Protein / target

Nectin-4

NECTIN4Q96NY8Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
1
Approved medicines
30
Clinical trials
Antibody-tractable
Druggability
UniProt loc high conf

Protein at a glance

Biological role

Cell adhesion mediator activity

Strongest disease association

Ectodermal dysplasia - syndactyly syndrome

Genetic literature evidence · score 0.83

Therapeutic maturity

Clinically validated target

1 approved medicine against this target

Druggability

Antibody

Open Targets tractability · UniProt loc high conf

Clinical development

1 approved

30 linked trials

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

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.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

enfortumab vedotin
ApprovedBinding agent

Nectin-4 binding agent

Appears in clinical studies involving urothelial carcinoma, transitional cell carcinoma, neoplasm, urinary bladder carcinoma

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

Ectodermal dysplasia - syndactyly syndrome0.83

Genetic literature · overall 0.78

ectodermal dysplasia-syndactyly syndrome0.61

Genetic literature · overall 0.38

amelogenesis imperfecta0.30

Genetic literature · overall 0.18

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

urothelial carcinoma0.83

Clinical · overall 0.51

neoplasm0.61

Clinical · overall 0.40

transitional cell carcinoma0.61

Clinical · overall 0.37

urinary bladder carcinoma0.60

Clinical · overall 0.38

urogenital neoplasm0.54

Clinical · overall 0.33

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

cancer0.35

Literature

urinary bladder cancer0.30

Literature

Show all associations
Ectodermal dysplasia - syndactyly syndrome0.78
urothelial carcinoma0.51
neoplasm0.40
urinary bladder carcinoma0.38
ectodermal dysplasia-syndactyly syndrome0.38
transitional cell carcinoma0.37
cancer0.35
urogenital neoplasm0.33
urinary bladder cancer0.30
amelogenesis imperfecta0.18

Open Targets ranks 292 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 1 total

ENFORTUMAB VEDOTINApproval

urothelial carcinoma · transitional cell carcinoma · neoplasm

Tractability

AB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locOC · Approved Drug

Safety liabilities

skin irritation

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.

Show remaining trials (24)

RECRUITING · via enfortumab vedotin · NCT06145308

RECRUITING · via enfortumab vedotin · NCT06434350

NOT_YET_RECRUITING · via enfortumab vedotin · NCT07139977

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

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

neoplasmModerately 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

24

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  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 publication2024-04-24
    <i>NECTIN4</i> Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024 · 95 citations · Europe PMC · via enfortumab vedotin

  5. 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

  6. Indication expanded2023-12-15

    Indication expansion: ENFORTUMAB VEDOTIN (BLA761137)

    fda · regulatory · fda · via enfortumab vedotin

  7. Indication expanded2023-12-15

    Indication expansion: ENFORTUMAB VEDOTIN (BLA761137)

    fda · regulatory · fda · via enfortumab vedotin

  8. 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

  9. 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

  10. 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

  11. Label change2023-04-18

    Label change: ENFORTUMAB VEDOTIN (BLA761137)

    fda · regulatory · fda · via enfortumab vedotin

  12. Indication expanded2023-04-03

    Indication expansion: 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.