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Kinase Fusion Gene:BMP2_TRIB3 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: BMP2_TRIB3 | KinaseFusionDB ID: KFG638 | FusionGDB2.0 ID: KFG638 | Hgene | Tgene | Gene symbol | BMP2 | TRIB3 | Gene ID | 650 | 57761 | |
| Gene name | bone morphogenetic protein 2 | tribbles pseudokinase 3 | ||||||||||
| Synonyms | BDA2|BMP2A|SSFSC|SSFSC1 | C20orf97|NIPK|SINK|SKIP3|TRB3 | ||||||||||
| Cytomap | 20p12.3 | 20p13 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | bone morphogenetic protein 2bone morphogenetic protein 2A | tribbles homolog 3TRB-3neuronal cell death inducible putative kinasep65-interacting inhibitor of NF-kappa-Bp65-interacting inhibitor of NF-kappaB | ||||||||||
| Modification date | 20240413 | 20240407 | ||||||||||
| UniProtAcc | Q9NSY1 | Q96RU7 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000378827, | ENST00000217233, ENST00000422053, ENST00000485293, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: BMP2 [Title/Abstract] AND TRIB3 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | BMP2(6749522)-TRIB3(368655), # 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 |
| Hgene | BMP2 | GO:0000122 | negative regulation of transcription by RNA polymerase II | 19736317 |
| Hgene | BMP2 | GO:0000122 | negative regulation of transcription by RNA polymerase II | 9187146 |
| Hgene | BMP2 | GO:0001649 | osteoblast differentiation | 15150273|22705305 |
| Hgene | BMP2 | GO:0001649 | osteoblast differentiation | 15254224|18436533|20576608|23399447 |
| Hgene | BMP2 | GO:0001837 | epithelial to mesenchymal transition | 15110716 |
| Hgene | BMP2 | GO:0001837 | epithelial to mesenchymal transition | 18184661 |
| Hgene | BMP2 | GO:0001934 | positive regulation of protein phosphorylation | 17472960 |
| Hgene | BMP2 | GO:0001934 | positive regulation of protein phosphorylation | 8653785 |
| Hgene | BMP2 | GO:0002062 | chondrocyte differentiation | 16194878 |
| Hgene | BMP2 | GO:0003129 | heart induction | 19736317 |
| Hgene | BMP2 | GO:0003133 | endodermal-mesodermal cell signaling | 19736317 |
| Hgene | BMP2 | GO:0006355 | regulation of DNA-templated transcription | 15671031 |
| Hgene | BMP2 | GO:0007507 | heart development | 18545679 |
| Hgene | BMP2 | GO:0008285 | negative regulation of cell population proliferation | 9187146 |
| Hgene | BMP2 | GO:0008285 | negative regulation of cell population proliferation | 19584291 |
| Hgene | BMP2 | GO:0010628 | positive regulation of gene expression | 18382765 |
| Hgene | BMP2 | GO:0010628 | positive regulation of gene expression | 16243309|22579779|28124060|28467929 |
| Hgene | BMP2 | GO:0010629 | negative regulation of gene expression | 23399447 |
| Hgene | BMP2 | GO:0010629 | negative regulation of gene expression | 28124060 |
| Hgene | BMP2 | GO:0010718 | positive regulation of epithelial to mesenchymal transition | 20890042 |
| Hgene | BMP2 | GO:0010894 | negative regulation of steroid biosynthetic process | 19584291 |
| Hgene | BMP2 | GO:0010922 | positive regulation of phosphatase activity | 9213002 |
| Hgene | BMP2 | GO:0021537 | telencephalon development | 9187146 |
| Hgene | BMP2 | GO:0030501 | positive regulation of bone mineralization | 18436533|20576608 |
| Hgene | BMP2 | GO:0030509 | BMP signaling pathway | 16049014|16771708|18184661|18382765|18436533|19736317|20427544|20843790 |
| Hgene | BMP2 | GO:0032092 | positive regulation of protein binding | 16604073 |
| Hgene | BMP2 | GO:0032348 | negative regulation of aldosterone biosynthetic process | 19584291 |
| Hgene | BMP2 | GO:0035051 | cardiocyte differentiation | 15110716 |
| Hgene | BMP2 | GO:0043065 | positive regulation of apoptotic process | 9187146 |
| Hgene | BMP2 | GO:0043407 | negative regulation of MAP kinase activity | 18382765 |
| Hgene | BMP2 | GO:0043410 | positive regulation of MAPK cascade | 22540193 |
| Hgene | BMP2 | GO:0043569 | negative regulation of insulin-like growth factor receptor signaling pathway | 19584291 |
| Hgene | BMP2 | GO:0045599 | negative regulation of fat cell differentiation | 23399447 |
| Hgene | BMP2 | GO:0045778 | positive regulation of ossification | 9213002 |
| Hgene | BMP2 | GO:0045786 | negative regulation of cell cycle | 11502704 |
| Hgene | BMP2 | GO:0045892 | negative regulation of DNA-templated transcription | 15254224 |
| Hgene | BMP2 | GO:0045893 | positive regulation of DNA-templated transcription | 16049014|16243309 |
| Hgene | BMP2 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 9187146 |
| Hgene | BMP2 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 16433617|16604073|19736317|20843790|20890042 |
| Hgene | BMP2 | GO:0048662 | negative regulation of smooth muscle cell proliferation | 18382765 |
| Hgene | BMP2 | GO:0048762 | mesenchymal cell differentiation | 9693150 |
| Hgene | BMP2 | GO:0051042 | negative regulation of calcium-independent cell-cell adhesion | 16194878 |
| Hgene | BMP2 | GO:0051091 | positive regulation of DNA-binding transcription factor activity | 18382765 |
| Hgene | BMP2 | GO:0060317 | cardiac epithelial to mesenchymal transition | 18184661 |
| Hgene | BMP2 | GO:0060391 | positive regulation of SMAD protein signal transduction | 18382765 |
| Hgene | BMP2 | GO:0060391 | positive regulation of SMAD protein signal transduction | 16049014|18184661|20427544 |
| Hgene | BMP2 | GO:0061036 | positive regulation of cartilage development | 3201241 |
| Hgene | BMP2 | GO:0070374 | positive regulation of ERK1 and ERK2 cascade | 22540193 |
| Hgene | BMP2 | GO:0090090 | negative regulation of canonical Wnt signaling pathway | 18545679 |
| Hgene | BMP2 | GO:1900159 | positive regulation of bone mineralization involved in bone maturation | 16433617 |
| Hgene | BMP2 | GO:1900745 | positive regulation of p38MAPK cascade | 22540193 |
| Hgene | BMP2 | GO:2000065 | negative regulation of cortisol biosynthetic process | 19584291 |
| Hgene | BMP2 | GO:2000726 | negative regulation of cardiac muscle cell differentiation | 18545679 |
| Tgene | TRIB3 | GO:0000122 | negative regulation of transcription by RNA polymerase II | 15775988 |
| Tgene | TRIB3 | GO:0006469 | negative regulation of protein kinase activity | 12791994 |
| Tgene | TRIB3 | GO:0034976 | response to endoplasmic reticulum stress | 15775988 |
| Tgene | TRIB3 | GO:0043405 | regulation of MAP kinase activity | 15299019 |
| Tgene | TRIB3 | GO:0070059 | intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | 15775988 |
| Kinase Fusion gene breakpoints across BMP2 (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 TRIB3 (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-DU-8163-01A | BMP2 | chr20 | 6749522 | TRIB3 | chr20 | 368655 |
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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/:6749522/:368655) - 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. |
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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| BMP2 | TRIB3 |
| FUNCTION: May be involved in osteoblast differentiation. {ECO:0000250|UniProtKB:Q91Z96}. | FUNCTION: Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:15781252, PubMed:15775988). Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress (PubMed:15781252, PubMed:15775988). May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells (PubMed:15781252, PubMed:15775988). Acts as a negative feedback regulator of the ATF4-dependent transcription during the ISR: while TRIB3 expression is promoted by ATF4, TRIB3 protein interacts with ATF4 and inhibits ATF4 transcription activity (By similarity). Disrupts insulin signaling by binding directly to Akt kinases and blocking their activation (By similarity). May bind directly to and mask the 'Thr-308' phosphorylation site in AKT1 (By similarity). Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity (PubMed:12736262). Interacts with MAPK kinases and regulates activation of MAP kinases (PubMed:15299019). Can inhibit APOBEC3A editing of nuclear DNA (PubMed:22977230). {ECO:0000250|UniProtKB:Q8K4K2, ECO:0000269|PubMed:12736262, ECO:0000269|PubMed:15299019, ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:15781252, ECO:0000269|PubMed:22977230}. |
| 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 BMP2_TRIB3 |
| 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 |
| 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 |
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Related Drugs to BMP2_TRIB3 |
| 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 BMP2-TRIB3 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 BMP2_TRIB3 |
| 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 |
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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 |
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