Protein / target
High affinity nerve growth factor receptor
Protein at a glance
Biological role
Transmembrane receptor protein tyrosine kinase activity
Primary system
Nervous system
Strongest disease association
hereditary sensory and autonomic neuropathy type 4
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
7 approved · 10 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
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
Domains and Gene Ontology detail (68)Hide
Domains & features
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
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Kinase signalling
- ·Receptor tyrosine kinase involved in the development and the maturation of the central a…
- ·protein tyrosine kinase activity
- ·transmembrane receptor protein tyrosine kinase activity
- ·peptidyl-tyrosine autophosphorylation
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
Excitatory neurotransmission
- ·positive regulation of synaptic transmission, glutamatergic
Synaptic signalling
- ·positive regulation of synaptic transmission, glutamatergic
Transcriptional regulation
- ·Receptor tyrosine kinase involved in the development and the maturation of the central a…
View underlying pathways (10)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
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.
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
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.
Nerve growth factor receptor Trk-A inhibitor
Appears in clinical studies involving non-small cell lung carcinoma, non-small cell lung carcinoma, non-small cell lung carcinoma, cancer
Nerve growth factor receptor Trk-A inhibitor
Appears in clinical studies involving colorectal cancer, metastatic colorectal cancer, colorectal neoplasm, neoplasm
Neurotrophic tyrosine kinase receptor inhibitor
Appears in clinical studies involving neoplasm, cancer, plasma cell myeloma, lymphoma
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
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.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 2,703 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
non-small cell lung carcinoma · non-small cell lung carcinoma · neoplasm
keratitis · eye disorder · Sensory neuropathy
neoplasm · cancer · plasma cell myeloma
cancer · pancreatic ductal adenocarcinoma · hematopoietic and lymphoid system neoplasm
non-small cell lung carcinoma · non-small cell lung carcinoma · neoplasm
psoriasis vulgaris · Pruritus · psoriasis vulgaris
glioblastoma
metastasis · cancer · neoplasm
Tractability
Safety liabilities
Clinical trials
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)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
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.
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
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Regulatory approval
Approval: Augtyro (EMA)
- New publicationEfficacy of pembrolizumab in microsatellite-stable, tumor mutational burden-high metastatic colorectal cancer: genomic signatures and clinical outcomes.
- New publicationLenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study.
- New publicationRepotrectinib in <i>ROS1</i> Fusion-Positive Non-Small-Cell Lung Cancer.
- New publicationTargeted therapy for hepatocellular carcinoma.
- New publicationMolecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma.
- New publicationRandomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma.
- New publicationEfficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children.
- New publicationRegorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial.
- Regulatory approval
Approval: Stivarga (EMA)
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.