NTRK2
Chr 9ADneurotrophic receptor tyrosine kinase 2
Also known as: DEE58, EIEE58, GP145-TrkB, OBHD, TRKB, trk-B
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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in 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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
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 RECRUITINGIntensive Weight Loss Intervention Versus Usual Care for Adults With Obesity
ACTIVE NOT RECRUITINGEffect of Exercise Gene Expression and Histone Modifications in Patients With Hemiplegia
RECRUITINGA Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children
ACTIVE NOT RECRUITINGA Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements
RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
ACTIVE NOT RECRUITINGTargeted 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 RECRUITINGIntensive Weight Loss Intervention Versus Bariatric Surgery for Adults With Severe and Complex Obesity: the LightBAR Randomised Trial
RECRUITINGStudy 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 RECRUITINGRNASARC - Molecular Screening Program of Soft Tissue Sarcomas With Complex Genomic Profile to Detect NTRK1/2/3, ROS1 or ALK Gene Fusions.
ACTIVE NOT RECRUITINGIntensive Weight Loss Intervention Versus Usual Care for Adults With Severe and Complex Obesity
RECRUITINGIntegrated Genomics in Oncogene-driven NSCLC With Acquired Resistance
ENROLLING BY INVITATIONExternal Resources
Links to major genomics databases and tools