Gene Function

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. 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. 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 Source: UniProt

Relationship to CMT

HSAN AR
1 subtype
1q23.1

First described 1996

Subtype	Inheritance	Class	OMIM	Sentinel Publication
SubtypeHSAN-4	Inheritanceautosomal recessive	ClassHSAN	OMIM256800	Sentinel Publication Mutations in the TRKA/NGF Receptor Gene in Patients with Congenital Insensitivity to Pain with Anhidrosis 1996 · 10.1038/ng0896-485

Stored Identifiers

No HGNC Aliases

hgnc_idHGNC:8031

ensembl_gene_idENSG00000198400

coords_grch38chr1:156815636-156881850

coords_grch37chr1:156785432-156851642

entrez_id4914

omim_gene191315

uniprot_idsP04629

refseq_accessionNM_002529

mane_refseqNM_002529.4

mane_ensemblENST00000524377.7

External recordsHGNC:8031OMIM 191315gnomADUniProt P04629ClinGenClinVar P/LPGeneReviewsOrphanetMANE NM_002529.4

EvidenceClinGen Definitive hereditary sensory and autonomic neuropathy type 4PanelApp Green

ClinVar Variants

Pathogenic and likely pathogenic variants in NTRK1, as classified in ClinVar, are read live from NCBI. Only aggregate germline records are shown. Uncertain and conflicting classifications are not. Experts in CMT makes no claim to the accuracy of ClinVar data. This index is provided for informational purposes only.

Review stars are ClinVar’s measure of how well a classification is supported: four for a practice guideline, three for an expert panel review, two for agreement among multiple submitters, one for a single submitter with criteria provided, and none where no criteria were provided.

Reported in CMT

Reported in Other Diseases

Reported in a disease other than CMT. Listed apart rather than counted as CMT variants.

Variants w/o a Recorded Disease

Pathogenic or likely pathogenic in ClinVar, submitted without a disease recorded.

The Dorsal Root

A Name That Does Too Much Work

Jean-Martin Charcot's name appears throughout medicine, but nowhere does it create more confusion than in the foot. Learn why the CMT foot and Charcot neuroarthropathy, also known as Charcot foot, share a name yet differ in how they develop, appear, and are managed.

When Medicine Lost Its Compass

Evidence failed not because it was wrong, but because it was weaponized. I lived the downstream effects of that failure for more than a decade. This is what happens when medicine forgets that data always ends in a human being.

Error 404: Gene Not Found

CMT genetic testing often fails to identify the cause of the disease, even when comprehensive panels are used. Here, we discuss why this happens, what genetic tests can and cannot do, and why a negative result still matters.