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 | Fusion Gene Summary |
| Fusion Gene ORF analysis |
| Fusion Genomic Features |
| Fusion Protein Features |
| Fusion Gene Sequence |
| Fusion Gene PPI analysis |
| Related Drugs |
| Related Diseases |
Fusion gene:CUL3-IRS1 (FusionGDB2 ID:20668) |
Fusion Gene Summary for CUL3-IRS1 |
 Fusion gene summary |
| Fusion gene information | Fusion gene name: CUL3-IRS1 | Fusion gene ID: 20668 | Hgene | Tgene | Gene symbol | CUL3 | IRS1 | Gene ID | 8452 | 3667 |
| Gene name | cullin 3 | insulin receptor substrate 1 | |
| Synonyms | CUL-3|PHA2E | HIRS-1 | |
| Cytomap | 2q36.2 | 2q36.3 | |
| Type of gene | protein-coding | protein-coding | |
| Description | cullin-3 | insulin receptor substrate 1IRS-1 | |
| Modification date | 20200327 | 20200313 | |
| UniProtAcc | Q13618 | P35568 | |
| Ensembl transtripts involved in fusion gene | ENST00000264414, ENST00000409096, ENST00000409777, ENST00000432260, ENST00000344951, | ENST00000305123, ENST00000498335, | |
| Fusion gene scores | * DoF score | 12 X 12 X 7=1008 | 1 X 2 X 1=2 |
| # samples | 14 | 2 | |
| ** MAII score | log2(14/1008*10)=-2.84799690655495 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(2/2*10)=3.32192809488736 | |
| Context | PubMed: CUL3 [Title/Abstract] AND IRS1 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint | CUL3(225422376)-IRS1(227600966), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | |||
| * 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 | CUL3 | GO:0000209 | protein polyubiquitination | 19261606 |
| Hgene | CUL3 | GO:0006511 | ubiquitin-dependent protein catabolic process | 25401743|27561354 |
| Hgene | CUL3 | GO:0006513 | protein monoubiquitination | 22358839 |
| Hgene | CUL3 | GO:0006888 | ER to Golgi vesicle-mediated transport | 22358839 |
| Hgene | CUL3 | GO:0016567 | protein ubiquitination | 17543862|19782033|19995937|20389280|23213400 |
| Hgene | CUL3 | GO:0031145 | anaphase-promoting complex-dependent catabolic process | 10500095 |
| Hgene | CUL3 | GO:0043161 | proteasome-mediated ubiquitin-dependent protein catabolic process | 19261606|19782033|20389280 |
| Hgene | CUL3 | GO:0071630 | nuclear protein quality control by the ubiquitin-proteasome system | 27561354 |
| Tgene | IRS1 | GO:0008286 | insulin receptor signaling pathway | 16516141|23401856 |
| Tgene | IRS1 | GO:0014065 | phosphatidylinositol 3-kinase signaling | 7782332 |
| Tgene | IRS1 | GO:0032868 | response to insulin | 16516141 |
| Tgene | IRS1 | GO:0046326 | positive regulation of glucose import | 7493946 |
| Tgene | IRS1 | GO:0046628 | positive regulation of insulin receptor signaling pathway | 7493946 |
| Tgene | IRS1 | GO:0046676 | negative regulation of insulin secretion | 15572028 |
| Fusion gene breakpoints across CUL3 (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Fusion gene breakpoints across IRS1 (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0) * 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 | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| ChimerDB4 | BRCA | TCGA-E9-A1NE-01A | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600965 | - |
| ChimerDB4 | BRCA | TCGA-E9-A1NE-01A | CUL3 | chr2 | 225422376 | - | IRS1 | chr2 | 227600966 | - |
| ChimerDB4 | BRCA | TCGA-E9-A1NE | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600966 | - |
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Fusion Gene ORF analysis for CUL3-IRS1 |
| Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
| ORF | Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| 5CDS-3UTR | ENST00000264414 | ENST00000305123 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600965 | - |
| 5CDS-3UTR | ENST00000264414 | ENST00000305123 | CUL3 | chr2 | 225422376 | - | IRS1 | chr2 | 227600966 | - |
| 5CDS-3UTR | ENST00000264414 | ENST00000305123 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600966 | - |
| 5CDS-3UTR | ENST00000409096 | ENST00000305123 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600965 | - |
| 5CDS-3UTR | ENST00000409096 | ENST00000305123 | CUL3 | chr2 | 225422376 | - | IRS1 | chr2 | 227600966 | - |
| 5CDS-3UTR | ENST00000409096 | ENST00000305123 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600966 | - |
| 5CDS-3UTR | ENST00000409777 | ENST00000305123 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600965 | - |
| 5CDS-3UTR | ENST00000409777 | ENST00000305123 | CUL3 | chr2 | 225422376 | - | IRS1 | chr2 | 227600966 | - |
| 5CDS-3UTR | ENST00000409777 | ENST00000305123 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600966 | - |
| 5CDS-intron | ENST00000264414 | ENST00000498335 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600965 | - |
| 5CDS-intron | ENST00000264414 | ENST00000498335 | CUL3 | chr2 | 225422376 | - | IRS1 | chr2 | 227600966 | - |
| 5CDS-intron | ENST00000264414 | ENST00000498335 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600966 | - |
| 5CDS-intron | ENST00000409096 | ENST00000498335 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600965 | - |
| 5CDS-intron | ENST00000409096 | ENST00000498335 | CUL3 | chr2 | 225422376 | - | IRS1 | chr2 | 227600966 | - |
| 5CDS-intron | ENST00000409096 | ENST00000498335 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600966 | - |
| 5CDS-intron | ENST00000409777 | ENST00000498335 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600965 | - |
| 5CDS-intron | ENST00000409777 | ENST00000498335 | CUL3 | chr2 | 225422376 | - | IRS1 | chr2 | 227600966 | - |
| 5CDS-intron | ENST00000409777 | ENST00000498335 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600966 | - |
| 5UTR-3UTR | ENST00000432260 | ENST00000305123 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600965 | - |
| 5UTR-3UTR | ENST00000432260 | ENST00000305123 | CUL3 | chr2 | 225422376 | - | IRS1 | chr2 | 227600966 | - |
| 5UTR-3UTR | ENST00000432260 | ENST00000305123 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600966 | - |
| 5UTR-intron | ENST00000432260 | ENST00000498335 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600965 | - |
| 5UTR-intron | ENST00000432260 | ENST00000498335 | CUL3 | chr2 | 225422376 | - | IRS1 | chr2 | 227600966 | - |
| 5UTR-intron | ENST00000432260 | ENST00000498335 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600966 | - |
| intron-3UTR | ENST00000344951 | ENST00000305123 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600965 | - |
| intron-3UTR | ENST00000344951 | ENST00000305123 | CUL3 | chr2 | 225422376 | - | IRS1 | chr2 | 227600966 | - |
| intron-3UTR | ENST00000344951 | ENST00000305123 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600966 | - |
| intron-intron | ENST00000344951 | ENST00000498335 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600965 | - |
| intron-intron | ENST00000344951 | ENST00000498335 | CUL3 | chr2 | 225422376 | - | IRS1 | chr2 | 227600966 | - |
| intron-intron | ENST00000344951 | ENST00000498335 | CUL3 | chr2 | 225422375 | - | IRS1 | chr2 | 227600966 | - |
| ORFfinder result based on the fusion transcript sequence of in-frame fusion genes. |
| 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) |
| 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 |
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Fusion Genomic Features for CUL3-IRS1 |
| FusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints. |
| Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | 1-p | p (fusion gene breakpoint) |
| Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page. |
| Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page. |
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Fusion Protein Features for CUL3-IRS1 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:225422376/:227600966) - 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 |
| CUL3 | IRS1 |
| FUNCTION: Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, MACROH2A1 and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27716508). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23576762). The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination (PubMed:20389280, PubMed:21840486, PubMed:21670212, PubMed:24768539). The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB (PubMed:19995937). The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation (PubMed:23455478). The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway (PubMed:29769719). The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) (PubMed:22578813). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41 (PubMed:15983046). In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. The BCR(KCTD17) E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis (PubMed:25270598). The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity (PubMed:27798626). The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination of AURKA leading to its activation at the centrosome which is required for initiating mitotic entry (PubMed:23213400). The BCR(KEAP1) E3 ubiquitin ligase complex acts as a key sensor of oxidative and electrophilic stress by mediating ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:15601839, PubMed:16006525). {ECO:0000269|PubMed:10500095, ECO:0000269|PubMed:11311237, ECO:0000269|PubMed:15601839, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16006525, ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:17543862, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:19261606, ECO:0000269|PubMed:19995937, ECO:0000269|PubMed:20389280, ECO:0000269|PubMed:21670212, ECO:0000269|PubMed:21840486, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22358839, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:23213400, ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:24768539, ECO:0000269|PubMed:25270598, ECO:0000269|PubMed:26399832, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27798626, ECO:0000269|PubMed:29769719}. | FUNCTION: May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity). {ECO:0000250, ECO:0000269|PubMed:16878150}. |
| 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. |
| - In-frame and retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| - In-frame and not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
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Fusion Gene Sequence for CUL3-IRS1 |
| For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
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Fusion Gene PPI Analysis for CUL3-IRS1 |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
| Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160) |
| Hgene | Hgene's interactors | Tgene | Tgene's interactors |
| - Retained PPIs in in-frame fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost PPIs in in-frame fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
| - Retained PPIs, but lost function due to frame-shift fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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Related Drugs for CUL3-IRS1 |
| Drugs targeting genes involved in this fusion gene. (DrugBank Version 5.1.8 2021-05-08) |
| Partner | Gene | UniProtAcc | DrugBank ID | Drug name | Drug activity | Drug type | Drug status |
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Related Diseases for CUL3-IRS1 |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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