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Fusion Protein:FIP1L1-PDGFRA |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: FIP1L1-PDGFRA | FusionPDB ID: 30424 | FusionGDB2.0 ID: 30424 | Hgene | Tgene | Gene symbol | FIP1L1 | PDGFRA | Gene ID | 81608 | 5156 |
| Gene name | factor interacting with PAPOLA and CPSF1 | platelet derived growth factor receptor alpha | |
| Synonyms | FIP1|Rhe|hFip1 | CD140A|PDGFR-2|PDGFR2 | |
| Cytomap | 4q12 | 4q12 | |
| Type of gene | protein-coding | protein-coding | |
| Description | pre-mRNA 3'-end-processing factor FIP1FIP1 like 1FIP1-like 1 proteinFIP1L1 cleavage and polyadenylation specific factor subunitfactor interacting with PAPrearranged in hypereosinophilia | platelet-derived growth factor receptor alphaCD140 antigen-like family member ACD140a antigenPDGF-R-alphaalpha-type platelet-derived growth factor receptorplatelet-derived growth factor receptor 2platelet-derived growth factor receptor, alpha polype | |
| Modification date | 20200313 | 20200329 | |
| UniProtAcc | Q6UN15 Main function of 5'-partner protein: FUNCTION: Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. FIP1L1 contributes to poly(A) site recognition and stimulates poly(A) addition. Binds to U-rich RNA sequence elements surrounding the poly(A) site. May act to tether poly(A) polymerase to the CPSF complex. {ECO:0000269|PubMed:14749727}. | P16234 Main function of 5'-partner protein: FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. {ECO:0000269|PubMed:10734113, ECO:0000269|PubMed:10947961, ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:12522257, ECO:0000269|PubMed:1646396, ECO:0000269|PubMed:17087943, ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:17141222, ECO:0000269|PubMed:20972453, ECO:0000269|PubMed:21224473, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:2554309, ECO:0000269|PubMed:8188664, ECO:0000269|PubMed:8760137, ECO:0000269|PubMed:8943348}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000306932, ENST00000337488, ENST00000358575, ENST00000507166, ENST00000507922, ENST00000510668, | ENST00000508170, ENST00000257290, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 9 X 10 X 8=720 | 18 X 27 X 8=3888 |
| # samples | 13 | 17 | |
| ** MAII score | log2(13/720*10)=-2.46948528330122 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(17/3888*10)=-4.51542156746808 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: FIP1L1 [Title/Abstract] AND PDGFRA [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: FIP1L1 [Title/Abstract] AND PDGFRA [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | FIP1L1(54310214)-PDGFRA(55156649), # samples:1 FIP1L1(54319107)-PDGFRA(55156689), # samples:1 FIP1L1(54292132)-PDGFRA(55141089), # samples:1 FIP1L1(54292132)-PDGFRA(55141092), # samples:1 PDGFRA(55156721)-FIP1L1(54310215), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | FIP1L1-PDGFRA seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. FIP1L1-PDGFRA seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. FIP1L1-PDGFRA seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. FIP1L1-PDGFRA seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. FIP1L1-PDGFRA seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF. FIP1L1-PDGFRA seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. FIP1L1-PDGFRA seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. FIP1L1-PDGFRA seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. FIP1L1-PDGFRA seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted ORF. | ||
| * DoF score (Degree of Frequency) = # partners X # break points X # cancer types ** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10) |
| 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 | PDGFRA | GO:0008284 | positive regulation of cell proliferation | 10806482 |
| Tgene | PDGFRA | GO:0010544 | negative regulation of platelet activation | 8188664 |
| Tgene | PDGFRA | GO:0018108 | peptidyl-tyrosine phosphorylation | 1646396|2536956|8188664 |
| Tgene | PDGFRA | GO:0030335 | positive regulation of cell migration | 17470632 |
| Tgene | PDGFRA | GO:0034614 | cellular response to reactive oxygen species | 24190966 |
| Tgene | PDGFRA | GO:0038091 | positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway | 17470632 |
| Tgene | PDGFRA | GO:0046777 | protein autophosphorylation | 1646396|2536956|8188664 |
| Tgene | PDGFRA | GO:0048008 | platelet-derived growth factor receptor signaling pathway | 2536956|10806482 |
| Tgene | PDGFRA | GO:0048146 | positive regulation of fibroblast proliferation | 10806482 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr4:54310214/chr4:55156649) - 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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| Retention analysis results 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, are available here. |
| Fusion gene breakpoints across FIP1L1 (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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| Fusion gene breakpoints across PDGFRA (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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Fusion Amino Acid Sequences |
| Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
| ENST00000507166 | FIP1L1 | chr4 | 54292132 | ENST00000257290 | PDGFRA | chr4 | 55141089 | 5527 | 1017 | 1019 | 2551 | 510 | ||
| ENST00000358575 | FIP1L1 | chr4 | 54292132 | ENST00000257290 | PDGFRA | chr4 | 55141089 | 5676 | 1166 | 1168 | 2700 | 510 | ||
| ENST00000337488 | FIP1L1 | chr4 | 54292132 | ENST00000257290 | PDGFRA | chr4 | 55141089 | 5721 | 1211 | 1213 | 2745 | 510 | ||
| ENST00000507922 | FIP1L1 | chr4 | 54292132 | ENST00000257290 | PDGFRA | chr4 | 55141089 | 5650 | 1140 | 1142 | 2674 | 510 | ||
| ENST00000306932 | FIP1L1 | chr4 | 54292132 | ENST00000257290 | PDGFRA | chr4 | 55141089 | 5448 | 938 | 940 | 2472 | 510 | ||
| ENST00000507166 | FIP1L1 | chr4 | 54292132 | + | ENST00000257290 | PDGFRA | chr4 | 55141092 | + | 5524 | 1017 | 1073 | 2548 | 491 |
| ENST00000358575 | FIP1L1 | chr4 | 54292132 | + | ENST00000257290 | PDGFRA | chr4 | 55141092 | + | 5673 | 1166 | 1222 | 2697 | 491 |
| ENST00000337488 | FIP1L1 | chr4 | 54292132 | + | ENST00000257290 | PDGFRA | chr4 | 55141092 | + | 5718 | 1211 | 1267 | 2742 | 491 |
| ENST00000507922 | FIP1L1 | chr4 | 54292132 | + | ENST00000257290 | PDGFRA | chr4 | 55141092 | + | 5647 | 1140 | 1196 | 2671 | 491 |
| ENST00000306932 | FIP1L1 | chr4 | 54292132 | + | ENST00000257290 | PDGFRA | chr4 | 55141092 | + | 5445 | 938 | 994 | 2469 | 491 |
| DeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
| ENST00000507166 | ENST00000257290 | FIP1L1 | chr4 | 54292132 | PDGFRA | chr4 | 55141089 | 0.000170798 | 0.9998292 | ||
| ENST00000358575 | ENST00000257290 | FIP1L1 | chr4 | 54292132 | PDGFRA | chr4 | 55141089 | 0.000174671 | 0.9998253 | ||
| ENST00000337488 | ENST00000257290 | FIP1L1 | chr4 | 54292132 | PDGFRA | chr4 | 55141089 | 0.000171373 | 0.9998286 | ||
| ENST00000507922 | ENST00000257290 | FIP1L1 | chr4 | 54292132 | PDGFRA | chr4 | 55141089 | 0.00017199 | 0.999828 | ||
| ENST00000306932 | ENST00000257290 | FIP1L1 | chr4 | 54292132 | PDGFRA | chr4 | 55141089 | 0.000164294 | 0.9998357 | ||
| ENST00000507166 | ENST00000257290 | FIP1L1 | chr4 | 54292132 | + | PDGFRA | chr4 | 55141092 | + | 0.000168597 | 0.9998313 |
| ENST00000358575 | ENST00000257290 | FIP1L1 | chr4 | 54292132 | + | PDGFRA | chr4 | 55141092 | + | 0.00017267 | 0.9998273 |
| ENST00000337488 | ENST00000257290 | FIP1L1 | chr4 | 54292132 | + | PDGFRA | chr4 | 55141092 | + | 0.000169334 | 0.9998306 |
| ENST00000507922 | ENST00000257290 | FIP1L1 | chr4 | 54292132 | + | PDGFRA | chr4 | 55141092 | + | 0.000169846 | 0.9998301 |
| ENST00000306932 | ENST00000257290 | FIP1L1 | chr4 | 54292132 | + | PDGFRA | chr4 | 55141092 | + | 0.000162303 | 0.99983764 |
| Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones. |
Get the fusion protein sequences from here. |
| Fusion protein sequence information is available in the fasta format. >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP |
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Fusion Protein Breakpoint Sequences for FIP1L1-PDGFRA |
| +/-13 AA sequence from the breakpoints of the fusion protein sequences. |
| Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Length(fusion protein) | BP in fusion protein | Peptide |
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Potential FusionNeoAntigen Information of FIP1L1-PDGFRA in HLA I |
| Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific. |
| Potential FusionNeoAntigen Information * We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5) |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA I | FusionNeoAntigen peptide | Binding score | Immunogenic score | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Potential FusionNeoAntigen Information of FIP1L1-PDGFRA in HLA II |
| Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific. |
| Potential FusionNeoAntigen Information * We used NetMHCIIpan v4.1 (%rank<0.5). |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA II | FusionNeoAntigen peptide | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Fusion breakpoint peptide structures of FIP1L1-PDGFRA |
| 3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens * The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA. |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FIP1L1-PDGFRA |
| Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens * We used Glide to predict the interaction between HLAs and neoantigens. |
| HLA allele | PDB ID | File name | BPseq | Docking score | Glide score |
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Vaccine Design for the FusionNeoAntigens of FIP1L1-PDGFRA |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide sequence | FusionNeoAntigen RNA sequence |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide | FusionNEoAntigen RNA sequence |
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Information of the samples that have these potential fusion neoantigens of FIP1L1-PDGFRA |
| These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens. |
| Cancer type | Fusion gene | Hchr | Hbp | Henst | Tchr | Tbp | Tenst | Sample |
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Potential target of CAR-T therapy development for FIP1L1-PDGFRA |
| Predicted 3D structure. We used RoseTTAFold. |
| 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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features * Minus value of BPloci means that the break point is located before the CDS. |
| - In-frame and retained 'Transmembrane'. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Tgene | PDGFRA | chr4:54292132 | chr4:55141092 | ENST00000257290 | 0 | 23 | 529_549 | 0 | 1090.0 | Transmembrane | Helical | |
| Tgene | PDGFRA | chr4:54292132 | chr4:55141092 | ENST00000508170 | 0 | 4 | 529_549 | 0 | 219.0 | Transmembrane | Helical |
| Subcellular localization prediction of the transmembrane domain retained fusion proteins * We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image. |
| Hgene | Hchr | Hbp | Henst | Tgene | Tchr | Tbp | Tenst | DeepLoc result |
| FIP1L1 | chr4 | 54292132 | ENST00000306932 | PDGFRA | chr4 | 55141089 | ENST00000257290 |  |
| FIP1L1 | chr4 | 54292132 | ENST00000306932 | PDGFRA | chr4 | 55141092 | ENST00000257290 |  |
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Related Drugs to FIP1L1-PDGFRA |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to FIP1L1-PDGFRA |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
| Tgene | PDGFRA | C0238198 | Gastrointestinal Stromal Tumors | 10 | CGI;CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT |
| Tgene | PDGFRA | C3179349 | Gastrointestinal Stromal Sarcoma | 9 | CLINGEN;CTD_human;ORPHANET |
| Tgene | PDGFRA | C0346421 | Chronic eosinophilic leukemia | 4 | ORPHANET |
| Tgene | PDGFRA | C0206141 | Idiopathic Hypereosinophilic Syndrome | 3 | CTD_human;GENOMICS_ENGLAND |
| Tgene | PDGFRA | C0006413 | Burkitt Lymphoma | 2 | ORPHANET |
| Tgene | PDGFRA | C0206142 | Eosinophilic leukemia | 2 | CTD_human |
| Tgene | PDGFRA | C0206143 | Loeffler's Endocarditis | 2 | CTD_human |
| Tgene | PDGFRA | C1292769 | Precursor B-cell lymphoblastic leukemia | 2 | ORPHANET |
| Tgene | PDGFRA | C1540912 | Hypereosinophilic syndrome | 2 | CGI;CTD_human |
| Tgene | PDGFRA | C0008925 | Cleft Palate | 1 | CTD_human |
| Tgene | PDGFRA | C0015923 | Fetal Alcohol Syndrome | 1 | PSYGENET |
| Tgene | PDGFRA | C0018801 | Heart failure | 1 | CTD_human |
| Tgene | PDGFRA | C0018802 | Congestive heart failure | 1 | CTD_human |
| Tgene | PDGFRA | C0023212 | Left-Sided Heart Failure | 1 | CTD_human |
| Tgene | PDGFRA | C0023893 | Liver Cirrhosis, Experimental | 1 | CTD_human |
| Tgene | PDGFRA | C0024115 | Lung diseases | 1 | CTD_human |
| Tgene | PDGFRA | C0025149 | Medulloblastoma | 1 | CTD_human |
| Tgene | PDGFRA | C0035238 | Congenital abnormality of respiratory system | 1 | CTD_human |
| Tgene | PDGFRA | C0038219 | Status Dysraphicus | 1 | CTD_human |
| Tgene | PDGFRA | C0080178 | Spina Bifida | 1 | CTD_human |
| Tgene | PDGFRA | C0205833 | Medullomyoblastoma | 1 | CTD_human |
| Tgene | PDGFRA | C0206637 | Mesenchymal Chondrosarcoma | 1 | CTD_human |
| Tgene | PDGFRA | C0235527 | Heart Failure, Right-Sided | 1 | CTD_human |
| Tgene | PDGFRA | C0266508 | Rachischisis | 1 | CTD_human |
| Tgene | PDGFRA | C0278510 | Childhood Medulloblastoma | 1 | CTD_human |
| Tgene | PDGFRA | C0278876 | Adult Medulloblastoma | 1 | CTD_human |
| Tgene | PDGFRA | C0376634 | Craniofacial Abnormalities | 1 | CTD_human |
| Tgene | PDGFRA | C0751291 | Desmoplastic Medulloblastoma | 1 | CTD_human |
| Tgene | PDGFRA | C1275668 | Melanotic medulloblastoma | 1 | CTD_human |
| Tgene | PDGFRA | C1837218 | Cleft palate, isolated | 1 | CTD_human |
| Tgene | PDGFRA | C1959583 | Myocardial Failure | 1 | CTD_human |
| Tgene | PDGFRA | C1961112 | Heart Decompensation | 1 | CTD_human |
| Tgene | PDGFRA | C2718076 | Fetal Mummification | 1 | CTD_human |
| Tgene | PDGFRA | C2985290 | Fetal Alcohol Spectrum Disorders | 1 | PSYGENET |
| Tgene | PDGFRA | C4545381 | Myeloid and/or lymphoid neoplasm associated with platelet derived growth factor receptor alpha rearrangement | 1 | ORPHANET |
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