claudin 18

Immunopharmacology Ligand Target has curated data in GtoImmuPdb

Target id: 2903

Nomenclature: claudin 18

Family: Claudins

Annotation status: Awaiting annotation » Email us

Quaternary Structure
Gene and Protein Information
Previous and Unofficial Names
Database Links
Selected 3D Structures
Associated Proteins
Functional Characteristics
Natural/Endogenous Ligands
Rank order lists
Activators
Inhibitors
Gating Inhibitors
Agonists
Antagonists
Channel Blockers
Allosteric Modulators
Antibodies
Other Binding Ligands
Whole Organism Assay Data
Large-scale Ligand Screening Data
Immunopharmacology Comments
Immuno Cell Type Associations
Immuno Process Associations
Immuno Disease Associations
Malaria Pharmacology Comments
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Xenobiotics Influencing Gene Expression
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
Gene Expression and Pathophysiology
Biologically Significant Variants
General Comments
Available Assays
References
Contributors
Citation information

Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	4	261	3q22.3	CLDN18	claudin 18
Mouse	4	264	9 E3.3	Cldn18	claudin 18
Rat	-	261	8q31	Cldn18	claudin 18

Previous and Unofficial Names
surfactant associated protein J \| SFTPJ

Previous and Unofficial Names

surfactant associated protein J | SFTPJ

Database Links
Alphafold	P56856 (Hs), P56856-2 (Hs), P56857 (Mm)
ChEMBL Target	CHEMBL3712859 (Hs)
Ensembl Gene	ENSG00000066405 (Hs), ENSMUSG00000032473 (Mm), ENSRNOG00000030386 (Rn)
Entrez Gene	51208 (Hs), 56492 (Mm), 315953 (Rn)
Human Protein Atlas	ENSG00000066405 (Hs)
KEGG Gene	hsa:51208 (Hs), mmu:56492 (Mm), rno:315953 (Rn)
OMIM	609210 (Hs)
Pharos	P56856 (Hs), P56856-2 (Hs)
RefSeq Nucleotide	NM_001002026 (Hs), NM_016369 (Hs), NM_019815 (Mm), NM_001194921 (Mm), NM_001014096 (Rn)
RefSeq Protein	NP_001002026 (Hs), NP_057453 (Hs), NP_001181850 (Mm), NP_062789 (Mm), NP_001014118 (Rn)
UniProtKB	P56856 (Hs), P56856-2 (Hs), P56857 (Mm)
Wikipedia	CLDN18 (Hs)

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Antibodies

Key to terms and symbols

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Antibody		Sp.	Action	Value	Parameter	Reference
zolbetuximab		Hs	Binding	-	-	3
⤷	[3]
ZWB67		Hs	Binding	-	-	6
⤷	[6] Description: EC50 ~2 μg/mL in cells expressing CLDN18.2

Antibody Comments

NOTE: to date the antibodies that target CLDN18 are designed to bind ONLY to the CLDN18.2 splice variant.
A clinical candidate in this class of agents is Amgen's bispecific CLDN18.2/CD3e gresonitamab (AMG910; Phase 1 NCT04260191), although there is nothing in the peer reviewed literature about this antibody. An anti-CLDN18.2 ADC was disclosed during the 'First Disclosures of New Drug Candidates' session at the April 2023 (Orlando) meeting of the AACR: EO-3021 (SYS1810), from Elevation Oncology, is loaded with the microtubule disrupting, antimitotic agent monomethyl auristatin E (MMAE; vedotin when linked to a mAb). Other clinical anti-CLDN18.2 candidates include IBI343 (exatecan topoisomerase I inhibitor ADC; advanced gastroesophageal junction adenocarcinoma, gastric and pancreatic cancers) [1] and SHR-A1904 (DNA topoisomerase I inhibitor ADC: advanced gastric or gastroesophageal junction cancer) [2].

Immunopharmacology Comments
Claudin-18.1 is expressed exclusively in the tight junctions of lung epithelia. Claudin-18 deficiency has been identified as a contributor to airway epithelial barrier dysfunction and asthmatic reactions to air-borne antigens [5].

Immunopharmacology Comments

Claudin-18.1 is expressed exclusively in the tight junctions of lung epithelia. Claudin-18 deficiency has been identified as a contributor to airway epithelial barrier dysfunction and asthmatic reactions to air-borne antigens [5].

Biologically Significant Variants

Type:	Splice variant
Species:	Human
Description:	CLDN18, transcript variant 2 has an alternate 5' exon, as compared to variant 1. The encoded protein, isoform 2 (CLDN18.2) is the same length as isoform 1, but has a different N-terminus.
Amino acids:	261
Nucleotide accession:	NM_001002026
Protein accession:	NP_001002026, P56856-2

General Comments
CLDN18 is a member of the claudins family of integral membrane proteins. Claudins are components of tight junction strands which serve as a physical barrier between epithelial or endothelial cell sheets. Alternatively spliced transcript variants encoding different protein isoforms have been identified in human and mouse. In normal human tissue the splice variant CLDN18.2 is expressed exclusively on short-lived differentiated gastric epithelial cells, so is therefore a highly selective surface marker of gastric lineage. Expression of CLDN18.2 is maintained through malignant transformation and hence, is frequently displayed on the surface of human gastric cancer cells. It is also found ectopically expressed in esophageal, pancreatic and lung adenocarcinomas. The limited expression of CLDN18.2 makes it a favourable target for immunotherapy based drug development, and it is being investigated as a target for gastrointestinal, and other cancers in which it is expressed. Zolbetuximab (IMAB362) is a first-in-class anti-CLDN18.2 therapeutic candidate [4].

General Comments

CLDN18 is a member of the claudins family of integral membrane proteins. Claudins are components of tight junction strands which serve as a physical barrier between epithelial or endothelial cell sheets. Alternatively spliced transcript variants encoding different protein isoforms have been identified in human and mouse.

In normal human tissue the splice variant CLDN18.2 is expressed exclusively on short-lived differentiated gastric epithelial cells, so is therefore a highly selective surface marker of gastric lineage. Expression of CLDN18.2 is maintained through malignant transformation and hence, is frequently displayed on the surface of human gastric cancer cells. It is also found ectopically expressed in esophageal, pancreatic and lung adenocarcinomas. The limited expression of CLDN18.2 makes it a favourable target for immunotherapy based drug development, and it is being investigated as a target for gastrointestinal, and other cancers in which it is expressed. Zolbetuximab (IMAB362) is a first-in-class anti-CLDN18.2 therapeutic candidate [4].

References

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1. Liu J, Yang J, Sun Y, Gong J, Yue J, Pan Y, Sun M, Song R, Xiao X, Tazbirkova A et al.. (2025) CLDN18.2-targeting antibody-drug conjugate IBI343 in advanced gastric or gastroesophageal junction adenocarcinoma: a phase 1 trial. Nat Med, [Epub ahead of print]. [PMID:40670773]

2. Ruan DY, Wu HX, Luo SX, Huang WW, Liang XJ, Niu ZX, Dang Q, Li HL, Pan ZY, Lu HX et al.. (2025) The antibody-drug conjugate SHR-A1904 for targeting CLDN18.2 in advanced gastric or gastroesophageal junction cancer: a phase 1 trial. Nat Med, [Epub ahead of print]. [PMID:40670772]

3. Sahin U, Koslowski M, Dhaene K, Usener D, Brandenburg G, Seitz G, Huber C, Türeci O. (2008) Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res, 14 (23): 7624-34. [PMID:19047087]

4. Sahin U, Tureci O. (2014) Therapy involving antibodies against claudin 18.2 for treatment of cancer. Patent number: WO2014146778. Assignee: Ganymed Pharmaceuticals Ag. Priority date: 18/03/2013. Publication date: 25/09/2014.

5. Sweerus K, Lachowicz-Scroggins M, Gordon E, LaFemina M, Huang X, Parikh M, Kanegai C, Fahy JV, Frank JA. (2017) Claudin-18 deficiency is associated with airway epithelial barrier dysfunction and asthma. J Allergy Clin Immunol, 139 (1): 72-81.e1. [PMID:27215490]

6. Xu G, Qian N, Liu Y, Li H, Yang C, Wang J, Wang F, Chen L, Bai G, Xu Q et al.. (2022) Preclinical characterization of a Fab-like CD3/CLDN18.2 XFab® bispecific antibody against solid tumors. Immunobiology, 227 (6): 152283. [PMID:36198215]