NTRK1
Chr 1ARneurotrophic receptor tyrosine kinase 1
Also known as: MTC, TRK, TRK1, TRKA, Trk-A, p140-TrkA
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]
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
NTRK1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
Gene2Phenotype Curations
NTRK1-related congenital insensitivity to pain with anhidrosis
definitiveGene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Study to Compare Uliledlimab Combined With Toripalimab, Toripalimab Monotherapy, and Pembrolizumab Monotherapy in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1- and CD73- Selected Non-Small Cell Lung Cancer
ACTIVE NOT RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
ACTIVE NOT RECRUITINGNTRK 1,2,3 Rearrangements in Patients With Solid Tumors
ACTIVE NOT RECRUITINGDevelopment of Patient Derived Xenografts (PDXs) and Analysis of Tyrosine Kinase Receptor Expression in Patients With Squamous Cell Head and Neck Cancer (HNSCC) to Study Resistance Mechanisms Induced by Standard Therapy
NOT YET RECRUITINGFudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy
RECRUITINGEntrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors
RECRUITINGStudy Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options
ACTIVE NOT RECRUITINGSpanish Study for Molecular Characterization of Thyroid Carcinoma
ACTIVE NOT RECRUITINGA Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children
ACTIVE NOT RECRUITINGIntegrated Genomics in Oncogene-driven NSCLC With Acquired Resistance
NOT YET RECRUITINGDETERMINE Trial Treatment Arm 06: Capmatinib in Adult Patients With Cancers Harbouring MET Dysregulations
RECRUITINGA Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements
RECRUITINGExternal Resources
Links to major genomics databases and tools