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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:EXOSC5-FCGBP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: EXOSC5-FCGBP
FusionPDB ID: 27983
FusionGDB2.0 ID: 27983
HgeneTgene
Gene symbol

EXOSC5

FCGBP

Gene ID

56915

8857

Gene nameexosome component 5Fc fragment of IgG binding protein
SynonymsRRP41B|RRP46|Rrp46p|hRrp46p|p12BFC(GAMMA)BP
Cytomap

19q13.2

19q13.2

Type of geneprotein-codingprotein-coding
Descriptionexosome complex component RRP46chronic myelogenous leukemia tumor antigen 28exosome complex exonuclease RRP46exosome component Rrp46ribosomal RNA-processing protein 46IgGFc-binding proteinHuman Fc gamma BPIgG Fc binding proteinfcgamma-binding protein antigenfcgammaBP
Modification date2020031320200313
UniProtAcc

Q9NQT4

Main function of 5'-partner protein: FUNCTION: Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. {ECO:0000269|PubMed:11782436, ECO:0000269|PubMed:21255825}.

Q9Y6R7

Main function of 5'-partner protein: FUNCTION: May be involved in the maintenance of the mucosal structure as a gel-like component of the mucosa. {ECO:0000269|PubMed:9182547}.
Ensembl transtripts involved in fusion geneENST idsENST00000221233, ENST00000596905, 
ENST00000595713, ENST00000221347, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 4 X 3=365 X 6 X 4=120
# samples 46
** MAII scorelog2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(6/120*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: EXOSC5 [Title/Abstract] AND FCGBP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: EXOSC5 [Title/Abstract] AND FCGBP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)EXOSC5(41893419)-FCGBP(40354532), # samples:2
Anticipated loss of major functional domain due to fusion event.EXOSC5-FCGBP 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.
EXOSC5-FCGBP 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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneEXOSC5

GO:0045006

DNA deamination

21255825



check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr19:41893419/chr19:40354532)
- 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.
FGviewer

check buttonRetention 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.

check buttonFusion gene breakpoints across EXOSC5 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across FCGBP (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000221233EXOSC5chr1941893419-ENST00000221347FCGBPchr1940354532-1212766521047331
ENST00000596905EXOSC5chr1941893419-ENST00000221347FCGBPchr1940354532-96151514796260
ENST00000221233EXOSC5chr1941893418-ENST00000221347FCGBPchr1940354532-1212766521047331
ENST00000596905EXOSC5chr1941893418-ENST00000221347FCGBPchr1940354532-96151514796260

check buttonDeepORF 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.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000221233ENST00000221347EXOSC5chr1941893419-FCGBPchr1940354532-0.0064425730.9935574
ENST00000596905ENST00000221347EXOSC5chr1941893419-FCGBPchr1940354532-0.0158734340.9841265
ENST00000221233ENST00000221347EXOSC5chr1941893418-FCGBPchr1940354532-0.0064425730.9935574
ENST00000596905ENST00000221347EXOSC5chr1941893418-FCGBPchr1940354532-0.0158734340.9841265

check button 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 EXOSC5-FCGBP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
EXOSC5chr1941893418FCGBPchr1940354532515167LMSSTKGLYSDTEVNGLRVDLPAEKL
EXOSC5chr1941893418FCGBPchr1940354532766238LMSSTKGLYSDTEVNGLRVDLPAEKL
EXOSC5chr1941893419FCGBPchr1940354532515167LMSSTKGLYSDTEVNGLRVDLPAEKL
EXOSC5chr1941893419FCGBPchr1940354532766238LMSSTKGLYSDTEVNGLRVDLPAEKL

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Potential FusionNeoAntigen Information of EXOSC5-FCGBP in HLA I

check button 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.
EXOSC5-FCGBP_41893418_40354532.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-A02:30GLYSDTEVNGL0.99690.5307617
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-A02:67GLYSDTEVNGL0.99690.5307617
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-A02:24GLYSDTEVNGL0.99690.5307617
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-A02:29GLYSDTEVNGL0.93870.5336617
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C04:07YSDTEVNGL0.99990.5067817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C05:09YSDTEVNGL0.99990.8176817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C04:10YSDTEVNGL0.99990.5039817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C08:15YSDTEVNGL0.99980.8771817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C01:17YSDTEVNGL0.99950.8061817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C03:07YSDTEVNGL0.99640.9751817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C04:06YSDTEVNGL0.99270.7001817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C15:06YSDTEVNGL0.99210.8855817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C03:19YSDTEVNGL0.9890.9849817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C03:08YSDTEVNGL0.9770.857817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C08:13YSDTEVNGL0.96430.9128817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C08:04YSDTEVNGL0.96430.9128817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C08:03YSDTEVNGL0.85110.9549817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C04:14YSDTEVNGL0.84760.5813817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C02:06YSDTEVNGL0.23820.9335817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C04:10LYSDTEVNGL0.99960.6064717
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C04:07LYSDTEVNGL0.99950.5825717
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C05:09YSDTEVNGLRV10.9102819
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-A02:01GLYSDTEVNGL0.99690.5307617
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C04:03YSDTEVNGL0.99990.5748817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C05:01YSDTEVNGL0.99990.8176817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C04:01YSDTEVNGL0.99990.5067817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C08:02YSDTEVNGL0.99980.8771817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C18:01YSDTEVNGL0.99980.5446817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C01:03YSDTEVNGL0.99970.7457817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C01:02YSDTEVNGL0.99960.7965817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C15:05YSDTEVNGL0.99180.8702817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C03:03YSDTEVNGL0.99040.9858817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C03:04YSDTEVNGL0.99040.9858817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C04:04YSDTEVNGL0.98930.6622817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C03:06YSDTEVNGL0.91080.9855817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C08:01YSDTEVNGL0.85110.9549817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C07:04YSDTEVNGL0.50360.7893817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C17:01YSDTEVNGL0.45570.5956817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-B07:13YSDTEVNGL0.00330.6274817
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C04:01LYSDTEVNGL0.99950.5825717
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C18:01LYSDTEVNGL0.99950.6789717
EXOSC5-FCGBPchr1941893418chr1940354532766HLA-C05:01YSDTEVNGLRV10.9102819

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Potential FusionNeoAntigen Information of EXOSC5-FCGBP in HLA II

check button 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.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of EXOSC5-FCGBP

check button3D 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 nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
2975GLYSDTEVNGLRVDEXOSC5FCGBPchr1941893418chr1940354532766

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of EXOSC5-FCGBP

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B53:011A1O2975GLYSDTEVNGLRVD-1.54455-2.57985
HLA-B51:011E282975GLYSDTEVNGLRVD-3.9567-4.992
HLA-B51:011E282975GLYSDTEVNGLRVD-2.78017-2.89357
HLA-B57:032BVO2975GLYSDTEVNGLRVD-2.28399-2.39739
HLA-A03:012XPG2975GLYSDTEVNGLRVD-5.29375-6.32905
HLA-A03:012XPG2975GLYSDTEVNGLRVD-5.13376-5.24716
HLA-B14:023BVN2975GLYSDTEVNGLRVD-5.94457-6.05797
HLA-B14:023BVN2975GLYSDTEVNGLRVD-4.02623-5.06153
HLA-B27:093CZF2975GLYSDTEVNGLRVD1.938620.90332
HLA-B52:013W392975GLYSDTEVNGLRVD-4.85197-4.96537
HLA-B52:013W392975GLYSDTEVNGLRVD-3.54046-4.57576
HLA-B18:014JQV2975GLYSDTEVNGLRVD-2.48822-2.60162
HLA-B18:014JQV2975GLYSDTEVNGLRVD-1.14207-2.17737
HLA-A11:014UQ22975GLYSDTEVNGLRVD-7.94504-8.05844
HLA-A11:014UQ22975GLYSDTEVNGLRVD-6.28371-7.31901
HLA-A24:025HGA2975GLYSDTEVNGLRVD-5.26524-5.37864
HLA-A24:025HGA2975GLYSDTEVNGLRVD-5.08104-6.11634
HLA-B57:015VUD2975GLYSDTEVNGLRVD-1.4053-2.4406
HLA-C08:026JTP2975GLYSDTEVNGLRVD-3.55917-3.67257
HLA-C08:026JTP2975GLYSDTEVNGLRVD-2.30839-3.34369
HLA-B27:056PYJ2975GLYSDTEVNGLRVD-3.69179-4.72709
HLA-B27:056PYJ2975GLYSDTEVNGLRVD-2.46172-2.57512
HLA-B27:036PZ52975GLYSDTEVNGLRVD-2.34314-3.37844
HLA-B27:036PZ52975GLYSDTEVNGLRVD-1.78038-1.89378
HLA-B44:053DX82975GLYSDTEVNGLRVD-5.34386-5.45726
HLA-B44:053DX82975GLYSDTEVNGLRVD-3.58277-4.61807
HLA-B44:021M6O2975GLYSDTEVNGLRVD-2.22341-2.33681
HLA-B44:021M6O2975GLYSDTEVNGLRVD-1.22324-2.25854
HLA-A02:016TDR2975GLYSDTEVNGLRVD-5.40572-5.51912
HLA-A02:016TDR2975GLYSDTEVNGLRVD-3.93841-4.97371

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Vaccine Design for the FusionNeoAntigens of EXOSC5-FCGBP

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
EXOSC5-FCGBPchr1941893418chr1940354532617GLYSDTEVNGLGGGCTCTACTCAGACACTGAGGTGAATGGTCTC
EXOSC5-FCGBPchr1941893418chr1940354532717LYSDTEVNGLCTCTACTCAGACACTGAGGTGAATGGTCTC
EXOSC5-FCGBPchr1941893418chr1940354532817YSDTEVNGLTACTCAGACACTGAGGTGAATGGTCTC
EXOSC5-FCGBPchr1941893418chr1940354532819YSDTEVNGLRVTACTCAGACACTGAGGTGAATGGTCTCCGAGTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of EXOSC5-FCGBP

check button 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 typeFusion geneHchrHbpHenstTchrTbpTenstSample
LIHCEXOSC5-FCGBPchr1941893418ENST00000221233chr1940354532ENST00000221347TCGA-DD-AADC

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Potential target of CAR-T therapy development for EXOSC5-FCGBP

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention 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'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button 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.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to EXOSC5-FCGBP

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to EXOSC5-FCGBP

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource