NTRK3

neurotrophic receptor tyrosine kinase 3, the group of I-set domain containing|Receptor tyrosine kinases

Basic information

Region (hg38): 15:87859750-88256791

Links

ENSG00000140538 ∙ NCBI:4916 ∙ OMIM:191316 ∙ HGNC:8033 ∙ Uniprot:Q16288 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital heart disease (Disputed Evidence), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NTRK3 gene.

• not provided (55 variants)
• Inborn genetic diseases (14 variants)
• not specified (1 variants)
• Neonatal cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NTRK3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				9	6	15
missense			14	1		15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				1	37	38
Total	0	0	14	11	43

Variants in NTRK3

This is a list of pathogenic ClinVar variants found in the NTRK3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-87876716-A-AAT			Benign (Jun 20, 2021)
15-87876836-C-T			Benign (Jun 20, 2021)
15-87877075-C-T		not specified	Uncertain significance (Mar 14, 2023)
15-87880105-AT-A			Benign (Jun 20, 2021)
15-87880232-C-T			Benign (Jun 19, 2021)
15-87880307-T-C		not specified	Uncertain significance (Feb 01, 2023)
15-87880348-A-G			Likely benign (Jan 01, 2024)
15-87885471-C-A			Benign (Nov 12, 2018)
15-87885845-A-G			Benign (Nov 12, 2018)
15-87885910-A-G			Benign (Jun 19, 2021)
15-87928939-A-G			Benign (Nov 12, 2018)
15-87929230-G-A			Likely benign (Dec 13, 2017)
15-87929391-G-A		NTRK3-related disorder	Benign (Nov 12, 2019)
15-87929428-A-G		NTRK3-related disorder	Likely benign (Sep 17, 2019)
15-87932935-A-C			Benign (Jun 20, 2021)
15-87933033-C-G		Entrectinib resistance	other (-)
15-87933033-C-T		Entrectinib resistance;Cabozantinib resistance;Repotrectinib resistance;Selitrectinib resistance;Larotrectinib resistance	other (-)
15-87933066-G-T		not specified	Uncertain significance (Oct 05, 2021)
15-87933083-C-A			Likely benign (Dec 31, 2019)
15-87933134-G-A		NTRK3-related disorder	Benign (Oct 03, 2019)
15-87933136-C-T		not specified	Uncertain significance (Jul 14, 2023)
15-87933149-A-G			Likely benign (Jul 26, 2018)
15-87933455-C-T			Benign (Jun 21, 2021)
15-87940363-A-G			Benign (Nov 12, 2018)
15-87940635-A-G		NTRK3-related disorder	Benign/Likely benign (Apr 01, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NTRK3	protein_coding	protein_coding	ENST00000360948	18	381770

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00170	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.83	375	489	0.767	0.0000293	5547
Missense in Polyphen		94	181.59	0.51765		2111
Synonymous	-2.15	229	191	1.20	0.0000119	1622
Loss of Function	5.18	5	40.6	0.123	0.00000202	469

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation. {ECO:0000269|PubMed:25196463}.
• Disease: DISEASE: Note=Defects in NTRK3 are associated with susceptibility to congenital heart defects (CHD). A disease characterized by congenital developmental abnormalities involving structures of the heart. CHD are the most common major birth defects and the leading cause of death from congenital malformations. {ECO:0000269|PubMed:25196463}.
• Pathway: Neurotrophin signaling pathway - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Neuronal System;SHP2 signaling;Receptor-type tyrosine-protein phosphatases;Protein-protein interactions at synapses;Neurotrophic factor-mediated Trk receptor signaling (Consensus)

Recessive Scores

• pRec: 0.527

Intolerance Scores

• loftool: 0.0394
• rvis_EVS: -1.99
• rvis_percentile_EVS: 1.76

Haploinsufficiency Scores

• pHI: 0.316
• hipred: Y
• hipred_score: 0.696
• ghis: 0.610

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.963

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ntrk3
• Phenotype: growth/size/body region phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: activation of MAPK activity;neuron migration;negative regulation of protein phosphorylation;positive regulation of protein phosphorylation;transmembrane receptor protein tyrosine kinase signaling pathway;nervous system development;heart development;circadian rhythm;positive regulation of cell population proliferation;positive regulation of gene expression;positive regulation of phospholipase C activity;positive regulation of neuron projection development;positive regulation of phosphatidylinositol 3-kinase signaling;peptidyl-tyrosine phosphorylation;modulation by virus of host transcription;neuronal action potential propagation;myelination in peripheral nervous system;positive regulation of cell migration;activation of protein kinase B activity;positive regulation of peptidyl-serine phosphorylation;neurotrophin signaling pathway;mechanoreceptor differentiation;positive regulation of apoptotic process;regulation of MAPK cascade;positive regulation of MAPK cascade;response to ethanol;ephrin receptor signaling pathway;neuron fate specification;response to axon injury;positive regulation of axon extension involved in regeneration;negative regulation of astrocyte differentiation;positive regulation of positive chemotaxis;response to corticosterone;positive regulation of synapse assembly;lens fiber cell differentiation;positive regulation of ERK1 and ERK2 cascade;cellular response to retinoic acid;cochlea development;activation of GTPase activity;regulation of postsynaptic density assembly;regulation of presynapse assembly;cellular response to nerve growth factor stimulus;positive regulation of actin cytoskeleton reorganization
• Cellular component: plasma membrane;integral component of plasma membrane;axon;receptor complex;glutamatergic synapse;integral component of postsynaptic membrane
• Molecular function: p53 binding;transmembrane receptor protein tyrosine kinase activity;GPI-linked ephrin receptor activity;neurotrophin receptor activity;protein binding;ATP binding;neurotrophin binding