NTRK2 Gene: Neurotrophic Receptor Tyrosine Kinase 2
A key regulator of neuronal survival, differentiation, and synaptic plasticity, implicated in neurodevelopmental disorders and cancer.
Gene Information Card
| Symbol | NTRK2 |
|---|---|
| Full Name | Neurotrophic Receptor Tyrosine Kinase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q21.33 |
| NCBI Gene ID | 4915 ncbi.nlm.nih.gov/gene/4915 |
| Ensembl ID | ENSG00000148053 |
| UniProt ID | Q16620 |
| OMIM ID | 600456 |
| HGNC ID | 8032 |
| Aliases | TrkB, GP145-TrkB, trk-B |
Description
The NTRK2 gene encodes the neurotrophic receptor tyrosine kinase 2 (TrkB), a receptor for brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5. This receptor is critical for the development and function of the nervous system, playing a key role in neuronal survival, differentiation, synaptic plasticity, and memory formation. Upon binding its ligands, TrkB undergoes dimerization and autophosphorylation, activating downstream signaling pathways such as MAPK, PI3K, and PLCγ. Alterations in NTRK2 are associated with various conditions, including neurodevelopmental disorders, obesity, and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Obesity | Loss-of-function mutations in NTRK2 impair BDNF signaling in the hypothalamus, leading to hyperphagia and severe early-onset obesity. | ClinVar, OMIM |
| Neurodevelopmental disorders | Mutations affecting the kinase domain or ligand binding can disrupt neuronal differentiation and survival, contributing to intellectual disability and developmental delay. | ClinVar, OMIM |
| Cancer | Gene fusions (e.g., ETV6-NTRK2) and activating mutations can lead to constitutive kinase activity, promoting uncontrolled cell proliferation and tumorigenesis in various tissues. | COSMIC, NCBI |
| Depression and anxiety | Polymorphisms and altered expression of NTRK2 are linked to impaired neuroplasticity, increasing susceptibility to mood disorders. | NCBI, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Brain | High | Tissue-specific |
| Adrenal gland | Medium | Tissue-specific |
| Pituitary gland | Medium | Tissue-specific |
| Salivary gland | Low | Tissue-specific |
| Lung | Low | Tissue-specific |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| SH-SY5Y | High | Neuroblastoma cell line, commonly used for neuronal studies. |
| SK-N-BE(2) | High | Neuroblastoma cell line. |
| U-87 MG | Low | Glioblastoma cell line. |
| A549 | Low | Lung carcinoma cell line. |
| MCF7 | Low | Breast adenocarcinoma cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| Y433F | Missense | Rare | Impairs PLCγ signaling, affecting synaptic plasticity. |
| R630W | Missense | Rare | Loss-of-function, associated with severe obesity. |
| G709A | Missense | Rare | Impaired kinase activity, linked to developmental delay. |
| ETV6-NTRK2 | Fusion | Rare | Constitutive activation, oncogenic in various cancers. |
| Q805R | Missense | Rare | Gain-of-function, potentially oncogenic. |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish TrkB kinase activity or ligand binding, leading to impaired neurotrophin signaling. These are associated with obesity, developmental delay, and cognitive deficits.
Gain of Function (GOF)
Mutations that enhance TrkB kinase activity, often through constitutive dimerization or autophosphorylation. These are oncogenic and can drive tumor growth.
Dominant Negative (DN)
Mutations that produce a receptor that can dimerize with wild-type TrkB but lacks kinase activity, thereby inhibiting the function of the normal receptor. This can exacerbate loss-of-function phenotypes.
View complete mutation data：
Gene Ontology (GO)
| • protein tyrosine kinase activity | • transmembrane receptor protein tyrosine kinase activity |
| • neurotrophin binding | • ATP binding |
| • plasma membrane | • integral component of plasma membrane |
| • neuron projection | • signal transduction |
| • nervous system development | • cell differentiation |
| • positive regulation of cell population proliferation | • MAPK cascade |
| • phosphatidylinositol 3-kinase signaling | • phospholipase C-activating G protein-coupled receptor signaling pathway |
Pathways
• MAPK/ERK signaling pathway
• PI3K/Akt signaling pathway
• PLCγ signaling pathway
• Neurotrophin signaling pathway
• BDNF signaling pathway
Protein Summary
The TrkB protein is a single-pass type I membrane protein that belongs to the neurotrophic receptor family. It consists of an extracellular domain with leucine-rich repeats and immunoglobulin-like domains for ligand binding, a single transmembrane domain, and an intracellular tyrosine kinase domain. Upon binding BDNF, TrkB dimerizes and autophosphorylates specific tyrosine residues, creating docking sites for adaptor proteins like Shc and PLCγ. This initiates downstream signaling cascades that regulate gene expression, cell survival, and synaptic function. Isoforms lacking the kinase domain can act as dominant-negative inhibitors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NTRK2 Overexpression HEK293T Stable Cell Line | EDJ-GQ128 | Human | 4915 | Details Get a Quote |
| NTRK2 Knockout HEK293 Cell Line | EDJ-KQ720 | Human | 4915 | Details Get a Quote |
| NTRK2 Knockout HeLa Cell Line | EDJ-KQ54030 | Human | 4915 | Details Get a Quote |
| NTRK2 Knockout A-549 Cell Line | EDJ-KQ62518 | Human | 4915 | Details Get a Quote |
| NTRK2 Knockout HCT 116 Cell Line | EDJ-KQ70990 | Human | 4915 | Details Get a Quote |
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