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Fusion Protein:DSTYK-INTS3 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: DSTYK-INTS3 | FusionPDB ID: 24328 | FusionGDB2.0 ID: 24328 | Hgene | Tgene | Gene symbol | DSTYK | INTS3 | Gene ID | 25778 | 65123 |
| Gene name | dual serine/threonine and tyrosine protein kinase | integrator complex subunit 3 | |
| Synonyms | CAKUT1|DustyPK|HDCMD38P|RIP5|RIPK5|SPG23 | C1orf193|C1orf60|INT3|SOSS-A|SOSSA | |
| Cytomap | 1q32.1 | 1q21.3 | |
| Type of gene | protein-coding | protein-coding | |
| Description | dual serine/threonine and tyrosine protein kinaseRIP-homologous kinasedusty PKdusty protein kinasereceptor-interacting serine/threonine-protein kinase 5sgK496spastic paraplegia 23 (autosomal recessive)sugen kinase 496 | integrator complex subunit 3SOSS complex subunit Asensor of single-strand DNA complex subunit Asensor of ssDNA subunit A | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | Q6XUX3 Main function of 5'-partner protein: FUNCTION: Acts as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor-receptor activation (PubMed:23862974, PubMed:28157540). Involved in the regulation of both caspase-dependent apoptosis and caspase-independent cell death (PubMed:15178406). In the skin, it plays a predominant role in suppressing caspase-dependent apoptosis in response to UV stress in a range of dermal cell types (PubMed:28157540). {ECO:0000269|PubMed:15178406, ECO:0000269|PubMed:23862974, ECO:0000269|PubMed:28157540}. | Q68E01 Main function of 5'-partner protein: FUNCTION: Component of the Integrator (INT) complex. The Integrator complex is involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes (Probable). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex (PubMed:23904267). {ECO:0000269|PubMed:23904267, ECO:0000305|PubMed:16239144}.; FUNCTION: Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. The SOSS complex associates with single-stranded DNA at DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. The SOSS complex is required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways. In the SOSS complex, it is required for the assembly of the complex and for stabilization of the complex at DNA damage sites. {ECO:0000269|PubMed:19605351, ECO:0000269|PubMed:19683501}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000367160, ENST00000367161, ENST00000367162, | ENST00000476843, ENST00000318967, ENST00000435409, ENST00000456435, ENST00000512605, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 8 X 5 X 7=280 | 7 X 5 X 2=70 |
| # samples | 11 | 7 | |
| ** MAII score | log2(11/280*10)=-1.34792330342031 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(7/70*10)=0 | |
| Fusion gene context | PubMed: DSTYK [Title/Abstract] AND INTS3 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: DSTYK [Title/Abstract] AND INTS3 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | DSTYK(205180399)-INTS3(153730048), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | DSTYK-INTS3 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. DSTYK-INTS3 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. DSTYK-INTS3 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. DSTYK-INTS3 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. | ||
| * 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 |
| Hgene | DSTYK | GO:0044344 | cellular response to fibroblast growth factor stimulus | 23862974 |
| Tgene | INTS3 | GO:0016180 | snRNA processing | 16239144 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr1:205180399/chr1:153730048) - 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 DSTYK (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 INTS3 (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) |
| ENST00000367160 | DSTYK | chr1 | 205180399 | - | ENST00000456435 | INTS3 | chr1 | 153730048 | + | 3508 | 329 | 293 | 2698 | 801 |
| ENST00000367160 | DSTYK | chr1 | 205180399 | - | ENST00000318967 | INTS3 | chr1 | 153730048 | + | 3310 | 329 | 293 | 2500 | 735 |
| ENST00000367160 | DSTYK | chr1 | 205180399 | - | ENST00000435409 | INTS3 | chr1 | 153730048 | + | 2766 | 329 | 293 | 2500 | 735 |
| ENST00000367160 | DSTYK | chr1 | 205180399 | - | ENST00000512605 | INTS3 | chr1 | 153730048 | + | 3157 | 329 | 293 | 2698 | 801 |
| ENST00000367161 | DSTYK | chr1 | 205180399 | - | ENST00000456435 | INTS3 | chr1 | 153730048 | + | 3475 | 296 | 260 | 2665 | 801 |
| ENST00000367161 | DSTYK | chr1 | 205180399 | - | ENST00000318967 | INTS3 | chr1 | 153730048 | + | 3277 | 296 | 260 | 2467 | 735 |
| ENST00000367161 | DSTYK | chr1 | 205180399 | - | ENST00000435409 | INTS3 | chr1 | 153730048 | + | 2733 | 296 | 260 | 2467 | 735 |
| ENST00000367161 | DSTYK | chr1 | 205180399 | - | ENST00000512605 | INTS3 | chr1 | 153730048 | + | 3124 | 296 | 260 | 2665 | 801 |
| ENST00000367162 | DSTYK | chr1 | 205180399 | - | ENST00000456435 | INTS3 | chr1 | 153730048 | + | 3475 | 296 | 260 | 2665 | 801 |
| ENST00000367162 | DSTYK | chr1 | 205180399 | - | ENST00000318967 | INTS3 | chr1 | 153730048 | + | 3277 | 296 | 260 | 2467 | 735 |
| ENST00000367162 | DSTYK | chr1 | 205180399 | - | ENST00000435409 | INTS3 | chr1 | 153730048 | + | 2733 | 296 | 260 | 2467 | 735 |
| ENST00000367162 | DSTYK | chr1 | 205180399 | - | ENST00000512605 | INTS3 | chr1 | 153730048 | + | 3124 | 296 | 260 | 2665 | 801 |
| 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 |
| ENST00000367160 | ENST00000456435 | DSTYK | chr1 | 205180399 | - | INTS3 | chr1 | 153730048 | + | 0.011662599 | 0.98833746 |
| ENST00000367160 | ENST00000318967 | DSTYK | chr1 | 205180399 | - | INTS3 | chr1 | 153730048 | + | 0.015788125 | 0.98421186 |
| ENST00000367160 | ENST00000435409 | DSTYK | chr1 | 205180399 | - | INTS3 | chr1 | 153730048 | + | 0.019909479 | 0.98009056 |
| ENST00000367160 | ENST00000512605 | DSTYK | chr1 | 205180399 | - | INTS3 | chr1 | 153730048 | + | 0.016852623 | 0.98314744 |
| ENST00000367161 | ENST00000456435 | DSTYK | chr1 | 205180399 | - | INTS3 | chr1 | 153730048 | + | 0.011660559 | 0.9883394 |
| ENST00000367161 | ENST00000318967 | DSTYK | chr1 | 205180399 | - | INTS3 | chr1 | 153730048 | + | 0.01596178 | 0.98403823 |
| ENST00000367161 | ENST00000435409 | DSTYK | chr1 | 205180399 | - | INTS3 | chr1 | 153730048 | + | 0.020168355 | 0.97983164 |
| ENST00000367161 | ENST00000512605 | DSTYK | chr1 | 205180399 | - | INTS3 | chr1 | 153730048 | + | 0.016922122 | 0.9830778 |
| ENST00000367162 | ENST00000456435 | DSTYK | chr1 | 205180399 | - | INTS3 | chr1 | 153730048 | + | 0.011660559 | 0.9883394 |
| ENST00000367162 | ENST00000318967 | DSTYK | chr1 | 205180399 | - | INTS3 | chr1 | 153730048 | + | 0.01596178 | 0.98403823 |
| ENST00000367162 | ENST00000435409 | DSTYK | chr1 | 205180399 | - | INTS3 | chr1 | 153730048 | + | 0.020168355 | 0.97983164 |
| ENST00000367162 | ENST00000512605 | DSTYK | chr1 | 205180399 | - | INTS3 | chr1 | 153730048 | + | 0.016922122 | 0.9830778 |
| 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 DSTYK-INTS3 |
| +/-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 DSTYK-INTS3 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 DSTYK-INTS3 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 DSTYK-INTS3 |
| 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 DSTYK-INTS3 |
| 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 DSTYK-INTS3 |
| 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 DSTYK-INTS3 |
| 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 DSTYK-INTS3 |
| 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 |
| 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 |
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Related Drugs to DSTYK-INTS3 |
| 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 DSTYK-INTS3 |
| 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 |
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