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Fusion Protein:WRN-ADAM9 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: WRN-ADAM9 | FusionPDB ID: 99398 | FusionGDB2.0 ID: 99398 | Hgene | Tgene | Gene symbol | WRN | ADAM9 | Gene ID | 7486 | 8754 |
| Gene name | WRN RecQ like helicase | ADAM metallopeptidase domain 9 | |
| Synonyms | RECQ3|RECQL2|RECQL3 | CORD9|MCMP|MDC9|Mltng | |
| Cytomap | 8p12 | 8p11.22 | |
| Type of gene | protein-coding | protein-coding | |
| Description | Werner syndrome ATP-dependent helicaseDNA helicase, RecQ-like type 3Werner syndrome RecQ like helicaseWerner syndrome, RecQ helicase-likeexonuclease WRNrecQ protein-like 2 | disintegrin and metalloproteinase domain-containing protein 9ADAM metallopeptidase domain 9 (meltrin gamma)cellular disintegrin-related proteincone rod dystrophy 9metalloprotease/disintegrin/cysteine-rich protein 9myeloma cell metalloproteinase | |
| Modification date | 20200320 | 20200313 | |
| UniProtAcc | . | Q13443 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000298139, | ENST00000484143, ENST00000481513, ENST00000466936, ENST00000487273, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 8 X 6 X 6=288 | 12 X 12 X 8=1152 |
| # samples | 8 | 13 | |
| ** MAII score | log2(8/288*10)=-1.84799690655495 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(13/1152*10)=-3.14755718841386 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: WRN [Title/Abstract] AND ADAM9 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | WRN(30982516)-ADAM9(38871484), # samples:2 | ||
| Anticipated loss of major functional domain due to fusion event. | WRN-ADAM9 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. WRN-ADAM9 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. WRN-ADAM9 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. WRN-ADAM9 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. WRN-ADAM9 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF. WRN-ADAM9 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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 |
| Hgene | WRN | GO:0000731 | DNA synthesis involved in DNA repair | 17563354 |
| Hgene | WRN | GO:0006259 | DNA metabolic process | 16622405 |
| Hgene | WRN | GO:0006284 | base-excision repair | 17611195 |
| Hgene | WRN | GO:0006974 | cellular response to DNA damage stimulus | 18203716 |
| Hgene | WRN | GO:0006979 | response to oxidative stress | 17611195 |
| Hgene | WRN | GO:0009267 | cellular response to starvation | 11420665 |
| Hgene | WRN | GO:0010225 | response to UV-C | 17563354 |
| Hgene | WRN | GO:0031297 | replication fork processing | 17115688 |
| Hgene | WRN | GO:0032508 | DNA duplex unwinding | 11735402|26420422 |
| Hgene | WRN | GO:0044806 | G-quadruplex DNA unwinding | 11735402 |
| Hgene | WRN | GO:0051345 | positive regulation of hydrolase activity | 17611195 |
| Hgene | WRN | GO:0061820 | telomeric D-loop disassembly | 15200954|19734539|26420422 |
| Hgene | WRN | GO:0071480 | cellular response to gamma radiation | 21639834 |
| Hgene | WRN | GO:0098530 | positive regulation of strand invasion | 26420422 |
| Hgene | WRN | GO:1902570 | protein localization to nucleolus | 11420665 |
| Tgene | ADAM9 | GO:0000186 | activation of MAPKK activity | 17704059 |
| Tgene | ADAM9 | GO:0006509 | membrane protein ectodomain proteolysis | 9920899 |
| Tgene | ADAM9 | GO:0034612 | response to tumor necrosis factor | 11831872 |
| Tgene | ADAM9 | GO:0050714 | positive regulation of protein secretion | 17704059 |
| Fusion gene breakpoints across WRN (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 ADAM9 (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 Gene Sample Information |
| Fusion gene information from FusionGDB2.0. |
| 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-B6-A0I1-01A | WRN | chr8 | 30982516 | - | ADAM9 | chr8 | 38871484 | + |
| ChimerDB4 | BRCA | TCGA-B6-A0I1-01A | WRN | chr8 | 30982516 | + | ADAM9 | chr8 | 38871484 | + |
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Fusion ORF Analysis |
| 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) |
| ENST00000298139 | WRN | chr8 | 30982516 | + | ENST00000487273 | ADAM9 | chr8 | 38871484 | + | 6581 | 3074 | 249 | 5279 | 1676 |
| ENST00000298139 | WRN | chr8 | 30982516 | + | ENST00000466936 | ADAM9 | chr8 | 38871484 | + | 4678 | 3074 | 249 | 3263 | 1004 |
| 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 |
| ENST00000298139 | ENST00000487273 | WRN | chr8 | 30982516 | + | ADAM9 | chr8 | 38871484 | + | 9.57E-05 | 0.9999043 |
| ENST00000298139 | ENST00000466936 | WRN | chr8 | 30982516 | + | ADAM9 | chr8 | 38871484 | + | 8.70E-05 | 0.999913 |
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Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP >99398_99398_1_WRN-ADAM9_WRN_chr8_30982516_ENST00000298139_ADAM9_chr8_38871484_ENST00000466936_length(amino acids)=1004AA_BP=940 MSEKKLETTAQQRKCPEWMNVQNKRCAVEERKACVRKSVFEDDLPFLEFTGSIVYSYDASDCSFLSEDISMSLSDGDVVGFDMEWPPLYN RGKLGKVALIQLCVSESKCYLFHVSSMSVFPQGLKMLLENKAVKKAGVGIEGDQWKLLRDFDIKLKNFVELTDVANKKLKCTETWSLNSL VKHLLGKQLLKDKSIRCSNWSKFPLTEDQKLYAATDAYAGFIIYRNLEILDDTVQRFAINKEEEILLSDMNKQLTSISEEVMDLAKHLPH AFSKLENPRRVSILLKDISENLYSLRRMIIGSTNIETELRPSNNLNLLSFEDSTTGGVQQKQIREHEVLIHVEDETWDPTLDHLAKHDGE DVLGNKVERKEDGFEDGVEDNKLKENMERACLMSLDITEHELQILEQQSQEEYLSDIAYKSTEHLSPNDNENDTSYVIESDEDLEMEMLK HLSPNDNENDTSYVIESDEDLEMEMLKSLENLNSGTVEPTHSKCLKMERNLGLPTKEEEEDDENEANEGEEDDDKDFLWPAPNEEQVTCL KMYFGHSSFKPVQWKVIHSVLEERRDNVAVMATGYGKSLCFQYPPVYVGKIGLVISPLISLMEDQVLQLKMSNIPACFLGSAQSENVLTD IKLGKYRIVYVTPEYCSGNMGLLQQLEADIGITLIAVDEAHCISEWGHDFRDSFRKLGSLKTALPMVPIVALTATASSSIREDIVRCLNL RNPQITCTGFDRPNLYLEVRRKTGNILQDLQPFLVKTSSHWEFEGPTIIYCPSRKMTQQVTGELRKLNLSCGTYHAGMSFSTRKDIHHRF VRDEIQCVIATIAFGMGINKADIRQVIHYGAPKDMESYYQEIGRAGRDGLQSSCHVLWAPADINLNRHLLTEIRNEKFRLYKLKMMAKME KYLHSSRCRRQIILSHFEDKQVQKASLGIMGTEKCCDNCRSRDLLPEDFVVYTYNKEGTLITDHPNIQRCGPLCIREQSTPGDRAGQNTQ -------------------------------------------------------------- >99398_99398_2_WRN-ADAM9_WRN_chr8_30982516_ENST00000298139_ADAM9_chr8_38871484_ENST00000487273_length(amino acids)=1676AA_BP=940 MSEKKLETTAQQRKCPEWMNVQNKRCAVEERKACVRKSVFEDDLPFLEFTGSIVYSYDASDCSFLSEDISMSLSDGDVVGFDMEWPPLYN RGKLGKVALIQLCVSESKCYLFHVSSMSVFPQGLKMLLENKAVKKAGVGIEGDQWKLLRDFDIKLKNFVELTDVANKKLKCTETWSLNSL VKHLLGKQLLKDKSIRCSNWSKFPLTEDQKLYAATDAYAGFIIYRNLEILDDTVQRFAINKEEEILLSDMNKQLTSISEEVMDLAKHLPH AFSKLENPRRVSILLKDISENLYSLRRMIIGSTNIETELRPSNNLNLLSFEDSTTGGVQQKQIREHEVLIHVEDETWDPTLDHLAKHDGE DVLGNKVERKEDGFEDGVEDNKLKENMERACLMSLDITEHELQILEQQSQEEYLSDIAYKSTEHLSPNDNENDTSYVIESDEDLEMEMLK HLSPNDNENDTSYVIESDEDLEMEMLKSLENLNSGTVEPTHSKCLKMERNLGLPTKEEEEDDENEANEGEEDDDKDFLWPAPNEEQVTCL KMYFGHSSFKPVQWKVIHSVLEERRDNVAVMATGYGKSLCFQYPPVYVGKIGLVISPLISLMEDQVLQLKMSNIPACFLGSAQSENVLTD IKLGKYRIVYVTPEYCSGNMGLLQQLEADIGITLIAVDEAHCISEWGHDFRDSFRKLGSLKTALPMVPIVALTATASSSIREDIVRCLNL RNPQITCTGFDRPNLYLEVRRKTGNILQDLQPFLVKTSSHWEFEGPTIIYCPSRKMTQQVTGELRKLNLSCGTYHAGMSFSTRKDIHHRF VRDEIQCVIATIAFGMGINKADIRQVIHYGAPKDMESYYQEIGRAGRDGLQSSCHVLWAPADINLNRHLLTEIRNEKFRLYKLKMMAKME KYLHSSRCRRQIILSHFEDKQVQKASLGIMGTEKCCDNCRSRDLLPEDFVVYTYNKEGTLITDHPNIQNHCHYRGYVEGVHNSSIALSDC FGLRGLLHLENASYGIEPLQNSSHFEHIIYRMDDVYKEPLKCGVSNKDIEKETAKDEEEEPPSMTQLLRRRRAVLPQTRYVELFIVVDKE RYDMMGRNQTAVREEMILLANYLDSMYIMLNIRIVLVGLEIWTNGNLINIVGGAGDVLGNFVQWREKFLITRRRHDSAQLVLKKGFGGTA GMAFVGTVCSRSHAGGINVFGQITVETFASIVAHELGHNLGMNHDDGRDCSCGAKSCIMNSGASGSRNFSSCSAEDFEKLTLNKGGNCLL NIPKPDEAYSAPSCGNKLVDAGEECDCGTPKECELDPCCEGSTCKLKSFAECAYGDCCKDCRFLPGGTLCRGKTSECDVPEYCNGSSQFC QPDVFIQNGYPCQNNKAYCYNGMCQYYDAQCQVIFGSKAKAAPKDCFIEVNSKGDRFGNCGFSGNEYKKCATGNALCGKLQCENVQEIPV FGIVPAIIQTPSRGTKCWGVDFQLGSDVPDPGMVNEGTKCGAGKICRNFQCVDASVLNYDCDVQKKCHGHGVCNSNKNCHCENGWAPPNC ETKGYGGSVDSGPTYNEMNTALRDGLLVFFFLIVPLIVCAIFIFIKRDQLWRSYFRKKRSQTYESDGKNQANPSRQPGSVPRHVSPVTPP -------------------------------------------------------------- |
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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/chr8:30982516/chr8:38871484) - 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 |
| . | ADAM9 |
| FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes. | FUNCTION: Cleaves and releases a number of molecules with important roles in tumorigenesis and angiogenesis, such as TEK, KDR, EPHB4, CD40, VCAM1 and CDH5. May mediate cell-cell, cell-matrix interactions and regulate the motility of cells via interactions with integrins. {ECO:0000250|UniProtKB:Q61072}.; FUNCTION: [Isoform 2]: May act as alpha-secretase for amyloid precursor protein (APP). {ECO:0000269|PubMed:12054541}. |
| 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 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 |
| Hgene | WRN | chr8:30982516 | chr8:38871484 | ENST00000298139 | + | 23 | 35 | 507_510 | 941.6666666666666 | 1433.0 | Compositional bias | Note=Poly-Glu |
| Hgene | WRN | chr8:30982516 | chr8:38871484 | ENST00000298139 | + | 23 | 35 | 558_724 | 941.6666666666666 | 1433.0 | Domain | Helicase ATP-binding |
| Hgene | WRN | chr8:30982516 | chr8:38871484 | ENST00000298139 | + | 23 | 35 | 60_228 | 941.6666666666666 | 1433.0 | Domain | Note=3'-5' exonuclease |
| Hgene | WRN | chr8:30982516 | chr8:38871484 | ENST00000298139 | + | 23 | 35 | 749_899 | 941.6666666666666 | 1433.0 | Domain | Helicase C-terminal |
| Hgene | WRN | chr8:30982516 | chr8:38871484 | ENST00000298139 | + | 23 | 35 | 668_671 | 941.6666666666666 | 1433.0 | Motif | Note=DEAH box |
| Hgene | WRN | chr8:30982516 | chr8:38871484 | ENST00000298139 | + | 23 | 35 | 571_578 | 941.6666666666666 | 1433.0 | Nucleotide binding | ATP |
| Hgene | WRN | chr8:30982516 | chr8:38871484 | ENST00000298139 | + | 23 | 35 | 424_477 | 941.6666666666666 | 1433.0 | Region | Note=2 X 27 AA tandem repeats of H-L-S-P-N-D-N-E-N-D-T-S-Y-V-I-E-S-D-E-D-L-E-M-E-M-L-K |
| Hgene | WRN | chr8:30982516 | chr8:38871484 | ENST00000298139 | + | 23 | 35 | 424_450 | 941.6666666666666 | 1433.0 | Repeat | 1 |
| Hgene | WRN | chr8:30982516 | chr8:38871484 | ENST00000298139 | + | 23 | 35 | 451_477 | 941.6666666666666 | 1433.0 | Repeat | 2 |
| Tgene | ADAM9 | chr8:30982516 | chr8:38871484 | ENST00000487273 | 2 | 22 | 505_634 | 84.66666666666667 | 820.0 | Compositional bias | Note=Cys-rich | |
| Tgene | ADAM9 | chr8:30982516 | chr8:38871484 | ENST00000487273 | 2 | 22 | 790_795 | 84.66666666666667 | 820.0 | Compositional bias | Note=Poly-Pro | |
| Tgene | ADAM9 | chr8:30982516 | chr8:38871484 | ENST00000487273 | 2 | 22 | 212_406 | 84.66666666666667 | 820.0 | Domain | Peptidase M12B | |
| Tgene | ADAM9 | chr8:30982516 | chr8:38871484 | ENST00000487273 | 2 | 22 | 414_501 | 84.66666666666667 | 820.0 | Domain | Disintegrin | |
| Tgene | ADAM9 | chr8:30982516 | chr8:38871484 | ENST00000487273 | 2 | 22 | 644_698 | 84.66666666666667 | 820.0 | Domain | EGF-like | |
| Tgene | ADAM9 | chr8:30982516 | chr8:38871484 | ENST00000487273 | 2 | 22 | 719_819 | 84.66666666666667 | 820.0 | Topological domain | Cytoplasmic | |
| Tgene | ADAM9 | chr8:30982516 | chr8:38871484 | ENST00000487273 | 2 | 22 | 698_718 | 84.66666666666667 | 820.0 | Transmembrane | Helical |
| - 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 |
| Hgene | WRN | chr8:30982516 | chr8:38871484 | ENST00000298139 | + | 23 | 35 | 1150_1229 | 941.6666666666666 | 1433.0 | Domain | HRDC |
| Tgene | ADAM9 | chr8:30982516 | chr8:38871484 | ENST00000487273 | 2 | 22 | 29_697 | 84.66666666666667 | 820.0 | Topological domain | Extracellular |
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Fusion Protein-Protein Interaction |
| 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 from validated records (BIOGRID-3.4.160) |
| Gene | PPI interactors |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| WRN | |
| ADAM9 |
| - Retained interactions in fusion protein (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost interactions due to fusion (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
| Hgene | WRN | chr8:30982516 | chr8:38871484 | ENST00000298139 | + | 23 | 35 | 987_993 | 941.6666666666666 | 1433.0 | DNA |
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Related Drugs to WRN-ADAM9 |
| 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 WRN-ADAM9 |
| 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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