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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:FUS-GBAS

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FUS-GBAS
FusionPDB ID: 31804
FusionGDB2.0 ID: 31804
HgeneTgene
Gene symbol

FUS

GBAS

Gene ID

2521

2631

Gene nameFUS RNA binding proteinnipsnap homolog 2
SynonymsALS6|ETM4|FUS1|HNRNPP2|POMP75|TLSGBAS
Cytomap

16p11.2

7p11.2

Type of geneprotein-codingprotein-coding
DescriptionRNA-binding protein FUS75 kDa DNA-pairing proteinfus-like proteinfused in sarcomafusion gene in myxoid liposarcomaheterogeneous nuclear ribonucleoprotein P2oncogene FUSoncogene TLStranslocated in liposarcoma proteinprotein NipSnap homolog 24-nitrophenylphosphatase domain and non-neuronal SNAP25-like 2glioblastoma amplified sequence
Modification date2020032920200313
UniProtAcc

P35637

Main function of 5'-partner protein: FUNCTION: DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response (PubMed:27731383). Binds to nascent pre-mRNAs and acts as a molecular mediator between RNA polymerase II and U1 small nuclear ribonucleoprotein thereby coupling transcription and splicing (PubMed:26124092). Binds also its own pre-mRNA and autoregulates its expression; this autoregulation mechanism is mediated by non-sense-mediated decay (PubMed:24204307). Plays a role in DNA repair mechanisms by promoting D-loop formation and homologous recombination during DNA double-strand break repair (PubMed:10567410). In neuronal cells, plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis (By similarity). {ECO:0000250|UniProtKB:P56959, ECO:0000269|PubMed:10567410, ECO:0000269|PubMed:24204307, ECO:0000269|PubMed:26124092, ECO:0000269|PubMed:27731383}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000254108, ENST00000380244, 
ENST00000568685, ENST00000474990, 
ENST00000487370, ENST00000322090, 
ENST00000446778, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score37 X 37 X 16=2190410 X 8 X 6=480
# samples 4411
** MAII scorelog2(44/21904*10)=-5.63754701773324
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/480*10)=-2.12553088208386
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: FUS [Title/Abstract] AND GBAS [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FUS [Title/Abstract] AND GBAS [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)FUS(31196500)-GBAS(56062586), # samples:1
Anticipated loss of major functional domain due to fusion event.FUS-GBAS 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.
FUS-GBAS 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.
FUS-GBAS 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.
FUS-GBAS 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
HgeneFUS

GO:0006355

regulation of transcription, DNA-templated

26124092

HgeneFUS

GO:0006357

regulation of transcription by RNA polymerase II

25453086

HgeneFUS

GO:0008380

RNA splicing

26124092

HgeneFUS

GO:0043484

regulation of RNA splicing

25453086|27731383

HgeneFUS

GO:0048255

mRNA stabilization

27378374

HgeneFUS

GO:0051260

protein homooligomerization

25453086

HgeneFUS

GO:1905168

positive regulation of double-strand break repair via homologous recombination

10567410



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/chr16:31196500/chr7:56062586)
- 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 FUS (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 GBAS (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)
ENST00000254108FUSchr1631196500+ENST00000446778GBASchr756062586+2222869271112361
ENST00000254108FUSchr1631196500+ENST00000322090GBASchr756062586+2222869271112361
ENST00000380244FUSchr1631196500+ENST00000446778GBASchr756062586+2190837521080342
ENST00000380244FUSchr1631196500+ENST00000322090GBASchr756062586+2190837521080342
ENST00000568685FUSchr1631196500+ENST00000446778GBASchr756062586+2181828401071343
ENST00000568685FUSchr1631196500+ENST00000322090GBASchr756062586+2181828401071343

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
ENST00000254108ENST00000446778FUSchr1631196500+GBASchr756062586+0.0023335120.9976665
ENST00000254108ENST00000322090FUSchr1631196500+GBASchr756062586+0.0023335120.9976665
ENST00000380244ENST00000446778FUSchr1631196500+GBASchr756062586+0.0005994240.9994006
ENST00000380244ENST00000322090FUSchr1631196500+GBASchr756062586+0.0005994240.9994006
ENST00000568685ENST00000446778FUSchr1631196500+GBASchr756062586+0.002315430.9976846
ENST00000568685ENST00000322090FUSchr1631196500+GBASchr756062586+0.002315430.9976846

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 FUS-GBAS

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FUSchr1631196500GBASchr756062586828220SGGGGSGGYGQQDRGGRGRGGSGGGG
FUSchr1631196500GBASchr756062586837219SGGGGSGGYGQQDRGGRGRGGSGGGG
FUSchr1631196500GBASchr756062586869238SGGGGSGGYGQQDRGGRGRGGSGGGG

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Potential FusionNeoAntigen Information of FUS-GBAS 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.

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)

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Potential FusionNeoAntigen Information of FUS-GBAS 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 FUS-GBAS

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FUS-GBAS

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

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Vaccine Design for the FusionNeoAntigens of FUS-GBAS

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

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 FUS-GBAS

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

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Potential target of CAR-T therapy development for FUS-GBAS

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 FUS-GBAS

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 FUS-GBAS

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
HgeneFUSC1842675AMYOTROPHIC LATERAL SCLEROSIS 6 (disorder)5UNIPROT
HgeneFUSC3468114Juvenile amyotrophic lateral sclerosis5ORPHANET
HgeneFUSC0002736Amyotrophic Lateral Sclerosis2CTD_human;ORPHANET
HgeneFUSC0206634Liposarcoma, Myxoid2CTD_human;ORPHANET
HgeneFUSC0393554Amyotrophic Lateral Sclerosis With Dementia1CTD_human
HgeneFUSC0497327Dementia1GENOMICS_ENGLAND
HgeneFUSC0543859Amyotrophic Lateral Sclerosis, Guam Form1CTD_human
HgeneFUSC3539195TREMOR, HEREDITARY ESSENTIAL, 41CTD_human;UNIPROT
HgeneFUSC3888102Frontotemporal Dementia With Motor Neuron Disease1ORPHANET