NTRK1

Chr 1

neurotrophic 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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCongenital insensitivity to pain with anhidrosis

Clinical highlights

Gene-disease validity (ClinGen)
hereditary sensory and autonomic neuropathy type 4 · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
220
Pubs (1 yr)
P/LP submissions
P/LP missense
0.66
LOEUF
LOF
Mechanism· G2P
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.66LOEUF
pLI 0.000
Z-score 3.19
OE 0.43 (0.290.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.03Z-score
OE missense 0.87 (0.800.94)
419 obs / 482.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.43 (0.290.66)
00.351.4
Missense OE?0.87 (0.800.94)
00.61.4
Synonymous OE?1.00
01.21.6
LoF obs/exp: 16 / 37.0Missense obs/exp: 419 / 482.6Syn Z: 0.04

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NTRK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Breast NeoplasmBreast CancerBreast Tumors

Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy

RECRUITING
NCT05582499Phase PHASE2Fudan UniversityStarted 2022-11-01
DalpiciclibPyrotinibSHR-A1811
Haematological MalignancySolid Tumour

DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial) - Master Screening Protocol

RECRUITING
NCT05722886Phase PHASE2, PHASE3Cancer Research UKStarted 2023-03-01
AlectinibAtezolizumabEntrectinib
Breast CancerCholangiocarcinomaColorectal Cancer

Basket 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 RECRUITING
NCT02568267Phase PHASE2Hoffmann-La RocheStarted 2015-11-19
Entrectinib
Solid Tumors Harboring NTRK Fusion

A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children

ACTIVE NOT RECRUITING
NCT02637687Phase PHASE1, PHASE2BayerStarted 2015-12-16
Larotrectinib (Vitrakvi, BAY2757556)
Non Small Cell Lung Cancer

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 RECRUITING
NCT06984588Phase PHASE2, PHASE3TJ Biopharma Co., Ltd.Started 2024-03-28
UliledlimabToripalimabPembrolizumab
Solid TumorsCNS Tumors

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 RECRUITING
NCT02650401Phase PHASE1, PHASE2Hoffmann-La RocheStarted 2016-05-03
Entrectinib
Solid TumourHaematological MalignancyMalignant Neoplasm

DETERMINE Trial Treatment Arm 06: Capmatinib in Adult Patients With Cancers Harbouring MET Dysregulations

RECRUITING
NCT06988475Phase PHASE2, PHASE3Cancer Research UKStarted 2024-11-19
Capmatinib
Squamous Cell Tumors of the Head and Neck (HNSCC)

Development 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 RECRUITING
NCT07471009IRCCS Azienda Ospedaliero-Universitaria di BolognaStarted 2026-03-31
Advanced Malignant Solid NeoplasmAnn Arbor Stage III Non-Hodgkin LymphomaAnn Arbor Stage IV Non-Hodgkin Lymphoma

Targeted 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 RECRUITING
NCT03155620Phase PHASE2National Cancer Institute (NCI)Started 2017-07-31
Biopsy ProcedureBiospecimen CollectionBone Marrow Aspiration and Biopsy
Advanced LymphomaAdvanced Malignant Solid NeoplasmBladder Carcinoma

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ACTIVE NOT RECRUITING
NCT02465060Phase PHASE2National Cancer Institute (NCI)Started 2015-08-17
AdavosertibAfatinibAfatinib Dimaleate
Oncogene-addicted Non Small Cell Lung CancerEGFR MutationALK Fusion-positive Solid or CNS Tumors

Integrated Genomics in Oncogene-driven NSCLC With Acquired Resistance

ENROLLING BY INVITATION
NCT07122882Chang Gung Memorial HospitalStarted 2025-09-01
High Grade GliomaCNS Tumor

Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors

RECRUITING
NCT06528691Phase PHASE2St. Jude Children's Research HospitalStarted 2026-05-01
EntrectinibCyclophosphamideEtoposide