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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:SLC35A1-FUS

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SLC35A1-FUS
FusionPDB ID: 82932
FusionGDB2.0 ID: 82932
HgeneTgene
Gene symbol

SLC35A1

FUS

Gene ID

10559

2521

Gene namesolute carrier family 35 member A1FUS RNA binding protein
SynonymsCDG2F|CMPST|CST|hCSTALS6|ETM4|FUS1|HNRNPP2|POMP75|TLS
Cytomap

6q15

16p11.2

Type of geneprotein-codingprotein-coding
DescriptionCMP-sialic acid transporterCMP-SA-TrCMP-Sia-Trmutated CMP-sialic acid transporter A1solute carrier family 35 (CMP-sialic acid transporter), member 1solute carrier family 35 (CMP-sialic acid transporter), member A1solute carrier family 35 (UDP-galactRNA-binding protein FUS75 kDa DNA-pairing proteinfus-like proteinfused in sarcomafusion gene in myxoid liposarcomaheterogeneous nuclear ribonucleoprotein P2oncogene FUSoncogene TLStranslocated in liposarcoma protein
Modification date2020031320200329
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 idsENST00000369552, ENST00000369556, 
ENST00000369557, ENST00000544441, 
ENST00000464978, 
ENST00000474990, 
ENST00000254108, ENST00000380244, 
ENST00000568685, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 3 X 3=3620 X 13 X 10=2600
# samples 322
** MAII scorelog2(3/36*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(22/2600*10)=-3.56293619439116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SLC35A1 [Title/Abstract] AND FUS [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SLC35A1 [Title/Abstract] AND FUS [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SLC35A1(88182737)-FUS(31199646), # samples:1
Anticipated loss of major functional domain due to fusion event.SLC35A1-FUS 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.
SLC35A1-FUS 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.
SLC35A1-FUS 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.
SLC35A1-FUS 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
TgeneFUS

GO:0006355

regulation of transcription, DNA-templated

26124092

TgeneFUS

GO:0006357

regulation of transcription by RNA polymerase II

25453086

TgeneFUS

GO:0008380

RNA splicing

26124092

TgeneFUS

GO:0043484

regulation of RNA splicing

25453086|27731383

TgeneFUS

GO:0048255

mRNA stabilization

27378374

TgeneFUS

GO:0051260

protein homooligomerization

25453086

TgeneFUS

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/chr6:88182737/chr16:31199646)
- 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 SLC35A1 (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 FUS (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)
ENST00000369556SLC35A1chr688182737+ENST00000254108FUSchr1631199646+12459522876284
ENST00000369556SLC35A1chr688182737+ENST00000380244FUSchr1631199646+10419522876284
ENST00000369556SLC35A1chr688182737+ENST00000568685FUSchr1631199646+10179522879285
ENST00000369552SLC35A1chr688182737+ENST00000254108FUSchr1631199646+11934327824265
ENST00000369552SLC35A1chr688182737+ENST00000380244FUSchr1631199646+9894327824265
ENST00000369552SLC35A1chr688182737+ENST00000568685FUSchr1631199646+9654327827266
ENST00000369557SLC35A1chr688182737+ENST00000254108FUSchr1631199646+1166160797265
ENST00000369557SLC35A1chr688182737+ENST00000380244FUSchr1631199646+962160797265
ENST00000369557SLC35A1chr688182737+ENST00000568685FUSchr1631199646+938160800266

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
ENST00000369556ENST00000254108SLC35A1chr688182737+FUSchr1631199646+0.0046750240.99532497
ENST00000369556ENST00000380244SLC35A1chr688182737+FUSchr1631199646+0.0049583410.99504167
ENST00000369556ENST00000568685SLC35A1chr688182737+FUSchr1631199646+0.0033327280.9966673
ENST00000369552ENST00000254108SLC35A1chr688182737+FUSchr1631199646+0.0061588420.9938412
ENST00000369552ENST00000380244SLC35A1chr688182737+FUSchr1631199646+0.0068049850.99319506
ENST00000369552ENST00000568685SLC35A1chr688182737+FUSchr1631199646+0.004584490.99541545
ENST00000369557ENST00000254108SLC35A1chr688182737+FUSchr1631199646+0.007194180.9928059
ENST00000369557ENST00000380244SLC35A1chr688182737+FUSchr1631199646+0.0081754510.99182457
ENST00000369557ENST00000568685SLC35A1chr688182737+FUSchr1631199646+0.0051984750.9948015

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 SLC35A1-FUS

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SLC35A1chr688182737FUSchr163119964616120ATRRADFNRGGGNGRGGRGRGGPMGR
SLC35A1chr688182737FUSchr163119964616121ATRRADFNRGGGNGRGGRGRGGPMGR
SLC35A1chr688182737FUSchr163119964616121TRRADFNRGGGNGRGGRGRGGPMGRG
SLC35A1chr688182737FUSchr163119964616122TRRADFNRGGGNGRGGRGRGGPMGRG
SLC35A1chr688182737FUSchr163119964643120ATRRADFNRGGGNGRGGRGRGGPMGR
SLC35A1chr688182737FUSchr163119964643121ATRRADFNRGGGNGRGGRGRGGPMGR
SLC35A1chr688182737FUSchr163119964643121TRRADFNRGGGNGRGGRGRGGPMGRG
SLC35A1chr688182737FUSchr163119964643122TRRADFNRGGGNGRGGRGRGGPMGRG
SLC35A1chr688182737FUSchr163119964695139ATRRADFNRGGGNGRGGRGRGGPMGR
SLC35A1chr688182737FUSchr163119964695140ATRRADFNRGGGNGRGGRGRGGPMGR
SLC35A1chr688182737FUSchr163119964695140TRRADFNRGGGNGRGGRGRGGPMGRG
SLC35A1chr688182737FUSchr163119964695141TRRADFNRGGGNGRGGRGRGGPMGRG
SLC35A1chr688182737FUSchr16311996469524SAGGCRGTMAAPRGPRDQGSRHDSAE
SLC35A1chr688182737FUSchr16311996469524SAGGCRGTMAAPRGPRDQGSRHDSEQ

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Potential FusionNeoAntigen Information of SLC35A1-FUS 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 SLC35A1-FUS 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 SLC35A1-FUS

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 SLC35A1-FUS

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 SLC35A1-FUS

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 SLC35A1-FUS

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 SLC35A1-FUS

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 SLC35A1-FUS

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 SLC35A1-FUS

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
TgeneFUSC1842675AMYOTROPHIC LATERAL SCLEROSIS 6 (disorder)5UNIPROT
TgeneFUSC3468114Juvenile amyotrophic lateral sclerosis5ORPHANET
TgeneFUSC0002736Amyotrophic Lateral Sclerosis2CTD_human;ORPHANET
TgeneFUSC0206634Liposarcoma, Myxoid2CTD_human;ORPHANET
TgeneFUSC0393554Amyotrophic Lateral Sclerosis With Dementia1CTD_human
TgeneFUSC0497327Dementia1GENOMICS_ENGLAND
TgeneFUSC0543859Amyotrophic Lateral Sclerosis, Guam Form1CTD_human
TgeneFUSC3539195TREMOR, HEREDITARY ESSENTIAL, 41CTD_human;UNIPROT
TgeneFUSC3888102Frontotemporal Dementia With Motor Neuron Disease1ORPHANET