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Kinase Fusion Gene:NTRK2_CHMP4B |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: NTRK2_CHMP4B | KinaseFusionDB ID: KFG4286 | FusionGDB2.0 ID: KFG4286 | Hgene | Tgene | Gene symbol | NTRK2 | CHMP4B | Gene ID | 4915 | 128866 | |
Gene name | neurotrophic receptor tyrosine kinase 2 | charged multivesicular body protein 4B | ||||||||||
Synonyms | DEE58|EIEE58|GP145-TrkB|OBHD|TRKB|trk-B | C20orf178|CHMP4A|CTPP3|CTRCT31|SNF7|SNF7-2|Shax1|VPS32B|Vps32-2|dJ553F4.4 | ||||||||||
Cytomap | 9q21.33 | 20q11.22 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | BDNF/NT-3 growth factors receptorBDNF-tropomyosine receptor kinase Bneurotrophic tyrosine kinase receptor type 2tropomyosin-related kinase Btyrosine kinase receptor B | charged multivesicular body protein 4bSNF7 homolog associated with Alix 1Snf7 homologue associated with Alix 1chromatin modifying protein 4Bchromatin-modifying protein 4bvacuolar protein-sorting-associated protein 32-2 | ||||||||||
Modification date | 20240411 | 20240407 | ||||||||||
UniProtAcc | Q16620 | Q9H444 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000277120, ENST00000304053, ENST00000323115, ENST00000359847, ENST00000376208, ENST00000376213, ENST00000376214, ENST00000395866, ENST00000395882, | ENST00000217402, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: NTRK2 [Title/Abstract] AND CHMP4B [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | NTRK2(87332969)-CHMP4B(32441302), # samples:1 |
Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
Partner | Gene | GO ID | GO term | PubMed ID |
Tgene | CHMP4B | GO:0001778 | plasma membrane repair | 24482116 |
Tgene | CHMP4B | GO:0039702 | viral budding via host ESCRT complex | 24878737 |
Tgene | CHMP4B | GO:0043162 | ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | 17984323 |
Tgene | CHMP4B | GO:0046761 | viral budding from plasma membrane | 24878737 |
Tgene | CHMP4B | GO:0051258 | protein polymerization | 18209100 |
Tgene | CHMP4B | GO:0071985 | multivesicular body sorting pathway | 16554368 |
Kinase Fusion gene breakpoints across NTRK2 (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
Kinase Fusion gene breakpoints across CHMP4B (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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Kinase Fusion Gene Sample Information |
Kinase Fusion gene information. |
Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE) * All genome coordinats were lifted-over on hg19. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
Source | Sample | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp |
ChiTaRS5.0 | EC575605 | NTRK2 | chr9 | 87332969 | CHMP4B | chr20 | 32441302 |
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Kinase Fusion ORF Analysis |
Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB. |
Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Seq length (transcript) | Seq length (amino acids) |
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Kinase Fusion Amino Acid Sequences |
For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
>Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq |
Multiple Sequence Alignment of All Fusion Protein Isoforms |
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Kinase Fusion Protein Functional Features |
Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:87332969/:32441302) - FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels. - How to search 1. Put your fusion gene symbol. 2. Press the tab key until there will be shown the breakpoint information filled. 4. Go down and press 'Search' tab twice. 4. Go down to have the hyperlink of the search result. 5. Click the hyperlink. 6. See the FGviewer result for your fusion gene. |
Main function of each fusion partner protein. (from UniProt) |
Hgene | Tgene |
NTRK2 | CHMP4B |
FUNCTION: Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity (By similarity). Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2 (PubMed:7574684, PubMed:15494731). Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:15494731). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia. {ECO:0000250|UniProtKB:P15209, ECO:0000269|PubMed:15494731, ECO:0000269|PubMed:7574684}. | FUNCTION: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released (PubMed:12860994, PubMed:18209100). The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:21310966). Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Plays a role in the endosomal sorting pathway. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4B filaments can promote or stabilize negative curvature and outward budding. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). {ECO:0000269|PubMed:12860994, ECO:0000269|PubMed:18209100, ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:26040712}.; FUNCTION: (Microbial infection) The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the budding of enveloped viruses (HIV-1 and other lentiviruses). Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release. {ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:22422861}. |
Retention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
- Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt). |
Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
- Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt). |
Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
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Kinase-Substrate Information of NTRK2_CHMP4B |
Phosphorylation target of the kinase (phosphosite, 03-17-2024) |
Kinase | Kinase UniProt Acc | Kinase species | Substrate | Substrate UniProt Acc | Substrate phosphorylated residues | Substrate phosphorylated sites (+/-7AA) | Domain |
NTRK2 | Q16620 | human | NTRK2 | Q16620 | Y516 | PVIENPQyFGITNSQ | |
NTRK2 | Q16620 | human | SHC3 | Q92529-2 | Y218 | GDGSDHPyyNSIPSK | |
NTRK2 | Q16620 | human | SHC3 | Q92529-2 | Y256 | FAGKEQTyyQGRHLG | |
NTRK2 | Q16620 | human | KCNA3 | P22001 | Y499 | EGEEQSQyMHVGsCQ | |
NTRK2 | Q16620 | human | KCNA3 | P22001 | Y161 | PSFDAILyyyQSGGR | BTB_2 |
NTRK2 | Q16620 | human | KCNA3 | P22001 | Y162 | SFDAILyyyQSGGRI | BTB_2 |
NTRK2 | Q16620 | human | SHC3 | Q92529-2 | Y301 | PTGEAPTyVNTQQIP | |
NTRK2 | Q16620 | human | SHC3 | Q92529-2 | Y257 | AGKEQTyyQGRHLGD | |
NTRK2 | Q16620 | human | SHC3 | Q92529-2 | Y283 | RQGSSDIySTPEGKL | |
NTRK2 | Q16620 | human | SHC3 | Q92529-2 | Y219 | DGSDHPyyNSIPSKM | |
NTRK2 | Q16620 | human | KCNA3 | P22001 | Y163 | FDAILyyyQSGGRIR | BTB_2 |
Biological Network Integration of This Kinase and Substrates (GeneMANIA website) |
Enriched GO biological processes of the phosphorylation target genes of the kinase |
Kinase | GOID | GO term | P.adjust |
NTRK2 | ID | Description | 0.00e+00 |
NTRK2 | GO:0021537 | telencephalon development | 3.61e-02 |
NTRK2 | GO:0030900 | forebrain development | 3.61e-02 |
NTRK2 | GO:0099550 | trans-synaptic signalin | 1.59e-03 |
NTRK2 | GO:0048935 | peripheral nervous system neuron development | 3.61e-02 |
NTRK2 | GO:0060221 | retinal rod cell differentiation | 3.61e-02 |
NTRK2 | GO:2000811 | negative regulation of anoikis | 3.61e-02 |
NTRK2 | GO:0021554 | optic nerve development | 3.61e-02 |
NTRK2 | GO:2000209 | regulation of anoikis | 3.61e-02 |
NTRK2 | GO:0022038 | corpus callosum development | 3.61e-02 |
NTRK2 | GO:0014047 | glutamate secretion | 3.61e-02 |
NTRK2 | GO:0022011 | myelination in peripheral nervous system | 3.61e-02 |
NTRK2 | GO:0032292 | peripheral nervous system axon ensheathment | 3.61e-02 |
NTRK2 | GO:1902430 | negative regulation of amyloid-beta formation | 3.61e-02 |
NTRK2 | GO:0060219 | camera-type eye photoreceptor cell differentiation | 3.61e-02 |
NTRK2 | GO:0014044 | Schwann cell development | 3.61e-02 |
NTRK2 | GO:1902992 | negative regulation of amyloid precursor protein catabolic process | 3.61e-02 |
NTRK2 | GO:0042462 | eye photoreceptor cell development | 3.61e-02 |
NTRK2 | GO:0043276 | anoikis | 3.61e-02 |
NTRK2 | GO:0014037 | Schwann cell differentiation | 3.74e-02 |
NTRK2 | GO:0038179 | neurotrophin signaling pathway | 3.74e-02 |
NTRK2 | GO:1990090 | cellular response to nerve growth factor stimulus | 3.75e-02 |
NTRK2 | GO:0001754 | eye photoreceptor cell differentiation | 3.75e-02 |
NTRK2 | GO:1902003 | regulation of amyloid-beta formation | 3.75e-02 |
NTRK2 | GO:1990089 | response to nerve growth factor | 3.75e-02 |
NTRK2 | GO:0042461 | photoreceptor cell development | 3.75e-02 |
NTRK2 | GO:1902991 | regulation of amyloid precursor protein catabolic process | 3.75e-02 |
NTRK2 | GO:0034205 | amyloid-beta formation | 3.75e-02 |
NTRK2 | GO:0021545 | cranial nerve development | 3.75e-02 |
NTRK2 | GO:0051965 | positive regulation of synapse assembly | 3.75e-02 |
NTRK2 | GO:0046530 | photoreceptor cell differentiation | 3.75e-02 |
NTRK2 | GO:0050435 | amyloid-beta metabolic process | 3.75e-02 |
NTRK2 | GO:0060042 | retina morphogenesis in camera-type eye | 3.75e-02 |
NTRK2 | GO:0015800 | acidic amino acid transport | 3.75e-02 |
NTRK2 | GO:0042490 | mechanoreceptor differentiation | 3.75e-02 |
NTRK2 | GO:0042987 | amyloid precursor protein catabolic process | 3.75e-02 |
NTRK2 | GO:0019226 | transmission of nerve impulse | 3.75e-02 |
NTRK2 | GO:0050772 | positive regulation of axonogenesis | 4.05e-02 |
NTRK2 | GO:0003407 | neural retina development | 4.05e-02 |
NTRK2 | GO:0007422 | peripheral nervous system development | 4.05e-02 |
NTRK2 | GO:0001570 | vasculogenesis | 4.05e-02 |
NTRK2 | GO:0071230 | cellular response to amino acid stimulus | 4.05e-02 |
NTRK2 | GO:0021954 | central nervous system neuron development | 4.05e-02 |
NTRK2 | GO:0071229 | cellular response to acid chemical | 4.05e-02 |
NTRK2 | GO:0042982 | amyloid precursor protein metabolic process | 4.05e-02 |
NTRK2 | GO:0021675 | nerve development | 4.05e-02 |
NTRK2 | GO:0006835 | dicarboxylic acid transport | 4.05e-02 |
NTRK2 | GO:0033138 | positive regulation of peptidyl-serine phosphorylation | 4.05e-02 |
NTRK2 | GO:0007631 | feeding behavior | 4.05e-02 |
NTRK2 | GO:0048709 | oligodendrocyte differentiation | 4.05e-02 |
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Related Drugs to NTRK2_CHMP4B |
Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Drug | Source | PMID |
Distribution of the number of studies mentioning NTRK2-CHMP4B and kinase inhibitors the PubMed Abstract (04-01-2024) |
Fusion gene - drug pair 1 | Fusion gene - drug pair 2 | PMID | Publication date | DOI | Study title |
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Related Diseases to NTRK2_CHMP4B |
Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
Hgene | Tgene | Disease | Source | PMID |
Related diseases from the literature mentioned this fusion gene and drug. (PubMed, 04-01-2024) |
MeSH ID | MeSH term |
Diseases associated with fusion partners. (DisGeNet 4.0) |
Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
Hgene | NTRK2 | C0011570 | Mental Depression | 5 | PSYGENET |
Hgene | NTRK2 | C0011581 | Depressive disorder | 5 | PSYGENET |
Hgene | NTRK2 | C0041696 | Unipolar Depression | 5 | PSYGENET |
Hgene | NTRK2 | C0525045 | Mood Disorders | 5 | PSYGENET |
Hgene | NTRK2 | C1269683 | Major Depressive Disorder | 5 | PSYGENET |
Hgene | NTRK2 | C3151303 | Obesity, Hyperphagia, and Developmental Delay | 4 | CTD_human;GENOMICS_ENGLAND;UNIPROT |
Hgene | NTRK2 | C0005586 | Bipolar Disorder | 3 | CTD_human;PSYGENET |
Hgene | NTRK2 | C4693367 | EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 58 | 3 | GENOMICS_ENGLAND;UNIPROT |
Hgene | NTRK2 | C0009171 | Cocaine Abuse | 2 | CTD_human |
Hgene | NTRK2 | C0036341 | Schizophrenia | 2 | PSYGENET |
Hgene | NTRK2 | C0038220 | Status Epilepticus | 2 | CTD_human |
Hgene | NTRK2 | C0236736 | Cocaine-Related Disorders | 2 | CTD_human |
Hgene | NTRK2 | C0270823 | Petit mal status | 2 | CTD_human |
Hgene | NTRK2 | C0311335 | Grand Mal Status Epilepticus | 2 | CTD_human |
Hgene | NTRK2 | C0393734 | Complex Partial Status Epilepticus | 2 | CTD_human |
Hgene | NTRK2 | C0600427 | Cocaine Dependence | 2 | CTD_human |
Hgene | NTRK2 | C0751217 | Hyperkinesia, Generalized | 2 | CTD_human |
Hgene | NTRK2 | C0751522 | Status Epilepticus, Subclinical | 2 | CTD_human |
Hgene | NTRK2 | C0751523 | Non-Convulsive Status Epilepticus | 2 | CTD_human |
Hgene | NTRK2 | C0751524 | Simple Partial Status Epilepticus | 2 | CTD_human |
Hgene | NTRK2 | C3887506 | Hyperkinesia | 2 | CTD_human |
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Clinical Trials of the Found Drugs/Small Molecules |
Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024) |
Clinical Trials from clinicaltrials.gov (06-17-2024) |
Fusion Gene | Kinase Inhibitor | NCT ID | Study Status | Phases | Disease | # Enrolment | Date |