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    Topic review

    NTRK1 Gene

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    Submitted by: Lily Guo
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    neurotrophic receptor tyrosine kinase 1

    1. Introduction

    The NTRK1 gene provides instructions for making a protein that is essential for the development and survival of nerve cells (neurons), especially those that transmit information about sensations such as pain, temperature, and touch (sensory neurons). 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 phosphorus atoms (a phosphate group) at specific positions. This process is called phosphorylation. The NTRK1 protein is turned on (activated) when another protein called nerve growth factor beta (NGFβ) attaches (binds) to it and signals the NTRK1 protein to phosphorylate itself (autophosphorylation). Then, the activated NTRK1 protein phosphorylates other proteins; this process is needed to transmit signals for cell growth and survival.

    2. Health Conditions Related to Genetic Changes

    2.1. Congenital insensitivity to pain with anhidrosis

    Mutations in the NTRK1 gene cause congenital insensitivity to pain with anhidrosis (CIPA), a condition characterized by the inability to feel pain and decreased or absent sweating (anhidrosis). Many mutations in the NTRK1 gene are known to cause the condition. Many of the NTRK1 gene mutations lead to a protein that cannot be activated by phosphorylation, which means the mutated NTRK1 protein cannot transmit cell growth and survival signals to neurons. Without the proper signaling, neurons die by a process of self-destruction called apoptosis. Loss of sensory neurons leads to the inability to feel pain in people with CIPA. In addition, people with CIPA lose the nerves leading to their sweat glands, which causes the anhidrosis seen in affected individuals.

    2.2. Cancers

    Mutations in the NTRK1 gene are frequently found in people with a common type of thyroid cancer called papillary thyroid carcinoma. These mutations are acquired during a person's lifetime and are present only in certain cells. Such mutations are called somatic mutations. The mutations involved in papillary thyroid carcinoma occur when rearrangements of genetic material combine part of the NTRK1 gene with another gene. At least three other genes are known to be involved in these rearrangements: the TPM3 gene, the TPR gene, and the TFG gene. All of these genetic rearrangements create mutated proteins called TRK oncoproteins. Unlike normal NTRK1 protein, TRK oncoproteins do not have to be activated by binding to the NGFβ protein; they are always turned on. Constant activation of the protein signals for the cells to grow and divide continuously, which can lead to papillary thyroid carcinoma.

    3. Other Names for This Gene

    • high affinity nerve growth factor receptor
    • MTC
    • neurotrophic tyrosine kinase, receptor, type 1
    • NTRK1_HUMAN
    • p140-TrkA
    • TRK
    • Trk-A
    • TRK1
    • TRK1-transforming tyrosine kinase protein
    • TRKA
    • tyrosine kinase receptor A

    This entry is adapted from https://medlineplus.gov/genetics/gene/ntrk1

    References

    1. Greco A, Miranda C, Pierotti MA. Rearrangements of NTRK1 gene in papillarythyroid carcinoma. Mol Cell Endocrinol. 2010 May 28;321(1):44-9. doi:10.1016/j.mce.2009.10.009.
    2. Indo Y, Tsuruta M, Hayashida Y, Karim MA, Ohta K, Kawano T, Mitsubuchi H,Tonoki H, Awaya Y, Matsuda I. Mutations in the TRKA/NGF receptor gene in patientswith congenital insensitivity to pain with anhidrosis. Nat Genet. 1996Aug;13(4):485-8.
    3. Indo Y. Molecular basis of congenital insensitivity to pain with anhidrosis(CIPA): mutations and polymorphisms in TRKA (NTRK1) gene encoding the receptortyrosine kinase for nerve growth factor. Hum Mutat. 2001 Dec;18(6):462-71.Review.
    4. Kaplan DR, Miller FD. Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol. 2000 Jun;10(3):381-91. Review.
    5. Miranda C, Di Virgilio M, Selleri S, Zanotti G, Pagliardini S, Pierotti MA,Greco A. Novel pathogenic mechanisms of congenital insensitivity to pain withanhidrosis genetic disorder unveiled by functional analysis of neurotrophictyrosine receptor kinase type 1/nerve growth factor receptor mutations. J BiolChem. 2002 Feb 22;277(8):6455-62.
    6. Pierotti MA, Greco A. Oncogenic rearrangements of the NTRK1/NGF receptor.Cancer Lett. 2006 Jan 28;232(1):90-8.
    7. Verpoorten N, De Jonghe P, Timmerman V. Disease mechanisms in hereditarysensory and autonomic neuropathies. Neurobiol Dis. 2006 Feb;21(2):247-55.
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