NTRK2

Chr 9AD

neurotrophic receptor tyrosine kinase 2

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

NCBI Gene: 4915ENSG00000148053UniProt: Q16620

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]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 58MIM #617830
AD
Obesity, hyperphagia, and developmental delayMIM #613886
AD
0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
12
Active trials
Clinical Summary— NTRK2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.02 (0.01–0.11)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.52 (0.46–0.57)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.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.

Gene2Phenotype Curations

NTRK2-related epilepsy and intellectual disability

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 58

MIM #617830

Molecular basis of disorder known

Autosomal dominant

Obesity, hyperphagia, and developmental delay

MIM #613886

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
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

RECRUITING
NCT06321458Phase NACarsten DirksenStarted 2024-04-29
Intensive weight loss interventionUsual care
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
Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING
NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19
Usual Care GroupControlled exercise with telerehabilitation
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
Obesity

Intensive Weight Loss Intervention Versus Bariatric Surgery for Adults With Severe and Complex Obesity: the LightBAR Randomised Trial

RECRUITING
NCT06309238Phase NACarsten DirksenStarted 2024-05-08
Intensive weight loss interventionBariatric surgery
Oncogene-addicted Non Small Cell Lung CancerEGFR MutationALK Fusion-positive Solid or CNS Tumors

Integrated Genomics in Oncogene-driven NSCLC With Acquired Resistance

NOT YET RECRUITING
NCT07122882Chang Gung Memorial HospitalStarted 2025-09-01
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)
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)
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
Ischemic Stroke, AcuteAcute Hemiparesis

Effect of Exercise Gene Expression and Histone Modifications in Patients With Hemiplegia

RECRUITING
NCT06726941Phase NAAfyonkarahisar Health Sciences UniversityStarted 2024-12-20
Physiotherapy and Rehabilitation Practices

External Resources

Links to major genomics databases and tools