 51208 | Details Get a Quote |
| CLDN18 Knockout A-549 Cell Line | EDJ-KQ64740 | Human | 51208 | Details Get a Quote |
| CLDN18 Knockout HCT 116 Cell Line | EDJ-KQ73185 | Human | 51208 | Details Get a Quote |
| CLDN18 Overexpression SNU-1 Stable Cell Line | EDC01674 | Human | 51208 | Details Get a Quote |
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