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Fusion Protein:BCAR3-ABCA4 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: BCAR3-ABCA4 | FusionPDB ID: 9162 | FusionGDB2.0 ID: 9162 | Hgene | Tgene | Gene symbol | BCAR3 | ABCA4 | Gene ID | 8412 | 24 |
| Gene name | BCAR3 adaptor protein, NSP family member | ATP binding cassette subfamily A member 4 | |
| Synonyms | AND-34|NSP2|SH2D3B | ABC10|ABCR|ARMD2|CORD3|FFM|RMP|RP19|STGD|STGD1 | |
| Cytomap | 1p22.1 | 1p22.1 | |
| Type of gene | protein-coding | protein-coding | |
| Description | breast cancer anti-estrogen resistance protein 3BCAR3, NSP family adaptor proteinSH2 domain-containing protein 3Bbreast cancer anti-estrogen resistance 3breast cancer antiestrogen resistance 3 proteindJ1033H22.2 (breast cancer anti-estrogen resistanc | retinal-specific phospholipid-transporting ATPase ABCA4ATP binding cassette transporterATP-binding cassette sub-family A member 4ATP-binding cassette transporter, retinal-specificATP-binding cassette, sub-family A (ABC1), member 4ATP-binding transpor | |
| Modification date | 20200313 | 20200315 | |
| UniProtAcc | O75815 Main function of 5'-partner protein: FUNCTION: Acts as an adapter protein downstream of several growth factor receptors to promote cell proliferation, migration, and redistribution of actin fibers (PubMed:24216110). Specifically involved in INS/insulin signaling pathway by mediating MAPK1/ERK2-MAPK3/ERK1 activation and DNA synthesis (PubMed:24216110). Promotes insulin-mediated membrane ruffling (By similarity). In response to vasoconstrictor peptide EDN1, involved in the activation of RAP1 downstream of PTK2B via interaction with phosphorylated BCAR1 (PubMed:19086031). Inhibits cell migration and invasion via regulation of TGFB-mediated matrix digestion, actin filament rearrangement, and inhibition of invadopodia activity (By similarity). May inhibit TGFB-SMAD signaling, via facilitating BCAR1 and SMAD2 and/or SMAD3 interaction (By similarity). Regulates EGF-induced DNA synthesis (PubMed:18722344). Required for the maintenance of ocular lens morphology and structural integrity, potentially via regulation of focal adhesion complex signaling (By similarity). Acts upstream of PTPRA to regulate the localization of BCAR1 and PTPRA to focal adhesions, via regulation of SRC-mediated phosphorylation of PTPRA (By similarity). Positively regulates integrin-induced tyrosine phosphorylation of BCAR1 (By similarity). Acts as a guanine nucleotide exchange factor (GEF) for small GTPases RALA, RAP1A and RRAS (By similarity). However, in a contrasting study, lacks GEF activity towards RAP1 (PubMed:22081014). {ECO:0000250|UniProtKB:D3ZAZ5, ECO:0000250|UniProtKB:Q9QZK2, ECO:0000269|PubMed:18722344, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:22081014, ECO:0000269|PubMed:24216110}. | P78363 Main function of 5'-partner protein: FUNCTION: Catalyzes the translocation of specific phospholipids from the extracellular/lumenal to the cytoplasmic leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981). Transports preferentially phosphatidylethanolamine (PubMed:24097981). In the visual cycle, acts as an inward-directed retinoid flipase, retinoid substrates imported by ABCA4 from the extracellular or intradiscal (rod) membrane surfaces to the cytoplasmic membrane surface are all-trans-retinaldehyde (ATR) and N-retinyl-phosphatidyl-ethanolamine (NR-PE). Once transported to the cytoplasmic surface, ATR is reduced to vitamin A by trans-retinol dehydrogenase (tRDH) and then transferred to the retinal pigment epithelium (RPE) where it is converted to 11-cis-retinal. May play a role in photoresponse, removing ATR/NR-PE from the extracellular photoreceptor surfaces during bleach recovery. {ECO:0000269|PubMed:10075733, ECO:0000269|PubMed:24097981}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000260502, ENST00000370243, ENST00000370244, ENST00000370247, ENST00000466632, ENST00000539242, | ENST00000465352, ENST00000535735, ENST00000535881, ENST00000536513, ENST00000370225, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 11 X 12 X 9=1188 | 4 X 5 X 5=100 |
| # samples | 12 | 7 | |
| ** MAII score | log2(12/1188*10)=-3.30742852519225 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(7/100*10)=-0.514573172829758 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: BCAR3 [Title/Abstract] AND ABCA4 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: BCAR3 [Title/Abstract] AND ABCA4 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | BCAR3(94054534)-ABCA4(94495187), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | BCAR3-ABCA4 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. BCAR3-ABCA4 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. BCAR3-ABCA4 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. BCAR3-ABCA4 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. BCAR3-ABCA4 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. BCAR3-ABCA4 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 |
| Tgene | ABCA4 | GO:0045332 | phospholipid translocation | 24097981 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr1:94054534/chr1:94495187) - 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 BCAR3 (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 ABCA4 (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) |
| ENST00000370243 | BCAR3 | chr1 | 94054534 | - | ENST00000370225 | ABCA4 | chr1 | 94495187 | - | 4074 | 1204 | 68 | 3673 | 1201 |
| ENST00000370247 | BCAR3 | chr1 | 94054534 | - | ENST00000370225 | ABCA4 | chr1 | 94495187 | - | 3693 | 823 | 167 | 3292 | 1041 |
| ENST00000370243 | BCAR3 | chr1 | 94054533 | - | ENST00000370225 | ABCA4 | chr1 | 94495187 | - | 4074 | 1204 | 68 | 3673 | 1201 |
| ENST00000370247 | BCAR3 | chr1 | 94054533 | - | ENST00000370225 | ABCA4 | chr1 | 94495187 | - | 3693 | 823 | 167 | 3292 | 1041 |
| ENST00000370247 | BCAR3 | chr1 | 94079404 | - | ENST00000370225 | ABCA4 | chr1 | 94505683 | - | 3951 | 251 | 167 | 3550 | 1127 |
| 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 |
| ENST00000370243 | ENST00000370225 | BCAR3 | chr1 | 94054534 | - | ABCA4 | chr1 | 94495187 | - | 0.001855568 | 0.9981444 |
| ENST00000370247 | ENST00000370225 | BCAR3 | chr1 | 94054534 | - | ABCA4 | chr1 | 94495187 | - | 0.001294702 | 0.99870527 |
| ENST00000370243 | ENST00000370225 | BCAR3 | chr1 | 94054533 | - | ABCA4 | chr1 | 94495187 | - | 0.001855568 | 0.9981444 |
| ENST00000370247 | ENST00000370225 | BCAR3 | chr1 | 94054533 | - | ABCA4 | chr1 | 94495187 | - | 0.001294702 | 0.99870527 |
| ENST00000370247 | ENST00000370225 | BCAR3 | chr1 | 94079404 | - | ABCA4 | chr1 | 94505683 | - | 0.001484465 | 0.99851555 |
| 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 BCAR3-ABCA4 |
| +/-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 |
| BCAR3 | chr1 | 94054533 | ABCA4 | chr1 | 94495187 | 1204 | 378 | QAREQNLPRGNLLREYPCGNSTPWKT |
| BCAR3 | chr1 | 94054533 | ABCA4 | chr1 | 94495187 | 823 | 218 | QAREQNLPRGNLLREYPCGNSTPWKT |
| BCAR3 | chr1 | 94054534 | ABCA4 | chr1 | 94495187 | 1204 | 378 | QAREQNLPRGNLLREYPCGNSTPWKT |
| BCAR3 | chr1 | 94054534 | ABCA4 | chr1 | 94495187 | 823 | 218 | QAREQNLPRGNLLREYPCGNSTPWKT |
| BCAR3 | chr1 | 94079404 | ABCA4 | chr1 | 94505683 | 251 | 28 | CCFYHRKSFIGVKGTCSCSSKGFSTT |
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Potential FusionNeoAntigen Information of BCAR3-ABCA4 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. |
| BCAR3-ABCA4_94054533_94495187.msa |
| 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) |
| BCAR3-ABCA4 | chr1 | 94054533 | chr1 | 94495187 | 1204 | HLA-B35:01 | LPRGNLLREY | 0.98 | 0.6575 | 6 | 16 |
| BCAR3-ABCA4 | chr1 | 94054533 | chr1 | 94495187 | 1204 | HLA-B35:08 | LPRGNLLREY | 0.963 | 0.7277 | 6 | 16 |
| BCAR3-ABCA4 | chr1 | 94054533 | chr1 | 94495187 | 1204 | HLA-B35:77 | LPRGNLLREY | 0.98 | 0.6575 | 6 | 16 |
| BCAR3-ABCA4 | chr1 | 94054533 | chr1 | 94495187 | 1204 | HLA-B35:23 | LPRGNLLREY | 0.9777 | 0.6539 | 6 | 16 |
| BCAR3-ABCA4 | chr1 | 94054533 | chr1 | 94495187 | 1204 | HLA-B35:24 | LPRGNLLREY | 0.9739 | 0.6875 | 6 | 16 |
| BCAR3-ABCA4 | chr1 | 94054533 | chr1 | 94495187 | 1204 | HLA-B15:11 | LPRGNLLREY | 0.965 | 0.5228 | 6 | 16 |
| BCAR3-ABCA4 | chr1 | 94054533 | chr1 | 94495187 | 1204 | HLA-B15:08 | LPRGNLLREY | 0.9613 | 0.5228 | 6 | 16 |
| BCAR3-ABCA4 | chr1 | 94054533 | chr1 | 94495187 | 1204 | HLA-B35:43 | LPRGNLLREY | 0.9551 | 0.5358 | 6 | 16 |
| BCAR3-ABCA4 | chr1 | 94054533 | chr1 | 94495187 | 1204 | HLA-B35:11 | LPRGNLLREY | 0.955 | 0.6495 | 6 | 16 |
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Potential FusionNeoAntigen Information of BCAR3-ABCA4 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 BCAR3-ABCA4 |
| 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. |
| File name | BPseq | Hgene | Tgene | Hchr | Hbp | Tchr | Tbp | AAlen |
| 5412 | LPRGNLLREYPCGN | BCAR3 | ABCA4 | chr1 | 94054533 | chr1 | 94495187 | 1204 |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of BCAR3-ABCA4 |
| 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 |
| HLA-B14:02 | 3BVN | 5412 | LPRGNLLREYPCGN | -7.9962 | -8.1096 |
| HLA-B14:02 | 3BVN | 5412 | LPRGNLLREYPCGN | -5.70842 | -6.74372 |
| HLA-B52:01 | 3W39 | 5412 | LPRGNLLREYPCGN | -6.83737 | -6.95077 |
| HLA-B52:01 | 3W39 | 5412 | LPRGNLLREYPCGN | -4.4836 | -5.5189 |
| HLA-A11:01 | 4UQ2 | 5412 | LPRGNLLREYPCGN | -10.0067 | -10.1201 |
| HLA-A11:01 | 4UQ2 | 5412 | LPRGNLLREYPCGN | -9.03915 | -10.0745 |
| HLA-A24:02 | 5HGA | 5412 | LPRGNLLREYPCGN | -6.56204 | -6.67544 |
| HLA-A24:02 | 5HGA | 5412 | LPRGNLLREYPCGN | -5.42271 | -6.45801 |
| HLA-B44:05 | 3DX8 | 5412 | LPRGNLLREYPCGN | -7.85648 | -8.89178 |
| HLA-B44:05 | 3DX8 | 5412 | LPRGNLLREYPCGN | -5.3978 | -5.5112 |
| HLA-A02:01 | 6TDR | 5412 | LPRGNLLREYPCGN | -3.37154 | -4.40684 |
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Vaccine Design for the FusionNeoAntigens of BCAR3-ABCA4 |
| 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 |
| BCAR3-ABCA4 | chr1 | 94054533 | chr1 | 94495187 | 6 | 16 | LPRGNLLREY | GCCCAGGGGAAACCTCCTCAGGGAGTACCC |
| 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 BCAR3-ABCA4 |
| 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 |
| UCEC | BCAR3-ABCA4 | chr1 | 94054533 | ENST00000370243 | chr1 | 94495187 | ENST00000370225 | TCGA-AJ-A3EJ |
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Potential target of CAR-T therapy development for BCAR3-ABCA4 |
| 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 |
| Tgene | ABCA4 | chr1:94054533 | chr1:94495187 | ENST00000370225 | 28 | 50 | 1728_1748 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94054533 | chr1:94495187 | ENST00000370225 | 28 | 50 | 1760_1780 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94054533 | chr1:94495187 | ENST00000370225 | 28 | 50 | 1793_1813 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94054533 | chr1:94495187 | ENST00000370225 | 28 | 50 | 1832_1852 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94054533 | chr1:94495187 | ENST00000370225 | 28 | 50 | 1874_1894 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94054534 | chr1:94495187 | ENST00000370225 | 28 | 50 | 1728_1748 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94054534 | chr1:94495187 | ENST00000370225 | 28 | 50 | 1760_1780 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94054534 | chr1:94495187 | ENST00000370225 | 28 | 50 | 1793_1813 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94054534 | chr1:94495187 | ENST00000370225 | 28 | 50 | 1832_1852 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94054534 | chr1:94495187 | ENST00000370225 | 28 | 50 | 1874_1894 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94079404 | chr1:94505683 | ENST00000370225 | 22 | 50 | 1377_1397 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94079404 | chr1:94505683 | ENST00000370225 | 22 | 50 | 1728_1748 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94079404 | chr1:94505683 | ENST00000370225 | 22 | 50 | 1760_1780 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94079404 | chr1:94505683 | ENST00000370225 | 22 | 50 | 1793_1813 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94079404 | chr1:94505683 | ENST00000370225 | 22 | 50 | 1832_1852 | 0 | 2274.0 | Transmembrane | Helical | |
| Tgene | ABCA4 | chr1:94079404 | chr1:94505683 | ENST00000370225 | 22 | 50 | 1874_1894 | 0 | 2274.0 | Transmembrane | Helical |
| 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 BCAR3-ABCA4 |
| 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 BCAR3-ABCA4 |
| 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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