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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:SSBP2-MSH3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SSBP2-MSH3
FusionPDB ID: 86714
FusionGDB2.0 ID: 86714
HgeneTgene
Gene symbol

SSBP2

MSH3

Gene ID

23635

4437

Gene namesingle stranded DNA binding protein 2mutS homolog 3
SynonymsHSPC116|SOSS-B2DUP|FAP4|MRP1
Cytomap

5q14.1

5q14.1

Type of geneprotein-codingprotein-coding
Descriptionsingle-stranded DNA-binding protein 2sequence-specific single-stranded-DNA-binding protein 2DNA mismatch repair protein Msh3divergent upstream proteinepididymis secretory sperm binding proteinhMSH3mismatch repair protein 1
Modification date2020031320200327
UniProtAcc

P81877

Main function of 5'-partner protein:

P20585

Main function of 5'-partner protein: FUNCTION: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS beta which binds to DNA mismatches thereby initiating DNA repair. When bound, the MutS beta heterodimer bends the DNA helix and shields approximately 20 base pairs. MutS beta recognizes large insertion-deletion loops (IDL) up to 13 nucleotides long. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis.
Ensembl transtripts involved in fusion geneENST idsENST00000320672, ENST00000505980, 
ENST00000509053, ENST00000514493, 
ENST00000515395, ENST00000510060, 
ENST00000512258, ENST00000265081, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 13 X 6=9366 X 7 X 2=84
# samples 147
** MAII scorelog2(14/936*10)=-2.74108170263844
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/84*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SSBP2 [Title/Abstract] AND MSH3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SSBP2 [Title/Abstract] AND MSH3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SSBP2(80733249)-MSH3(79974746), # samples:1
Anticipated loss of major functional domain due to fusion event.SSBP2-MSH3 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.
SSBP2-MSH3 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.
SSBP2-MSH3 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.
SSBP2-MSH3 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
TgeneMSH3

GO:0006281

DNA repair

8942985

TgeneMSH3

GO:0045910

negative regulation of DNA recombination

17715146

TgeneMSH3

GO:0051096

positive regulation of helicase activity

17715146



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/chr5:80733249/chr5:79974746)
- 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 SSBP2 (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 MSH3 (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)
ENST00000320672SSBP2chr580733249-ENST00000265081MSH3chr579974746+4007116821134081065
ENST00000509053SSBP2chr580733249-ENST00000265081MSH3chr579974746+3712873631131035
ENST00000514493SSBP2chr580733249-ENST00000265081MSH3chr579974746+3914107520833151035
ENST00000505980SSBP2chr580733249-ENST00000265081MSH3chr579974746+3741902531421045
ENST00000515395SSBP2chr580733249-ENST00000265081MSH3chr579974746+37859465531861043

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
ENST00000320672ENST00000265081SSBP2chr580733249-MSH3chr579974746+0.0003470860.99965286
ENST00000509053ENST00000265081SSBP2chr580733249-MSH3chr579974746+0.0003175230.99968255
ENST00000514493ENST00000265081SSBP2chr580733249-MSH3chr579974746+0.0003601730.99963987
ENST00000505980ENST00000265081SSBP2chr580733249-MSH3chr579974746+0.0004353050.9995647
ENST00000515395ENST00000265081SSBP2chr580733249-MSH3chr579974746+0.0002533030.99974674

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 SSBP2-MSH3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SSBP2chr580733249MSH3chr5799747461075289GSLGSGDMDSISKGVQPATGEVVFDS
SSBP2chr580733249MSH3chr5799747461168319GSLGSGDMDSISKGVQPATGEVVFDS
SSBP2chr580733249MSH3chr579974746873289GSLGSGDMDSISKGVQPATGEVVFDS
SSBP2chr580733249MSH3chr579974746902299GSLGSGDMDSISKGVQPATGEVVFDS
SSBP2chr580733249MSH3chr579974746946297GSLGSGDMDSISKGVQPATGEVVFDS

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Potential FusionNeoAntigen Information of SSBP2-MSH3 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 SSBP2-MSH3 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.
SSBP2-MSH3_80733249_79974746.msa

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)
SSBP2-MSH3chr580733249chr5799747461168DRB1-0102SKGVQPATGEVVFDS1126
SSBP2-MSH3chr580733249chr5799747461168DRB1-0901SKGVQPATGEVVFDS1126
SSBP2-MSH3chr580733249chr5799747461168DRB1-0901ISKGVQPATGEVVFD1025
SSBP2-MSH3chr580733249chr5799747461168DRB1-0901SISKGVQPATGEVVF924
SSBP2-MSH3chr580733249chr5799747461168DRB1-0904SKGVQPATGEVVFDS1126
SSBP2-MSH3chr580733249chr5799747461168DRB1-0904ISKGVQPATGEVVFD1025
SSBP2-MSH3chr580733249chr5799747461168DRB1-0905SKGVQPATGEVVFDS1126
SSBP2-MSH3chr580733249chr5799747461168DRB1-0905ISKGVQPATGEVVFD1025
SSBP2-MSH3chr580733249chr5799747461168DRB1-0906SKGVQPATGEVVFDS1126
SSBP2-MSH3chr580733249chr5799747461168DRB1-0906ISKGVQPATGEVVFD1025
SSBP2-MSH3chr580733249chr5799747461168DRB1-0906SISKGVQPATGEVVF924
SSBP2-MSH3chr580733249chr5799747461168DRB1-0907SKGVQPATGEVVFDS1126
SSBP2-MSH3chr580733249chr5799747461168DRB1-0907ISKGVQPATGEVVFD1025
SSBP2-MSH3chr580733249chr5799747461168DRB1-0909SKGVQPATGEVVFDS1126
SSBP2-MSH3chr580733249chr5799747461168DRB1-0909ISKGVQPATGEVVFD1025
SSBP2-MSH3chr580733249chr5799747461168DRB1-0909SISKGVQPATGEVVF924
SSBP2-MSH3chr580733249chr5799747461168DRB1-1154SGDMDSISKGVQPAT419

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Fusion breakpoint peptide structures of SSBP2-MSH3

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 SSBP2-MSH3

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 SSBP2-MSH3

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
SSBP2-MSH3chr580733249chr5799747461025ISKGVQPATGEVVFDATTTCCAAGGGAGTGCAGCCTGCCACAGGCGAGGTTGTGTTTGAT
SSBP2-MSH3chr580733249chr5799747461126SKGVQPATGEVVFDSTCCAAGGGAGTGCAGCCTGCCACAGGCGAGGTTGTGTTTGATAGT
SSBP2-MSH3chr580733249chr579974746419SGDMDSISKGVQPATTCAGGAGATATGGACAGTATTTCCAAGGGAGTGCAGCCTGCCACA
SSBP2-MSH3chr580733249chr579974746924SISKGVQPATGEVVFAGTATTTCCAAGGGAGTGCAGCCTGCCACAGGCGAGGTTGTGTTT

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Information of the samples that have these potential fusion neoantigens of SSBP2-MSH3

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 SSBP2-MSH3

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 SSBP2-MSH3

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 SSBP2-MSH3

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
HgeneSSBP2C0005586Bipolar Disorder1CTD_human
HgeneSSBP2C0005587Depression, Bipolar1CTD_human
HgeneSSBP2C0024713Manic Disorder1CTD_human
HgeneSSBP2C0033578Prostatic Neoplasms1CTD_human
HgeneSSBP2C0338831Manic1CTD_human
HgeneSSBP2C0376358Malignant neoplasm of prostate1CTD_human