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Kinase Fusion Gene:IL34_TYRO3 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: IL34_TYRO3 | KinaseFusionDB ID: KFG2858 | FusionGDB2.0 ID: KFG2858 | Hgene | Tgene | Gene symbol | IL34 | TYRO3 | Gene ID | 146433 | 7301 | |
| Gene name | interleukin 34 | TYRO3 protein tyrosine kinase | ||||||||||
| Synonyms | C16orf77|IL-34 | BYK|Dtk|Etk-2|RSE|Rek|Sky|Tif | ||||||||||
| Cytomap | 16q22.1 | 15q15.1 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | interleukin-34 | tyrosine-protein kinase receptor TYRO3tyrosine-protein kinase DTKtyrosine-protein kinase RSEtyrosine-protein kinase SKYtyrosine-protein kinase TIFtyrosine-protein kinase byk | ||||||||||
| Modification date | 20240331 | 20240411 | ||||||||||
| UniProtAcc | Q6ZMJ4 | Q06418 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000288098, ENST00000429149, ENST00000566361, ENST00000569641, | ENST00000263798, ENST00000559066, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: IL34 [Title/Abstract] AND TYRO3 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | IL34(70652788)-TYRO3(41859366), # 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 | IL34 | GO:0001934 | positive regulation of protein phosphorylation | 18467591 |
| Hgene | IL34 | GO:0008284 | positive regulation of cell population proliferation | 18467591 |
| Hgene | IL34 | GO:0010759 | positive regulation of macrophage chemotaxis | 26754294 |
| Hgene | IL34 | GO:0043406 | positive regulation of MAP kinase activity | 26754294 |
| Hgene | IL34 | GO:0045651 | positive regulation of macrophage differentiation | 23409120 |
| Hgene | IL34 | GO:0045657 | positive regulation of monocyte differentiation | 23409120 |
| Hgene | IL34 | GO:0061098 | positive regulation of protein tyrosine kinase activity | 26754294 |
| Hgene | IL34 | GO:0061514 | interleukin-34-mediated signaling pathway | 26754294 |
| Hgene | IL34 | GO:0120041 | positive regulation of macrophage proliferation | 26754294 |
| Tgene | TYRO3 | GO:0046777 | protein autophosphorylation | 7511603|7537495 |
| Kinase Fusion gene breakpoints across IL34 (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 TYRO3 (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 | EU981398 | IL34 | chr16 | 70652788 | TYRO3 | chr15 | 41859366 |
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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/:70652788/:41859366) - 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 |
| IL34 | TYRO3 |
| FUNCTION: Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of pro-inflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1. {ECO:0000269|PubMed:18467591, ECO:0000269|PubMed:20489731, ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:20829061}. | FUNCTION: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. Activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes. TYRO3 signaling plays a role in various processes such as neuron protection from excitotoxic injury, platelet aggregation and cytoskeleton reorganization. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. {ECO:0000269|PubMed:20546121}.; FUNCTION: (Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269|PubMed:22156524, ECO:0000269|PubMed:22673088, ECO:0000269|PubMed:25277499}.; FUNCTION: (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269|PubMed:17005688}. |
| 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 IL34_TYRO3 |
| 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 |
| TYRO3 | Q06418 | human | MLKL | Q8NB16 | Y376 | DRVkstAyLSPQELE | PK_Tyr_Ser-Thr |
| TYRO3 | Q06418 | human | AKT1 | P31749 | T308 | kDGAtMKtFCGtPEy | Pkinase |
| 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 |
| TYRO3 | ID | Description | 0.00e+00 |
| TYRO3 | GO:0010918 | positive regulation of mitochondrial membrane potential | 2.48e-02 |
| TYRO3 | GO:0015911 | long-chain fatty acid import across plasma membrane | 2.48e-02 |
| TYRO3 | GO:0032070 | regulation of deoxyribonuclease activity | 2.48e-02 |
| TYRO3 | GO:0070673 | response to interleukin-18 | 2.48e-02 |
| TYRO3 | GO:0022605 | mammalian oogenesis stage | 2.48e-02 |
| TYRO3 | GO:0046322 | negative regulation of fatty acid oxidation | 2.48e-02 |
| TYRO3 | GO:0070141 | response to UV-A | 2.48e-02 |
| TYRO3 | GO:0140052 | cellular response to oxidised low-density lipoprotein particle stimulus | 2.48e-02 |
| TYRO3 | GO:0003376 | sphingosine-1-phosphate receptor signaling pathway | 2.48e-02 |
| TYRO3 | GO:0010763 | positive regulation of fibroblast migration | 2.48e-02 |
| TYRO3 | GO:0045725 | positive regulation of glycogen biosynthetic process | 2.48e-02 |
| TYRO3 | GO:0045737 | positive regulation of cyclin-dependent protein serine/threonine kinase activity | 2.48e-02 |
| TYRO3 | GO:0045838 | positive regulation of membrane potential | 2.48e-02 |
| TYRO3 | GO:0070207 | protein homotrimerization | 2.48e-02 |
| TYRO3 | GO:2000402 | negative regulation of lymphocyte migration | 2.48e-02 |
| TYRO3 | GO:0071380 | cellular response to prostaglandin E stimulus | 2.48e-02 |
| TYRO3 | GO:0007252 | I-kappaB phosphorylation | 2.48e-02 |
| TYRO3 | GO:0044539 | long-chain fatty acid import into cell | 2.48e-02 |
| TYRO3 | GO:0060644 | mammary gland epithelial cell differentiation | 2.48e-02 |
| TYRO3 | GO:0070206 | protein trimerization | 2.48e-02 |
| TYRO3 | GO:0070875 | positive regulation of glycogen metabolic process | 2.48e-02 |
| TYRO3 | GO:0043217 | myelin maintenance | 2.48e-02 |
| TYRO3 | GO:0051000 | positive regulation of nitric-oxide synthase activity | 2.48e-02 |
| TYRO3 | GO:0090520 | sphingolipid mediated signaling pathway | 2.48e-02 |
| TYRO3 | GO:1904031 | positive regulation of cyclin-dependent protein kinase activity | 2.48e-02 |
| TYRO3 | GO:0035821 | modulation of process of another organism | 2.48e-02 |
| TYRO3 | GO:0048266 | behavioral response to pain | 2.48e-02 |
| TYRO3 | GO:0060716 | labyrinthine layer blood vessel development | 2.48e-02 |
| TYRO3 | GO:0031998 | regulation of fatty acid beta-oxidation | 2.48e-02 |
| TYRO3 | GO:0090201 | negative regulation of release of cytochrome c from mitochondria | 2.48e-02 |
| TYRO3 | GO:0140354 | lipid import into cell | 2.48e-02 |
| TYRO3 | GO:1902001 | fatty acid transmembrane transport | 2.48e-02 |
| TYRO3 | GO:1902018 | negative regulation of cilium assembly | 2.48e-02 |
| TYRO3 | GO:0071379 | cellular response to prostaglandin stimulus | 2.48e-02 |
| TYRO3 | GO:2000010 | positive regulation of protein localization to cell surface | 2.48e-02 |
| TYRO3 | GO:0032069 | regulation of nuclease activity | 2.48e-02 |
| TYRO3 | GO:0003323 | type B pancreatic cell development | 2.48e-02 |
| TYRO3 | GO:0032891 | negative regulation of organic acid transport | 2.48e-02 |
| TYRO3 | GO:0034695 | response to prostaglandin E | 2.48e-02 |
| TYRO3 | GO:0071676 | negative regulation of mononuclear cell migration | 2.48e-02 |
| TYRO3 | GO:0050995 | negative regulation of lipid catabolic process | 2.48e-02 |
| TYRO3 | GO:0022011 | myelination in peripheral nervous system | 2.48e-02 |
| TYRO3 | GO:0032292 | peripheral nervous system axon ensheathment | 2.48e-02 |
| TYRO3 | GO:0032770 | positive regulation of monooxygenase activity | 2.48e-02 |
| TYRO3 | GO:0003309 | type B pancreatic cell differentiation | 2.48e-02 |
| TYRO3 | GO:0005979 | regulation of glycogen biosynthetic process | 2.48e-02 |
| TYRO3 | GO:0010962 | regulation of glucan biosynthetic process | 2.48e-02 |
| TYRO3 | GO:0014044 | Schwann cell development | 2.48e-02 |
| TYRO3 | GO:0050999 | regulation of nitric-oxide synthase activity | 2.48e-02 |
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Related Drugs to IL34_TYRO3 |
| 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 IL34-TYRO3 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 IL34_TYRO3 |
| 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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