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Fusion Protein:DDX21-BEX2 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: DDX21-BEX2 | FusionPDB ID: 21927 | FusionGDB2.0 ID: 21927 | Hgene | Tgene | Gene symbol | DDX21 | BEX2 | Gene ID | 54606 | 84707 |
| Gene name | DEAD-box helicase 56 | brain expressed X-linked 2 | |
| Synonyms | DDX21|DDX26|NOH61 | BEX1|DJ79P11.1 | |
| Cytomap | 7p13 | Xq22.2 | |
| Type of gene | protein-coding | protein-coding | |
| Description | probable ATP-dependent RNA helicase DDX5661-kd nucleolar helicaseATP-dependent 61 kDa nucleolar RNA helicaseDEAD (Asp-Glu-Ala-Asp) box helicase 56DEAD (Asp-Glu-Ala-Asp) box polypeptide 56DEAD box protein 21DEAD box protein 56DEAD-box RNA helicasen | protein BEX2brain-expressed X-linked protein 2hBex2 | |
| Modification date | 20200313 | 20200315 | |
| UniProtAcc | Q9NR30 Main function of 5'-partner protein: FUNCTION: RNA helicase that acts as a sensor of the transcriptional status of both RNA polymerase (Pol) I and II: promotes ribosomal RNA (rRNA) processing and transcription from polymerase II (Pol II) (PubMed:25470060, PubMed:28790157). Binds various RNAs, such as rRNAs, snoRNAs, 7SK and, at lower extent, mRNAs (PubMed:25470060). In the nucleolus, localizes to rDNA locus, where it directly binds rRNAs and snoRNAs, and promotes rRNA transcription, processing and modification. Required for rRNA 2'-O-methylation, possibly by promoting the recruitment of late-acting snoRNAs SNORD56 and SNORD58 with pre-ribosomal complexes (PubMed:25470060, PubMed:25477391). In the nucleoplasm, binds 7SK RNA and is recruited to the promoters of Pol II-transcribed genes: acts by facilitating the release of P-TEFb from inhibitory 7SK snRNP in a manner that is dependent on its helicase activity, thereby promoting transcription of its target genes (PubMed:25470060). Functions as cofactor for JUN-activated transcription: required for phosphorylation of JUN at 'Ser-77' (PubMed:11823437, PubMed:25260534). Can unwind double-stranded RNA (helicase) and can fold or introduce a secondary structure to a single-stranded RNA (foldase) (PubMed:9461305). Together with SIRT7, required to prevent R-loop-associated DNA damage and transcription-associated genomic instability: deacetylation by SIRT7 activates the helicase activity, thereby overcoming R-loop-mediated stalling of RNA polymerases (PubMed:28790157). Involved in rRNA processing (PubMed:14559904, PubMed:18180292). May bind to specific miRNA hairpins (PubMed:28431233). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of proinflammatory cytokines via the adapter molecule TICAM1 (By similarity). {ECO:0000250|UniProtKB:Q9JIK5, ECO:0000269|PubMed:11823437, ECO:0000269|PubMed:14559904, ECO:0000269|PubMed:18180292, ECO:0000269|PubMed:25260534, ECO:0000269|PubMed:25470060, ECO:0000269|PubMed:25477391, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:9461305}. | Q9BXY8 Main function of 5'-partner protein: FUNCTION: Regulator of mitochondrial apoptosis and G1 cell cycle in breast cancer. Protects the breast cancer cells against mitochondrial apoptosis and this effect is mediated through the modulation of BCL2 protein family, which involves the positive regulation of anti-apoptotic member BCL2 and the negative regulation of pro-apoptotic members BAD, BAK1 and PUMA. Required for the normal cell cycle progression during G1 in breast cancer cells through the regulation of CCND1 and CDKN1A. Regulates the level of PP2A regulatory subunit B and PP2A phosphatase activity. {ECO:0000269|PubMed:19711341}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000354185, | ENST00000372674, ENST00000372677, ENST00000536889, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 11 X 11 X 2=242 | 3 X 2 X 1=6 |
| # samples | 12 | 3 | |
| ** MAII score | log2(12/242*10)=-1.01197264166608 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(3/6*10)=2.32192809488736 | |
| Fusion gene context | PubMed: DDX21 [Title/Abstract] AND BEX2 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: DDX21 [Title/Abstract] AND BEX2 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | DDX21(70742402)-BEX2(102564533), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | DDX21-BEX2 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. DDX21-BEX2 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. DDX21-BEX2 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF. DDX21-BEX2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. DDX21-BEX2 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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 |
| Tgene | BEX2 | GO:0042981 | regulation of apoptotic process | 19711341 |
| Tgene | BEX2 | GO:0051726 | regulation of cell cycle | 19711341 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr10:70742402/chrX:102564533) - 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 DDX21 (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 BEX2 (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) |
| ENST00000354185 | DDX21 | chr10 | 70742402 | - | ENST00000536889 | BEX2 | chrX | 102564533 | - | 4859 | 4607 | 92 | 2248 | 718 |
| 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 |
| ENST00000354185 | ENST00000536889 | DDX21 | chr10 | 70742402 | - | BEX2 | chrX | 102564533 | - | 0.000162236 | 0.99983776 |
| 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 DDX21-BEX2 |
| +/-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 DDX21-BEX2 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 DDX21-BEX2 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 DDX21-BEX2 |
| 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 DDX21-BEX2 |
| 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 DDX21-BEX2 |
| 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 DDX21-BEX2 |
| 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 DDX21-BEX2 |
| 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 DDX21-BEX2 |
| 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 DDX21-BEX2 |
| 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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