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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:DSG3-DSC3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DSG3-DSC3
FusionPDB ID: 24251
FusionGDB2.0 ID: 24251
HgeneTgene
Gene symbol

DSG3

DSC3

Gene ID

1830

1825

Gene namedesmoglein 3desmocollin 3
SynonymsCDHF6|PVACDHF3|DSC|DSC1|DSC2|DSC4|HT-CP
Cytomap

18q12.1

18q12.1

Type of geneprotein-codingprotein-coding
Descriptiondesmoglein-3130 kDa pemphigus vulgaris antigencadherin family member 6desmocollin-3cadherin family member 3desmocollin-4
Modification date2020031320200313
UniProtAcc

P32926

Main function of 5'-partner protein: FUNCTION: Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.

Q14574

Main function of 5'-partner protein: FUNCTION: Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms.
Ensembl transtripts involved in fusion geneENST idsENST00000257189, ENST00000360428, 
ENST00000434452, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 2=181 X 1 X 1=1
# samples 31
** MAII scorelog2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(1/1*10)=3.32192809488736
Fusion gene context

PubMed: DSG3 [Title/Abstract] AND DSC3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DSG3 [Title/Abstract] AND DSC3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DSG3(29027888)-DSC3(28588491), # samples:2
Anticipated loss of major functional domain due to fusion event.DSG3-DSC3 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.
DSG3-DSC3 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.
DSG3-DSC3 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.
DSG3-DSC3 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


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/chr18:29027888/chr18:28588491)
- 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 DSG3 (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 DSC3 (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)
ENST00000257189DSG3chr1829027888+ENST00000360428DSC3chr1828588491-5726131831558491
ENST00000257189DSG3chr1829027888+ENST00000434452DSC3chr1828588491-5691131831387434

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
ENST00000257189ENST00000360428DSG3chr1829027888+DSC3chr1828588491-0.0001717670.9998282
ENST00000257189ENST00000434452DSG3chr1829027888+DSC3chr1828588491-0.0002467280.9997533

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 DSG3-DSC3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DSG3chr1829027888DSC3chr182858849113116LFPRTTGALAIFVPLNYEENRQVNLE

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Potential FusionNeoAntigen Information of DSG3-DSC3 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.
DSG3-DSC3_29027888_28588491.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)
DSG3-DSC3chr1829027888chr1828588491131HLA-B15:25LAIFVPLNY0.99930.8804817
DSG3-DSC3chr1829027888chr1828588491131HLA-B15:02LAIFVPLNY0.99880.8909817
DSG3-DSC3chr1829027888chr1828588491131HLA-B35:01LAIFVPLNY0.99770.8195817
DSG3-DSC3chr1829027888chr1828588491131HLA-B35:08LAIFVPLNY0.99740.7547817
DSG3-DSC3chr1829027888chr1828588491131HLA-B15:17LAIFVPLNY0.99590.8255817
DSG3-DSC3chr1829027888chr1828588491131HLA-B15:16LAIFVPLNY0.98730.5858817
DSG3-DSC3chr1829027888chr1828588491131HLA-B58:01LAIFVPLNY0.97930.7689817
DSG3-DSC3chr1829027888chr1828588491131HLA-B15:05LAIFVPLNY0.99880.7691817
DSG3-DSC3chr1829027888chr1828588491131HLA-B15:21LAIFVPLNY0.99870.8753817
DSG3-DSC3chr1829027888chr1828588491131HLA-B15:31LAIFVPLNY0.99750.7844817
DSG3-DSC3chr1829027888chr1828588491131HLA-B15:07LAIFVPLNY0.990.5263817
DSG3-DSC3chr1829027888chr1828588491131HLA-C15:04LAIFVPLNY0.92370.8635817
DSG3-DSC3chr1829027888chr1828588491131HLA-C03:14LAIFVPLNY0.75470.967817
DSG3-DSC3chr1829027888chr1828588491131HLA-C12:12LAIFVPLNY0.50850.9187817
DSG3-DSC3chr1829027888chr1828588491131HLA-C06:03LAIFVPLNY0.23960.9922817
DSG3-DSC3chr1829027888chr1828588491131HLA-C12:04LAIFVPLNY0.23670.9935817
DSG3-DSC3chr1829027888chr1828588491131HLA-B15:39LAIFVPLNY0.99910.7774817
DSG3-DSC3chr1829027888chr1828588491131HLA-B15:20LAIFVPLNY0.99890.8459817
DSG3-DSC3chr1829027888chr1828588491131HLA-B35:11LAIFVPLNY0.99860.8694817
DSG3-DSC3chr1829027888chr1828588491131HLA-B35:28LAIFVPLNY0.99840.8416817
DSG3-DSC3chr1829027888chr1828588491131HLA-B35:23LAIFVPLNY0.99770.7752817
DSG3-DSC3chr1829027888chr1828588491131HLA-B35:77LAIFVPLNY0.99770.8195817
DSG3-DSC3chr1829027888chr1828588491131HLA-B35:20LAIFVPLNY0.99750.8551817
DSG3-DSC3chr1829027888chr1828588491131HLA-B35:17LAIFVPLNY0.99450.6151817
DSG3-DSC3chr1829027888chr1828588491131HLA-B35:30LAIFVPLNY0.99450.6151817
DSG3-DSC3chr1829027888chr1828588491131HLA-B15:11LAIFVPLNY0.98990.7808817
DSG3-DSC3chr1829027888chr1828588491131HLA-B35:24LAIFVPLNY0.98960.8734817
DSG3-DSC3chr1829027888chr1828588491131HLA-B15:08LAIFVPLNY0.98880.7862817
DSG3-DSC3chr1829027888chr1828588491131HLA-B35:43LAIFVPLNY0.98540.7812817
DSG3-DSC3chr1829027888chr1828588491131HLA-C03:02LAIFVPLNY0.98260.9627817
DSG3-DSC3chr1829027888chr1828588491131HLA-B15:35LAIFVPLNY0.97550.8005817
DSG3-DSC3chr1829027888chr1828588491131HLA-B58:06LAIFVPLNY0.96810.715817
DSG3-DSC3chr1829027888chr1828588491131HLA-C15:09LAIFVPLNY0.92370.8635817
DSG3-DSC3chr1829027888chr1828588491131HLA-C16:04LAIFVPLNY0.83920.9781817
DSG3-DSC3chr1829027888chr1828588491131HLA-C12:02LAIFVPLNY0.79270.971817
DSG3-DSC3chr1829027888chr1828588491131HLA-B18:04LAIFVPLNY0.69340.8828817
DSG3-DSC3chr1829027888chr1828588491131HLA-C12:03LAIFVPLNY0.5830.9776817
DSG3-DSC3chr1829027888chr1828588491131HLA-C16:01LAIFVPLNY0.44940.9703817
DSG3-DSC3chr1829027888chr1828588491131HLA-B18:07LAIFVPLNY0.38650.818817
DSG3-DSC3chr1829027888chr1828588491131HLA-C16:02LAIFVPLNY0.20970.9858817
DSG3-DSC3chr1829027888chr1828588491131HLA-C02:02LAIFVPLNY0.10790.9778817
DSG3-DSC3chr1829027888chr1828588491131HLA-C02:10LAIFVPLNY0.10790.9778817

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Potential FusionNeoAntigen Information of DSG3-DSC3 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.
DSG3-DSC3_29027888_28588491.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)
DSG3-DSC3chr1829027888chr1828588491131DRB1-1201TGALAIFVPLNYEEN520
DSG3-DSC3chr1829027888chr1828588491131DRB1-1203TGALAIFVPLNYEEN520
DSG3-DSC3chr1829027888chr1828588491131DRB1-1203TTGALAIFVPLNYEE419
DSG3-DSC3chr1829027888chr1828588491131DRB1-1205TGALAIFVPLNYEEN520
DSG3-DSC3chr1829027888chr1828588491131DRB1-1206TGALAIFVPLNYEEN520
DSG3-DSC3chr1829027888chr1828588491131DRB1-1207TGALAIFVPLNYEEN520
DSG3-DSC3chr1829027888chr1828588491131DRB1-1208TGALAIFVPLNYEEN520
DSG3-DSC3chr1829027888chr1828588491131DRB1-1210TGALAIFVPLNYEEN520
DSG3-DSC3chr1829027888chr1828588491131DRB1-1211TGALAIFVPLNYEEN520
DSG3-DSC3chr1829027888chr1828588491131DRB1-1214TGALAIFVPLNYEEN520
DSG3-DSC3chr1829027888chr1828588491131DRB1-1217TGALAIFVPLNYEEN520
DSG3-DSC3chr1829027888chr1828588491131DRB1-1525FVPLNYEENRQVNLE1126

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Fusion breakpoint peptide structures of DSG3-DSC3

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
2657GALAIFVPLNYEENDSG3DSC3chr1829027888chr1828588491131

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DSG3-DSC3

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-B14:023BVN2657GALAIFVPLNYEEN-7.15543-7.26883
HLA-B14:023BVN2657GALAIFVPLNYEEN-4.77435-5.80965
HLA-B52:013W392657GALAIFVPLNYEEN-6.80875-6.92215
HLA-B52:013W392657GALAIFVPLNYEEN-4.20386-5.23916
HLA-A11:014UQ22657GALAIFVPLNYEEN-7.5194-8.5547
HLA-A11:014UQ22657GALAIFVPLNYEEN-6.9601-7.0735
HLA-A24:025HGA2657GALAIFVPLNYEEN-7.52403-7.63743
HLA-A24:025HGA2657GALAIFVPLNYEEN-5.82433-6.85963
HLA-B27:056PYJ2657GALAIFVPLNYEEN-3.28285-4.31815
HLA-B44:053DX82657GALAIFVPLNYEEN-5.91172-6.94702
HLA-B44:053DX82657GALAIFVPLNYEEN-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of DSG3-DSC3

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
DSG3-DSC3chr1829027888chr1828588491817LAIFVPLNYCTGGCCATCTTCGTGCCACTGAATTAT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
DSG3-DSC3chr1829027888chr18285884911126FVPLNYEENRQVNLETTCGTGCCACTGAATTATGAAGAAAACCGTCAAGTGAACCTGGAA
DSG3-DSC3chr1829027888chr1828588491419TTGALAIFVPLNYEEACTACAGGGGCTCTGGCCATCTTCGTGCCACTGAATTATGAAGAA
DSG3-DSC3chr1829027888chr1828588491520TGALAIFVPLNYEENACAGGGGCTCTGGCCATCTTCGTGCCACTGAATTATGAAGAAAAC

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Information of the samples that have these potential fusion neoantigens of DSG3-DSC3

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
ESCADSG3-DSC3chr1829027888ENST00000257189chr1828588491ENST00000360428TCGA-L5-A8NW

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Potential target of CAR-T therapy development for DSG3-DSC3

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
TgeneDSC3chr18:29027888chr18:28588491ENST00000360428816691_7110897.0TransmembraneHelical
TgeneDSC3chr18:29027888chr18:28588491ENST00000434452817691_71102180.3333333333335TransmembraneHelical

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 DSG3-DSC3

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 DSG3-DSC3

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