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This gene encodes a member of the neurotrophic tyrosine kinase receptor (NTKR) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. The presence of this kinase leads to cell differentiation and may play a role in specifying sensory neuron subtypes. Mutations in this gene have been associated with congenital insensitivity to pain, anhidrosis, self-mutilating behavior, cognitive disability and cancer. Alternate transcriptional splice variants of this gene have been found, but only three have been characterized to date. [provided by RefSeq, Jul 2008]
NTRK1 (Neurotrophic Receptor Tyrosine Kinase 1) is a Protein Coding gene. Diseases associated with NTRK1 include Insensitivity To Pain, Congenital, With Anhidrosis and Thyroid Carcinoma, Familial Medullary. Among its related pathways are Neuroscience and Transcriptional misregulation in cancer. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is NTRK3.
Trk (neurotrophin) receptors are single transmembrane catalytic receptors with intracellular tyrosine kinase activity. Trk receptors are coupled to the Ras, Cdc42/Rac/RhoG, MAPK, PI3K and PLCgamma signaling pathways. Four members of the Trk family have been identified.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | IEA,TAS | -- |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | IEA,IMP | 1281417 |
GO:0005004 | GPI-linked ephrin receptor activity | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000139 | Golgi membrane | TAS | -- |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005768 | endosome | IEA | -- |
GO:0005769 | early endosome | IEA,ISS | -- |
GO:0005770 | late endosome | IEA,ISS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Apoptotic Pathways in Synovial Fibroblasts |
Cellular Apoptosis Pathway
.85
Mitochondrial Apoptosis
.85
Apoptotic Pathways in Synovial Fibroblasts
.84
p53 Mediated Apoptosis
.84
DHA Signaling
.74
Telomerase Components in Cell Signaling
.72
PPAR Pathway
.66
|
Rac1 Pathway
.65
Actin-Based Motility by Rho Family GTPases
.62
ERK5 Signaling
.61
eIF2 Pathway
.60
Rap1 Pathway
.57
Nuclear Receptor Activation by Vitamin-A
.57
|
2 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
|
3 | RET signaling | ||
4 | ERK Signaling |
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
|
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
|
5 | Development HGF signaling pathway |
Development Neurotrophin family signaling
.44
Apoptosis and survival Role of CDK5 in neuronal death and survival
.37
|
Apoptosis and survival NGF signaling pathway
.36
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000186 | activation of MAPKK activity | TAS | -- |
GO:0001934 | positive regulation of protein phosphorylation | IEA,TAS | 19036963 |
GO:0006468 | protein phosphorylation | IEA,IDA | 15488758 |
GO:0007169 | transmembrane receptor protein tyrosine kinase signaling pathway | IEA,IBA | 21873635 |
GO:0007275 | multicellular organism development | IBA | 21873635 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Entrectinib | Approved, Investigational | Pharma | Target, inhibitor | Orally active inhibitor of ALK kinase | 15 | |
imatinib | Approved | Pharma | Target, antagonist, inhibitor | Kinase Inhibitors, SRC/BCR-ABL tyrosine kinase inhibitors | 0 | |
regorafenib | Approved | Pharma | Target, inhibitor | Inhibitor of VEGFR/PDGFR/FGFR/mutant kit/RET/Raf-1, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 0 | |
Tyrosine | Approved, Investigational | Nutra | 1044 | |||
Amitriptyline | Approved | Pharma | Antagonist, Target, agonist, activator | 105 |
Compound | Action | Cas Number |
---|---|---|
AG 879 | TrkA inhibitor | 148741-30-4 |
BDNF (human) | Activates TrkB and p75 receptors | 218441-99-7 |
LM11A 31 dihydrochloride | Nonpeptide p75NTR ligand; neuroprotective | 1243259-19-9 |
TLQP 21 | VGF-derived peptide | 869988-94-3 |
Compound | Action | Cas Number |
---|---|---|
7,8-Dihydroxyflavone | 38183-03-8 | |
BDNF (human) | 218441-99-7 | |
Cyclotraxin B | 1203586-72-4 | |
Danusertib (PHA-739358) | Pan-aurora kinase inhibitor | 827318-97-8 |
GNF-5837 | Pan-Trk inhibitor | 1033769-28-6 |
GW441756 | TrkA inhibitor,potent and selective | 504433-23-2 |
Lestaurtinib | JAK2/FLT3/TrkA inhibitor | 111358-88-4 |
LM 22A4 | 37988-18-4 | |
NTR 368 | 197230-90-3 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | NTRK1 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | NTRK1 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | NTRK1 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Ntrk1 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Ntrk1 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | NTRK1 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | NTRK1 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | NTRK1 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | ntrk1 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | ntrk1 30 31 |
|
OneToOne | |
Worm (Caenorhabditis elegans) |
Secernentea | trk-1 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 01 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
637365 | Likely Benign: Charcot-Marie-Tooth disease | 156,868,250(+) | G/A | SPLICE_DONOR_VARIANT | |
637366 | Uncertain Significance: Charcot-Marie-Tooth disease | 156,876,133(+) | G/C | MISSENSE_VARIANT | |
637367 | Uncertain Significance: Charcot-Marie-Tooth disease | 156,881,559(+) | C/T | NONSENSE | |
637368 | Likely Pathogenic: Hereditary insensitivity to pain with anhidrosis; Charcot-Marie-Tooth disease | 156,864,792(+) | AGTCGCCTGT/A | SPLICE_DONOR_VARIANT | |
637369 | Uncertain Significance: Charcot-Marie-Tooth disease | 156,868,171(+) | G/T | NONSENSE |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv108e212 | CNV | loss | 25503493 |
dgv37e201 | CNV | deletion | 23290073 |
esv1001917 | CNV | deletion | 20482838 |
esv1010343 | CNV | deletion | 20482838 |
esv1637866 | CNV | deletion | 17803354 |
esv2718451 | CNV | deletion | 23290073 |
esv2718462 | CNV | deletion | 23290073 |
esv3578202 | CNV | loss | 25503493 |
nsv1006558 | CNV | gain | 25217958 |
nsv1133913 | CNV | deletion | 24896259 |
nsv1145375 | CNV | deletion | 24896259 |
nsv831648 | CNV | loss | 17160897 |
nsv831659 | CNV | loss | 17160897 |
nsv998265 | CNV | gain | 25217958 |
Disorder | Aliases | PubMed IDs |
---|---|---|
insensitivity to pain, congenital, with anhidrosis |
|
|
thyroid carcinoma, familial medullary |
|
|
differentiated thyroid carcinoma |
|
|
charcot-marie-tooth disease/hereditary motor and sensory neuropathy |
|
|
charcot-marie-tooth disease |
|
|