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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:DSC3-RPS6

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DSC3-RPS6
FusionPDB ID: 24188
FusionGDB2.0 ID: 24188
HgeneTgene
Gene symbol

DSC3

RPS6

Gene ID

1825

6194

Gene namedesmocollin 3ribosomal protein S6
SynonymsCDHF3|DSC|DSC1|DSC2|DSC4|HT-CPS6
Cytomap

18q12.1

9p22.1

Type of geneprotein-codingprotein-coding
Descriptiondesmocollin-3cadherin family member 3desmocollin-440S ribosomal protein S6phosphoprotein NP33small ribosomal subunit protein eS6
Modification date2020031320200313
UniProtAcc

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 idsENST00000360428, ENST00000434452, 
ENST00000380381, ENST00000315377, 
ENST00000380384, ENST00000498815, 
ENST00000380394, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 7 X 4=16815 X 15 X 4=900
# samples 617
** MAII scorelog2(6/168*10)=-1.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(17/900*10)=-2.40439025507934
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DSC3 [Title/Abstract] AND RPS6 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DSC3 [Title/Abstract] AND RPS6 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DSC3(28576756)-RPS6(19378916), # samples:1
DSC3(28576757)-RPS6(19378916), # samples:1
Anticipated loss of major functional domain due to fusion event.DSC3-RPS6 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.
DSC3-RPS6 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
TgeneRPS6

GO:0031929

TOR signaling

16428328

TgeneRPS6

GO:0043065

positive regulation of apoptotic process

18362888



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/chr18:28576756/chr9:19378916)
- 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 DSC3 (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 RPS6 (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)
ENST00000360428DSC3chr1828576756-ENST00000380394RPS6chr919378916-37642574931851058
ENST00000434452DSC3chr1828576756-ENST00000380394RPS6chr919378916-383826488332591058
ENST00000360428DSC3chr1828576757-ENST00000380394RPS6chr919378916-37642574931851058
ENST00000434452DSC3chr1828576757-ENST00000380394RPS6chr919378916-383826488332591058

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
ENST00000360428ENST00000380394DSC3chr1828576756-RPS6chr919378916-0.000316290.99968374
ENST00000434452ENST00000380394DSC3chr1828576756-RPS6chr919378916-0.0003783980.9996216
ENST00000360428ENST00000380394DSC3chr1828576757-RPS6chr919378916-0.000316290.99968374
ENST00000434452ENST00000380394DSC3chr1828576757-RPS6chr919378916-0.0003783980.9996216

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 DSC3-RPS6

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DSC3chr1828576756RPS6chr9193789162574855SEWHSFTQPRLGEGYVVRISGGNDKQ
DSC3chr1828576756RPS6chr9193789162648855SEWHSFTQPRLGEGYVVRISGGNDKQ
DSC3chr1828576757RPS6chr9193789162574855SEWHSFTQPRLGEGYVVRISGGNDKQ
DSC3chr1828576757RPS6chr9193789162648855SEWHSFTQPRLGEGYVVRISGGNDKQ

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Potential FusionNeoAntigen Information of DSC3-RPS6 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.
DSC3-RPS6_28576756_19378916.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)
DSC3-RPS6chr1828576756chr9193789162574HLA-B15:01TQPRLGEGY0.99710.8696615
DSC3-RPS6chr1828576756chr9193789162574HLA-B07:02QPRLGEGYV0.99670.5731716
DSC3-RPS6chr1828576756chr9193789162574HLA-B07:05QPRLGEGYV0.99660.6119716
DSC3-RPS6chr1828576756chr9193789162574HLA-A74:11RLGEGYVVR0.98380.9254918
DSC3-RPS6chr1828576756chr9193789162574HLA-A74:03RLGEGYVVR0.98380.9254918
DSC3-RPS6chr1828576756chr9193789162574HLA-A74:09RLGEGYVVR0.98380.9254918
DSC3-RPS6chr1828576756chr9193789162574HLA-A31:06RLGEGYVVR0.96030.7928918
DSC3-RPS6chr1828576756chr9193789162574HLA-A31:02RLGEGYVVR0.94060.9048918
DSC3-RPS6chr1828576756chr9193789162574HLA-B15:03TQPRLGEGY0.32930.7635615
DSC3-RPS6chr1828576756chr9193789162574HLA-B07:05QPRLGEGYVV0.99810.6825717
DSC3-RPS6chr1828576756chr9193789162574HLA-B07:02QPRLGEGYVV0.99810.647717
DSC3-RPS6chr1828576756chr9193789162574HLA-B55:01QPRLGEGYVV0.82310.5912717
DSC3-RPS6chr1828576756chr9193789162574HLA-B82:01QPRLGEGYVV0.74550.8693717
DSC3-RPS6chr1828576756chr9193789162574HLA-A31:01RLGEGYVVR0.98290.8942918
DSC3-RPS6chr1828576756chr9193789162574HLA-B07:12QPRLGEGYV0.82130.7085716
DSC3-RPS6chr1828576756chr9193789162574HLA-B07:04QPRLGEGYV0.76180.5513716
DSC3-RPS6chr1828576756chr9193789162574HLA-B15:05TQPRLGEGY0.74670.9206615
DSC3-RPS6chr1828576756chr9193789162574HLA-B42:02QPRLGEGYV0.63870.8147716
DSC3-RPS6chr1828576756chr9193789162574HLA-B42:01QPRLGEGYV0.62450.8044716
DSC3-RPS6chr1828576756chr9193789162574HLA-B07:12QPRLGEGYVV0.97350.7381717
DSC3-RPS6chr1828576756chr9193789162574HLA-B07:04QPRLGEGYVV0.95690.6289717
DSC3-RPS6chr1828576756chr9193789162574HLA-B42:02QPRLGEGYVV0.91910.8723717
DSC3-RPS6chr1828576756chr9193789162574HLA-B42:01QPRLGEGYVV0.91590.8632717
DSC3-RPS6chr1828576756chr9193789162574HLA-B15:125TQPRLGEGY0.99710.8696615
DSC3-RPS6chr1828576756chr9193789162574HLA-B15:33TQPRLGEGY0.99710.8696615
DSC3-RPS6chr1828576756chr9193789162574HLA-B15:34TQPRLGEGY0.99710.8696615
DSC3-RPS6chr1828576756chr9193789162574HLA-B15:27TQPRLGEGY0.9970.88615
DSC3-RPS6chr1828576756chr9193789162574HLA-B15:135TQPRLGEGY0.99680.8997615
DSC3-RPS6chr1828576756chr9193789162574HLA-B07:22QPRLGEGYV0.99670.5731716
DSC3-RPS6chr1828576756chr9193789162574HLA-B15:50TQPRLGEGY0.99060.9025615
DSC3-RPS6chr1828576756chr9193789162574HLA-A74:01RLGEGYVVR0.98380.9254918
DSC3-RPS6chr1828576756chr9193789162574HLA-B15:12TQPRLGEGY0.96710.823615
DSC3-RPS6chr1828576756chr9193789162574HLA-A03:02RLGEGYVVR0.94820.6337918
DSC3-RPS6chr1828576756chr9193789162574HLA-B15:53TQPRLGEGY0.93320.863615
DSC3-RPS6chr1828576756chr9193789162574HLA-B56:05QPRLGEGYV0.76350.6053716
DSC3-RPS6chr1828576756chr9193789162574HLA-B15:20TQPRLGEGY0.74730.9331615
DSC3-RPS6chr1828576756chr9193789162574HLA-B35:20TQPRLGEGY0.65930.9414615
DSC3-RPS6chr1828576756chr9193789162574HLA-B35:28TQPRLGEGY0.65830.9377615
DSC3-RPS6chr1828576756chr9193789162574HLA-B15:54TQPRLGEGY0.63960.8339615
DSC3-RPS6chr1828576756chr9193789162574HLA-B07:26QPRLGEGYV0.38180.6233716
DSC3-RPS6chr1828576756chr9193789162574HLA-B48:02TQPRLGEGY0.15820.9296615
DSC3-RPS6chr1828576756chr9193789162574HLA-B07:22QPRLGEGYVV0.99810.647717
DSC3-RPS6chr1828576756chr9193789162574HLA-B56:05QPRLGEGYVV0.83620.7774717
DSC3-RPS6chr1828576756chr9193789162574HLA-B07:26QPRLGEGYVV0.76320.6755717
DSC3-RPS6chr1828576756chr9193789162574HLA-B82:02QPRLGEGYVV0.74550.8693717
DSC3-RPS6chr1828576756chr9193789162574HLA-B55:04QPRLGEGYVV0.72230.8084717

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Potential FusionNeoAntigen Information of DSC3-RPS6 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.
DSC3-RPS6_28576756_19378916.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)
DSC3-RPS6chr1828576756chr9193789162574DRB1-0801GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-0802GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-0802LGEGYVVRISGGNDK1025
DSC3-RPS6chr1828576756chr9193789162574DRB1-0808GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-0808LGEGYVVRISGGNDK1025
DSC3-RPS6chr1828576756chr9193789162574DRB1-0809GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-0809LGEGYVVRISGGNDK1025
DSC3-RPS6chr1828576756chr9193789162574DRB1-0811GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-0811LGEGYVVRISGGNDK1025
DSC3-RPS6chr1828576756chr9193789162574DRB1-0813GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-0813LGEGYVVRISGGNDK1025
DSC3-RPS6chr1828576756chr9193789162574DRB1-0815GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-0815LGEGYVVRISGGNDK1025
DSC3-RPS6chr1828576756chr9193789162574DRB1-0816GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-0821GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-0821LGEGYVVRISGGNDK1025
DSC3-RPS6chr1828576756chr9193789162574DRB1-0826GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-0830GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-0830LGEGYVVRISGGNDK1025
DSC3-RPS6chr1828576756chr9193789162574DRB1-0839GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-1130GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-1130LGEGYVVRISGGNDK1025
DSC3-RPS6chr1828576756chr9193789162574DRB1-1347GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-1367GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-1367LGEGYVVRISGGNDK1025
DSC3-RPS6chr1828576756chr9193789162574DRB1-1403GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-1427GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-1427LGEGYVVRISGGNDK1025
DSC3-RPS6chr1828576756chr9193789162574DRB1-1440GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-1467GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB1-1477GEGYVVRISGGNDKQ1126
DSC3-RPS6chr1828576756chr9193789162574DRB5-0103GEGYVVRISGGNDKQ1126

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Fusion breakpoint peptide structures of DSC3-RPS6

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
9575TQPRLGEGYVVRISDSC3RPS6chr1828576756chr9193789162574

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DSC3-RPS6

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-B14:023BVN9575TQPRLGEGYVVRIS-8.85616-8.96956
HLA-B14:023BVN9575TQPRLGEGYVVRIS-5.66423-6.69953
HLA-B52:013W399575TQPRLGEGYVVRIS-6.49489-6.60829
HLA-B52:013W399575TQPRLGEGYVVRIS-3.99785-5.03315
HLA-A11:014UQ29575TQPRLGEGYVVRIS-4.90759-5.94289
HLA-A24:025HGA9575TQPRLGEGYVVRIS-7.27887-7.39227
HLA-A24:025HGA9575TQPRLGEGYVVRIS-7.11524-8.15054
HLA-B27:056PYJ9575TQPRLGEGYVVRIS-6.11615-6.22955
HLA-B27:056PYJ9575TQPRLGEGYVVRIS-4.78818-5.82348
HLA-B44:053DX89575TQPRLGEGYVVRIS-7.22602-7.33942
HLA-B44:053DX89575TQPRLGEGYVVRIS-4.86671-5.90201

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Vaccine Design for the FusionNeoAntigens of DSC3-RPS6

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
DSC3-RPS6chr1828576756chr919378916615TQPRLGEGYACTCAACCCCGTCTCGGTGAAGGTTAT
DSC3-RPS6chr1828576756chr919378916716QPRLGEGYVCAACCCCGTCTCGGTGAAGGTTATGTG
DSC3-RPS6chr1828576756chr919378916717QPRLGEGYVVCAACCCCGTCTCGGTGAAGGTTATGTGGTC
DSC3-RPS6chr1828576756chr919378916918RLGEGYVVRCGTCTCGGTGAAGGTTATGTGGTCCGA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
DSC3-RPS6chr1828576756chr9193789161025LGEGYVVRISGGNDKCTCGGTGAAGGTTATGTGGTCCGAATCAGTGGTGGGAACGACAAA
DSC3-RPS6chr1828576756chr9193789161126GEGYVVRISGGNDKQGGTGAAGGTTATGTGGTCCGAATCAGTGGTGGGAACGACAAACAA

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Information of the samples that have these potential fusion neoantigens of DSC3-RPS6

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
Non-CancerDSC3-RPS6chr1828576756ENST00000360428chr919378916ENST00000380394TCGA-IP-7968-11A

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Potential target of CAR-T therapy development for DSC3-RPS6

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
HgeneDSC3chr18:28576756chr9:19378916ENST00000360428-1516691_711831897.0TransmembraneHelical
HgeneDSC3chr18:28576756chr9:19378916ENST00000434452-1517691_7118312180.3333333333335TransmembraneHelical
HgeneDSC3chr18:28576757chr9:19378916ENST00000360428-1516691_711831897.0TransmembraneHelical
HgeneDSC3chr18:28576757chr9:19378916ENST00000434452-1517691_7118312180.3333333333335TransmembraneHelical

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 DSC3-RPS6

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 DSC3-RPS6

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