| UTHEALTH HOME ABOUT SBMI A-Z WEBMAIL INSIDE THE UNIVERSITY |
|
|||||||
|
Kinase Fusion Gene:RET_FGFR3 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: RET_FGFR3 | KinaseFusionDB ID: KFG5344 | FusionGDB2.0 ID: KFG5344 | Hgene | Tgene | Gene symbol | RET | FGFR3 | Gene ID | 5979 | 2261 | |
| Gene name | ret proto-oncogene | fibroblast growth factor receptor 3 | ||||||||||
| Synonyms | CDHF12|CDHR16|HSCR1|MEN2A|MEN2B|MTC1|PTC|RET-ELE1 | ACH|CD333|CEK2|HSFGFR3EX|JTK4 | ||||||||||
| Cytomap | 10q11.21 | 4p16.3 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | proto-oncogene tyrosine-protein kinase receptor RetRET receptor tyrosine kinasecadherin family member 12cadherin-related family member 16proto-oncogene c-Retrearranged during transfectionret proto-oncogene (multiple endocrine neoplasia and medullary | fibroblast growth factor receptor 3FGFR-3fibroblast growth factor receptor 3-Shydroxyaryl-protein kinasetyrosine kinase JTK4 | ||||||||||
| Modification date | 20240416 | 20240413 | ||||||||||
| UniProtAcc | P07949 | P22607 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000340058, ENST00000355710, | ENST00000474521, ENST00000260795, ENST00000340107, ENST00000352904, ENST00000412135, ENST00000440486, ENST00000481110, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: RET [Title/Abstract] AND FGFR3 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | RET(43612179)-FGFR3(1807285), # 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 | RET | GO:0030155 | regulation of cell adhesion | 21357690 |
| Hgene | RET | GO:0030335 | positive regulation of cell migration | 20702524 |
| Hgene | RET | GO:0033619 | membrane protein proteolysis | 21357690 |
| Hgene | RET | GO:0033630 | positive regulation of cell adhesion mediated by integrin | 20702524 |
| Hgene | RET | GO:0035860 | glial cell-derived neurotrophic factor receptor signaling pathway | 24560924|25242331|28953886|31535977 |
| Hgene | RET | GO:0043410 | positive regulation of MAPK cascade | 28846099 |
| Tgene | FGFR3 | GO:0008543 | fibroblast growth factor receptor signaling pathway | 8663044 |
| Kinase Fusion gene breakpoints across RET (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 FGFR3 (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
 |
Top |
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-FP-7916 | RET | chr10 | 43612179 | FGFR3 | chr4 | 1807285 |
Top |
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) |
| ENST00000355710 | ENST00000481110 | RET | chr10 | 43612179 | FGFR3 | chr4 | 1807285 | 4935 | 1041 |
Top |
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 >ENST00000355710_ENST00000481110_RET_chr10_43612179_FGFR3_chr4_1807285_length(amino acids)=1041 MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAPEEVPSFRLGQHLYGTYRTRLHENNWICIQE DTGLLYLNRSLDHSSWEKLSVRNRGFPLLTVYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELVAVCTVHAGAREEVVMVPFPVTVYDEDDSAP TFPAGVDTASAVVEFKRKEDTVVATLRVFDADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFAQIGKVCVENCQAFSGINVQYKLHSSGANCS TLGVVTSAEDTSGILFVNDTKALRRPKCAELHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLC DELCRTVIAAAVLFSFIVSVLLSAFCIHCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILEDPKWEFP RKNLVLGKTLGEGEFGKVVKATAFHLKGRAGYTTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQGGPLYVLVEYAAK GNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNLDYYKK TTNLVLWGPALGDLHAGGLPVPRHPCGGALQAAEGGPPHGQARQLHTRPVHDHAGVLACRALPEAHLQAAGGGPGPCPYRDVHRRVPGPV -------------------------------------------------------------- |
Multiple Sequence Alignment of All Fusion Protein Isoforms |
Top |
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/chr10:43612179/chr4:1807285) - 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 |
| RET | FGFR3 |
| FUNCTION: Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways (PubMed:28846097, PubMed:28953886, PubMed:28846099). Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL (PubMed:28846099). {ECO:0000269|PubMed:20064382, ECO:0000269|PubMed:20616503, ECO:0000269|PubMed:20702524, ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886}. | FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Phosphorylates PLCG1, CBL and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its capacity to bind FGF1 and FGF2 and hence may interfere with FGF signaling. {ECO:0000269|PubMed:10611230, ECO:0000269|PubMed:11294897, ECO:0000269|PubMed:11703096, ECO:0000269|PubMed:14534538, ECO:0000269|PubMed:16410555, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17145761, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:17561467, ECO:0000269|PubMed:19088846, ECO:0000269|PubMed:19286672, ECO:0000269|PubMed:8663044}. |
| 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 |
| Hgene | RET | 43612179 | FGFR3 | 1807285 | ENST00000355710 | 12 | 19 | 168_272 | 7611 | 1073 | Domain | Note=Cadherin;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00043 |
| Hgene | RET | 43612179 | FGFR3 | 1807285 | ENST00000355710 | 12 | 20 | 168_272 | 7611 | 1115 | Domain | Note=Cadherin;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00043 |
| - 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 |
| Tgene | RET | 43612179 | FGFR3 | 1807285 | ENST00000355710 | 7 | 15 | 472_761 | 399 | 695 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Tgene | RET | 43612179 | FGFR3 | 1807285 | ENST00000355710 | 8 | 16 | 472_761 | 399 | 695 | Domain | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
Top |
Kinase Fusion Protein Structures |
| CIF files of the predicted kinase fusion proteins * Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB) | Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | AA seq | Len(AA seq) |
| PDB file >>>226_RET_FGFR3 | ENST00000355710 | ENST00000481110 | RET | chr10 | 43612179 | FGFR3 | chr4 | 1807285 | MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAPEEVPSFRLGQHLYGTYRTRLHENNWICIQE DTGLLYLNRSLDHSSWEKLSVRNRGFPLLTVYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELVAVCTVHAGAREEVVMVPFPVTVYDEDDSAP TFPAGVDTASAVVEFKRKEDTVVATLRVFDADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFAQIGKVCVENCQAFSGINVQYKLHSSGANCS TLGVVTSAEDTSGILFVNDTKALRRPKCAELHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLC DELCRTVIAAAVLFSFIVSVLLSAFCIHCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILEDPKWEFP RKNLVLGKTLGEGEFGKVVKATAFHLKGRAGYTTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQGGPLYVLVEYAAK GNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNLDYYKK TTNLVLWGPALGDLHAGGLPVPRHPCGGALQAAEGGPPHGQARQLHTRPVHDHAGVLACRALPEAHLQAAGGGPGPCPYRDVHRRVPGPV | 1041 |
| 3D view using mol* of 226_RET_FGFR3 | ||||||||||
| PDB file >>>HKFP_328_RET_FGFR3 | ENST00000355710 | ENST00000481110 | RET | chr10 | 43612179 | FGFR3 | chr4 | 1807285 | MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAPEEVPSFRLGQHLYGTYRTRLHENNWICIQE DTGLLYLNRSLDHSSWEKLSVRNRGFPLLTVYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELVAVCTVHAGAREEVVMVPFPVTVYDEDDSAP TFPAGVDTASAVVEFKRKEDTVVATLRVFDADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFAQIGKVCVENCQAFSGINVQYKLHSSGANCS TLGVVTSAEDTSGILFVNDTKALRRPKCAELHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLC DELCRTVIAAAVLFSFIVSVLLSAFCIHCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILEDPKWEFP RKNLVLGKTLGEGEFGKVVKATAFHLKGRAGYTTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQGGPLYVLVEYAAK GNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNLDYYKK TTNLVLWGPALGDLHAGGLPVPRHPCGGALQAAEGGPPHGQARQLHTRPVHDHAGVLACRALPEAHLQAAGGGPGPCPYRDVHRRVPGPV | 1041_RET_FGFR3 |
| PDB file >>>417_RET_FGFR3 | ENST00000355710 | ENST00000481110 | RET | chr10 | 43612179 | FGFR3 | chr4 | 1807285 | MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAPEEVPSFRLGQHLYGTYRTRLHENNWICIQE DTGLLYLNRSLDHSSWEKLSVRNRGFPLLTVYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELVAVCTVHAGAREEVVMVPFPVTVYDEDDSAP TFPAGVDTASAVVEFKRKEDTVVATLRVFDADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFAQIGKVCVENCQAFSGINVQYKLHSSGANCS TLGVVTSAEDTSGILFVNDTKALRRPKCAELHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLC DELCRTVIAAAVLFSFIVSVLLSAFCIHCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILEDPKWEFP RKNLVLGKTLGEGEFGKVVKATAFHLKGRAGYTTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQGGPLYVLVEYAAK GNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNLDYYKK TTNLVLWGPALGDLHAGGLPVPRHPCGGALQAAEGGPPHGQARQLHTRPVHDHAGVLACRALPEAHLQAAGGGPGPCPYRDVHRRVPGPV | 1041 |
| 3D view using mol* of 417_RET_FGFR3 | ||||||||||
| PDB file >>>TKFP_701_RET_FGFR3 | ENST00000355710 | ENST00000481110 | RET | chr10 | 43612179 | FGFR3 | chr4 | 1807285 | MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAPEEVPSFRLGQHLYGTYRTRLHENNWICIQE DTGLLYLNRSLDHSSWEKLSVRNRGFPLLTVYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELVAVCTVHAGAREEVVMVPFPVTVYDEDDSAP TFPAGVDTASAVVEFKRKEDTVVATLRVFDADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFAQIGKVCVENCQAFSGINVQYKLHSSGANCS TLGVVTSAEDTSGILFVNDTKALRRPKCAELHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPRGIKAGYGTCNCFPEEEKCFCEPEDIQDPLC DELCRTVIAAAVLFSFIVSVLLSAFCIHCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILEDPKWEFP RKNLVLGKTLGEGEFGKVVKATAFHLKGRAGYTTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQGGPLYVLVEYAAK GNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNLDYYKK TTNLVLWGPALGDLHAGGLPVPRHPCGGALQAAEGGPPHGQARQLHTRPVHDHAGVLACRALPEAHLQAAGGGPGPCPYRDVHRRVPGPV | 1041_RET_FGFR3 |
Top |
Comparison of Fusion Protein Isoforms |
| Superimpose the 3D Structures Among All Fusion Protein Isoforms * Download the pdb file and open it from the molstar online viewer. |
| Comparison of the Secondary Structures of Fusion Protein Isoforms |
Top |
Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB |
Top |
pLDDT score distribution |
| pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. * The blue color at the bottom marks the best active site residues. |
| 226_RET_FGFR3.png |
 |
| 226_RET_FGFR3.png |
 |
| 417_RET_FGFR3.png |
 |
| 417_RET_FGFR3.png |
 |
Top |
Potential Active Site Information |
| The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite. |
| Kinase Fusion AA seq ID in KinaseFusionDB | Site score | Size | Dscore | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
Top |
Ramachandran Plot of Kinase Fusion Protein Structure |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide. |
| 226_RET_FGFR3_ramachandran.png |
 |
| 417_RET_FGFR3_ramachandran.png |
 |
Top |
Virtual Screening Results |
| Distribution of the average docking score across all approved kinase inhibitors. Distribution of the number of occurrence across all approved kinase inhibitors. |
| 5'-kinase fusion protein case |
 |
| 3'-kinase fusion protein case |
Top |
| Drug information from DrugBank of the top 20 interacting small molecules. * The detailed information of individual kinase inhibitors are available in the download page. |
| Fusion gene name info | Drug | Docking score | Glide g score | Glide energy |
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Ruxolitinib | 10000.0 | 10000.0 | 20.2814 |
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Asciminib | 10000.5 | 10000.0 | 31.8036 |
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Asciminib | 10000.5 | 10000.0 | 8.134 |
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Asciminib | 10000.5 | 10000.0 | 19.2734 |
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Asciminib | 10000.5 | 10000.0 | 3.2791099999999997 |
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus | |||
| 226_RET_FGFR3-DOCK_HTVS_1-001 | Sirolimus |
Top |
Kinase-Substrate Information of RET_FGFR3 |
| 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 |
| FGFR3 | P22607 | human | FGFR3 | P22607 | Y724 | ANCTHDLyMIMRECW | PK_Tyr_Ser-Thr |
| FGFR3 | P22607 | human | CTNNB1 | P35222 | Y142 | AVVNLINyQDDAELA | |
| FGFR3 | P22607 | human | PTEN | P60484 | Y240 | RREDKFMyFEFPQPL | PTEN_C2 |
| FGFR3 | P22607 | human | FGFR3 | P22607 | Y648 | DVHNLDyyKKTTNGR | PK_Tyr_Ser-Thr |
| FGFR3 | P22607 | human | FGFR3 | P22607 | Y647 | RDVHNLDyyKKTTNG | PK_Tyr_Ser-Thr |
| FGFR3 | P22607 | human | GLO1 | Q04760 | Y136 | GIAVPDVysACkRFE | Glyoxalase |
| FGFR3 | P22607 | human | TET2 | Q6N021 | Y1902 | TRISLVFyQHKSMNE | Tet_JBP |
| FGFR3 | P22607 | human | RPS6KA3 | P51812 | Y529 | TITKTVEyLHAQGVV | Pkinase |
| FGFR3 | P22607 | human | CILK1 | Q9UPZ9 | Y15 | RQLGDGtyGsVLLGR | Pkinase |
| FGFR3 | P22607 | human | RPS6KA3 | P51812 | Y488 | DVyDDGKyVYVVTEL | Pkinase |
| FGFR3 | P22607 | human | STAT1 | P42224 | Y701 | DGPkGtGyIktELIs | |
| RET | Q15300 | human | STAT3 | P40763 | Y705 | DPGsAAPyLktKFIC | |
| RET | Q15300 | human | RET | Q15300 | Y586 | TWIENKLyGRISHAF | |
| RET | P07949 | human | RET | P07949 | Y981 | DNCSEEMyRLMLQCW | PK_Tyr_Ser-Thr |
| RET | P07949 | human | PTK2 | Q05397 | Y925 | DRsNDkVyENVtGLV | Focal_AT |
| RET | P07949 | human | RET | P07949 | Y1090 | TNTGFPRyPNDSVyA | |
| RET | P07949 | human | ATF4 | P18848 | T107 | LGIDDLEtMPDDLLt | |
| RET | P07949 | human | PTK2 | Q05397 | Y577 | yMEDstyyKAsKGKL | PK_Tyr_Ser-Thr |
| RET | P07949 | human | ATF4 | P18848 | T115 | MPDDLLttLDDtCDL | |
| RET | P07949 | human | MAPK9 | P45984 | Y185 | tNFMMtPyVVtRYYR | Pkinase |
| RET | P07949 | human | RET | P07949 | Y1096 | RyPNDSVyANWMLSP | |
| RET | P07949 | human | MAPK8 | P45983 | Y185 | tsFMMtPyVVtRYYR | Pkinase |
| RET | P07949 | human | PIK3R1 | P27986 | Y203 | PVIPAAVySEMIsLA | RhoGAP |
| RET | P07949 | human | RET | P07949 | Y826 | SRKVGPGyLGSGGSR | PK_Tyr_Ser-Thr |
| RET | P07949 | human | RET | P07949 | Y1015 | MMVKRRDyLDLAAST | |
| RET | P07949 | human | PDPK1 | O15530 | Y9 | ARTTSQLyDAVPIQS | |
| RET | P07949 | human | ATF4 | P18848 | T114 | tMPDDLLttLDDtCD | |
| RET | P07949 | human | DOK1 | Q99704 | Y398 | ARVkEEGyELPyNPA | |
| RET | P07949 | human | RET | P07949 | Y809 | LIVEyAKyGSLRGFL | PK_Tyr_Ser-Thr |
| RET | P07949 | human | PTK2 | Q05397 | Y861 | PIGNQHIyQPVGKPD | |
| RET | P07949 | human | ATF4 | P18848 | T119 | LLttLDDtCDLFAPL | |
| RET | P07949 | human | RET | P07949 | Y1029 | TPSDSLIyDDGLSEE | |
| RET | P07949 | human | RET | P07949 | Y687 | AQAFPVsysSSGARR | |
| RET | P07949 | human | PLCG1 | P19174 | Y783 | EGRNPGFyVEANPMP | |
| RET | P07949 | human | MAPK3 | P27361 | T202 | HDHtGFLtEyVAtRW | Pkinase |
| RET | P07949 | human | AFAP1L2 | Q8N4X5 | Y54 | SSSsDEEyIyMNKVt | |
| RET | P07949 | human | AKT1 | P31749 | Y315 | tFCGtPEyLAPEVLE | Pkinase |
| RET | P07949 | human | RET | P07949 | Y806 | PLLLIVEyAKyGSLR | PK_Tyr_Ser-Thr |
| RET | P07949 | human | RET | P07949 | Y900 | FGLSRDVyEEDsyVK | PK_Tyr_Ser-Thr |
| RET | P07949 | human | MAPK1 | P28482 | Y187 | HtGFLtEyVAtRWyr | Pkinase |
| RET | P07949 | human | RET | P07949 | Y905 | DVyEEDsyVKRsQGR | PK_Tyr_Ser-Thr |
| RET | P07949 | human | PTK2 | Q05397 | Y576 | RyMEDstyyKAsKGK | PK_Tyr_Ser-Thr |
| RET | P07949 | human | MAPK3 | P27361 | Y204 | HtGFLtEyVAtRWyr | Pkinase |
| RET | P07949 | human | RET | P07949 | Y1062 | TWIENkLyGMsDPNW | |
| RET | P07949 | human | MAPK14 | Q16539 | Y182 | tDDEMtGyVAtRWYR | 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 |
| FGFR3 | ID | Description | 0.00e+00 |
| FGFR3 | GO:0003337 | mesenchymal to epithelial transition involved in metanephros morphogenesis | 2.21e-03 |
| FGFR3 | GO:0072182 | regulation of nephron tubule epithelial cell differentiation | 2.21e-03 |
| FGFR3 | GO:0072160 | nephron tubule epithelial cell differentiation | 2.21e-03 |
| FGFR3 | GO:0072283 | metanephric renal vesicle morphogenesis | 2.21e-03 |
| FGFR3 | GO:0030099 | myeloid cell differentiation | 2.21e-03 |
| FGFR3 | GO:0097091 | synaptic vesicle clustering | 2.21e-03 |
| FGFR3 | GO:2000696 | regulation of epithelial cell differentiation involved in kidney development | 2.21e-03 |
| FGFR3 | GO:0072077 | renal vesicle morphogenesis | 2.21e-03 |
| FGFR3 | GO:0072087 | renal vesicle development | 2.21e-03 |
| FGFR3 | GO:0060231 | mesenchymal to epithelial transition | 2.22e-03 |
| FGFR3 | GO:0048660 | regulation of smooth muscle cell proliferation | 2.56e-03 |
| FGFR3 | GO:0072202 | cell differentiation involved in metanephros development | 2.56e-03 |
| FGFR3 | GO:0048659 | smooth muscle cell proliferation | 2.56e-03 |
| FGFR3 | GO:0072273 | metanephric nephron morphogenesis | 2.56e-03 |
| FGFR3 | GO:0002053 | positive regulation of mesenchymal cell proliferation | 2.59e-03 |
| FGFR3 | GO:0003338 | metanephros morphogenesis | 3.77e-03 |
| FGFR3 | GO:0010464 | regulation of mesenchymal cell proliferation | 3.78e-03 |
| FGFR3 | GO:0033002 | muscle cell proliferation | 5.44e-03 |
| FGFR3 | GO:0072210 | metanephric nephron development | 5.58e-03 |
| FGFR3 | GO:0048762 | mesenchymal cell differentiation | 5.82e-03 |
| FGFR3 | GO:0010463 | mesenchymal cell proliferation | 5.82e-03 |
| FGFR3 | GO:0035850 | epithelial cell differentiation involved in kidney development | 6.35e-03 |
| FGFR3 | GO:0097479 | synaptic vesicle localization | 8.02e-03 |
| FGFR3 | GO:0030857 | negative regulation of epithelial cell differentiation | 8.23e-03 |
| FGFR3 | GO:0061005 | cell differentiation involved in kidney development | 8.23e-03 |
| FGFR3 | GO:0060485 | mesenchyme development | 8.54e-03 |
| FGFR3 | GO:0021700 | developmental maturation | 8.54e-03 |
| FGFR3 | GO:0072088 | nephron epithelium morphogenesis | 1.41e-02 |
| FGFR3 | GO:0072028 | nephron morphogenesis | 1.43e-02 |
| FGFR3 | GO:0051347 | positive regulation of transferase activity | 1.49e-02 |
| FGFR3 | GO:0008543 | fibroblast growth factor receptor signaling pathway | 1.51e-02 |
| FGFR3 | GO:0001656 | metanephros development | 1.75e-02 |
| FGFR3 | GO:0060993 | kidney morphogenesis | 1.84e-02 |
| FGFR3 | GO:0072080 | nephron tubule development | 1.86e-02 |
| FGFR3 | GO:0061326 | renal tubule development | 1.92e-02 |
| FGFR3 | GO:0030316 | osteoclast differentiation | 1.92e-02 |
| FGFR3 | GO:0048709 | oligodendrocyte differentiation | 1.92e-02 |
| FGFR3 | GO:0010717 | regulation of epithelial to mesenchymal transition | 2.05e-02 |
| FGFR3 | GO:0044344 | cellular response to fibroblast growth factor stimulus | 2.07e-02 |
| FGFR3 | GO:0048640 | negative regulation of developmental growth | 2.07e-02 |
| FGFR3 | GO:0002062 | chondrocyte differentiation | 2.07e-02 |
| FGFR3 | GO:0072009 | nephron epithelium development | 2.16e-02 |
| FGFR3 | GO:0021761 | limbic system development | 2.17e-02 |
| FGFR3 | GO:0071774 | response to fibroblast growth factor | 2.17e-02 |
| FGFR3 | GO:0042552 | myelination | 2.82e-02 |
| FGFR3 | GO:0007272 | ensheathment of neurons | 2.82e-02 |
| FGFR3 | GO:0008366 | axon ensheathment | 2.82e-02 |
| FGFR3 | GO:0050768 | negative regulation of neurogenesis | 2.82e-02 |
| FGFR3 | GO:0016525 | negative regulation of angiogenesis | 2.82e-02 |
Top |
Related Drugs to RET_FGFR3 |
| 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 RET-FGFR3 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 |
Top |
Related Diseases to RET_FGFR3 |
| 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 |
| Hgene | RET | C1833921 | Familial medullary thyroid carcinoma | 23 | CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT |
| Hgene | RET | C3888239 | HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 1 | 16 | GENOMICS_ENGLAND;UNIPROT |
| Hgene | RET | C0025268 | Multiple Endocrine Neoplasia Type 2a | 15 | CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT |
| Hgene | RET | C1708353 | Hereditary Paraganglioma-Pheochromocytoma Syndrome | 12 | CLINGEN |
| Hgene | RET | C0025269 | Multiple Endocrine Neoplasia Type 2b | 10 | CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT |
| Hgene | RET | C0238463 | Papillary thyroid carcinoma | 3 | CTD_human;ORPHANET |
| Hgene | RET | C1275808 | Congenital central hypoventilation | 3 | CTD_human;GENOMICS_ENGLAND;UNIPROT |
| Hgene | RET | C1859049 | CCHS WITH HIRSCHSPRUNG DISEASE | 3 | CTD_human;ORPHANET |
| Hgene | RET | C0009402 | Colorectal Carcinoma | 2 | CTD_human;UNIPROT |
| Hgene | RET | C0009404 | Colorectal Neoplasms | 2 | CTD_human |
| Hgene | RET | C0019569 | Hirschsprung Disease | 2 | CTD_human |
| Hgene | RET | C0027662 | Multiple Endocrine Neoplasia | 2 | CTD_human;GENOMICS_ENGLAND |
| Hgene | RET | C0085758 | Aganglionosis, Colonic | 2 | CTD_human |
| Hgene | RET | C0266294 | Unilateral agenesis of kidney | 2 | ORPHANET |
| Hgene | RET | C1257840 | Aganglionosis, Rectosigmoid Colon | 2 | CTD_human |
| Hgene | RET | C3661523 | Congenital Intestinal Aganglionosis | 2 | CTD_human |
| Tgene | FGFR3 | C0001080 | Achondroplasia | 13 | CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT |
| Tgene | FGFR3 | C0410529 | Hypochondroplasia (disorder) | 10 | CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT |
| Tgene | FGFR3 | C1864436 | Muenke Syndrome | 9 | CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT |
| Tgene | FGFR3 | C1868678 | THANATOPHORIC DYSPLASIA, TYPE I (disorder) | 9 | CTD_human;GENOMICS_ENGLAND;UNIPROT |
| Tgene | FGFR3 | C2677099 | CROUZON SYNDROME WITH ACANTHOSIS NIGRICANS (disorder) | 7 | CTD_human;GENOMICS_ENGLAND;UNIPROT |
| Tgene | FGFR3 | C0005684 | Malignant neoplasm of urinary bladder | 6 | CGI;CTD_human;UNIPROT |
| Tgene | FGFR3 | C0005695 | Bladder Neoplasm | 4 | CGI;CTD_human |
| Tgene | FGFR3 | C1300257 | Thanatophoric dysplasia, type 2 | 4 | CTD_human;GENOMICS_ENGLAND;UNIPROT |
| Tgene | FGFR3 | C1864852 | CATSHL syndrome | 4 | CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT |
| Tgene | FGFR3 | C2674173 | Achondroplasia, Severe, With Developmental Delay And Acanthosis Nigricans | 3 | CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT |
| Tgene | FGFR3 | C0265269 | Lacrimoauriculodentodigital syndrome | 2 | CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT |
Top |
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 |
Copyright 2024-Present -The University of Texas Health Science Center at Houston
Web File Viewing | Emergency Information |Campus Carry|Site Policies |