Protein / target

Receptor tyrosine-protein kinase erbB-3

ERBB3P21860Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
24
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Protein tyrosine kinase activator activity

Primary system

Nervous system

Strongest disease association

visceral neuropathy, familial, 1, autosomal recessive

Genetic evidence · score 0.86

Therapeutic maturity

Clinically validated target

3 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

3 approved · 14 in clinical development

24 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

Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). May also be activated by CSPG5 (PubMed:15358134). Involved in the regulation of myeloid cell differentiation (PubMed:27416908)

Subcellular location

Cell membraneSecreted
Domains and Gene Ontology detail (47)

Domains & features

Protein kinase

Gene Ontology

  • Capical plasma membrane
  • Cbasal plasma membrane
  • Cbasolateral plasma membrane
  • CERBB3:ERBB2 complex
  • Cextracellular space
  • Clateral plasma membrane
  • Cplasma membrane
  • Cpostsynaptic membrane
  • Creceptor complex
  • FATP binding
  • FErbB-3 class receptor binding
  • Fgrowth factor binding

1342 aa · 148 kDa · 5 isoforms

Biological roles

Reactome v97

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

Kinase signallingUniProt · GOApoptosis & cell deathGOSynaptic signallingGOCell adhesionGO
View supporting evidence

Kinase signalling

  • ·Tyrosine-protein kinase that plays an essential role as cell surface receptor for neureg…
  • ·protein kinase activity
  • ·phosphatidylinositol 3-kinase/protein kinase B signal transduction
  • ·positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction

Apoptosis & cell death

  • ·negative regulation of apoptotic process
  • ·negative regulation of neuron apoptotic process
  • ·neuron apoptotic process

Synaptic signalling

  • ·postsynaptic membrane

Cell adhesion

  • ·negative regulation of cell adhesion
View underlying pathways (15)

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.

GRB2NRG2SHC1EGFERBB4EGFRNRG1ERBB2TGFAPIK3R1ERBB3

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

2

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.

patritumab deruxtecan
Narrow target profileApprovedBinding agent

Receptor tyrosine-protein kinase erbB-3 binding agent

Appears in clinical studies involving neoplasm, non-small cell lung carcinoma, breast cancer, colorectal cancer

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

zenocutuzumab
ApprovedInhibitor

ErbB-2/ErbB-3 heterodimer inhibitor

Appears in clinical studies involving non-small cell lung carcinoma, pancreatic neoplasm, breast cancer, malignant pancreatic neoplasm

Acts on a complex — shared with ERBB2 · 1 of 2 recorded protein targets — narrow recorded profile

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.

visceral neuropathy, familial, 1, autosomal recessive0.86

Genetic · overall 0.73

Lethal congenital contracture syndrome type 20.83

Genetic literature · overall 0.60

lethal congenital contracture syndrome 20.78

Genetic · overall 0.69

neoplasm0.26

Genetic · overall 0.56

Highest-confidence therapeutic associations

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

medullary thyroid gland carcinoma0.89

Clinical · overall 0.54

non-small cell lung carcinoma0.84

Clinical · overall 0.59

urinary bladder carcinoma0.12

Clinical · overall 0.60

colorectal adenocarcinoma0.08

Clinical · overall 0.53

cancer0.06

Clinical · overall 0.66

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

urinary bladder cancer0.60

Somatic mutation

Show all associations
visceral neuropathy, familial, 1, autosomal recessive0.73
lethal congenital contracture syndrome 20.69
cancer0.66
urinary bladder cancer0.60
urinary bladder carcinoma0.60
Lethal congenital contracture syndrome type 20.60
non-small cell lung carcinoma0.59
neoplasm0.56
medullary thyroid gland carcinoma0.54
colorectal adenocarcinoma0.53

Open Targets ranks 2,062 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 · 17 total

PATRITUMAB DERUXTECANApproval

neoplasm · non-small cell lung carcinoma · breast cancer

AV-203Phase 1

neoplasm

DULIGOTUZUMABPhase 2

colorectal cancer · head and neck squamous cell carcinoma · head and neck squamous cell carcinoma

VANDETANIBApproval

thyroid gland carcinoma · medullary thyroid gland carcinoma · medullary thyroid gland carcinoma

ZENOCUTUZUMABApproval

non-small cell lung carcinoma · pancreatic neoplasm · breast cancer

POZIOTINIBPhase 3

non-small cell lung carcinoma · HER2 positive breast carcinoma · non-small cell lung carcinoma

KBP5209Phase 1
SERIBANTUMABPhase 2

colorectal cancer · head and neck cancer · non-small cell lung carcinoma

MM-111Phase 2

breast cancer · gastric adenocarcinoma · gastric carcinoma

LUMRETUZUMABPhase 1 2

non-small cell lung carcinoma · breast cancer

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Half-life Data

Clinical trials

24

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 (18)

WITHDRAWN · via patritumab deruxtecan · NCT05620914

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.

visceral neuropathy, familial, 1, autosomal recessiveWell supported
0.88
agreement 0.751.00
Genetic89%Animal model11%Genetic literaturedup

Open Targets aggregate 0.73 · 2 independent evidence families · 1 not counted as duplicate

neoplasmWell supported
0.81
agreement 0.720.91
Clinical45%Somatic mutation23%Genetic21%Literature12%

Open Targets aggregate 0.56 · 4 independent evidence families

lethal congenital contracture syndrome 2Well supported
0.78
agreement 0.640.92
Genetic99%Literature1%Genetic literaturedup

Open Targets aggregate 0.69 · 2 independent evidence families · 1 not counted as duplicate

non-small cell lung carcinomaWell supported
0.78
agreement 0.660.90
Clinical59%Somatic mutation28%Literature13%

Open Targets aggregate 0.59 · 3 independent evidence families

urinary bladder carcinomaModerately supported
0.71
agreement 0.600.82
Somatic mutation49%Pathway31%Literature11%Clinical9%

Open Targets aggregate 0.60 · 4 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

4

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2025-05-30
    Patritumab deruxtecan in leptomeningeal metastatic disease of solid tumors: the phase 2 TUXEDO-3 trial.

    Nature medicine · 2025 · 16 citations · Europe PMC · via patritumab deruxtecan

  2. New publication2025-02-01
    Efficacy of Zenocutuzumab in <i>NRG1</i> Fusion-Positive Cancer.

    The New England journal of medicine · 2025 · 78 citations · Europe PMC · via zenocutuzumab

  3. New publication2023-10-06
    Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023 · 102 citations · Europe PMC · via patritumab deruxtecan

  4. New publication2023-09-10
    HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023 · 188 citations · Europe PMC · via patritumab deruxtecan

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.