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Fusion Protein:NKD1-BRD7 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: NKD1-BRD7 | FusionPDB ID: 59266 | FusionGDB2.0 ID: 59266 | Hgene | Tgene | Gene symbol | NKD1 | BRD7 | Gene ID | 85407 | 29117 |
| Gene name | NKD inhibitor of WNT signaling pathway 1 | bromodomain containing 7 | |
| Synonyms | Naked1 | BP75|CELTIX1|NAG4 | |
| Cytomap | 16q12.1 | 16q12.1 | |
| Type of gene | protein-coding | protein-coding | |
| Description | protein naked cuticle homolog 1Dvl-binding proteinNKD1, WNT signaling pathway inhibitornaked cuticle homolog 1naked cuticle-1naked-1 | bromodomain-containing protein 775 kDa bromodomain proteinprotein CELTIX-1 | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | Q969G9 Main function of 5'-partner protein: FUNCTION: Cell autonomous antagonist of the canonical Wnt signaling pathway. May activate a second Wnt signaling pathway that controls planar cell polarity. {ECO:0000269|PubMed:11752446, ECO:0000269|PubMed:15687260, ECO:0000269|PubMed:16567647}. | Q9NPI1 Main function of 5'-partner protein: FUNCTION: Acts both as coactivator and as corepressor. May play a role in chromatin remodeling. Activator of the Wnt signaling pathway in a DVL1-dependent manner by negatively regulating the GSK3B phosphotransferase activity. Induces dephosphorylation of GSK3B at 'Tyr-216'. Down-regulates TRIM24-mediated activation of transcriptional activation by AR (By similarity). Transcriptional corepressor that down-regulates the expression of target genes. Binds to target promoters, leading to increased histone H3 acetylation at 'Lys-9' (H3K9ac). Binds to the ESR1 promoter. Recruits BRCA1 and POU2F1 to the ESR1 promoter. Coactivator for TP53-mediated activation of transcription of a set of target genes. Required for TP53-mediated cell-cycle arrest in response to oncogene activation. Promotes acetylation of TP53 at 'Lys-382', and thereby promotes efficient recruitment of TP53 to target promoters. Inhibits cell cycle progression from G1 to S phase. {ECO:0000250, ECO:0000269|PubMed:16265664, ECO:0000269|PubMed:16475162, ECO:0000269|PubMed:20215511, ECO:0000269|PubMed:20228809, ECO:0000269|PubMed:20660729}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000564336, ENST00000268459, | ENST00000394688, ENST00000394689, ENST00000401491, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 7 X 4 X 6=168 | 5 X 5 X 3=75 |
| # samples | 8 | 5 | |
| ** MAII score | log2(8/168*10)=-1.0703893278914 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(5/75*10)=-0.584962500721156 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: NKD1 [Title/Abstract] AND BRD7 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: NKD1 [Title/Abstract] AND BRD7 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | NKD1(50583466)-BRD7(50388833), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | NKD1-BRD7 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. NKD1-BRD7 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. NKD1-BRD7 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. NKD1-BRD7 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. | ||
| * 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 | BRD7 | GO:0006357 | regulation of transcription by RNA polymerase II | 12489984 |
| Tgene | BRD7 | GO:0008285 | negative regulation of cell proliferation | 20228809 |
| Tgene | BRD7 | GO:0035066 | positive regulation of histone acetylation | 20228809 |
| Tgene | BRD7 | GO:0045892 | negative regulation of transcription, DNA-templated | 16265664 |
| Tgene | BRD7 | GO:0045893 | positive regulation of transcription, DNA-templated | 20228809 |
| Tgene | BRD7 | GO:2000134 | negative regulation of G1/S transition of mitotic cell cycle | 16265664 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr16:50583466/chr16:50388833) - 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 NKD1 (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 BRD7 (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) |
| ENST00000268459 | NKD1 | chr16 | 50583466 | + | ENST00000394688 | BRD7 | chr16 | 50388833 | - | 5368 | 416 | 134 | 2113 | 659 |
| ENST00000268459 | NKD1 | chr16 | 50583466 | + | ENST00000394689 | BRD7 | chr16 | 50388833 | - | 2298 | 416 | 134 | 2116 | 660 |
| 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 |
| ENST00000268459 | ENST00000394688 | NKD1 | chr16 | 50583466 | + | BRD7 | chr16 | 50388833 | - | 0.00040003 | 0.9996 |
| ENST00000268459 | ENST00000394689 | NKD1 | chr16 | 50583466 | + | BRD7 | chr16 | 50388833 | - | 0.002033719 | 0.9979663 |
| 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 NKD1-BRD7 |
| +/-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 NKD1-BRD7 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 NKD1-BRD7 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 NKD1-BRD7 |
| 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 NKD1-BRD7 |
| 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 NKD1-BRD7 |
| 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 NKD1-BRD7 |
| 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 NKD1-BRD7 |
| 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 NKD1-BRD7 |
| 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 NKD1-BRD7 |
| 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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