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Kinase Fusion Gene:ROR1_ITGB3BP |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: ROR1_ITGB3BP | KinaseFusionDB ID: KFG5470 | FusionGDB2.0 ID: KFG5470 | Hgene | Tgene | Gene symbol | ROR1 | ITGB3BP | Gene ID | 6095 | 23421 | |
| Gene name | RAR related orphan receptor A | integrin subunit beta 3 binding protein | ||||||||||
| Synonyms | IDDECA|NR1F1|ROR1|ROR2|ROR3|RORa1|RORalpha|RZR-ALPHA|RZRA | CENP-R|CENPR|HSU37139|NRIF3|TAP20 | ||||||||||
| Cytomap | 15q22.2 | 1p31.3 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | nuclear receptor ROR-alphaRAR-related orphan nuclear receptor alphaROR-alphanuclear receptor RZR-alphanuclear receptor subfamily 1 group F member 1retinoic acid receptor-related orphan receptor alpharetinoid-related orphan receptor alphatranscripti | centromere protein Rbeta 3 endonexinbeta3-endonexinintegrin beta 3 binding protein (beta3-endonexin)integrin beta-3-binding proteinnuclear receptor-interacting factor 3 | ||||||||||
| Modification date | 20240403 | 20240305 | ||||||||||
| UniProtAcc | Q01973 | Q13352 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000482426, ENST00000371079, ENST00000371080, ENST00000545203, | ENST00000271002, ENST00000283568, ENST00000371092, ENST00000461681, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: ROR1 [Title/Abstract] AND ITGB3BP [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | ROR1(64516388)-ITGB3BP(63974241), # 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 | ROR1 | GO:0006355 | regulation of DNA-templated transcription | 9328355 |
| Hgene | ROR1 | GO:0030522 | intracellular receptor signaling pathway | 19965867 |
| Hgene | ROR1 | GO:0036315 | cellular response to sterol | 19965867 |
| Hgene | ROR1 | GO:0045893 | positive regulation of DNA-templated transcription | 7926749 |
| Hgene | ROR1 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 17545671|19955433 |
| Kinase Fusion gene breakpoints across ROR1 (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 ITGB3BP (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-R5-A7ZF | ROR1 | chr1 | 64516388 | ITGB3BP | chr1 | 63974241 |
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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) |
| ENST00000371080 | ENST00000371092 | ROR1 | chr1 | 64516388 | ITGB3BP | chr1 | 63974241 | 1739 | 349 |
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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 >ENST00000371080_ENST00000371092_ROR1_chr1_64516388_ITGB3BP_chr1_63974241_length(amino acids)=349 MGAAAAAASARGGMHRPRRRGTRPPLLALLAALLLAARGAAAQETELSVSAELVPTSSWNISSELNKDSYLTLDEPMNNITTSLGQTAEL HCKVSGNPPPTIRWFKNDAPVVQEPRRLSFRSTIYGSRLRIRNLDTTDTGYFQCVATNGKEVVSSTGVLFVKFGPPPTASPGYSVKRSLK LDGLLEENSFDPSKITRKKSVITYSPTTGTCQMSLFASPTSSEEQKHRNGLSNEKRKKLNHPSLTESKESTTKDNDEFMMLLSKVEKLSE -------------------------------------------------------------- |
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/chr1:64516388/chr1:63974241) - 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 |
| ROR1 | ITGB3BP |
| FUNCTION: Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo (PubMed:25029443). Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443, PubMed:27162350). In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells (PubMed:27162350). {ECO:0000269|PubMed:25029443, ECO:0000269|PubMed:27162350}. | FUNCTION: Transcription coregulator that can have both coactivator and corepressor functions. Isoform 1, but not other isoforms, is involved in the coactivation of nuclear receptors for retinoid X (RXRs) and thyroid hormone (TRs) in a ligand-dependent fashion. In contrast, it does not coactivate nuclear receptors for retinoic acid, vitamin D, progesterone receptor, nor glucocorticoid. Acts as a coactivator for estrogen receptor alpha. Acts as a transcriptional corepressor via its interaction with the NFKB1 NF-kappa-B subunit, possibly by interfering with the transactivation domain of NFKB1. Induces apoptosis in breast cancer cells, but not in other cancer cells, via a caspase-2 mediated pathway that involves mitochondrial membrane permeabilization but does not require other caspases. May also act as an inhibitor of cyclin A-associated kinase. Also acts a component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex. {ECO:0000269|PubMed:11713274, ECO:0000269|PubMed:12244126, ECO:0000269|PubMed:15082778, ECO:0000269|PubMed:15254226, ECO:0000269|PubMed:16622420}. |
| 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 | ROR1 | 64516388 | ITGB3BP | 63974241 | ENST00000371080 | 4 | 7 | 42_147 | 1601 | 394 | Domain | Note=Ig-like C2-type |
| Hgene | ROR1 | 64516388 | ITGB3BP | 63974241 | ENST00000371080 | 4 | 9 | 42_147 | 1601 | 938 | Domain | Note=Ig-like C2-type |
| - 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 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 >>>242_ROR1_ITGB3BP | ENST00000371080 | ENST00000371092 | ROR1 | chr1 | 64516388 | ITGB3BP | chr1 | 63974241 | MGAAAAAASARGGMHRPRRRGTRPPLLALLAALLLAARGAAAQETELSVSAELVPTSSWNISSELNKDSYLTLDEPMNNITTSLGQTAEL HCKVSGNPPPTIRWFKNDAPVVQEPRRLSFRSTIYGSRLRIRNLDTTDTGYFQCVATNGKEVVSSTGVLFVKFGPPPTASPGYSVKRSLK LDGLLEENSFDPSKITRKKSVITYSPTTGTCQMSLFASPTSSEEQKHRNGLSNEKRKKLNHPSLTESKESTTKDNDEFMMLLSKVEKLSE | 349 |
| 3D view using mol* of 242_ROR1_ITGB3BP | ||||||||||
| PDB file >>>HKFP_352_ROR1_ITGB3BP | ENST00000371080 | ENST00000371092 | ROR1 | chr1 | 64516388 | ITGB3BP | chr1 | 63974241 | MGAAAAAASARGGMHRPRRRGTRPPLLALLAALLLAARGAAAQETELSVSAELVPTSSWNISSELNKDSYLTLDEPMNNITTSLGQTAEL HCKVSGNPPPTIRWFKNDAPVVQEPRRLSFRSTIYGSRLRIRNLDTTDTGYFQCVATNGKEVVSSTGVLFVKFGPPPTASPGYSVKRSLK LDGLLEENSFDPSKITRKKSVITYSPTTGTCQMSLFASPTSSEEQKHRNGLSNEKRKKLNHPSLTESKESTTKDNDEFMMLLSKVEKLSE | 349_ROR1_ITGB3BP |
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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 |
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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB |
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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. |
| 242_ROR1_ITGB3BP.png |
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| 242_ROR1_ITGB3BP.png |
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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 |
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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. |
| 242_ROR1_ITGB3BP_ramachandran.png |
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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 |
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| 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 |
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Kinase-Substrate Information of ROR1_ITGB3BP |
| 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 |
| ROR1 | Q01973 | human | ERBB3 | P21860 | Y1307 | HQAPHVHyARLKtLR |
| 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 |
| ROR1 | ID | Description | 0.00e+00 |
| ROR1 | GO:2000672 | negative regulation of motor neuron apoptotic process | 7.49e-03 |
| ROR1 | GO:2000671 | regulation of motor neuron apoptotic process | 7.49e-03 |
| ROR1 | GO:0016202 | regulation of striated muscle tissue development | 7.49e-03 |
| ROR1 | GO:0038128 | ERBB2 signaling pathway | 7.49e-03 |
| ROR1 | GO:0070886 | positive regulation of calcineurin-NFAT signaling cascade | 7.49e-03 |
| ROR1 | GO:0097049 | motor neuron apoptotic process | 7.49e-03 |
| ROR1 | GO:0106058 | positive regulation of calcineurin-mediated signaling | 7.49e-03 |
| ROR1 | GO:0048634 | regulation of muscle organ development | 7.49e-03 |
| ROR1 | GO:1901863 | positive regulation of muscle tissue development | 7.49e-03 |
| ROR1 | GO:0061098 | positive regulation of protein tyrosine kinase activity | 7.93e-03 |
| ROR1 | GO:0014037 | Schwann cell differentiation | 7.93e-03 |
| ROR1 | GO:0070884 | regulation of calcineurin-NFAT signaling cascade | 7.93e-03 |
| ROR1 | GO:0106056 | regulation of calcineurin-mediated signaling | 7.93e-03 |
| ROR1 | GO:0050850 | positive regulation of calcium-mediated signaling | 7.93e-03 |
| ROR1 | GO:0033173 | calcineurin-NFAT signaling cascade | 7.93e-03 |
| ROR1 | GO:1901861 | regulation of muscle tissue development | 7.93e-03 |
| ROR1 | GO:0097720 | calcineurin-mediated signaling | 7.93e-03 |
| ROR1 | GO:0003197 | endocardial cushion development | 8.11e-03 |
| ROR1 | GO:0061097 | regulation of protein tyrosine kinase activity | 8.28e-03 |
| ROR1 | GO:0021545 | cranial nerve development | 8.55e-03 |
| ROR1 | GO:0038034 | signal transduction in absence of ligand | 8.55e-03 |
| ROR1 | GO:0097192 | extrinsic apoptotic signaling pathway in absence of ligand | 8.55e-03 |
| ROR1 | GO:0007422 | peripheral nervous system development | 9.71e-03 |
| ROR1 | GO:0050848 | regulation of calcium-mediated signaling | 9.71e-03 |
| ROR1 | GO:0021675 | nerve development | 1.09e-02 |
| ROR1 | GO:0038127 | ERBB signaling pathway | 1.34e-02 |
| ROR1 | GO:0043524 | negative regulation of neuron apoptotic process | 1.61e-02 |
| ROR1 | GO:0050731 | positive regulation of peptidyl-tyrosine phosphorylation | 1.61e-02 |
| ROR1 | GO:0051897 | positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 1.61e-02 |
| ROR1 | GO:0051048 | negative regulation of secretion | 1.61e-02 |
| ROR1 | GO:0019722 | calcium-mediated signaling | 1.89e-02 |
| ROR1 | GO:0097191 | extrinsic apoptotic signaling pathway | 1.89e-02 |
| ROR1 | GO:0050730 | regulation of peptidyl-tyrosine phosphorylation | 1.89e-02 |
| ROR1 | GO:0043523 | regulation of neuron apoptotic process | 1.89e-02 |
| ROR1 | GO:0048738 | cardiac muscle tissue development | 1.89e-02 |
| ROR1 | GO:0051896 | regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 1.89e-02 |
| ROR1 | GO:0010001 | glial cell differentiation | 1.89e-02 |
| ROR1 | GO:0014706 | striated muscle tissue development | 1.89e-02 |
| ROR1 | GO:0018108 | peptidyl-tyrosine phosphorylation | 1.89e-02 |
| ROR1 | GO:0018212 | peptidyl-tyrosine modification | 1.89e-02 |
| ROR1 | GO:0051402 | neuron apoptotic process | 1.89e-02 |
| ROR1 | GO:0045860 | positive regulation of protein kinase activity | 1.89e-02 |
| ROR1 | GO:0043491 | phosphatidylinositol 3-kinase/protein kinase B signal transduction | 1.89e-02 |
| ROR1 | GO:0019932 | second-messenger-mediated signaling | 1.95e-02 |
| ROR1 | GO:0007162 | negative regulation of cell adhesion | 1.95e-02 |
| ROR1 | GO:0060485 | mesenchyme development | 1.98e-02 |
| ROR1 | GO:0033674 | positive regulation of kinase activity | 1.98e-02 |
| ROR1 | GO:0042063 | gliogenesis | 1.98e-02 |
| ROR1 | GO:0007517 | muscle organ development | 2.03e-02 |
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Related Drugs to ROR1_ITGB3BP |
| 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 ROR1-ITGB3BP 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 ROR1_ITGB3BP |
| 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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