claudin 18 | Claudins | IUPHAR/BPS Guide to PHARMACOLOGY

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claudin 18

target has curated data in GtoImmuPdb

Target id: 2903

Nomenclature: claudin 18

Family: Claudins

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

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-F1 Cldn18 claudin 18
Rat - 261 8q31 Cldn18 claudin 18
Previous and Unofficial Names
surfactant associated protein J | SFTPJ
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Antibodies
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Antibody Sp. Action Value Parameter Reference
IMAB362 Hs Binding - - 1
[1]
Antibody Comments
NOTE: IMAB362 ONLY binds to the CLDN18.2 splice variant.
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 [3].
Immuno Process Associations
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:2001205 negative regulation of osteoclast development IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:2001205 negative regulation of osteoclast development IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes, IEA only
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GO:0071847 TNFSF11-mediated signaling pathway IEA
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: 
Protein accession: 
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. IMAB362 is a first-in-class anti-CLDN18.2 clinical candidate antibody [2].

References

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1. 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]

2. 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.

3. 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]

How to cite this page

Claudins: claudin 18. Last modified on 11/12/2018. Accessed on 09/12/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2903.