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…
LOFmechanismLOEUF 0.66
Clinical SummaryNTRK1
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Gene-Disease Validity (ClinGen)
hereditary sensory and autonomic neuropathy type 4 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
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
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveNTRK1-related congenital insensitivity to pain with anhidrosisLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.78top 25%
GOF
0.85top 5%
LOF
0.2581th %ile

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

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

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)
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
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
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
Soft Tissue SarcomaAdvanced CancerMetastatic Cancer

RNASARC - Molecular Screening Program of Soft Tissue Sarcomas With Complex Genomic Profile to Detect NTRK1/2/3, ROS1 or ALK Gene Fusions.

ACTIVE NOT RECRUITING
NCT03375437Phase NACentre Leon BerardStarted 2018-02-15
Blood and tumor samples
Locally Advanced Solid TumorsMetastatic Solid Tumors

A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements

RECRUITING
NCT03093116Phase PHASE1, PHASE2Turning Point Therapeutics, Inc.Started 2017-03-07
Oral repotrectinib (TPX-0005)
NTRK1/2/3 Fusion Gene Detection

NTRK 1,2,3 Rearrangements in Patients With Solid Tumors

ACTIVE NOT RECRUITING
NCT06780384Federico CappuzzoStarted 2020-02-05
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
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
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
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
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