NTRK1
Neurotrophic Receptor Tyrosine Kinase 1
Gene Information Card
| Symbol | NTRK1 |
|---|---|
| Full Name | Neurotrophic Receptor Tyrosine Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q23.1 |
| NCBI Gene ID | 4914 ncbi.nlm.nih.gov/gene/4914 |
| Ensembl ID | ENSG00000198400 |
| UniProt ID | P04629 |
| OMIM ID | 191315 |
| HGNC ID | 8031 |
| Aliases | TRKA, TRK1, MTC, NTRK1-2, p140-TrkA |
Description
NTRK1 (Neurotrophic Receptor Tyrosine Kinase 1) encodes the TRKA receptor, a member of the neurotrophic tyrosine kinase receptor family. TRKA is the high-affinity receptor for nerve growth factor (NGF) and mediates neuronal survival, differentiation, and synaptic plasticity. Mutations in NTRK1 cause congenital insensitivity to pain with anhidrosis (CIPA), while gene fusions and activating mutations are oncogenic drivers in various cancers, including papillary thyroid carcinoma and lung adenocarcinoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital insensitivity to pain with anhidrosis (CIPA) | Loss-of-function mutations impair NGF/TRKA signaling, leading to absence of pain perception, anhidrosis, and intellectual disability. | OMIM #256800; ClinVar |
| Papillary thyroid carcinoma | NTRK1 gene fusions (e.g., TPM3-NTRK1) produce constitutive TRKA kinase activity, driving tumorigenesis. | COSMIC; PMID: 12808449 |
| Lung adenocarcinoma | NTRK1 fusions (e.g., MPRIP-NTRK1, CD74-NTRK1) activate MAPK/ERK pathway, promoting cell proliferation. | ClinVar; PMID: 25231345 |
| Spindle cell sarcoma | NTRK1 fusions (e.g., LMNA-NTRK1) result in oncogenic TRKA signaling. | COSMIC; PMID: 27160803 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Adrenal gland | 8.7 | Medium |
| Thyroid | 4.2 | Low |
| Lung | 1.5 | Low |
| Heart | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 15.6 | Neuroblastoma cell line; high TRKA expression |
| HEK293 | 2.1 | Low endogenous expression |
| A549 | 0.3 | Lung carcinoma; very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1726C>T (p.Arg576Trp) | Missense | Rare | Loss of NGF binding; associated with CIPA |
| c.851-2A>G | Splice site | Rare | Exon skipping; loss of function in CIPA |
| TPM3-NTRK1 fusion | Gene fusion | Somatic | Constitutive kinase activation; oncogenic in thyroid cancer |
| LMNA-NTRK1 fusion | Gene fusion | Somatic | Oncogenic TRKA signaling in sarcoma |
Mutation functional classification
Loss of Function (LOF)
Missense, nonsense, and splice-site mutations that disrupt NGF binding or TRKA kinase activity, leading to CIPA.
Gain of Function (GOF)
Gene fusions (e.g., TPM3-NTRK1, LMNA-NTRK1) that produce constitutively active TRKA chimeras, driving oncogenesis.
Dominant Negative (DN)
Not well documented; some missense mutations may interfere with wild-type TRKA dimerization.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• Neurotrophin signaling pathway (KEGG: hsa04722)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Ras signaling pathway (KEGG: hsa04014)
Protein Summary
TRKA (UniProt P04629) is a 796-amino-acid single-pass transmembrane receptor tyrosine kinase. The extracellular domain contains leucine-rich repeats and immunoglobulin-like domains that bind NGF. Ligand binding induces dimerization and autophosphorylation of tyrosine residues in the intracellular kinase domain, activating downstream signaling cascades (MAPK, PI3K, PLCγ). TRKA is essential for development and maintenance of nociceptive neurons. Aberrant TRKA signaling due to mutations or fusions underlies hereditary pain insensitivity and multiple cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NTRK1 Knockout HEK293 Cell Line | EDJ-KQ719 | Human | 4914 | Details Get a Quote |
| NTRK1 Knockout HeLa Cell Line | EDJ-KQ54029 | Human | 4914 | Details Get a Quote |
| NTRK1 Knockout A-549 Cell Line | EDJ-KQ62517 | Human | 4914 | Details Get a Quote |
| NTRK1 Knockout HCT 116 Cell Line | EDJ-KQ70989 | Human | 4914 | Details Get a Quote |
| NTRK1 (p.Q522=) Point Mutation in HAP1 Cell Line | EDC03568 | Human | 4914 | Details Get a Quote |
| NTRK1 (p.A629=) Point Mutation in HAP1 Cell Line | EDC03570 | Human | 4914 | Details Get a Quote |
| NTRK1 (c.122+2042G>A )Point Mutation in HAP1 Cell Line | EDC03566 | Human | 4914 | Details Get a Quote |
| NTRK1 (c.122+2493G>A )Point Mutation in HAP1 Cell Line | EDC03567 | Human | 4914 | Details Get a Quote |
| NTRK1 (c.1645del )Point Mutation in HAP1 Cell Line | EDC03569 | Human | 4914 | Details Get a Quote |
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