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Fusion Protein:LGMN-DGCR8 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: LGMN-DGCR8 | FusionPDB ID: 44573 | FusionGDB2.0 ID: 44573 | Hgene | Tgene | Gene symbol | LGMN | DGCR8 | Gene ID | 5641 | 54487 |
| Gene name | legumain | DGCR8 microprocessor complex subunit | |
| Synonyms | AEP|LGMN1|PRSC1 | C22orf12|DGCRK6|Gy1|pasha | |
| Cytomap | 14q32.12 | 22q11.21 | |
| Type of gene | protein-coding | protein-coding | |
| Description | legumainasparaginyl endopeptidasecysteine protease 1protease, cysteine 1protease, cysteine, 1 (legumain) | microprocessor complex subunit DGCR8DiGeorge syndrome critical region 8DiGeorge syndrome critical region gene 8 | |
| Modification date | 20200313 | 20200320 | |
| UniProtAcc | Q99538 | Q8WYQ5 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000334869, ENST00000555699, ENST00000557434, ENST00000393218, ENST00000557034, | ENST00000351989, ENST00000383024, ENST00000407755, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 6 X 6 X 3=108 | 9 X 8 X 6=432 |
| # samples | 6 | 9 | |
| ** MAII score | log2(6/108*10)=-0.84799690655495 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(9/432*10)=-2.26303440583379 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: LGMN [Title/Abstract] AND DGCR8 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | LGMN(93180168)-DGCR8(20077499), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | LGMN-DGCR8 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. LGMN-DGCR8 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. LGMN-DGCR8 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. LGMN-DGCR8 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. LGMN-DGCR8 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF. LGMN-DGCR8 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. LGMN-DGCR8 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. LGMN-DGCR8 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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 | LGMN | GO:0010447 | response to acidic pH | 18374643 |
| Hgene | LGMN | GO:0035729 | cellular response to hepatocyte growth factor stimulus | 21237226 |
| Hgene | LGMN | GO:0071277 | cellular response to calcium ion | 21237226 |
| Hgene | LGMN | GO:0090026 | positive regulation of monocyte chemotaxis | 18377911 |
| Hgene | LGMN | GO:0097202 | activation of cysteine-type endopeptidase activity | 9821970|18374643 |
| Hgene | LGMN | GO:0097264 | self proteolysis | 9821970|18374643 |
| Hgene | LGMN | GO:1904646 | cellular response to amyloid-beta | 25326800 |
| Hgene | LGMN | GO:2001028 | positive regulation of endothelial cell chemotaxis | 18377911 |
| Tgene | DGCR8 | GO:0031053 | primary miRNA processing | 15531877|15574589|24449907|24910438 |
| Fusion gene breakpoints across LGMN (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 DGCR8 (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 | STAD | TCGA-D7-6820-01A | LGMN | chr14 | 93180168 | - | DGCR8 | chr22 | 20077499 | + |
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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) |
| ENST00000393218 | LGMN | chr14 | 93180168 | - | ENST00000351989 | DGCR8 | chr22 | 20077499 | + | 3943 | 881 | 338 | 2179 | 613 |
| ENST00000393218 | LGMN | chr14 | 93180168 | - | ENST00000383024 | DGCR8 | chr22 | 20077499 | + | 3848 | 881 | 338 | 2080 | 580 |
| ENST00000393218 | LGMN | chr14 | 93180168 | - | ENST00000407755 | DGCR8 | chr22 | 20077499 | + | 3845 | 881 | 338 | 2080 | 580 |
| 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 |
| ENST00000393218 | ENST00000351989 | LGMN | chr14 | 93180168 | - | DGCR8 | chr22 | 20077499 | + | 0.001904641 | 0.99809533 |
| ENST00000393218 | ENST00000383024 | LGMN | chr14 | 93180168 | - | DGCR8 | chr22 | 20077499 | + | 0.002046708 | 0.9979533 |
| ENST00000393218 | ENST00000407755 | LGMN | chr14 | 93180168 | - | DGCR8 | chr22 | 20077499 | + | 0.002059775 | 0.99794024 |
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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 >44573_44573_1_LGMN-DGCR8_LGMN_chr14_93180168_ENST00000393218_DGCR8_chr22_20077499_ENST00000351989_length(amino acids)=613AA_BP=181 MVWKVAVFLSVALGIGAVPIDDPEDGGKHWVVIVAGSNGWYNYRHQADACHAYQIIHRNGIPDEQIVVMMYDDIAYSEDNPTPGIVINRP NGTDVYQGVPKDYTGEDVTPQNFLAVLRGDAEAVKGIGSGKVLKSGPQDHVFIYFTDHGSTGILVFPNEDLHVKDLNETIHYMYKHKMYR KKHDPPLSSIPCLHYKKMKDNEEREQSSDLTPSGDVSPVKPLSRSAELEFPLDEPDSMGADPGPPDEKDPLGAEAAPGALGQVKAKVEVC KDESVDLEEFRSYLEKRFDFEQVTVKKFRTWAERRQFNREMKRKQAESERPILPANQKLITLSVQDAPTKKEFVINPNGKSEVCILHEYM QRVLKVRPVYNFFECENPSEPFGASVTIDGVTYGSGTASSKKLAKNKAARATLEILIPDFVKQTSEEKPKDSEELEYFNHISIEDSRVYE LTSKAGLLSPYQILHECLKRNHGMGDTSIKFEVVPGKNQKSEYVMACGKHTVRGWCKNKRVGKQLASQKILQLLHPHVKNWGSLLRMYGR -------------------------------------------------------------- >44573_44573_2_LGMN-DGCR8_LGMN_chr14_93180168_ENST00000393218_DGCR8_chr22_20077499_ENST00000383024_length(amino acids)=580AA_BP=181 MVWKVAVFLSVALGIGAVPIDDPEDGGKHWVVIVAGSNGWYNYRHQADACHAYQIIHRNGIPDEQIVVMMYDDIAYSEDNPTPGIVINRP NGTDVYQGVPKDYTGEDVTPQNFLAVLRGDAEAVKGIGSGKVLKSGPQDHVFIYFTDHGSTGILVFPNEDLHVKDLNETIHYMYKHKMYR KKHDPPLSSIPCLHYKKMKDNEEREQSSDLTPSGDVSPVKPLSRSAELEFPLDEPDSMGADPGPPDEKDPLGAEAAPGALGQVKAKVEVC KDESVDLEEFRSYLEKRFDFEQVTVKKFRTWAERRQFNREMKRKQAESERPILPANQKLITLSVQDAPTKKEFVINPNGKSEVCILHEYM QRVLKVRPVYNFFECARATLEILIPDFVKQTSEEKPKDSEELEYFNHISIEDSRVYELTSKAGLLSPYQILHECLKRNHGMGDTSIKFEV VPGKNQKSEYVMACGKHTVRGWCKNKRVGKQLASQKILQLLHPHVKNWGSLLRMYGRESSKMVKQETSDKSVIELQQYAKKNKPNLHILS -------------------------------------------------------------- >44573_44573_3_LGMN-DGCR8_LGMN_chr14_93180168_ENST00000393218_DGCR8_chr22_20077499_ENST00000407755_length(amino acids)=580AA_BP=181 MVWKVAVFLSVALGIGAVPIDDPEDGGKHWVVIVAGSNGWYNYRHQADACHAYQIIHRNGIPDEQIVVMMYDDIAYSEDNPTPGIVINRP NGTDVYQGVPKDYTGEDVTPQNFLAVLRGDAEAVKGIGSGKVLKSGPQDHVFIYFTDHGSTGILVFPNEDLHVKDLNETIHYMYKHKMYR KKHDPPLSSIPCLHYKKMKDNEEREQSSDLTPSGDVSPVKPLSRSAELEFPLDEPDSMGADPGPPDEKDPLGAEAAPGALGQVKAKVEVC KDESVDLEEFRSYLEKRFDFEQVTVKKFRTWAERRQFNREMKRKQAESERPILPANQKLITLSVQDAPTKKEFVINPNGKSEVCILHEYM QRVLKVRPVYNFFECARATLEILIPDFVKQTSEEKPKDSEELEYFNHISIEDSRVYELTSKAGLLSPYQILHECLKRNHGMGDTSIKFEV VPGKNQKSEYVMACGKHTVRGWCKNKRVGKQLASQKILQLLHPHVKNWGSLLRMYGRESSKMVKQETSDKSVIELQQYAKKNKPNLHILS -------------------------------------------------------------- |
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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/chr14:93180168/chr22:20077499) - 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 |
| LGMN | DGCR8 |
| FUNCTION: Has a strict specificity for hydrolysis of asparaginyl bonds. Can also cleave aspartyl bonds slowly, especially under acidic conditions. Required for normal lysosomal protein degradation in renal proximal tubules. Required for normal degradation of internalized EGFR. Plays a role in the regulation of cell proliferation via its role in EGFR degradation (By similarity). May be involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system. {ECO:0000250, ECO:0000269|PubMed:23776206}. | FUNCTION: Component of the microprocessor complex that acts as a RNA- and heme-binding protein that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DGCR8 function as a molecular anchor necessary for the recognition of pri-miRNA at dsRNA-ssRNA junction and directs DROSHA to cleave 11 bp away form the junction to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs (PubMed:26027739, PubMed:26748718). The heme-bound DGCR8 dimer binds pri-miRNAs as a cooperative trimer (of dimers) and is active in triggering pri-miRNA cleavage, whereas the heme-free DGCR8 monomer binds pri-miRNAs as a dimer and is much less active. Both double-stranded and single-stranded regions of a pri-miRNA are required for its binding (PubMed:15531877, PubMed:15574589, PubMed:15589161, PubMed:16751099, PubMed:16906129, PubMed:16963499, PubMed:17159994). Specifically recognizes and binds N6-methyladenosine (m6A)-containing pri-miRNAs, a modification required for pri-miRNAs processing (PubMed:25799998). Involved in the silencing of embryonic stem cell self-renewal (By similarity). {ECO:0000250|UniProtKB:Q9EQM6, ECO:0000269|PubMed:15531877, ECO:0000269|PubMed:15574589, ECO:0000269|PubMed:15589161, ECO:0000269|PubMed:16751099, ECO:0000269|PubMed:16906129, ECO:0000269|PubMed:16963499, ECO:0000269|PubMed:17159994, ECO:0000269|PubMed:25799998, ECO:0000269|PubMed:26027739, ECO:0000269|PubMed:26748718}. |
| 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 | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000351989 | 3 | 14 | 511_578 | 341.0 | 774.0 | Domain | DRBM 1 | |
| Tgene | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000351989 | 3 | 14 | 620_685 | 341.0 | 774.0 | Domain | DRBM 2 | |
| Tgene | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000383024 | 3 | 13 | 511_578 | 341.0 | 741.0 | Domain | DRBM 1 | |
| Tgene | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000383024 | 3 | 13 | 620_685 | 341.0 | 741.0 | Domain | DRBM 2 | |
| Tgene | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000407755 | 2 | 12 | 511_578 | 341.0 | 741.0 | Domain | DRBM 1 | |
| Tgene | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000407755 | 2 | 12 | 620_685 | 341.0 | 741.0 | Domain | DRBM 2 |
| - 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 | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000351989 | 3 | 14 | 301_334 | 341.0 | 774.0 | Domain | WW | |
| Tgene | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000383024 | 3 | 13 | 301_334 | 341.0 | 741.0 | Domain | WW | |
| Tgene | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000407755 | 2 | 12 | 301_334 | 341.0 | 741.0 | Domain | WW | |
| Tgene | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000351989 | 3 | 14 | 1_275 | 341.0 | 774.0 | Region | Note=Necessary for nuclear localization and retention | |
| Tgene | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000351989 | 3 | 14 | 276_751 | 341.0 | 774.0 | Region | Note=Necessary for heme-binding and pri-miRNA processing | |
| Tgene | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000383024 | 3 | 13 | 1_275 | 341.0 | 741.0 | Region | Note=Necessary for nuclear localization and retention | |
| Tgene | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000383024 | 3 | 13 | 276_751 | 341.0 | 741.0 | Region | Note=Necessary for heme-binding and pri-miRNA processing | |
| Tgene | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000407755 | 2 | 12 | 1_275 | 341.0 | 741.0 | Region | Note=Necessary for nuclear localization and retention | |
| Tgene | DGCR8 | chr14:93180168 | chr22:20077499 | ENST00000407755 | 2 | 12 | 276_751 | 341.0 | 741.0 | Region | Note=Necessary for heme-binding and pri-miRNA processing |
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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 |
| LGMN | |
| DGCR8 |
| - 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 LGMN-DGCR8 |
| 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 LGMN-DGCR8 |
| 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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