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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:SOS2-CHD8

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SOS2-CHD8
FusionPDB ID: 85267
FusionGDB2.0 ID: 85267
HgeneTgene
Gene symbol

SOS2

CHD8

Gene ID

6655

57680

Gene nameSOS Ras/Rho guanine nucleotide exchange factor 2chromodomain helicase DNA binding protein 8
SynonymsNS9|SOS-2AUTS18|HELSNF1
Cytomap

14q21.3

14q11.2

Type of geneprotein-codingprotein-coding
Descriptionson of sevenless homolog 2guanine nucleotide releasing factorchromodomain-helicase-DNA-binding protein 8ATP-dependent helicase CHD8axis duplication inhibitorduplinhelicase with SNF2 domain 1
Modification date2020032720200329
UniProtAcc.

Q9HCK8

Main function of 5'-partner protein: FUNCTION: DNA helicase that acts as a chromatin remodeling factor and regulates transcription. Acts as a transcription repressor by remodeling chromatin structure and recruiting histone H1 to target genes. Suppresses p53/TP53-mediated apoptosis by recruiting histone H1 and preventing p53/TP53 transactivation activity. Acts as a negative regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) activity. Negatively regulates CTNNB1-targeted gene expression by being recruited specifically to the promoter regions of several CTNNB1 responsive genes. Involved in both enhancer blocking and epigenetic remodeling at chromatin boundary via its interaction with CTCF. Acts as a suppressor of STAT3 activity by suppressing the LIF-induced STAT3 transcriptional activity. Also acts as a transcription activator via its interaction with ZNF143 by participating in efficient U6 RNA polymerase III transcription. {ECO:0000255|HAMAP-Rule:MF_03071, ECO:0000269|PubMed:17938208, ECO:0000269|PubMed:18378692}.
Ensembl transtripts involved in fusion geneENST idsENST00000216373, ENST00000543680, 
ENST00000555794, 
ENST00000555962, 
ENST00000399982, ENST00000430710, 
ENST00000557364, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 11 X 6=79210 X 10 X 6=600
# samples 1513
** MAII scorelog2(15/792*10)=-2.40053792958373
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/600*10)=-2.20645087746743
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SOS2 [Title/Abstract] AND CHD8 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SOS2 [Title/Abstract] AND CHD8 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SOS2(50612194)-CHD8(21854335), # samples:2
Anticipated loss of major functional domain due to fusion event.SOS2-CHD8 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.
SOS2-CHD8 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.
SOS2-CHD8 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.
SOS2-CHD8 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
TgeneCHD8

GO:0045893

positive regulation of transcription, DNA-templated

17938208

TgeneCHD8

GO:0090090

negative regulation of canonical Wnt signaling pathway

18378692|22083958



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/chr14:50612194/chr14:21854335)
- 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 SOS2 (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 CHD8 (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)
ENST00000216373SOS2chr1450612194-ENST00000430710CHD8chr1421854335-376227792092884891
ENST00000216373SOS2chr1450612194-ENST00000399982CHD8chr1421854335-376127792092884891
ENST00000216373SOS2chr1450612194-ENST00000557364CHD8chr1421854335-347027792092884891
ENST00000543680SOS2chr1450612194-ENST00000430710CHD8chr1421854335-34142431262536836
ENST00000543680SOS2chr1450612194-ENST00000399982CHD8chr1421854335-34132431262536836
ENST00000543680SOS2chr1450612194-ENST00000557364CHD8chr1421854335-31222431262536836

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
ENST00000216373ENST00000430710SOS2chr1450612194-CHD8chr1421854335-0.0025395360.9974605
ENST00000216373ENST00000399982SOS2chr1450612194-CHD8chr1421854335-0.0025348670.99746513
ENST00000216373ENST00000557364SOS2chr1450612194-CHD8chr1421854335-0.0030659390.99693406
ENST00000543680ENST00000430710SOS2chr1450612194-CHD8chr1421854335-0.0026207110.9973793
ENST00000543680ENST00000399982SOS2chr1450612194-CHD8chr1421854335-0.0026112630.9973888
ENST00000543680ENST00000557364SOS2chr1450612194-CHD8chr1421854335-0.0034615840.9965384

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 SOS2-CHD8

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SOS2chr1450612194CHD8chr14218543352431802IRHTTNLTLWFEKVITLKRCSTGFCQ
SOS2chr1450612194CHD8chr14218543352779857IRHTTNLTLWFEKVITLKRCSTGFCQ

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Potential FusionNeoAntigen Information of SOS2-CHD8 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.
SOS2-CHD8_50612194_21854335.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)
SOS2-CHD8chr1450612194chr14218543352779HLA-B08:01WFEKVITL0.99730.617917
SOS2-CHD8chr1450612194chr14218543352779HLA-B14:01LWFEKVITL0.99240.8898817
SOS2-CHD8chr1450612194chr14218543352779HLA-B14:02LWFEKVITL0.99240.8898817
SOS2-CHD8chr1450612194chr14218543352779HLA-B08:01LWFEKVITL0.96880.7288817
SOS2-CHD8chr1450612194chr14218543352779HLA-B08:09LWFEKVITL0.96210.7062817
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:04LWFEKVITL0.91010.6958817
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:19NLTLWFEKV0.87290.8118514
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:22TLWFEKVITL0.99150.6441717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:11TLWFEKVITL0.98780.7004717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:67TLWFEKVITL0.98750.6618717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:30TLWFEKVITL0.98750.6618717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:24TLWFEKVITL0.98750.6618717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:60TLWFEKVITL0.98720.6221717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:04TLWFEKVITL0.98710.654717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:27TLWFEKVITL0.9870.6908717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:21TLWFEKVITL0.9860.7719717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:13TLWFEKVITL0.98580.7877717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:16TLWFEKVITL0.98230.6447717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:38TLWFEKVITL0.96940.752717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:35TLWFEKVITL0.9330.6914717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:29TLWFEKVITL0.88890.6654717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:20TLWFEKVITL0.87540.6677717
SOS2-CHD8chr1450612194chr14218543352779HLA-A31:02LWFEKVITLKR0.9970.5697819
SOS2-CHD8chr1450612194chr14218543352779HLA-C04:10WFEKVITL0.99890.9176917
SOS2-CHD8chr1450612194chr14218543352779HLA-C04:07WFEKVITL0.99890.928917
SOS2-CHD8chr1450612194chr14218543352779HLA-C04:14WFEKVITL0.99230.9147917
SOS2-CHD8chr1450612194chr14218543352779HLA-C12:16LWFEKVITL0.97840.9792817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:05LWFEKVITL0.9480.9733817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:13LWFEKVITL0.91890.9536817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:67LWFEKVITL0.90740.9676817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:80LWFEKVITL0.90740.9676817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:10LWFEKVITL0.90190.9707817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:19LWFEKVITL0.89470.8122817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:27LWFEKVITL0.89290.972817
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:07LWFEKVITL0.88470.6507817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:29LWFEKVITL0.88080.9555817
SOS2-CHD8chr1450612194chr14218543352779HLA-C04:14LWFEKVITL0.86880.9128817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:46LWFEKVITL0.85680.9269817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:95LWFEKVITL0.8520.8077817
SOS2-CHD8chr1450612194chr14218543352779HLA-B14:03LWFEKVITL0.76710.8304817
SOS2-CHD8chr1450612194chr14218543352779HLA-C04:07LWFEKVITL0.73450.888817
SOS2-CHD8chr1450612194chr14218543352779HLA-B39:12LWFEKVITL0.73310.9347817
SOS2-CHD8chr1450612194chr14218543352779HLA-C04:10LWFEKVITL0.72740.9056817
SOS2-CHD8chr1450612194chr14218543352779HLA-C01:30LWFEKVITL0.69480.9477817
SOS2-CHD8chr1450612194chr14218543352779HLA-C01:17LWFEKVITL0.66520.9482817
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:05TLWFEKVITL0.99190.563717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:07TLWFEKVITL0.98920.6689717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:01TLWFEKVITL0.98750.6618717
SOS2-CHD8chr1450612194chr14218543352779HLA-C04:01WFEKVITL0.99890.928917
SOS2-CHD8chr1450612194chr14218543352779HLA-C18:01WFEKVITL0.99850.9344917
SOS2-CHD8chr1450612194chr14218543352779HLA-B08:18WFEKVITL0.99730.617917
SOS2-CHD8chr1450612194chr14218543352779HLA-C04:04WFEKVITL0.99590.9341917
SOS2-CHD8chr1450612194chr14218543352779HLA-C14:02WFEKVITL0.99510.9636917
SOS2-CHD8chr1450612194chr14218543352779HLA-C14:03WFEKVITL0.99510.9636917
SOS2-CHD8chr1450612194chr14218543352779HLA-B08:12WFEKVITL0.98370.7993917
SOS2-CHD8chr1450612194chr14218543352779HLA-C06:02LWFEKVITL0.98790.9961817
SOS2-CHD8chr1450612194chr14218543352779HLA-C06:17LWFEKVITL0.98790.9961817
SOS2-CHD8chr1450612194chr14218543352779HLA-C03:67LWFEKVITL0.98180.9824817
SOS2-CHD8chr1450612194chr14218543352779HLA-B08:18LWFEKVITL0.96880.7288817
SOS2-CHD8chr1450612194chr14218543352779HLA-B08:12LWFEKVITL0.96690.8627817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:04LWFEKVITL0.96390.9616817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:02LWFEKVITL0.90740.9676817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:17LWFEKVITL0.9030.9745817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:22LWFEKVITL0.89460.8263817
SOS2-CHD8chr1450612194chr14218543352779HLA-C07:01LWFEKVITL0.8690.7775817
SOS2-CHD8chr1450612194chr14218543352779HLA-C04:04LWFEKVITL0.85390.9048817
SOS2-CHD8chr1450612194chr14218543352779HLA-C14:03LWFEKVITL0.85220.9682817
SOS2-CHD8chr1450612194chr14218543352779HLA-C14:02LWFEKVITL0.85220.9682817
SOS2-CHD8chr1450612194chr14218543352779HLA-C06:06LWFEKVITL0.83640.9901817
SOS2-CHD8chr1450612194chr14218543352779HLA-C04:01LWFEKVITL0.73450.888817
SOS2-CHD8chr1450612194chr14218543352779HLA-C18:01LWFEKVITL0.72460.914817
SOS2-CHD8chr1450612194chr14218543352779HLA-C06:08LWFEKVITL0.71480.9945817
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:03TLWFEKVITL0.99030.7582717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:14TLWFEKVITL0.98650.7121717
SOS2-CHD8chr1450612194chr14218543352779HLA-A02:06TLWFEKVITL0.9860.7719717

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Potential FusionNeoAntigen Information of SOS2-CHD8 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 SOS2-CHD8

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
5723LTLWFEKVITLKRCSOS2CHD8chr1450612194chr14218543352779

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SOS2-CHD8

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-B14:023BVN5723LTLWFEKVITLKRC-7.69222-7.69942
HLA-B52:013W395723LTLWFEKVITLKRC-7.60148-7.60868
HLA-A11:014UQ25723LTLWFEKVITLKRC-6.66327-6.67047
HLA-A24:025HGA5723LTLWFEKVITLKRC-9.4375-9.4447
HLA-B27:056PYJ5723LTLWFEKVITLKRC-4.77117-4.77837
HLA-B44:053DX85723LTLWFEKVITLKRC-6.68497-6.69217

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Vaccine Design for the FusionNeoAntigens of SOS2-CHD8

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
SOS2-CHD8chr1450612194chr1421854335514NLTLWFEKVAAATCTCACCCTCTGGTTTGAAAAGGT
SOS2-CHD8chr1450612194chr1421854335717TLWFEKVITLCACCCTCTGGTTTGAAAAGGTCATCACACT
SOS2-CHD8chr1450612194chr1421854335817LWFEKVITLCCTCTGGTTTGAAAAGGTCATCACACT
SOS2-CHD8chr1450612194chr1421854335819LWFEKVITLKRCCTCTGGTTTGAAAAGGTCATCACACTGAAACG
SOS2-CHD8chr1450612194chr1421854335917WFEKVITLCTGGTTTGAAAAGGTCATCACACT

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 SOS2-CHD8

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
ESCASOS2-CHD8chr1450612194ENST00000216373chr1421854335ENST00000399982TCGA-LN-A4A1

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Potential target of CAR-T therapy development for SOS2-CHD8

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 SOS2-CHD8

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 SOS2-CHD8

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