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Fusion Protein:MGMT-DOCK1 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: MGMT-DOCK1 | FusionPDB ID: 53402 | FusionGDB2.0 ID: 53402 | Hgene | Tgene | Gene symbol | MGMT | DOCK1 | Gene ID | 4255 | 1793 |
| Gene name | O-6-methylguanine-DNA methyltransferase | dedicator of cytokinesis 1 | |
| Synonyms | - | DOCK180|ced5 | |
| Cytomap | 10q26.3 | 10q26.2 | |
| Type of gene | protein-coding | protein-coding | |
| Description | methylated-DNA--protein-cysteine methyltransferase6-O-methylguanine-DNA methyltransferaseO-6-methylguanine-DNA-alkyltransferaseO6-methylguanine-DNA methyltransferasemethylguanine-DNA methyltransferase | dedicator of cytokinesis protein 1180 kDa protein downstream of CRKDOwnstream of CrK | |
| Modification date | 20200315 | 20200327 | |
| UniProtAcc | P16455 | Q5JSL3 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000306010, ENST00000462672, | ENST00000484400, ENST00000280333, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 10 X 7 X 6=420 | 16 X 15 X 8=1920 |
| # samples | 11 | 16 | |
| ** MAII score | log2(11/420*10)=-1.93288580414146 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(16/1920*10)=-3.58496250072116 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: MGMT [Title/Abstract] AND DOCK1 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | MGMT(131334641)-DOCK1(129237291), # samples:3 DOCK1(128769049)-MGMT(131506159), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | MGMT-DOCK1 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. MGMT-DOCK1 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. MGMT-DOCK1 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. MGMT-DOCK1 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. DOCK1-MGMT seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. DOCK1-MGMT seems lost the major protein functional domain in Tgene partner, which is a CGC 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 | MGMT | GO:0043066 | negative regulation of apoptotic process | 24147153 |
| Hgene | MGMT | GO:2000781 | positive regulation of double-strand break repair | 24147153 |
| Fusion gene breakpoints across MGMT (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 DOCK1 (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 | LIHC | TCGA-EP-A2KA-01A | MGMT | chr10 | 131334641 | - | DOCK1 | chr10 | 129237291 | + |
| ChimerDB4 | LIHC | TCGA-EP-A2KA-01A | MGMT | chr10 | 131334641 | + | DOCK1 | chr10 | 129237291 | + |
| ChimerDB4 | STAD | TCGA-BR-8284-01A | MGMT | chr10 | 131334641 | + | DOCK1 | chr10 | 128859932 | + |
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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) |
| ENST00000306010 | MGMT | chr10 | 131334641 | + | ENST00000280333 | DOCK1 | chr10 | 129237291 | + | 1941 | 250 | 32 | 850 | 272 |
| ENST00000306010 | MGMT | chr10 | 131334641 | + | ENST00000280333 | DOCK1 | chr10 | 128859932 | + | 4665 | 250 | 32 | 3574 | 1180 |
| 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 |
| ENST00000306010 | ENST00000280333 | MGMT | chr10 | 131334641 | + | DOCK1 | chr10 | 129237291 | + | 0.005283263 | 0.9947167 |
| ENST00000306010 | ENST00000280333 | MGMT | chr10 | 131334641 | + | DOCK1 | chr10 | 128859932 | + | 0.000733614 | 0.9992663 |
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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 >53402_53402_1_MGMT-DOCK1_MGMT_chr10_131334641_ENST00000306010_DOCK1_chr10_128859932_ENST00000280333_length(amino acids)=1180AA_BP=73 MLGQPAPLERFASRRPQVLAVRTVCDLVLGKMDKDCEMKRTTLDSPLGKLELSGCEQGLHEIKLLGKGTSAAELYENKGEADFVESLLQL FRSINDMMSSMSDQTVRVKGAALKYLPTIVNDVKLVFDPKELSKMFTEFILNVPMGLLTIQKLYCLIEIVHSDLFTQHDCREILLPMMTD QLKYHLERQEDLEACCQLLSHILEVLYRKDVGPTQRHVQIIMEKLLRTVNRTVISMGRDSELIGNFVACMTAILRQMEDYHYAHLIKTFG KMRTDVVDFLMETFIMFKNLIGKNVYPFDWVIMNMVQNKVFLRAINQYADMLNKKFLDQANFELQLWNNYFHLAVAFLTQESLQLENFSS AKRAKILNKYGDMRRQIGFEIRDMWYNLGQHKIKFIPEMVGPILEMTLIPETELRKATIPIFFDMMQCEFHSTRSFQMFENEIITKLDHE VEGGRGDEQYKVLFDKILLEHCRKHKYLAKTGETFVKLVVRLMERLLDYRTIMHDENKENRMSCTVNVLNFYKEIEREEMYIRYLYKLCD LHKECDNYTEAAYTLLLHAKLLKWSEDVCVAHLTQRDGYQATTQGQLKEQLYQEIIHYFDKGKMWEEAIALGKELAEQYENEMFDYEQLS ELLKKQAQFYENIVKVIRPKPDYFAVGYYGQGFPTFLRGKVFIYRGKEYERREDFEARLLTQFPNAEKMKTTSPPGDDIKNSPGQYIQCF TVKPKLDLPPKFHRPVSEQIVSFYRVNEVQRFEYSRPIRKGEKNPDNEFANMWIERTIYTTAYKLPGILRWFEVKSVFMVEISPLENAIE TMQLTNDKINSMVQQHLDDPSLPINPLSMLLNGIVDPAVMGGFANYEKAFFTDRYLQEHPEAHEKIEKLKDLIAWQIPFLAEGIRIHGDK VTEALRPFHERMEACFKQLKEKVEKEYGVRIMPSSLDDRRGSRPRSMVRSFTMPSSSRPLSVASVSSLSSDSTPSRPGSDGFALEPLLPK KMHSRSQDKLDKDDLEKEKKDKKKEKRNSKHQEIFEKEFKPTDISLQQSEAVILSETISPLRPQRPKSQVMNVIGSERRFSVSPSSPSSQ QTPPPVTPRAKLSFSMQSSLELNGMTGADVADVPPPLPLKGSVADYGNLMENQDLLGSPTPPPPPPHQRHLPPPLPSKTPPPPPPKTTRK -------------------------------------------------------------- >53402_53402_2_MGMT-DOCK1_MGMT_chr10_131334641_ENST00000306010_DOCK1_chr10_129237291_ENST00000280333_length(amino acids)=272AA_BP=73 MLGQPAPLERFASRRPQVLAVRTVCDLVLGKMDKDCEMKRTTLDSPLGKLELSGCEQGLHEIKLLGKGTSAAEFALEPLLPKKMHSRSQD KLDKDDLEKEKKDKKKEKRNSKHQEIFEKEFKPTDISLQQSEAVILSETISPLRPQRPKSQVMNVIGSERRFSVSPSSPSSQQTPPPVTP RAKLSFSMQSSLELNGMTGADVADVPPPLPLKGSVADYGNLMENQDLLGSPTPPPPPPHQRHLPPPLPSKTPPPPPPKTTRKQASVDSGI -------------------------------------------------------------- |
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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/chr10:131334641/chr10:129237291) - 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 |
| MGMT | DOCK1 |
| FUNCTION: Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated. | FUNCTION: Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP. Required for marginal zone (MZ) B-cell development, is associated with early bone marrow B-cell development, MZ B-cell formation, MZ B-cell number and marginal metallophilic macrophages morphology. Facilitates filopodia formation through the activation of CDC42. {ECO:0000250|UniProtKB:A2AF47}. |
| 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 |
| Tgene | DOCK1 | chr10:131334641 | chr10:128859932 | ENST00000280333 | 21 | 52 | 1207_1617 | 757.6666666666666 | 1866.0 | Domain | DOCKER | |
| Tgene | DOCK1 | chr10:131334641 | chr10:128859932 | ENST00000280333 | 21 | 52 | 1687_1695 | 757.6666666666666 | 1866.0 | Region | Phosphoinositide-binding | |
| Tgene | DOCK1 | chr10:131334641 | chr10:129237291 | ENST00000280333 | 47 | 52 | 1687_1695 | 1665.6666666666667 | 1866.0 | Region | Phosphoinositide-binding |
| - 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 |
| Tgene | DOCK1 | chr10:131334641 | chr10:128859932 | ENST00000280333 | 21 | 52 | 425_609 | 757.6666666666666 | 1866.0 | Domain | C2 DOCK-type | |
| Tgene | DOCK1 | chr10:131334641 | chr10:128859932 | ENST00000280333 | 21 | 52 | 9_70 | 757.6666666666666 | 1866.0 | Domain | SH3 | |
| Tgene | DOCK1 | chr10:131334641 | chr10:129237291 | ENST00000280333 | 47 | 52 | 1207_1617 | 1665.6666666666667 | 1866.0 | Domain | DOCKER | |
| Tgene | DOCK1 | chr10:131334641 | chr10:129237291 | ENST00000280333 | 47 | 52 | 425_609 | 1665.6666666666667 | 1866.0 | Domain | C2 DOCK-type | |
| Tgene | DOCK1 | chr10:131334641 | chr10:129237291 | ENST00000280333 | 47 | 52 | 9_70 | 1665.6666666666667 | 1866.0 | Domain | SH3 |
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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 |
| MGMT | |
| DOCK1 |
| - 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 |
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Related Drugs to MGMT-DOCK1 |
| 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 MGMT-DOCK1 |
| 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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