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]
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 — mechanism propensity
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
1805 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 90 | 11 | 7 | 1 | 109 |
Likely Pathogenic | 62 | 27 | 12 | 1 | 102 |
VUS | 13 | 587 | 20 | 12 | 632 |
Likely Benign | 0 | 35 | 282 | 464 | 781 |
Benign | 0 | 3 | 51 | 10 | 64 |
Conflicting | — | 97 | |||
| Total | 165 | 663 | 372 | 488 | 1,785 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →16 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap NTRK1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
NTRK1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Study 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 RECRUITINGDETERMINE Trial Treatment Arm 06: Capmatinib in Adult Patients With Cancers Harbouring MET Dysregulations
RECRUITINGBasket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)
ACTIVE NOT RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
ACTIVE NOT RECRUITINGIntegrated Genomics in Oncogene-driven NSCLC With Acquired Resistance
ENROLLING BY INVITATIONTargeted 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 RECRUITINGSpanish Study for Molecular Characterization of Thyroid Carcinoma
ACTIVE NOT RECRUITINGRNASARC - Molecular Screening Program of Soft Tissue Sarcomas With Complex Genomic Profile to Detect NTRK1/2/3, ROS1 or ALK Gene Fusions.
ACTIVE NOT RECRUITINGA 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 RECRUITINGA Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children
ACTIVE NOT RECRUITINGNTRK 1,2,3 Rearrangements in Patients With Solid Tumors
ACTIVE NOT RECRUITINGEntrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors
RECRUITINGExternal Resources
Links to major genomics databases and tools