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
Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Homodimerization is induced by binding of a NGF dimer (PubMed:10490030, PubMed:1281417, PubMed:17196528). Interacts with SQSTM1; bridges NTRK1 to NGFR (PubMed:11244088).
Forms a ternary complex with NGFR and KIDINS220; this complex is affected by the expression levels of KIDINS220 and an increase in KIDINS220 expression leads to a decreased association of NGFR and NTRK1 (By similarity). Interacts with SH2D1A; regulates NTRK1 (By similarity). Interacts (phosphorylated upon activation by NGF) with SHC1; mediates SHC1 phosphorylation and activation (PubMed:15488758, PubMed:8155326).
Interacts (phosphorylated upon activation by NGF) with PLCG1; mediates PLCG1 phosphorylation and activation (PubMed:15488758, PubMed:7510697). Interacts (phosphorylated) with SH2B1 and SH2B2 (By similarity). Interacts with GRB2 (PubMed:15488758).
Interacts with PIK3R1 (PubMed:15488758). Interacts with FRS2 (PubMed:15488758). Interacts with SORT1; may regulate NTRK1 anterograde axonal transport (PubMed:21102451).
Interacts with RAB7A (By similarity). Found in a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a nerve growth factor (NGF)-dependent manner (By similarity). Interacts with RAPGEF2; the interaction is strengthened after NGF stimulation (By similarity).
Interacts with PTPRS (By similarity). Interacts with USP36; USP36 does not deubiquitinate NTRK1 (PubMed:27445338). Interacts with GGA3 (PubMed:26446845).
Interacts with TSPAN1; this interaction promotes NTRK1 stability (By similarity)
Isoform TrkA-I is found in most non-neuronal tissues. Isoform TrkA-II is primarily expressed in neuronal cells. TrkA-III is specifically expressed by pluripotent neural stem and neural crest progenitors
The transmembrane domain mediates interaction with KIDINS220
The extracellular domain mediates interaction with NGFR
Characterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and intellectual disability. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II.
| Cancer Type | Mutation Percentage |
|---|---|
| Central Nervous System Astrocytoma Grade Iv | 0.76% |
| Lung Adenocarcinoma | 6.81% |
| Lung Small Cell Carcinoma | 4.15% |
| Lung Squamous Cell Carcinoma | 4.76% |
| Oesophagus Adenocarcinoma | 1.55% |
| Oesophagus Squamous Cell Carcinoma | 1.41% |
| Pancreas Ductal Carcinoma | 1.22% |
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to NTRK1, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 32
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT02637687 | Solid Tumors Harboring NTRK Fusion | A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children | PHASE1, PHASE2 | ACTIVE_NOT_RECRUITING |
| NCT03556228 | Head and Neck Carcinoma, Adenoid Cystic Carcinoma, Lung Cancer, Non-Small Cell Lung Cancer, Pancreatic Cancer, Mesothelioma, Esophageal Cancer, Any Solid Tumors Progressed After a Prior Immunotherapy, Head and Neck Squamous Cell Carcinoma, Head and Neck Squamous Cell Carcinoma HNSCC, Salivary Gland Carcinomas, Head and Neck Cancers - Salivary Gland, Head and Neck Cancers - Nasopharyngeal, Head and Neck Cancers - Throat, Small Cell Lung Cancer ( SCLC ), Lung Cancer (Locally Advanced or Metastatic), Head and Neck Cancers - Tonsils, Head and Neck Cancers Hypopharynx, Head and Neck Cancers Larynx, Head and Neck Cancers Lip, Head and Neck Cancers Nasopharynx, Head and Neck Cancers Oral Cavity, Head and Neck Cancers, Head and Neck Cancers Oropharynx, Head and Neck Cancers Trachea | VMD-928 Monotherapy and in Combination With Pembrolizumab to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma | PHASE1, PHASE2 | RECRUITING |
| NCT03375437 | Soft Tissue Sarcoma, Advanced Cancer, Metastatic Cancer | RNASARC - Molecular Screening Program of Soft Tissue Sarcomas With Complex Genomic Profile to Detect NTRK1/2/3, ROS1 or ALK Gene Fusions. | NA | ACTIVE_NOT_RECRUITING |
| NCT05722886 | Haematological Malignancy, Solid Tumour | DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial) - Master Screening Protocol | PHASE2, PHASE3 | RECRUITING |
| NCT04557813 | NTRK Family Gene Mutation | Registry for Molecular Testing, Treatment and Outcome of Patients With Solid Tumors Harboring a NTRK Gene Fusion | N/A | COMPLETED |
| NCT02097810 | Locally Advanced Solid Tumors, Metastatic Solid Tumors | Study of Oral RXDX-101 in Adult Patients With Locally Advanced or Metastatic Cancer Targeting NTRK1, NTRK2, NTRK3, ROS1, or ALK Molecular Alterations. | PHASE1 | COMPLETED |
| NCT02048488 | Solid Tumors, Lymphomas | A Phase I/IIa Open-Label, Dose Escalation and Cohort Expansion Trial of Oral TSR-011 in Patients With Advanced Solid Tumors and Lymphomas | PHASE1, PHASE2 | COMPLETED |
| NCT02624570 | Acute Myeloid Leukemia (AML) With, FLT3 Mutation, Internal Tandem Duplication (ITD) or Tyrosine Kinase Domain (TKD) | Midostaurin Access Program for Newly Diagnosed FLT3 (ITD or TKD) Mutated AML Adult Patients Eligible for Standard Induction and Consolidation Chemotherapy | N/A | NO_LONGER_AVAILABLE |
| NCT07471009 | Squamous Cell Tumors of the Head and Neck (HNSCC) | Development of Patient Derived Xenografts (PDXs) and Analysis of Tyrosine Kinase Receptor Expression in Patients With Squamous Cell Head and Neck Cancer (HNSCC) to Study Resistance Mechanisms Induced by Standard Therapy | N/A | NOT_YET_RECRUITING |
| NCT06528691 | High Grade Glioma, CNS Tumor | Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors | PHASE2 | RECRUITING |