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Kinase Fusion Gene:VRK3_TGFB1 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: VRK3_TGFB1 | KinaseFusionDB ID: KFG7098 | FusionGDB2.0 ID: KFG7098 | Hgene | Tgene | Gene symbol | VRK3 | TGFB1 | Gene ID | 51231 | 7040 | |
| Gene name | VRK serine/threonine kinase 3 | transforming growth factor beta 1 | ||||||||||
| Synonyms | - | CED|DPD1|IBDIMDE|LAP|TGF-beta1|TGFB|TGFbeta | ||||||||||
| Cytomap | 19q13.33 | 19q13.2 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | inactive serine/threonine-protein kinase VRK3serine/threonine-protein kinase VRK3serine/threonine-protein pseudokinase VRK3vaccinia related kinase 3 | transforming growth factor beta-1 proproteinTGF-beta-1latency-associated peptideprepro-transforming growth factor beta-1transforming growth factor beta1 | ||||||||||
| Modification date | 20240411 | 20240416 | ||||||||||
| UniProtAcc | Q8IV63 | P01137 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000424804, ENST00000316763, ENST00000377011, ENST00000593919, ENST00000594948, ENST00000601341, ENST00000601912, ENST00000443401, ENST00000594092, ENST00000599538, | ENST00000221930, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: VRK3 [Title/Abstract] AND TGFB1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | VRK3(50504047)-TGFB1(41838186), # samples:2 | |||||||||||
| 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 | TGFB1 | GO:0001837 | epithelial to mesenchymal transition | 28373289 |
| Tgene | TGFB1 | GO:0001837 | epithelial to mesenchymal transition | 29529050 |
| Tgene | TGFB1 | GO:0001837 | epithelial to mesenchymal transition | 25893292 |
| Tgene | TGFB1 | GO:0001933 | negative regulation of protein phosphorylation | 8053900 |
| Tgene | TGFB1 | GO:0002062 | chondrocyte differentiation | 15040835 |
| Tgene | TGFB1 | GO:0002244 | hematopoietic progenitor cell differentiation | 15451575 |
| Tgene | TGFB1 | GO:0002859 | negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target | 24586048 |
| Tgene | TGFB1 | GO:0006611 | protein export from nucleus | 17438144 |
| Tgene | TGFB1 | GO:0006754 | ATP biosynthetic process | 10513816 |
| Tgene | TGFB1 | GO:0006796 | phosphate-containing compound metabolic process | 10513816 |
| Tgene | TGFB1 | GO:0007179 | transforming growth factor beta receptor signaling pathway | 9389648|11157754|18453574|18625725|19736306|26572508|27693460|28373289|28467929|31023188|32644293 |
| Tgene | TGFB1 | GO:0008284 | positive regulation of cell population proliferation | 10513816|14633705 |
| Tgene | TGFB1 | GO:0008285 | negative regulation of cell population proliferation | 14555988|15334054 |
| Tgene | TGFB1 | GO:0010628 | positive regulation of gene expression | 18625725|18832382|18941241|19913496|25322725|26634652|26687115|27162619|28467929|29167509|31694982 |
| Tgene | TGFB1 | GO:0010629 | negative regulation of gene expression | 29529050 |
| Tgene | TGFB1 | GO:0010629 | negative regulation of gene expression | 19913496|20067797|22269326|25163461|26634652|28467929|29167509 |
| Tgene | TGFB1 | GO:0010718 | positive regulation of epithelial to mesenchymal transition | 17999987|18505915|26572508 |
| Tgene | TGFB1 | GO:0010763 | positive regulation of fibroblast migration | 18555217 |
| Tgene | TGFB1 | GO:0010936 | negative regulation of macrophage cytokine production | 20875417 |
| Tgene | TGFB1 | GO:0017015 | regulation of transforming growth factor beta receptor signaling pathway | 15334054 |
| Tgene | TGFB1 | GO:0022408 | negative regulation of cell-cell adhesion | 18593713 |
| Tgene | TGFB1 | GO:0030214 | hyaluronan catabolic process | 17324121 |
| Tgene | TGFB1 | GO:0030308 | negative regulation of cell growth | 15334054 |
| Tgene | TGFB1 | GO:0030335 | positive regulation of cell migration | 19736306 |
| Tgene | TGFB1 | GO:0031293 | membrane protein intracellular domain proteolysis | 25310401 |
| Tgene | TGFB1 | GO:0031334 | positive regulation of protein-containing complex assembly | 19366691 |
| Tgene | TGFB1 | GO:0032355 | response to estradiol | 18039789 |
| Tgene | TGFB1 | GO:0032570 | response to progesterone | 18039789 |
| Tgene | TGFB1 | GO:0032740 | positive regulation of interleukin-17 production | 18453574 |
| Tgene | TGFB1 | GO:0032801 | receptor catabolic process | 17878231 |
| Tgene | TGFB1 | GO:0032930 | positive regulation of superoxide anion generation | 22073128 |
| Tgene | TGFB1 | GO:0032967 | positive regulation of collagen biosynthetic process | 19734317|22269326|25310401 |
| Tgene | TGFB1 | GO:0035307 | positive regulation of protein dephosphorylation | 14555988 |
| Tgene | TGFB1 | GO:0042307 | positive regulation of protein import into nucleus | 19366691 |
| Tgene | TGFB1 | GO:0043117 | positive regulation of vascular permeability | 21168935 |
| Tgene | TGFB1 | GO:0043410 | positive regulation of MAPK cascade | 26572508 |
| Tgene | TGFB1 | GO:0043536 | positive regulation of blood vessel endothelial cell migration | 18555217 |
| Tgene | TGFB1 | GO:0043537 | negative regulation of blood vessel endothelial cell migration | 18555217 |
| Tgene | TGFB1 | GO:0045066 | regulatory T cell differentiation | 32644293 |
| Tgene | TGFB1 | GO:0045216 | cell-cell junction organization | 18505915 |
| Tgene | TGFB1 | GO:0045599 | negative regulation of fat cell differentiation | 15040835 |
| Tgene | TGFB1 | GO:0045662 | negative regulation of myoblast differentiation | 9770491 |
| Tgene | TGFB1 | GO:0045742 | positive regulation of epidermal growth factor receptor signaling pathway | 18625725 |
| Tgene | TGFB1 | GO:0045786 | negative regulation of cell cycle | 11502704 |
| Tgene | TGFB1 | GO:0045892 | negative regulation of DNA-templated transcription | 15702480|18832382 |
| Tgene | TGFB1 | GO:0045893 | positive regulation of DNA-templated transcription | 9389648|14517293|15334054 |
| Tgene | TGFB1 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 18832382|22073128 |
| Tgene | TGFB1 | GO:0048298 | positive regulation of isotype switching to IgA isotypes | 14988498 |
| Tgene | TGFB1 | GO:0048642 | negative regulation of skeletal muscle tissue development | 9770491 |
| Tgene | TGFB1 | GO:0048661 | positive regulation of smooth muscle cell proliferation | 28467929|31023188 |
| Tgene | TGFB1 | GO:0050680 | negative regulation of epithelial cell proliferation | 9950587 |
| Tgene | TGFB1 | GO:0050714 | positive regulation of protein secretion | 18505915 |
| Tgene | TGFB1 | GO:0050731 | positive regulation of peptidyl-tyrosine phosphorylation | 21168935 |
| Tgene | TGFB1 | GO:0050921 | positive regulation of chemotaxis | 18555217 |
| Tgene | TGFB1 | GO:0051247 | positive regulation of protein metabolic process | 15219857 |
| Tgene | TGFB1 | GO:0051897 | positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 18625725 |
| Tgene | TGFB1 | GO:0060391 | positive regulation of SMAD protein signal transduction | 9389648|17438144|17999987|18453574|19366691|19736306|25196641|25893292|26634652|27693460|28467929|29167509|31023188 |
| Tgene | TGFB1 | GO:0070168 | negative regulation of biomineral tissue development | 26634652 |
| Tgene | TGFB1 | GO:0070374 | positive regulation of ERK1 and ERK2 cascade | 25310401 |
| Tgene | TGFB1 | GO:0070723 | response to cholesterol | 17878231 |
| Tgene | TGFB1 | GO:0071560 | cellular response to transforming growth factor beta stimulus | 19736306|22269326 |
| Tgene | TGFB1 | GO:0085029 | extracellular matrix assembly | 19734317 |
| Tgene | TGFB1 | GO:0090263 | positive regulation of canonical Wnt signaling pathway | 12893825|15040835 |
| Tgene | TGFB1 | GO:0097191 | extrinsic apoptotic signaling pathway | 15334054|26572508 |
| Tgene | TGFB1 | GO:1900126 | negative regulation of hyaluronan biosynthetic process | 17324121 |
| Tgene | TGFB1 | GO:1900182 | positive regulation of protein localization to nucleus | 26634652 |
| Tgene | TGFB1 | GO:1902895 | positive regulation of miRNA transcription | 26311719|26493107 |
| Tgene | TGFB1 | GO:1903077 | negative regulation of protein localization to plasma membrane | 21168935|24586048 |
| Tgene | TGFB1 | GO:1904018 | positive regulation of vasculature development | 27693460 |
| Tgene | TGFB1 | GO:1904894 | positive regulation of receptor signaling pathway via STAT | 28467929 |
| Tgene | TGFB1 | GO:2000636 | positive regulation of primary miRNA processing | 18548003 |
| Tgene | TGFB1 | GO:2000727 | positive regulation of cardiac muscle cell differentiation | 25163461 |
| Kinase Fusion gene breakpoints across VRK3 (5'-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 breakpoints across TGFB1 (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-IR-A3LH-01A | VRK3 | chr19 | 50504046 | TGFB1 | chr19 | 41838185 |
| ChimerDB4 | TCGA-IR-A3LH-01A | VRK3 | chr19 | 50504047 | TGFB1 | chr19 | 41838186 |
| ChimerDB4 | TCGA-IR-A3LH | VRK3 | chr19 | 50504046 | TGFB1 | chr19 | 41838186 |
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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/chr19:50504047/chr19:41838186) - 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 |
| VRK3 | TGFB1 |
| FUNCTION: Inactive kinase that suppresses ERK activity by promoting phosphatase activity of DUSP3 which specifically dephosphorylates and inactivates ERK in the nucleus. {ECO:0000250, ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:19141289}. | FUNCTION: Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively. {ECO:0000269|PubMed:29109152, ECO:0000303|PubMed:27252363}.; FUNCTION: [Latency-associated peptide]: Required to maintain the Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state during storage in extracellular matrix (PubMed:28117447). Associates non-covalently with TGF-beta-1 and regulates its activation via interaction with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control activation of TGF-beta-1 (PubMed:2022183, PubMed:8617200, PubMed:8939931, PubMed:19750484, PubMed:22278742, PubMed:19651619). Interaction with LRRC33/NRROS regulates activation of TGF-beta-1 in macrophages and microglia (Probable). Interaction with LRRC32/GARP controls activation of TGF-beta-1 on the surface of activated regulatory T-cells (Tregs) (PubMed:19750484, PubMed:22278742, PubMed:19651619). Interaction with integrins (ITGAV:ITGB6 or ITGAV:ITGB8) results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447). {ECO:0000269|PubMed:19651619, ECO:0000269|PubMed:19750484, ECO:0000269|PubMed:2022183, ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:8617200, ECO:0000269|PubMed:8939931, ECO:0000305|PubMed:29909984}.; FUNCTION: [Transforming growth factor beta-1]: Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains remain non-covalently linked rendering TGF-beta-1 inactive during storage in extracellular matrix (PubMed:29109152). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 and maintain it in a latent state during storage in extracellular milieus (PubMed:2022183, PubMed:8617200, PubMed:8939931, PubMed:19750484, PubMed:22278742, PubMed:19651619). TGF-beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-binding to LAP stabilizes an alternative conformation of the LAP bowtie tail and results in distortion of the LAP chain and subsequent release of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447). Once activated following release of LAP, TGF-beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (PubMed:20207738). While expressed by many cells types, TGF-beta-1 only has a very localized range of action within cell environment thanks to fine regulation of its activation by Latency-associated peptide chain (LAP) and 'milieu molecules' (By similarity). Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts (By similarity). Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner (By similarity). At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development (By similarity). At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells (By similarity). Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP) (PubMed:25310401). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus (PubMed:25893292, PubMed:29483653, PubMed:30696809). Positively regulates odontoblastic differentiation in dental papilla cells, via promotion of IPO7-mediated translocation of phosphorylated SMAD2 to the nucleus and subsequent transcription of target genes (By similarity). Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (PubMed:25893292, PubMed:30696809). {ECO:0000250|UniProtKB:P04202, ECO:0000269|PubMed:19651619, ECO:0000269|PubMed:19750484, ECO:0000269|PubMed:20207738, ECO:0000269|PubMed:2022183, ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:25310401, ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:29109152, ECO:0000269|PubMed:29483653, ECO:0000269|PubMed:30696809, ECO:0000269|PubMed:8617200, ECO:0000269|PubMed:8939931}. |
| 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 VRK3_TGFB1 |
| 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 |
| VRK3 | Q8IV63 | human | BANF1 | O75531 | S4 | ____MttsQkHRDFV | BAF |
| 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 |
| VRK3 | ID | Description | 0.00e+00 |
| VRK3 | GO:0007084 | mitotic nuclear membrane reassembly | 7.81e-03 |
| VRK3 | GO:0101024 | mitotic nuclear membrane organization | 7.81e-03 |
| VRK3 | GO:0015074 | DNA integration | 7.81e-03 |
| VRK3 | GO:0031468 | nuclear membrane reassembly | 1.15e-02 |
| VRK3 | GO:0071763 | nuclear membrane organization | 1.15e-02 |
| VRK3 | GO:0032480 | negative regulation of type I interferon production | 1.15e-02 |
| VRK3 | GO:0006998 | nuclear envelope organization | 1.15e-02 |
| VRK3 | GO:0045071 | negative regulation of viral genome replication | 1.15e-02 |
| VRK3 | GO:0071709 | membrane assembly | 1.15e-02 |
| VRK3 | GO:0044091 | membrane biogenesis | 1.15e-02 |
| VRK3 | GO:0045069 | regulation of viral genome replication | 1.29e-02 |
| VRK3 | GO:0045824 | negative regulation of innate immune response | 1.29e-02 |
| VRK3 | GO:0048525 | negative regulation of viral process | 1.29e-02 |
| VRK3 | GO:0032479 | regulation of type I interferon production | 1.42e-02 |
| VRK3 | GO:0032606 | type I interferon production | 1.42e-02 |
| VRK3 | GO:0019079 | viral genome replication | 1.42e-02 |
| VRK3 | GO:1903900 | regulation of viral life cycle | 1.42e-02 |
| VRK3 | GO:0006997 | nucleus organization | 1.42e-02 |
| VRK3 | GO:0002832 | negative regulation of response to biotic stimulus | 1.42e-02 |
| VRK3 | GO:0050792 | regulation of viral process | 1.51e-02 |
| VRK3 | GO:0050777 | negative regulation of immune response | 1.76e-02 |
| VRK3 | GO:0051348 | negative regulation of transferase activity | 1.84e-02 |
| VRK3 | GO:0140014 | mitotic nuclear division | 2.15e-02 |
| VRK3 | GO:0019058 | viral life cycle | 2.31e-02 |
| VRK3 | GO:0031348 | negative regulation of defense response | 2.31e-02 |
| VRK3 | GO:0001818 | negative regulation of cytokine production | 2.56e-02 |
| VRK3 | GO:0006979 | response to oxidative stress | 2.56e-02 |
| VRK3 | GO:0045088 | regulation of innate immune response | 2.56e-02 |
| VRK3 | GO:0016032 | viral process | 2.56e-02 |
| VRK3 | GO:0009615 | response to virus | 2.56e-02 |
| VRK3 | GO:0000280 | nuclear division | 2.56e-02 |
| VRK3 | GO:0043086 | negative regulation of catalytic activity | 2.59e-02 |
| VRK3 | GO:0032102 | negative regulation of response to external stimulus | 2.59e-02 |
| VRK3 | GO:0048285 | organelle fission | 2.59e-02 |
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Related Drugs to VRK3_TGFB1 |
| 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 VRK3-TGFB1 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 VRK3_TGFB1 |
| 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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