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Protein / target

Nectin-4

Encoded byNECTIN4Q96NY8Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Antibody-tractable
Druggability
UniProt loc high conf

Protein at a glance

Biological role

Cell adhesion mediator

Strongest disease association

Ectodermal dysplasia - syndactyly syndrome

Via encoding gene NECTIN4 · Genetic literature evidence · score 0.83

Therapeutic position

Established drug target

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

Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1.

View complete UniProt function annotation

Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvirus entry into cells

Subcellular location

Cell membraneCell junction, adherens junctionSecreted
Domains and Gene Ontology detail (13)

Domains & features

Ig-like V-typeIg-like C2-type 1Ig-like C2-type 2

Gene Ontology

  • Cadherens junction
  • Cextracellular exosome
  • Cplasma membrane
  • Fcell adhesion mediator activity
  • Fidentical protein binding
  • Freceptor ligand activity
  • Fvirus receptor activity
  • Pheterophilic cell-cell adhesion
  • Phomophilic cell-cell adhesion
  • Pnegative regulation of natural killer cell mediated cytotoxicity

510 aa · 55 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
View supporting evidence

Cell adhesion

  • ·Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interac…
  • ·Cell junction, adherens junction
  • ·cell adhesion mediator activity
  • ·heterophilic cell-cell adhesion
View underlying pathways (2)

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.

AFDNMYBPHNECTIN1NECTIN2NECTIN3PARD3SLAMF1CD46EIF2B1ITGB4NECTIN4

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 · 3 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.

Carcinoma, Transitional Cell1 medicine
Urologic Neoplasms1 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.

enfortumab vedotin
ApprovedBinding agent

Nectin-4 binding agent

Indicated for Carcinoma, Transitional Cell, Urologic Neoplasms, Neoplasms

Direct interaction with this protein · 1 of 16 recorded protein targets — broad pharmacology

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 NECTIN4

Gene-level evidence surfaced through the gene NECTIN4that 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.

Ectodermal dysplasia - syndactyly syndrome
0.81Well supported

Genetic evidence dominant · Open Targets 0.78

Urothelial carcinoma
0.64Moderately supported

Clinical evidence dominant · Open Targets 0.51

Neoplasms
0.54Moderately supported

Clinical evidence dominant · Open Targets 0.40

Ectodermal dysplasia-syndactyly syndrome
0.51Moderately supported

Genetic literature evidence dominant · Open Targets 0.38

Urinary bladder carcinoma
0.50Limited support

Clinical evidence dominant · Open Targets 0.38

View evidence synthesis (5)
Ectodermal dysplasia - syndactyly syndromeWell supported
0.81
agreement 0.670.94
Genetic94%Literature6%Genetic literaturedup

Open Targets aggregate 0.78 · 2 independent evidence families · 1 not counted as duplicate

Urothelial carcinomaModerately supported
0.64
agreement 0.480.80
Clinical94%Literature6%

Open Targets aggregate 0.51 · 2 independent evidence families

NeoplasmsModerately supported
0.54
agreement 0.380.69
Clinical76%Literature24%

Open Targets aggregate 0.40 · 2 independent evidence families

Ectodermal dysplasia-syndactyly syndromeModerately supported
0.51
agreement 0.360.66
Genetic literature91%Literature9%

Open Targets aggregate 0.38 · 2 independent evidence families

Urinary bladder carcinomaLimited support
0.50
agreement 0.340.65
Clinical84%Literature16%

Open Targets aggregate 0.38 · 2 independent evidence families

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
Ectodermal dysplasia - syndactyly syndrome0.78
Urothelial carcinoma0.51
Neoplasms0.40
Urinary bladder carcinoma0.38
Ectodermal dysplasia-syndactyly syndrome0.38
Urogenital Neoplasms0.33
Urinary Bladder Neoplasms0.30
Amelogenesis imperfecta0.18

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)
ENFORTUMAB VEDOTINApproval

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

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Approved Drug support this modality.

View underlying tractability evidence (5)
AB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

skin irritationClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

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 (26)

NOT_YET_RECRUITING · via enfortumab vedotin · NCT07139977

RECRUITING · via enfortumab vedotin · NCT06434350

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

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. Indication expanded2026-07-10

    Indication expansion: ENFORTUMAB VEDOTIN (BLA761137)

    fda · regulatory · fda · via enfortumab vedotin

  2. Indication expanded2025-11-21

    Indication expansion: ENFORTUMAB VEDOTIN (BLA761137)

    fda · regulatory · fda · via enfortumab vedotin

  3. Label change2025-02-27

    Label change: ENFORTUMAB VEDOTIN (BLA761137)

    fda · regulatory · fda · via enfortumab vedotin

  4. New publication2024-03-01
    Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer.

    The New England journal of medicine · 2024 · 719 citations · Europe PMC · via enfortumab vedotin

  5. Indication expanded2023-12-15

    Indication expansion: ENFORTUMAB VEDOTIN (BLA761137)

    fda · regulatory · fda · via enfortumab vedotin

  6. Indication expanded2023-12-15

    Indication expansion: ENFORTUMAB VEDOTIN (BLA761137)

    fda · regulatory · fda · via enfortumab vedotin

  7. New publication2023-10-21
    The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma.

    Annals of oncology : official journal of the European Society for Medical Oncology · 2024 · 69 citations · Europe PMC · via enfortumab vedotin

  8. New publication2023-09-09
    EV-301 long-term outcomes: 24-month findings from the phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma.

    Annals of oncology : official journal of the European Society for Medical Oncology · 2023 · 114 citations · Europe PMC · via enfortumab vedotin

  9. New publication2023-06-27
    Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023 · 154 citations · Europe PMC · via enfortumab vedotin

  10. Label change2023-04-18

    Label change: ENFORTUMAB VEDOTIN (BLA761137)

    fda · regulatory · fda · via enfortumab vedotin

  11. Indication expanded2023-04-03

    Indication expansion: ENFORTUMAB VEDOTIN (BLA761137)

    fda · regulatory · fda · via enfortumab vedotin

  12. Label change2023-04-03

    Label change: ENFORTUMAB VEDOTIN (BLA761137)

    fda · regulatory · fda · via enfortumab vedotin

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.