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Fusion Protein:HOXB3-FAP |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: HOXB3-FAP | FusionPDB ID: 37427 | FusionGDB2.0 ID: 37427 | Hgene | Tgene | Gene symbol | HOXB3 | FAP | Gene ID | 3213 | 11146 |
| Gene name | homeobox B3 | glomulin, FKBP associated protein | |
| Synonyms | HOX2|HOX2G|Hox-2.7 | FAP|FAP48|FAP68|FKBPAP|GLML|GVM|VMGLOM | |
| Cytomap | 17q21.32 | 1p22.1 | |
| Type of gene | protein-coding | protein-coding | |
| Description | homeobox protein Hox-B3homeo box 2Ghomeobox protein Hox-2.7homeobox protein Hox-2G | glomulinFK506-binding protein-associated proteinFKBP-associated protein | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | P14651 Main function of 5'-partner protein: FUNCTION: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. | Q12884 Main function of 5'-partner protein: FUNCTION: Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammation and tumor growth. Both plasma membrane and soluble forms exhibit post-proline cleaving endopeptidase activity, with a marked preference for Ala/Ser-Gly-Pro-Ser/Asn/Ala consensus sequences, on substrate such as alpha-2-antiplasmin SERPINF2 and SPRY2 (PubMed:14751930, PubMed:16223769, PubMed:16480718, PubMed:16410248, PubMed:17381073, PubMed:18095711, PubMed:21288888, PubMed:24371721). Degrade also gelatin, heat-denatured type I collagen, but not native collagen type I and IV, vibronectin, tenascin, laminin, fibronectin, fibrin or casein (PubMed:9065413, PubMed:2172980, PubMed:7923219, PubMed:10347120, PubMed:10455171, PubMed:12376466, PubMed:16223769, PubMed:16651416, PubMed:18095711). Also has dipeptidyl peptidase activity, exhibiting the ability to hydrolyze the prolyl bond two residues from the N-terminus of synthetic dipeptide substrates provided that the penultimate residue is proline, with a preference for Ala-Pro, Ile-Pro, Gly-Pro, Arg-Pro and Pro-Pro (PubMed:10347120, PubMed:10593948, PubMed:16175601, PubMed:16223769, PubMed:16651416, PubMed:16410248, PubMed:17381073, PubMed:21314817, PubMed:24371721, PubMed:24717288). Natural neuropeptide hormones for dipeptidyl peptidase are the neuropeptide Y (NPY), peptide YY (PYY), substance P (TAC1) and brain natriuretic peptide 32 (NPPB) (PubMed:21314817). The plasma membrane form, in association with either DPP4, PLAUR or integrins, is involved in the pericellular proteolysis of the extracellular matrix (ECM), and hence promotes cell adhesion, migration and invasion through the ECM. Plays a role in tissue remodeling during development and wound healing. Participates in the cell invasiveness towards the ECM in malignant melanoma cancers. Enhances tumor growth progression by increasing angiogenesis, collagen fiber degradation and apoptosis and by reducing antitumor response of the immune system. Promotes glioma cell invasion through the brain parenchyma by degrading the proteoglycan brevican. Acts as a tumor suppressor in melanocytic cells through regulation of cell proliferation and survival in a serine protease activity-independent manner. {ECO:0000250|UniProtKB:P97321, ECO:0000269|PubMed:10347120, ECO:0000269|PubMed:10455171, ECO:0000269|PubMed:10593948, ECO:0000269|PubMed:12376466, ECO:0000269|PubMed:14751930, ECO:0000269|PubMed:16175601, ECO:0000269|PubMed:16223769, ECO:0000269|PubMed:16410248, ECO:0000269|PubMed:16480718, ECO:0000269|PubMed:16651416, ECO:0000269|PubMed:17105646, ECO:0000269|PubMed:17381073, ECO:0000269|PubMed:18095711, ECO:0000269|PubMed:20707604, ECO:0000269|PubMed:21288888, ECO:0000269|PubMed:21314817, ECO:0000269|PubMed:2172980, ECO:0000269|PubMed:24371721, ECO:0000269|PubMed:24717288, ECO:0000269|PubMed:7923219, ECO:0000269|PubMed:9065413}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000465120, ENST00000490677, ENST00000311626, ENST00000460160, ENST00000485909, ENST00000489475, ENST00000498678, ENST00000470495, ENST00000472863, ENST00000476342, ENST00000552000, | ENST00000493182, ENST00000188790, ENST00000443424, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 9 X 6 X 6=324 | 3 X 4 X 3=36 |
| # samples | 10 | 3 | |
| ** MAII score | log2(10/324*10)=-1.6959938131099 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(3/36*10)=-0.263034405833794 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: HOXB3 [Title/Abstract] AND FAP [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: HOXB3 [Title/Abstract] AND FAP [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | HOXB3(46651199)-FAP(163046264), # samples:1 HOXB3(46651199)-FAP(163044873), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | HOXB3-FAP 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. HOXB3-FAP 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. HOXB3-FAP seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF. HOXB3-FAP 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 |
| Hgene | HOXB3 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 9556594 |
| Tgene | FAP | GO:0007166 | cell surface receptor signaling pathway | 12604780 |
| Tgene | FAP | GO:0008285 | negative regulation of cell proliferation | 12604780 |
| Tgene | FAP | GO:0042130 | negative regulation of T cell proliferation | 12604780 |
| Tgene | FAP | GO:0042327 | positive regulation of phosphorylation | 11571281 |
| Tgene | FAP | GO:0045086 | positive regulation of interleukin-2 biosynthetic process | 12604780 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr17:46651199/chr2:163046264) - 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 HOXB3 (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 FAP (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) |
| ENST00000465120 | HOXB3 | chr17 | 46651199 | - | ENST00000188790 | FAP | chr2 | 163044873 | - | 1252 | 299 | 231 | 962 | 243 |
| ENST00000465120 | HOXB3 | chr17 | 46651199 | - | ENST00000443424 | FAP | chr2 | 163044873 | - | 1224 | 299 | 231 | 962 | 243 |
| 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 |
| ENST00000465120 | ENST00000188790 | HOXB3 | chr17 | 46651199 | - | FAP | chr2 | 163044873 | - | 0.000744289 | 0.9992557 |
| ENST00000465120 | ENST00000443424 | HOXB3 | chr17 | 46651199 | - | FAP | chr2 | 163044873 | - | 0.000765931 | 0.9992341 |
| 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 HOXB3-FAP |
| +/-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 |
| HOXB3 | chr17 | 46651199 | FAP | chr2 | 163044873 | 299 | 22 | DLQSSGERRREAQRYGGPCSQSVRSV |
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Potential FusionNeoAntigen Information of HOXB3-FAP 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. |
| HOXB3-FAP_46651199_163044873.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) |
| HOXB3-FAP | chr17 | 46651199 | chr2 | 163044873 | 299 | HLA-B50:01 | REAQRYGGP | 0.1275 | 0.7937 | 9 | 18 |
| HOXB3-FAP | chr17 | 46651199 | chr2 | 163044873 | 299 | HLA-B27:04 | QRYGGPCSQSV | 1 | 0.582 | 12 | 23 |
| HOXB3-FAP | chr17 | 46651199 | chr2 | 163044873 | 299 | HLA-B27:07 | QRYGGPCSQSV | 1 | 0.6003 | 12 | 23 |
| HOXB3-FAP | chr17 | 46651199 | chr2 | 163044873 | 299 | HLA-B39:06 | QRYGGPCSQSV | 0.9972 | 0.8831 | 12 | 23 |
| HOXB3-FAP | chr17 | 46651199 | chr2 | 163044873 | 299 | HLA-B73:01 | QRYGGPCSQSV | 0.9997 | 0.8045 | 12 | 23 |
| HOXB3-FAP | chr17 | 46651199 | chr2 | 163044873 | 299 | HLA-B50:05 | REAQRYGGP | 0.1275 | 0.7937 | 9 | 18 |
| HOXB3-FAP | chr17 | 46651199 | chr2 | 163044873 | 299 | HLA-B50:04 | REAQRYGGP | 0.1275 | 0.7937 | 9 | 18 |
| HOXB3-FAP | chr17 | 46651199 | chr2 | 163044873 | 299 | HLA-B27:06 | QRYGGPCSQSV | 1 | 0.603 | 12 | 23 |
| HOXB3-FAP | chr17 | 46651199 | chr2 | 163044873 | 299 | HLA-B27:10 | QRYGGPCSQSV | 1 | 0.5875 | 12 | 23 |
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Potential FusionNeoAntigen Information of HOXB3-FAP 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 HOXB3-FAP |
| 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 |
| 2102 | ERRREAQRYGGPCS | HOXB3 | FAP | chr17 | 46651199 | chr2 | 163044873 | 299 |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HOXB3-FAP |
| 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 | 2102 | ERRREAQRYGGPCS | -7.15543 | -7.26883 |
| HLA-B14:02 | 3BVN | 2102 | ERRREAQRYGGPCS | -4.77435 | -5.80965 |
| HLA-B52:01 | 3W39 | 2102 | ERRREAQRYGGPCS | -6.80875 | -6.92215 |
| HLA-B52:01 | 3W39 | 2102 | ERRREAQRYGGPCS | -4.20386 | -5.23916 |
| HLA-A11:01 | 4UQ2 | 2102 | ERRREAQRYGGPCS | -7.5194 | -8.5547 |
| HLA-A11:01 | 4UQ2 | 2102 | ERRREAQRYGGPCS | -6.9601 | -7.0735 |
| HLA-A24:02 | 5HGA | 2102 | ERRREAQRYGGPCS | -7.52403 | -7.63743 |
| HLA-A24:02 | 5HGA | 2102 | ERRREAQRYGGPCS | -5.82433 | -6.85963 |
| HLA-B27:05 | 6PYJ | 2102 | ERRREAQRYGGPCS | -3.28285 | -4.31815 |
| HLA-B44:05 | 3DX8 | 2102 | ERRREAQRYGGPCS | -5.91172 | -6.94702 |
| HLA-B44:05 | 3DX8 | 2102 | ERRREAQRYGGPCS | -4.24346 | -4.35686 |
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Vaccine Design for the FusionNeoAntigens of HOXB3-FAP |
| 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 |
| HOXB3-FAP | chr17 | 46651199 | chr2 | 163044873 | 12 | 23 | QRYGGPCSQSV | AAGGTATGGTGGTCCCTGCAGTCAGAGTGTAAG |
| HOXB3-FAP | chr17 | 46651199 | chr2 | 163044873 | 9 | 18 | REAQRYGGP | AGAGGCGCAAAGGTATGGTGGTCCCTG |
| 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 HOXB3-FAP |
| 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 | HOXB3-FAP | chr17 | 46651199 | ENST00000465120 | chr2 | 163044873 | ENST00000188790 | TCGA-B5-A5OD-01A |
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Potential target of CAR-T therapy development for HOXB3-FAP |
| 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 HOXB3-FAP |
| 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 HOXB3-FAP |
| 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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