NTRK3 (Neurotrophic Receptor Tyrosine Kinase 3)
A key receptor tyrosine kinase involved in neuronal development and cancer, with gene fusions driving tumorigenesis.
Gene Information Card
| Symbol | NTRK3 |
|---|---|
| Full Name | Neurotrophic Receptor Tyrosine Kinase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 15q25.3 |
| NCBI Gene ID | 4916 ncbi.nlm.nih.gov/gene/4916 |
| Ensembl ID | ENSG00000140538 |
| UniProt ID | Q16288 |
| OMIM ID | 191316 |
| HGNC ID | 8033 |
| Aliases | TRKC, gp145(trkC) |
Description
The NTRK3 gene encodes the neurotrophic receptor tyrosine kinase 3 (TRKC), a member of the TRK family of receptors for neurotrophins. TRKC is primarily expressed in the central and peripheral nervous systems, where it binds to neurotrophin-3 (NT-3) and mediates neuronal survival, differentiation, and synaptic plasticity. In addition to its physiological roles, NTRK3 is implicated in various cancers through gene fusions, such as ETV6-NTRK3, which lead to constitutive activation of the kinase domain and oncogenic signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital insensitivity to pain with anhidrosis (CIPA) | Loss-of-function mutations in NTRK3 impair TRKC signaling, affecting nociceptive neuron development. | OMIM, ClinVar |
| Secretory breast carcinoma | ETV6-NTRK3 gene fusion results in a chimeric protein with constitutive kinase activity, driving tumorigenesis. | COSMIC, literature |
| Congenital fibrosarcoma | ETV6-NTRK3 fusion is a hallmark, leading to aberrant activation of RAS/MAPK and PI3K/AKT pathways. | COSMIC, literature |
| Acute myeloid leukemia (AML) | NTRK3 fusions (e.g., ETV6-NTRK3) have been reported, contributing to leukemogenesis. | COSMIC, literature |
| Colorectal cancer | NTRK3 fusions are rare but present, leading to oncogenic signaling. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Cerebellum | 10.2 | High |
| Adrenal gland | 5.1 | Medium |
| Testis | 3.4 | Low |
| Lung | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.7 | High expression |
| MCF7 (breast cancer) | 2.3 | Low expression |
| A549 (lung cancer) | 1.1 | Low expression |
| HepG2 (liver cancer) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| ETV6-NTRK3 fusion | Chromosomal translocation | Rare in most cancers, common in secretory breast carcinoma and congenital fibrosarcoma | Constitutive kinase activation, oncogenic transformation |
| p.R649W | Missense | Rare | Impaired kinase activity, loss of function |
| p.G623R | Missense | Rare | Altered ligand binding, potential gain of function |
| p.D716N | Missense | Rare | Kinase domain mutation, uncertain effect |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair TRKC kinase activity or ligand binding, leading to reduced neuronal survival signaling, as seen in CIPA.
Gain of Function (GOF)
Gene fusions (e.g., ETV6-NTRK3) that produce constitutively active chimeric kinases, driving oncogenic signaling.
Dominant Negative (DN)
Not well-documented for NTRK3; some missense mutations may exert dominant-negative effects on receptor dimerization, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • protein tyrosine kinase activity |
| • neurotrophin binding | • receptor signaling protein tyrosine kinase activity |
| • transmembrane receptor protein tyrosine kinase signaling pathway | • nervous system development |
| • cell differentiation | • positive regulation of cell proliferation |
Pathways
• MAPK/ERK signaling pathway
• PI3K/AKT signaling pathway
• PLC-gamma signaling pathway
• Neurotrophin signaling pathway
Protein Summary
The TRKC protein is a single-pass type I membrane receptor with an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyrosine kinase domain. Upon binding to NT-3, TRKC dimerizes and autophosphorylates, activating downstream signaling cascades such as RAS/MAPK, PI3K/AKT, and PLC-gamma, which regulate neuronal survival, differentiation, and proliferation. In cancer, fusion proteins involving the NTRK3 kinase domain lose the extracellular domain and become constitutively active, promoting tumor growth.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NTRK3 Overexpression HEK293T Stable Cell Line | EDJ0048-G19 | Human | 4916 | Details Get a Quote |
| NTRK3 Knockout HEK293 Cell Line | EDJ-KQ1613 | Human | 4916 | Details Get a Quote |
| NTRK3 Knockout A-549 Cell Line | EDJ-KQ21297 | Human | 4916 | Details Get a Quote |
| NTRK3 Knockout HeLa Cell Line | EDJ-KQ54031 | Human | 4916 | Details Get a Quote |
| NTRK3 Knockout HCT 116 Cell Line | EDJ-KQ70991 | Human | 4916 | Details Get a Quote |
| NTRK3 (p.A496=) Point Mutation in HAP1 Cell Line | EDC03571 | Human | 4916 | Details Get a Quote |
| NTRK3 (p.N191=) Point Mutation in HAP1 Cell Line | EDC03572 | Human | 4916 | Details Get a Quote |
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