NTRK2

Chr 9

neurotrophic receptor tyrosine kinase 2

Also known as: DEE58, EIEE58, GP145-TrkB, OBHD, TRKB, trk-B

NCBI Gene: 4915 ENSG00000148053 UniProt: Q16620

The protein functions as a membrane-bound neurotrophic tyrosine receptor kinase that phosphorylates itself and MAPK pathway members upon neurotrophin binding, leading to cell differentiation. Mutations cause developmental and epileptic encephalopathy 58 or obesity with hyperphagia and developmental delay through an autosomal dominant inheritance pattern. The gene is extremely intolerant to loss-of-function variants, indicating haploinsufficiency as the likely pathogenic mechanism.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation. Mutations in this gene have been associated with obesity and mood disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDevelopmental and epileptic encephalopathy 58

UniProtObesity, hyperphagia, and developmental delay

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

142

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.11

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

📖

GeneReview available — NTRK2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.11LOEUF

pLI 1.000

Z-score 5.89

OE 0.02 (0.01–0.11)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

3.73Z-score

OE missense 0.52 (0.46–0.57)

244 obs / 472.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.02 (0.01–0.11)

0≤0.351.4

Missense OE?0.52 (0.46–0.57)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 1 / 42.4Missense obs/exp: 244 / 472.4Syn Z: -0.21

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NTRK2 · 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

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — NTRK2

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING

NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19

Usual Care GroupControlled exercise with telerehabilitation

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)

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

Post Traumatic Stress DisorderComplex Posttraumatic Stress DisorderStress

Building Resilience at Schools: Emotional and Biological Assessment and Treatment of Traumatic Stress

RECRUITING

NCT05701111Phase NAStanford UniversityStarted 2024-02-23

Start with the Heart StudentsStart with the Heart TeachersCue Centered Therapy Counselors

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

Obesity

Intensive Weight Loss Intervention Versus Usual Care for Adults With Obesity

ACTIVE NOT RECRUITING

NCT06321432Phase NACarsten DirksenStarted 2024-06-05

Intensive weight loss interventionUsual care

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

Obesity

Intensive Weight Loss Intervention Versus Usual Care for Adults With Severe and Complex Obesity

ACTIVE NOT RECRUITING

NCT06321458Phase NACarsten DirksenStarted 2024-04-29

Intensive weight loss interventionUsual care

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