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Protein / target

Claudin-18

Encoded byCLDN18P56856Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
16
Clinical trials
Antibody-tractable
Druggability
Advanced Clinical

Protein at a glance

Biological role

Structural molecule

Strongest disease association

Retinal Diseases

Via encoding gene CLDN18 · Genetic evidence · score 0.42

Therapeutic position

Established drug target

Antibodies

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Involved in alveolar fluid homeostasis via regulation of alveolar epithelial tight junction composition and therefore ion transport and solute permeability, potentially via downstream regulation of the actin cytoskeleton organization and beta-2-adrenergic signaling.

View complete UniProt function annotation

Involved in alveolar fluid homeostasis via regulation of alveolar epithelial tight junction composition and therefore ion transport and solute permeability, potentially via downstream regulation of the actin cytoskeleton organization and beta-2-adrenergic signaling (By similarity). Required for lung alveolarization and maintenance of the paracellular alveolar epithelial barrier (By similarity). Acts to maintain epithelial progenitor cell proliferation and organ size, via regulation of YAP1 localization away from the nucleus and thereby restriction of YAP1 target gene transcription (By similarity). Acts as a negative regulator of RANKL-induced osteoclast differentiation, potentially via relocation of TJP2/ZO-2 away from the nucleus, subsequently involved in bone resorption in response to calcium deficiency (By similarity). Mediates the osteoprotective effects of estrogen, potentially via acting downstream of estrogen signaling independently of RANKL signaling pathways (By similarity)

Subcellular location

Cell junction, tight junctionCell membraneLateral cell membrane
Domains and Gene Ontology detail (16)

Gene Ontology

  • Cbicellular tight junction
  • Ccell-cell junction
  • Clateral plasma membrane
  • Cplasma membrane
  • Fidentical protein binding
  • Fstructural molecule activity
  • Pcalcium-independent cell-cell adhesion
  • Pcellular response to estrogen stimulus
  • Pepithelial cell proliferation
  • Pepithelial fluid transport
  • Plung alveolus development
  • Pnegative regulation of protein localization to nucleus

261 aa · 28 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell adhesionUniProt · GO · Reactome
View supporting evidence

Cell adhesion

  • ·Involved in alveolar fluid homeostasis via regulation of alveolar epithelial tight junct…
  • ·Cell junction, tight junction
  • ·bicellular tight junction
  • ·cell-cell junction
View underlying pathways (1)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

OCLNNKX2-1TJP1CLDN15CLDN8CLDN34CLDN16TJP3CLDN10CLDN23CLDN18

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

1 medicine · 2 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Adenocarcinoma1 medicine
Broader indication categories (1)
Neoplasms1 medicine

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

zolbetuximab
Narrow target profileApprovedBinding agent

Claudin-18 binding agent

Indicated for Adenocarcinoma, Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CLDN18

Gene-level evidence surfaced through the gene CLDN18that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Stomach Neoplasms
0.63Moderately supported

Clinical evidence dominant · Open Targets 0.49

Gastric adenocarcinoma
0.63Moderately supported

Clinical evidence dominant · Open Targets 0.50

Gastroesophageal junction adenocarcinoma
0.61Moderately supported

Clinical evidence dominant · Open Targets 0.49

Neoplasms
0.53Moderately supported

Clinical evidence dominant · Open Targets 0.40

Neoplasm of esophagus
0.46Limited support

Clinical evidence dominant · Open Targets 0.37

View evidence synthesis (5)
Stomach NeoplasmsModerately supported
0.63
agreement 0.470.78
Clinical81%Literature19%

Open Targets aggregate 0.49 · 2 independent evidence families

Gastric adenocarcinomaModerately supported
0.63
agreement 0.470.78
Clinical95%Literature5%

Open Targets aggregate 0.50 · 2 independent evidence families

Gastroesophageal junction adenocarcinomaModerately supported
0.61
agreement 0.460.77
Clinical95%Literature5%

Open Targets aggregate 0.49 · 2 independent evidence families

NeoplasmsModerately supported
0.53
agreement 0.380.69
Clinical77%Literature23%

Open Targets aggregate 0.40 · 2 independent evidence families

Neoplasm of esophagusLimited support
0.46
agreement 0.300.61
Clinical99%Literature1%

Open Targets aggregate 0.37 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Gastric adenocarcinoma0.50
Gastroesophageal junction adenocarcinoma0.49
Stomach Neoplasms0.49
Neoplasms0.40
Neoplasm of esophagus0.37
Retinal Diseases0.25
Diabetes Mellitus, Type 20.24
Subarachnoid Hemorrhage0.22
Esophageal Neoplasms0.21

Drug development

1 compounds recorded · 1 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (1)
ZOLBETUXIMABApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

AntibodiesStrong

Advanced Clinical and UniProt loc med conf support this modality.

View underlying tractability evidence (4)
AB · Advanced ClinicalAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · GO CC med conf

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

16

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (12)

ClinicalTrials.gov via the drug-target graph.

What's happening now

2

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Regulatory approval2024-09-19

    Approval: Vyloy (EMA)

    ema · regulatory · ema · via zolbetuximab

  2. New publication2023-10-01
    ILUSTRO: Phase II Multicohort Trial of Zolbetuximab in Patients with Advanced or Metastatic Claudin 18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma.

    Clinical cancer research : an official journal of the American Association for Cancer Research · 2023 · 65 citations · Europe PMC · via zolbetuximab

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.

Related family literature

9

Papers about “Claudins” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

Global prevalence of claudin 18 isoform 2 in tumors of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

Shitara K · Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024

via Claudins

Heterogeneity of claudin 18.2 expression in metastatic gastric cancer.

Choi E · Scientific reports · 2024

via Claudins

ILUSTRO: Phase II Multicohort Trial of Zolbetuximab in Patients with Advanced or Metastatic Claudin 18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma.

Klempner SJ · Clinical cancer research : an official journal of the American Association for Cancer Research · 2023

via Claudins

CT041 CAR T cell therapy for Claudin18.2-positive metastatic pancreatic cancer.

Qi C · Journal of hematology & oncology · 2023

via Claudins

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.