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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:EXT1-RSF1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: EXT1-RSF1
FusionPDB ID: 28012
FusionGDB2.0 ID: 28012
HgeneTgene
Gene symbol

EXT1

RSF1

Gene ID

2131

51773

Gene nameexostosin glycosyltransferase 1remodeling and spacing factor 1
SynonymsEXT|LGCR|LGS|TRPS2|TTVHBXAP|RSF-1|XAP8|p325
Cytomap

8q24.11

11q14.1

Type of geneprotein-codingprotein-coding
Descriptionexostosin-1Glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N- acetylglucosaminyltransferaseLanger-Giedion syndrome chromosome regionN-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferaseexostoses (multiple) 1glucuronosyl-N-acetylglucremodeling and spacing factor 1HBV pX-associated protein 8hepatitis B virus x-associated proteinp325 subunit of RSF chromatin-remodeling complex
Modification date2020031320200313
UniProtAcc

Q16394

Main function of 5'-partner protein: FUNCTION: Glycosyltransferase required for the biosynthesis of heparan-sulfate. The EXT1/EXT2 complex possesses substantially higher glycosyltransferase activity than EXT1 or EXT2 alone. Appears to be a tumor suppressor. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). {ECO:0000269|PubMed:11518722, ECO:0000269|PubMed:22660413}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000378204, ENST00000480887, 
ENST00000530604, ENST00000308488, 
ENST00000360355, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score17 X 15 X 9=229516 X 11 X 7=1232
# samples 2319
** MAII scorelog2(23/2295*10)=-3.3187883873568
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(19/1232*10)=-2.69693093236395
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: EXT1 [Title/Abstract] AND RSF1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: EXT1 [Title/Abstract] AND RSF1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)EXT1(118825111)-RSF1(77451981), # samples:3
Anticipated loss of major functional domain due to fusion event.EXT1-RSF1 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.
EXT1-RSF1 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.
EXT1-RSF1 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.
EXT1-RSF1 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
HgeneEXT1

GO:0006024

glycosaminoglycan biosynthetic process

12907669

HgeneEXT1

GO:0015012

heparan sulfate proteoglycan biosynthetic process

9620772|10639137

HgeneEXT1

GO:0033692

cellular polysaccharide biosynthetic process

12907669

TgeneRSF1

GO:0006334

nucleosome assembly

12972596

TgeneRSF1

GO:0006338

chromatin remodeling

9836642

TgeneRSF1

GO:0006352

DNA-templated transcription, initiation

9836642

TgeneRSF1

GO:0016584

nucleosome positioning

9836642

TgeneRSF1

GO:0043392

negative regulation of DNA binding

12972596

TgeneRSF1

GO:0045892

negative regulation of transcription, DNA-templated

11944984

TgeneRSF1

GO:0045893

positive regulation of transcription, DNA-templated

11788598

TgeneRSF1

GO:0050434

positive regulation of viral transcription

11788598



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/chr8:118825111/chr11:77451981)
- 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 EXT1 (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 RSF1 (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)
ENST00000378204EXT1chr8118825111-ENST00000308488RSF1chr1177451981-13404252976864821904
ENST00000378204EXT1chr8118825111-ENST00000360355RSF1chr1177451981-7170252976864821904
ENST00000378204EXT1chr8118825110-ENST00000308488RSF1chr1177451981-13404252976864821904
ENST00000378204EXT1chr8118825110-ENST00000360355RSF1chr1177451981-7170252976864821904

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
ENST00000378204ENST00000308488EXT1chr8118825111-RSF1chr1177451981-0.0003482910.9996517
ENST00000378204ENST00000360355EXT1chr8118825111-RSF1chr1177451981-0.0015268580.9984731
ENST00000378204ENST00000308488EXT1chr8118825110-RSF1chr1177451981-0.0003482910.9996517
ENST00000378204ENST00000360355EXT1chr8118825110-RSF1chr1177451981-0.0015268580.9984731

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 EXT1-RSF1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
EXT1chr8118825110RSF1chr11774519812529587LSLDEDTVLSTTEYLCECQFDDNLKF
EXT1chr8118825111RSF1chr11774519812529587LSLDEDTVLSTTEYLCECQFDDNLKF

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Potential FusionNeoAntigen Information of EXT1-RSF1 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.
EXT1-RSF1_118825110_77451981.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)
EXT1-RSF1chr8118825110chr11774519812529HLA-B15:02TVLSTTEY0.99350.8997614
EXT1-RSF1chr8118825110chr11774519812529HLA-B44:03TEYLCECQF0.98620.81441120
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:01TEYLCECQF0.97980.62841120
EXT1-RSF1chr8118825110chr11774519812529HLA-B35:08DTVLSTTEY0.97430.6493514
EXT1-RSF1chr8118825110chr11774519812529HLA-B35:01DTVLSTTEY0.93120.7008514
EXT1-RSF1chr8118825110chr11774519812529HLA-A02:21TVLSTTEYL0.91960.7543615
EXT1-RSF1chr8118825110chr11774519812529HLA-B15:02DTVLSTTEY0.90930.7564514
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:01DEDTVLSTTEY0.99560.8686314
EXT1-RSF1chr8118825110chr11774519812529HLA-B15:31DTVLSTTEY0.93140.6098514
EXT1-RSF1chr8118825110chr11774519812529HLA-B15:21DTVLSTTEY0.91350.7153514
EXT1-RSF1chr8118825110chr11774519812529HLA-B44:07TEYLCECQF0.98620.81441120
EXT1-RSF1chr8118825110chr11774519812529HLA-B44:26TEYLCECQF0.98620.81441120
EXT1-RSF1chr8118825110chr11774519812529HLA-B44:13TEYLCECQF0.98620.81441120
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:05TEYLCECQF0.97980.62841120
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:06TEYLCECQF0.97830.64161120
EXT1-RSF1chr8118825110chr11774519812529HLA-B35:24DTVLSTTEY0.96350.6228514
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:03TEYLCECQF0.95890.60851120
EXT1-RSF1chr8118825110chr11774519812529HLA-B35:77DTVLSTTEY0.93120.7008514
EXT1-RSF1chr8118825110chr11774519812529HLA-B35:23DTVLSTTEY0.9310.6507514
EXT1-RSF1chr8118825110chr11774519812529HLA-B35:20DTVLSTTEY0.92780.733514
EXT1-RSF1chr8118825110chr11774519812529HLA-A02:14TVLSTTEYL0.92270.6409615
EXT1-RSF1chr8118825110chr11774519812529HLA-A02:06TVLSTTEYL0.91960.7543615
EXT1-RSF1chr8118825110chr11774519812529HLA-A69:01TVLSTTEYL0.90690.7269615
EXT1-RSF1chr8118825110chr11774519812529HLA-B35:11DTVLSTTEY0.90120.7004514
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:11TEYLCECQF0.88570.66031120
EXT1-RSF1chr8118825110chr11774519812529HLA-C03:06TVLSTTEYL0.87230.9918615
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:04DTVLSTTEY0.78090.6737514
EXT1-RSF1chr8118825110chr11774519812529HLA-B15:08DTVLSTTEY0.62320.5377514
EXT1-RSF1chr8118825110chr11774519812529HLA-B15:11DTVLSTTEY0.61680.5412514
EXT1-RSF1chr8118825110chr11774519812529HLA-B35:43DTVLSTTEY0.54470.5396514
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:07DTVLSTTEY0.44260.5811514
EXT1-RSF1chr8118825110chr11774519812529HLA-C17:01TVLSTTEYL0.43370.9185615
EXT1-RSF1chr8118825110chr11774519812529HLA-A25:01EDTVLSTTEY0.4740.6603414
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:04DEDTVLSTTEY0.99690.8867314
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:08DEDTVLSTTEY0.99620.7749314
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:07DEDTVLSTTEY0.99590.8155314
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:05DEDTVLSTTEY0.99560.8686314
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:06DEDTVLSTTEY0.99450.8731314
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:03DEDTVLSTTEY0.99180.8588314
EXT1-RSF1chr8118825110chr11774519812529HLA-B18:11DEDTVLSTTEY0.97510.8144314

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Potential FusionNeoAntigen Information of EXT1-RSF1 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 EXT1-RSF1

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
9731TVLSTTEYLCECQFEXT1RSF1chr8118825110chr11774519812529

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of EXT1-RSF1

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-B14:023BVN9731TVLSTTEYLCECQF-7.9962-8.1096
HLA-B14:023BVN9731TVLSTTEYLCECQF-5.70842-6.74372
HLA-B52:013W399731TVLSTTEYLCECQF-6.83737-6.95077
HLA-B52:013W399731TVLSTTEYLCECQF-4.4836-5.5189
HLA-A11:014UQ29731TVLSTTEYLCECQF-10.0067-10.1201
HLA-A11:014UQ29731TVLSTTEYLCECQF-9.03915-10.0745
HLA-A24:025HGA9731TVLSTTEYLCECQF-6.56204-6.67544
HLA-A24:025HGA9731TVLSTTEYLCECQF-5.42271-6.45801
HLA-B44:053DX89731TVLSTTEYLCECQF-7.85648-8.89178
HLA-B44:053DX89731TVLSTTEYLCECQF-5.3978-5.5112
HLA-A02:016TDR9731TVLSTTEYLCECQF-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of EXT1-RSF1

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
EXT1-RSF1chr8118825110chr11774519811120TEYLCECQFACAGAGTACCTCTGTGAGTGTCAGTTT
EXT1-RSF1chr8118825110chr1177451981314DEDTVLSTTEYGACGAGGACACGGTGCTTTCAACAACAGAGTAC
EXT1-RSF1chr8118825110chr1177451981414EDTVLSTTEYGAGGACACGGTGCTTTCAACAACAGAGTAC
EXT1-RSF1chr8118825110chr1177451981514DTVLSTTEYGACACGGTGCTTTCAACAACAGAGTAC
EXT1-RSF1chr8118825110chr1177451981614TVLSTTEYACGGTGCTTTCAACAACAGAGTAC
EXT1-RSF1chr8118825110chr1177451981615TVLSTTEYLACGGTGCTTTCAACAACAGAGTACCTC

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 EXT1-RSF1

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
BRCAEXT1-RSF1chr8118825110ENST00000378204chr1177451981ENST00000308488TCGA-BH-A1EN

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Potential target of CAR-T therapy development for EXT1-RSF1

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
HgeneEXT1chr8:118825110chr11:77451981ENST00000378204-8118_28574747.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneEXT1chr8:118825111chr11:77451981ENST00000378204-8118_28574747.0TransmembraneHelical%3B Signal-anchor for type II membrane protein

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 EXT1-RSF1

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 EXT1-RSF1

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