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Kinase Fusion Gene:ZBTB7B_NTRK1 |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: ZBTB7B_NTRK1 | KinaseFusionDB ID: KFG7229 | FusionGDB2.0 ID: KFG7229 | Hgene | Tgene | Gene symbol | ZBTB7B | NTRK1 | Gene ID | 51043 | 4914 | |
Gene name | zinc finger and BTB domain containing 7B | neurotrophic receptor tyrosine kinase 1 | ||||||||||
Synonyms | CKROX|THPOK|ZBTB15|ZFP-67|ZFP67|ZNF857B|c-KROX|hcKROX|vGAF | MTC|TRK|TRK1|TRKA|Trk-A|p140-TrkA | ||||||||||
Cytomap | 1q21.3 | 1q23.1 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | zinc finger and BTB domain-containing protein 7BT-helper-inducing POZ/Krueppel-like factorkrueppel-related zinc finger protein cKroxzinc finger and BTB domain containing 15zinc finger protein 67 homologzinc finger protein 857Bzinc finger protein Th- | high affinity nerve growth factor receptorOncogene TRKTRK1-transforming tyrosine kinase proteingp140trkneurotrophic tyrosine kinase, receptor, type 1tropomyosin receptor kinase Atropomyosin-related kinase Atyrosine kinase receptor A | ||||||||||
Modification date | 20240403 | 20240411 | ||||||||||
UniProtAcc | O15156 | P04629 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000487542, ENST00000368426, ENST00000417934, ENST00000535420, ENST00000292176, | ENST00000358660, ENST00000368196, ENST00000392302, ENST00000524377, ENST00000531606, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: ZBTB7B [Title/Abstract] AND NTRK1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | ZBTB7B(154975419)-NTRK1(156807518), # 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 | NTRK1 | GO:0006468 | protein phosphorylation | 15488758 |
Tgene | NTRK1 | GO:0008285 | negative regulation of cell population proliferation | 15488758 |
Tgene | NTRK1 | GO:0010976 | positive regulation of neuron projection development | 15488758 |
Tgene | NTRK1 | GO:0018108 | peptidyl-tyrosine phosphorylation | 2927393 |
Tgene | NTRK1 | GO:0043547 | positive regulation of GTPase activity | 15488758 |
Tgene | NTRK1 | GO:0046579 | positive regulation of Ras protein signal transduction | 15488758 |
Tgene | NTRK1 | GO:0046777 | protein autophosphorylation | 15488758 |
Tgene | NTRK1 | GO:0048011 | neurotrophin TRK receptor signaling pathway | 15488758 |
Tgene | NTRK1 | GO:0051092 | positive regulation of NF-kappaB transcription factor activity | 15488758 |
Tgene | NTRK1 | GO:0070374 | positive regulation of ERK1 and ERK2 cascade | 15488758 |
Tgene | NTRK1 | GO:1904646 | cellular response to amyloid-beta | 11927634 |
Kinase Fusion gene breakpoints across ZBTB7B (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 NTRK1 (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 |
ChimerDB4 | TCGA-GU-A764-01A | ZBTB7B | chr1 | 154975419 | NTRK1 | chr1 | 156807518 |
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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/:154975419/:156807518) - 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 |
ZBTB7B | NTRK1 |
FUNCTION: Transcription regulator that acts as a key regulator of lineage commitment of immature T-cell precursors. Exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner. Necessary and sufficient for commitment of CD4 lineage, while its absence causes CD8 commitment. Development of immature T-cell precursors (thymocytes) to either the CD4 helper or CD8 killer T-cell lineages correlates precisely with their T-cell receptor specificity for major histocompatibility complex class II or class I molecules, respectively. Cross-antagonism between ZBTB7B and CBF complexes are determinative to CD4 versus CD8 cell fate decision. Suppresses RUNX3 expression and imposes CD4+ lineage fate by inducing the SOCS suppressors of cytokine signaling. induces, as a transcriptional activator, SOCS genes expression which represses RUNX3 expression and promotes the CD4+ lineage fate. During CD4 lineage commitment, associates with multiple sites at the CD8 locus, acting as a negative regulator of the CD8 promoter and enhancers by epigenetic silencing through the recruitment of class II histone deacetylases, such as HDAC4 and HDAC5, to these loci. Regulates the development of IL17-producing CD1d-restricted naural killer (NK) T cells. Also functions as an important metabolic regulator in the lactating mammary glands. Critical feed-forward regulator of insulin signaling in mammary gland lactation, directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling (By similarity). Transcriptional repressor of the collagen COL1A1 and COL1A2 genes. May also function as a repressor of fibronectin and possibly other extracellular matrix genes (PubMed:9370309). Potent driver of brown fat development, thermogenesis and cold-induced beige fat formation. Recruits the brown fat lncRNA 1 (Blnc1):HNRNPU ribonucleoprotein complex to activate thermogenic gene expression in brown and beige adipocytes (By similarity). {ECO:0000250|UniProtKB:Q64321, ECO:0000269|PubMed:9370309}. | FUNCTION: Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand (PubMed:1850821, PubMed:1849459, PubMed:1281417, PubMed:8325889, PubMed:15488758, PubMed:22649032, PubMed:17196528, PubMed:27445338). Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity). Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:1281417). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors. {ECO:0000250|UniProtKB:P35739, ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:1849459, ECO:0000269|PubMed:1850821, ECO:0000269|PubMed:22649032, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:8155326, ECO:0000269|PubMed:8325889}.; FUNCTION: [Isoform TrkA-III]: Resistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed. {ECO:0000269|PubMed:15488758}. |
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 ZBTB7B_NTRK1 |
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 |
NTRK1 | P04629 | human | SH2B1 | Q9NRF2 | Y753 | PRAINNQySFV____ | |
NTRK1 | P04629 | human | CTNNB1 | P35222 | Y142 | AVVNLINyQDDAELA | |
NTRK1 | P04629 | human | NTRK1 | P04629-2 | Y490 | HIIENPQyFSDACVH | |
NTRK1 | P04629 | human | NTRK1 | P04629-2 | Y674 | RDIySTDyyRVGGRT | PK_Tyr_Ser-Thr |
NTRK1 | P04629 | human | NTRK1 | P04629 | Y680 | RDIySTDyyRVGGRT | PK_Tyr_Ser-Thr |
NTRK1 | P04629 | human | SHC3 | Q92529-2 | Y218 | GDGSDHPyyNSIPSK | |
NTRK1 | P04629 | human | SHC3 | Q92529-2 | Y256 | FAGKEQTyyQGRHLG | |
NTRK1 | P04629 | human | NTRK1 | P04629-2 | Y670 | FGMSRDIySTDyyRV | PK_Tyr_Ser-Thr |
NTRK1 | P04629 | human | NTRK1 | P04629 | Y496 | HIIENPQyFSDACVH | |
NTRK1 | P04629 | human | STAT3 | P40763 | Y705 | DPGsAAPyLktKFIC | |
NTRK1 | P04629 | human | SHC1 | P29353-2 | Y317 | ELFDDPSyVNVQNLD | |
NTRK1 | P04629 | human | PLCG1 | P19174 | Y771 | IGtAEPdyGALyEGR | |
NTRK1 | P04629 | human | PLCG1 | P19174 | Y783 | EGRNPGFyVEANPMP | |
NTRK1 | P04629 | human | NTRK1 | P04629-2 | Y675 | DIySTDyyRVGGRTM | PK_Tyr_Ser-Thr |
NTRK1 | P04629 | human | NTRK1 | P04629-2 | Y751 | RACPPEVyAIMRGCW | PK_Tyr_Ser-Thr |
NTRK1 | P04629 | human | NTRK1 | P04629 | Y681 | DIySTDyyRVGGRTM | PK_Tyr_Ser-Thr |
NTRK1 | P04629 | human | NTRK1 | P04629-2 | Y785 | LAQAPPVyLDVLG__ | |
NTRK1 | P04629 | human | SHC3 | Q92529-2 | Y301 | PTGEAPTyVNTQQIP | |
NTRK1 | P04629 | human | SHC3 | Q92529-2 | Y257 | AGKEQTyyQGRHLGD | |
NTRK1 | P04629 | human | SHC3 | Q92529-2 | Y283 | RQGSSDIySTPEGKL | |
NTRK1 | P04629 | human | SHC3 | Q92529-2 | Y219 | DGSDHPyyNSIPSKM |
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 |
NTRK1 | ID | Description | 0.00e+00 |
NTRK1 | GO:0007173 | epidermal growth factor receptor signaling pathway | 3.89e-03 |
NTRK1 | GO:0038127 | ERBB signaling pathway | 3.89e-03 |
NTRK1 | GO:0048485 | sympathetic nervous system development | 7.40e-03 |
NTRK1 | GO:1905564 | positive regulation of vascular endothelial cell proliferation | 8.42e-03 |
NTRK1 | GO:0050679 | positive regulation of epithelial cell proliferation | 8.42e-03 |
NTRK1 | GO:0051091 | positive regulation of DNA-binding transcription factor activity | 9.81e-03 |
NTRK1 | GO:0048483 | autonomic nervous system development | 1.32e-02 |
NTRK1 | GO:0101023 | vascular endothelial cell proliferation | 1.32e-02 |
NTRK1 | GO:1905562 | regulation of vascular endothelial cell proliferation | 1.32e-02 |
NTRK1 | GO:0050982 | detection of mechanical stimulus | 1.32e-02 |
NTRK1 | GO:0045765 | regulation of angiogenesis | 1.43e-02 |
NTRK1 | GO:1901342 | regulation of vasculature development | 1.43e-02 |
NTRK1 | GO:0021545 | cranial nerve development | 1.43e-02 |
NTRK1 | GO:0051090 | regulation of DNA-binding transcription factor activity | 1.78e-02 |
NTRK1 | GO:0050678 | regulation of epithelial cell proliferation | 1.78e-02 |
NTRK1 | GO:0030098 | lymphocyte differentiation | 1.95e-02 |
NTRK1 | GO:0043410 | positive regulation of MAPK cascade | 2.21e-02 |
NTRK1 | GO:0050673 | epithelial cell proliferation | 2.21e-02 |
NTRK1 | GO:1903131 | mononuclear cell differentiation | 2.21e-02 |
NTRK1 | GO:0021675 | nerve development | 2.21e-02 |
NTRK1 | GO:0001938 | positive regulation of endothelial cell proliferation | 2.65e-02 |
NTRK1 | GO:0032355 | response to estradiol | 2.65e-02 |
NTRK1 | GO:0051963 | regulation of synapse assembly | 2.65e-02 |
NTRK1 | GO:2000278 | regulation of DNA biosynthetic process | 2.67e-02 |
NTRK1 | GO:0048593 | camera-type eye morphogenesis | 3.31e-02 |
NTRK1 | GO:0009581 | detection of external stimulus | 3.42e-02 |
NTRK1 | GO:0009582 | detection of abiotic stimulus | 3.44e-02 |
NTRK1 | GO:0051092 | positive regulation of NF-kappaB transcription factor activity | 3.62e-02 |
NTRK1 | GO:0048592 | eye morphogenesis | 3.62e-02 |
NTRK1 | GO:0043524 | negative regulation of neuron apoptotic process | 3.62e-02 |
NTRK1 | GO:0046661 | male sex differentiation | 3.62e-02 |
NTRK1 | GO:0001764 | neuron migration | 3.62e-02 |
NTRK1 | GO:0001936 | regulation of endothelial cell proliferation | 3.62e-02 |
NTRK1 | GO:0019827 | stem cell population maintenance | 3.62e-02 |
NTRK1 | GO:0045766 | positive regulation of angiogenesis | 3.62e-02 |
NTRK1 | GO:1904018 | positive regulation of vasculature development | 3.62e-02 |
NTRK1 | GO:0098727 | maintenance of cell number | 3.62e-02 |
NTRK1 | GO:0071897 | DNA biosynthetic process | 3.62e-02 |
NTRK1 | GO:0007416 | synapse assembly | 3.62e-02 |
NTRK1 | GO:0001935 | endothelial cell proliferation | 3.62e-02 |
NTRK1 | GO:0050728 | negative regulation of inflammatory response | 3.62e-02 |
NTRK1 | GO:0009612 | response to mechanical stimulus | 3.62e-02 |
NTRK1 | GO:0045637 | regulation of myeloid cell differentiation | 3.62e-02 |
NTRK1 | GO:1901888 | regulation of cell junction assembly | 3.62e-02 |
NTRK1 | GO:0070374 | positive regulation of ERK1 and ERK2 cascade | 3.62e-02 |
NTRK1 | GO:0043523 | regulation of neuron apoptotic process | 3.62e-02 |
NTRK1 | GO:0050807 | regulation of synapse organization | 3.62e-02 |
NTRK1 | GO:0048863 | stem cell differentiation | 3.62e-02 |
NTRK1 | GO:0050803 | regulation of synapse structure or activity | 3.62e-02 |
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Related Drugs to ZBTB7B_NTRK1 |
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 ZBTB7B-NTRK1 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 ZBTB7B_NTRK1 |
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 |
Tgene | NTRK1 | C0020074 | HSAN Type IV | 17 | CTD_human;GENOMICS_ENGLAND;UNIPROT |
Tgene | NTRK1 | C0238463 | Papillary thyroid carcinoma | 3 | ORPHANET |
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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 |