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Protein / target

High affinity nerve growth factor receptor

Encoded byNTRK1P04629Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
7
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Transmembrane receptor protein tyrosine kinase

Strongest disease association

Hereditary sensory and autonomic neuropathy type 4

Via encoding gene NTRK1 · Genetic evidence · score 0.94

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

1 papers · latest 2019

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

Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons.

View complete UniProt function annotation

Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand (PubMed:1281417, PubMed:15488758, PubMed:17196528, PubMed:1849459, PubMed:1850821, PubMed:22649032, PubMed:27445338, PubMed:8325889). Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity). Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:1281417). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors

Subcellular location

Cell membraneEarly endosome membraneLate endosome membraneRecycling endosome membrane
Domains and Gene Ontology detail (68)

Domains & features

LRRCTIg-like C2-type 1Ig-like C2-type 2Protein kinase

Gene Ontology

  • Caxon
  • Ccell surface
  • Cdendrite
  • Cearly endosome
  • Cearly endosome membrane
  • Cendosome membrane
  • Clate endosome
  • Clate endosome membrane
  • Cmitochondrion
  • Cneuronal cell body
  • Cplasma membrane
  • Cprotein-containing complex

796 aa · 87 kDa · 4 isoforms

Biological roles

Reactome v97

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

Receptor tyrosine kinase signallingUniProt · GOCell proliferation & survivalUniProt · GOExcitatory neurotransmissionGOApoptosis & cell deathGO
View supporting evidence

Receptor tyrosine kinase signalling

  • ·Receptor tyrosine kinase involved in the development and the maturation of the central a…
  • ·transmembrane receptor protein tyrosine kinase activity
  • ·cell surface receptor protein tyrosine kinase signaling pathway

Cell proliferation & survival

  • ·Receptor tyrosine kinase involved in the development and the maturation of the central a…
  • ·negative regulation of cell population proliferation

Excitatory neurotransmission

  • ·positive regulation of synaptic transmission, glutamatergic

Apoptosis & cell death

  • ·negative regulation of apoptotic process
  • ·negative regulation of neuron apoptotic process
  • ·positive regulation of programmed cell death
  • ·programmed cell death involved in cell development
View underlying pathways (10)

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.

BDNFNGFSHC1NTF4NTF3NGFRKITLGEGFHGFINSNTRK1

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

4 medicines · 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, Non-Small-Cell Lung1 medicine
Colorectal Neoplasms1 medicine

7 medicines meet Open Targets' target-level approved-medicine definition; the 4 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

4

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.

repotrectinib
ApprovedInhibitor

Nerve growth factor receptor Trk-A inhibitor

Indicated for Neoplasms

Direct interaction with this protein · 1 of 6 recorded protein targets

regorafenib
ApprovedInhibitor

Nerve growth factor receptor Trk-A inhibitor

Indicated for Colorectal Neoplasms, Neoplasms

Direct interaction with this protein · 1 of 18 recorded protein targets — broad pharmacology

larotrectinib
ApprovedInhibitor

Neurotrophic tyrosine kinase receptor inhibitor

Indicated for Neoplasms

Acts on a complex — shared with NTRK2, NTRK3 · 1 of 3 recorded protein targets — narrow recorded profile

entrectinib
ApprovedInhibitor

Neurotrophic tyrosine kinase receptor inhibitor

Indicated for Carcinoma, Non-Small-Cell Lung, Neoplasms

Acts on a complex — shared with NTRK2, NTRK3 · 1 of 5 recorded protein targets

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 NTRK1

Gene-level evidence surfaced through the gene NTRK1that 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.

Hereditary sensory and autonomic neuropathy type 4
0.96Well supported

Genetic evidence dominant · Open Targets 0.86

Neoplasms
0.88Well supported

Clinical evidence dominant · Open Targets 0.62

Genetic Diseases, Inborn
0.86Well supported

Genetic evidence dominant · Open Targets 0.53

Carcinoma, Non-Small-Cell Lung
0.82Well supported

Clinical evidence dominant · Open Targets 0.66

Familial medullary thyroid carcinoma
0.74Moderately supported

Genetic evidence dominant · Open Targets 0.57

View evidence synthesis (5)
Hereditary sensory and autonomic neuropathy type 4Well supported
0.96
agreement 0.841.00
Genetic77%Animal model15%Literature8%Genetic literaturedup

Open Targets aggregate 0.86 · 3 independent evidence families · 1 not counted as duplicate

NeoplasmsWell supported
0.88
agreement 0.790.96
Clinical45%Pathway20%Somatic mutation13%Genetic13%Literature9%

Open Targets aggregate 0.62 · 5 independent evidence families

Genetic Diseases, InbornWell supported
0.86
agreement 0.721.00
Genetic98%Literature2%

Open Targets aggregate 0.53 · 2 independent evidence families

Carcinoma, Non-Small-Cell LungWell supported
0.82
agreement 0.700.94
Clinical64%Somatic mutation27%Literature10%

Open Targets aggregate 0.66 · 3 independent evidence families

Familial medullary thyroid carcinomaModerately supported
0.74
agreement 0.610.88
Genetic99%Literature1%

Open Targets aggregate 0.57 · 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
Hereditary sensory and autonomic neuropathy type 40.86
Carcinoma, Non-Small-Cell Lung0.66
Neoplasms0.62
Colorectal Neoplasms0.58
Familial medullary thyroid carcinoma0.57
Genetic Diseases, Inborn0.53
Neurodegenerative Diseases0.52
Colorectal adenocarcinoma0.44

Drug development

17 compounds recorded · 7 approved · 10 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 4 drugs that target this protein in Forefront's canonical graph (4 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
ENTRECTINIBApproval
CENEGERMINApproval
LAROTRECTINIBApproval
SELITRECTINIBPhase 1
TALETRECTINIBPhase 3
PEGCANTRATINIBPhase 2
ALTIRATINIBPhase 1
AZD-6918Phase 1
AZD-7451Phase 1
LAROTRECTINIB SULFATEApproval

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

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

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

Protein degradersEmerging

Feasibility evidence (literature and uniprot ubiquitination) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Approved Drug support this modality.

View underlying tractability evidence (12)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · LiteraturePR · UniProt UbiquitinationPR · Small Molecule BinderOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

grey matter heterotopiaBrennan et al. (2024)weight gainBrennan et al. (2024)seizuresBrennan et al. (2024)peripheral sensory neuropathyBrennan et al. (2024)AnxietyBrennan et al. (2024)dizzinessBrennan et al. (2024)Cognitive disorderBrennan et al. (2024)weight lossBrennan et al. (2024)dysgeusiaBrennan et al. (2024)ataxiaBrennan et al. (2024)require glucarpidase treatmentClinPGxregulation of catalytic activityToxCast

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)

ClinicalTrials.gov via the drug-target graph.

What's happening now

10

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 4 drugs that target 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 approval2025-01-13

    Approval: Augtyro (EMA)

    ema · regulatory · ema · via repotrectinib

  2. New publication2024-06-04
    Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024 · 69 citations · Europe PMC · via regorafenib

  3. New publication2024-01-01
    Repotrectinib in <i>ROS1</i> Fusion-Positive Non-Small-Cell Lung Cancer.

    The New England journal of medicine · 2024 · 168 citations · Europe PMC · via repotrectinib

  4. New publication2020-08-11
    Targeted therapy for hepatocellular carcinoma.

    Signal transduction and targeted therapy · 2020 · 565 citations · Europe PMC · via regorafenib

  5. Regulatory approval2020-07-31

    Approval: Rozlytrek (EMA)

    ema · regulatory · ema · via entrectinib

  6. New publication2019-11-04
    Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma.

    Journal of experimental & clinical cancer research : CR · 2019 · 162 citations · Europe PMC · via regorafenib

  7. New publication2019-04-23
    Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019 · 199 citations · Europe PMC · via regorafenib

  8. New publication2018-02-01
    Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children.

    The New England journal of medicine · 2018 · 1,987 citations · Europe PMC · via larotrectinib

  9. New publication2016-12-06
    Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial.

    Lancet (London, England) · 2017 · 2,767 citations · Europe PMC · via regorafenib

  10. Regulatory approval2013-08-26

    Approval: Stivarga (EMA)

    ema · regulatory · ema · via regorafenib

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.

Research activity

1 papers · to 2019

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Guerreiro Stucklin AS · Nature communications · 2019

Recent

Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas.

Guerreiro Stucklin AS · Nature communications · 2019

Europe PMC papers linked directly to this protein.