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

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)

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

Antibodies
Key to terms and symbols		Click column headers to sort
Antibody Sp. Action Value Parameter Reference zolbetuximab Hs Binding - - 1 ⤷ [1] ZWB67 Hs Binding - - 4 ⤷ [4] 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).

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

Immuno Process:  Immune system development

Immuno Process:  Cytokine production & signalling

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 [2].