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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:SIM1-ASCC3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SIM1-ASCC3
FusionPDB ID: 81899
FusionGDB2.0 ID: 81899
HgeneTgene
Gene symbol

SIM1

ASCC3

Gene ID

6492

10973

Gene nameSIM bHLH transcription factor 1activating signal cointegrator 1 complex subunit 3
SynonymsbHLHe14ASC1p200|HELIC1|RNAH
Cytomap

6q16.3

6q16.3

Type of geneprotein-codingprotein-coding
Descriptionsingle-minded homolog 1class E basic helix-loop-helix protein 14single-minded family bHLH transcription factor 1activating signal cointegrator 1 complex subunit 3ASC-1 complex subunit P200RNA helicase familyhelicase, ATP binding 1trip4 complex subunit p200
Modification date2020031320200313
UniProtAcc.

Q8N3C0

Main function of 5'-partner protein: FUNCTION: 3'-5' DNA helicase involved in repair of alkylated DNA. Promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3, enabling ALKBH3 to process alkylated N3-methylcytosine (3mC) within double-stranded regions (PubMed:22055184). Part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation (PubMed:12077347). {ECO:0000269|PubMed:12077347, ECO:0000269|PubMed:22055184}.
Ensembl transtripts involved in fusion geneENST idsENST00000262901, ENST00000369208, 
ENST00000369143, ENST00000522650, 
ENST00000369162, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score1 X 1 X 1=114 X 10 X 11=1540
# samples 118
** MAII scorelog2(1/1*10)=3.32192809488736log2(18/1540*10)=-3.09686153925259
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SIM1 [Title/Abstract] AND ASCC3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SIM1 [Title/Abstract] AND ASCC3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SIM1(100868666)-ASCC3(100988263), # samples:2
ASCC3(101037510)-SIM1(100901720), # samples:1
Anticipated loss of major functional domain due to fusion event.ASCC3-SIM1 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.
ASCC3-SIM1 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.
SIM1-ASCC3 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.
SIM1-ASCC3 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.
SIM1-ASCC3 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.
SIM1-ASCC3 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
TgeneASCC3

GO:0006307

DNA dealkylation involved in DNA repair

22055184

TgeneASCC3

GO:0032508

DNA duplex unwinding

22055184



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/chr6:100868666/chr6:100988263)
- 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 SIM1 (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 ASCC3 (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)
ENST00000369208SIM1chr6100868666-ENST00000369162ASCC3chr6100988263-420119507833008741
ENST00000262901SIM1chr6100868666-ENST00000369162ASCC3chr6100988263-362713762092434741

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
ENST00000369208ENST00000369162SIM1chr6100868666-ASCC3chr6100988263-0.0009675750.9990325
ENST00000262901ENST00000369162SIM1chr6100868666-ASCC3chr6100988263-0.0007831620.9992168

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 SIM1-ASCC3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SIM1chr6100868666ASCC3chr61009882631376388SSSKSKSRTSPYPQDAEEYTDLPVRH
SIM1chr6100868666ASCC3chr61009882631950388SSSKSKSRTSPYPQDAEEYTDLPVRH

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Potential FusionNeoAntigen Information of SIM1-ASCC3 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.
SIM1-ASCC3_100868666_100988263.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)
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:01YPQDAEEY0.98960.80541119
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:08YPQDAEEY0.96410.79371119
SIM1-ASCC3chr6100868666chr61009882631376HLA-A30:08RTSPYPQDA0.87110.701716
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:01SPYPQDAEEY0.99220.6608919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:08SPYPQDAEEY0.99020.7203919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B15:02SPYPQDAEEY0.95620.7686919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:02SPYPQDAEEY0.45920.7918919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:04SPYPQDAEEY0.45920.7918919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:03YPQDAEEYTDL0.9960.83551122
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:01TSPYPQDAEEY0.99390.7315819
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:02YPQDAEEYTDL0.97960.93871122
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:04YPQDAEEYTDL0.97960.93871122
SIM1-ASCC3chr6100868666chr61009882631376HLA-B15:31SPYPQDAEEY0.99150.621919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B15:21SPYPQDAEEY0.96240.7347919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B73:01SRTSPYPQDA0.94620.8649616
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:12SPYPQDAEEY0.45920.7918919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B39:10YPQDAEEYTDL0.98050.87011122
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:12YPQDAEEYTDL0.97960.93871122
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:77YPQDAEEY0.98960.80541119
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:20YPQDAEEY0.98920.8521119
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:23YPQDAEEY0.98920.82951119
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:11YPQDAEEY0.96930.8411119
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:24YPQDAEEY0.95790.8781119
SIM1-ASCC3chr6100868666chr61009882631376HLA-B15:08YPQDAEEY0.93960.78191119
SIM1-ASCC3chr6100868666chr61009882631376HLA-B15:11YPQDAEEY0.93730.79181119
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:43YPQDAEEY0.92890.78441119
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:30YPQDAEEY0.92020.58111119
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:17YPQDAEEY0.92020.58111119
SIM1-ASCC3chr6100868666chr61009882631376HLA-B18:04YPQDAEEY0.78020.89031119
SIM1-ASCC3chr6100868666chr61009882631376HLA-B18:07YPQDAEEY0.72820.84491119
SIM1-ASCC3chr6100868666chr61009882631376HLA-A30:01KSRTSPYPQ0.93230.7659514
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:77SPYPQDAEEY0.99220.6608919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:23SPYPQDAEEY0.99160.6731919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:20SPYPQDAEEY0.98990.7198919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:24SPYPQDAEEY0.97370.7467919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:11SPYPQDAEEY0.96090.7228919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B15:11SPYPQDAEEY0.90460.6887919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B15:08SPYPQDAEEY0.9040.6868919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:43SPYPQDAEEY0.90020.6896919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B18:04SPYPQDAEEY0.61590.7485919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:09SPYPQDAEEY0.45920.7918919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B18:07SPYPQDAEEY0.31630.6872919
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:77TSPYPQDAEEY0.99390.7315819
SIM1-ASCC3chr6100868666chr61009882631376HLA-B35:09YPQDAEEYTDL0.97960.93871122
SIM1-ASCC3chr6100868666chr61009882631376HLA-B67:01YPQDAEEYTDL0.97350.82381122

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Potential FusionNeoAntigen Information of SIM1-ASCC3 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 SIM1-ASCC3

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
8992SRTSPYPQDAEEYTSIM1ASCC3chr6100868666chr61009882631376

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SIM1-ASCC3

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-B14:023BVN8992SRTSPYPQDAEEYT-7.15543-7.26883
HLA-B14:023BVN8992SRTSPYPQDAEEYT-4.77435-5.80965
HLA-B52:013W398992SRTSPYPQDAEEYT-6.80875-6.92215
HLA-B52:013W398992SRTSPYPQDAEEYT-4.20386-5.23916
HLA-A11:014UQ28992SRTSPYPQDAEEYT-7.5194-8.5547
HLA-A11:014UQ28992SRTSPYPQDAEEYT-6.9601-7.0735
HLA-A24:025HGA8992SRTSPYPQDAEEYT-7.52403-7.63743
HLA-A24:025HGA8992SRTSPYPQDAEEYT-5.82433-6.85963
HLA-B27:056PYJ8992SRTSPYPQDAEEYT-3.28285-4.31815
HLA-B44:053DX88992SRTSPYPQDAEEYT-5.91172-6.94702
HLA-B44:053DX88992SRTSPYPQDAEEYT-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of SIM1-ASCC3

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
SIM1-ASCC3chr6100868666chr61009882631119YPQDAEEYCCTCAGGATGCAGAAGAATATACA
SIM1-ASCC3chr6100868666chr61009882631122YPQDAEEYTDLCCTCAGGATGCAGAAGAATATACAGATTTGCCA
SIM1-ASCC3chr6100868666chr6100988263514KSRTSPYPQTCCAGGACTTCCCCATACCCTCAGGAT
SIM1-ASCC3chr6100868666chr6100988263616SRTSPYPQDAAGGACTTCCCCATACCCTCAGGATGCAGAA
SIM1-ASCC3chr6100868666chr6100988263716RTSPYPQDAACTTCCCCATACCCTCAGGATGCAGAA
SIM1-ASCC3chr6100868666chr6100988263819TSPYPQDAEEYTCCCCATACCCTCAGGATGCAGAAGAATATACA
SIM1-ASCC3chr6100868666chr6100988263919SPYPQDAEEYCCATACCCTCAGGATGCAGAAGAATATACA

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 SIM1-ASCC3

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
LUADSIM1-ASCC3chr6100868666ENST00000262901chr6100988263ENST00000369162TCGA-69-7760-01A

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Potential target of CAR-T therapy development for SIM1-ASCC3

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 SIM1-ASCC3

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 SIM1-ASCC3

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