NTRK1

NTRK1 Background

The NTRK1 gene encodes a protein that is essential for the development and survival of neurons, especially those that transmit information about sensations such as pain, temperature, and sensory neurons ^[1]. The NTRK1 protein is found on the surface of cells, particularly sensory neurons. It acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and a phosphate group at specific positions, a process known as phosphorylation. The NTRK1 protein is activated when another protein called nerve growth factor beta (NGFβ) binds to it and signals the NTRK1 protein to phosphorylate itself (autophosphorylation). The activated NTRK1 protein and then phosphorylates other proteins, thus finishing the delivery of signals for cell growth and survival. Gene fusions involving NTRK1 have been shown to be oncogenic, leading to the constitutive TrkA activation ^[2]. Mutations in NTRK1 gene have been associated with congenital insensitivity to pain with anhidrosis, self-mutilating behaviors, intellectual disability and/or cognitive impairment and certain cancers.

[1] Martin-Zanca D, Hughes SH, et al. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences [J]. Nature. 1986, 319 (6056): 743–8.
[2] Vaishnavi, Aria; Capelletti, Marzia; et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer [J]. Nature Medicine. 2013, 19 (11): 1469–1472.