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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:SDC4-YWHAB

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SDC4-YWHAB
FusionPDB ID: 79829
FusionGDB2.0 ID: 79829
HgeneTgene
Gene symbol

SDC4

YWHAB

Gene ID

6385

7529

Gene namesyndecan 4tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta
SynonymsSYND4GW128|HEL-S-1|HS1|KCIP-1|YWHAA
Cytomap

20q13.12

20q13.12

Type of geneprotein-codingprotein-coding
Descriptionsyndecan-4amphiglycanryudocan amphiglycanryudocan core proteinsyndecan 4 (amphiglycan, ryudocan)syndecan proteoglycan 414-3-3 protein beta/alpha14-3-3 alphabrain protein 14-3-3, beta isoformepididymis secretory protein Li 1protein 1054protein kinase C inhibitor protein-1tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, alpha polypeptidetyrosin
Modification date2020031320200327
UniProtAcc

P31431

Main function of 5'-partner protein: FUNCTION: Cell surface proteoglycan that bears heparan sulfate. Regulates exosome biogenesis in concert with SDCBP and PDCD6IP (PubMed:22660413). {ECO:0000269|PubMed:22660413}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000372733, ENST00000537976, 
ENST00000372839, ENST00000479421, 
ENST00000353703, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 12 X 10=144013 X 25 X 12=3900
# samples 2130
** MAII scorelog2(21/1440*10)=-2.77760757866355
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(30/3900*10)=-3.70043971814109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SDC4 [Title/Abstract] AND YWHAB [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SDC4 [Title/Abstract] AND YWHAB [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SDC4(43976965)-YWHAB(43532634), # samples:2
Anticipated loss of major functional domain due to fusion event.
* 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
TgeneYWHAB

GO:0035308

negative regulation of protein dephosphorylation

17255105

TgeneYWHAB

GO:0043085

positive regulation of catalytic activity

17255105

TgeneYWHAB

GO:0051220

cytoplasmic sequestering of protein

10869435



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/chr20:43976965/chr20:43532634)
- 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 SDC4 (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 YWHAB (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)
ENST00000372733SDC4chr2043976964-ENST00000353703YWHABchr2043532633+263510040540166
ENST00000372733SDC4chr2043976965-ENST00000353703YWHABchr2043532634+263510040540166

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
ENST00000372733ENST00000353703SDC4chr2043976964-YWHABchr2043532633+0.0009838750.99901617
ENST00000372733ENST00000353703SDC4chr2043976965-YWHABchr2043532634+0.0009838750.99901617

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 SDC4-YWHAB

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SDC4chr2043976964YWHABchr204353263310020ALLLFFVGGVAESELLDKYLIPNATQ
SDC4chr2043976965YWHABchr204353263410020ALLLFFVGGVAESELLDKYLIPNATQ

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Potential FusionNeoAntigen Information of SDC4-YWHAB 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.
SDC4-YWHAB_43976964_43532633.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)
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:03AESELLDKY0.99920.92821019
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:03SELLDKYLI0.9950.94891221
SDC4-YWHABchr2043976964chr2043532633100HLA-B45:01SELLDKYLI0.98410.61061221
SDC4-YWHABchr2043976964chr2043532633100HLA-B18:01AESELLDKY0.98350.89561019
SDC4-YWHABchr2043976964chr2043532633100HLA-B45:01AESELLDKY0.68340.62821019
SDC4-YWHABchr2043976964chr2043532633100HLA-B41:01SELLDKYLI0.4130.87261221
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:03AESELLDKYL0.99380.95421020
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:03VAESELLDKY0.59270.9198919
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:03GVAESELLDKY0.79880.963819
SDC4-YWHABchr2043976964chr2043532633100HLA-B39:08AESELLDKYL0.9130.73211020
SDC4-YWHABchr2043976964chr2043532633100HLA-B40:04SELLDKYL0.99950.56151220
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:07AESELLDKY0.99920.92821019
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:26AESELLDKY0.99920.92821019
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:13AESELLDKY0.99920.92821019
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:07SELLDKYLI0.9950.94891221
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:13SELLDKYLI0.9950.94891221
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:26SELLDKYLI0.9950.94891221
SDC4-YWHABchr2043976964chr2043532633100HLA-B40:04SELLDKYLI0.99430.5711221
SDC4-YWHABchr2043976964chr2043532633100HLA-B18:04AESELLDKY0.98760.90391019
SDC4-YWHABchr2043976964chr2043532633100HLA-B18:07AESELLDKY0.98740.85321019
SDC4-YWHABchr2043976964chr2043532633100HLA-B18:05AESELLDKY0.98350.89561019
SDC4-YWHABchr2043976964chr2043532633100HLA-B18:08AESELLDKY0.9810.69351019
SDC4-YWHABchr2043976964chr2043532633100HLA-B18:06AESELLDKY0.9740.91221019
SDC4-YWHABchr2043976964chr2043532633100HLA-B18:03AESELLDKY0.97080.89251019
SDC4-YWHABchr2043976964chr2043532633100HLA-B18:11AESELLDKY0.88580.87951019
SDC4-YWHABchr2043976964chr2043532633100HLA-B35:28AESELLDKY0.60010.80171019
SDC4-YWHABchr2043976964chr2043532633100HLA-B40:04AESELLDKY0.57860.54921019
SDC4-YWHABchr2043976964chr2043532633100HLA-B35:20AESELLDKY0.53890.82381019
SDC4-YWHABchr2043976964chr2043532633100HLA-B15:12AESELLDKY0.5330.77391019
SDC4-YWHABchr2043976964chr2043532633100HLA-B15:53AESELLDKY0.22010.79971019
SDC4-YWHABchr2043976964chr2043532633100HLA-B48:02AESELLDKY0.1390.7911019
SDC4-YWHABchr2043976964chr2043532633100HLA-B15:54AESELLDKY0.01890.77331019
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:26AESELLDKYL0.99380.95421020
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:13AESELLDKYL0.99380.95421020
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:07AESELLDKYL0.99380.95421020
SDC4-YWHABchr2043976964chr2043532633100HLA-B40:04AESELLDKYL0.99090.60231020
SDC4-YWHABchr2043976964chr2043532633100HLA-B18:11VAESELLDKY0.64090.8973919
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:07VAESELLDKY0.59270.9198919
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:13VAESELLDKY0.59270.9198919
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:26VAESELLDKY0.59270.9198919
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:07GVAESELLDKY0.79880.963819
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:26GVAESELLDKY0.79880.963819
SDC4-YWHABchr2043976964chr2043532633100HLA-B44:13GVAESELLDKY0.79880.963819

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Potential FusionNeoAntigen Information of SDC4-YWHAB 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 SDC4-YWHAB

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
9947VGGVAESELLDKYLSDC4YWHABchr2043976964chr2043532633100

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SDC4-YWHAB

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-B14:023BVN9947VGGVAESELLDKYL-7.9962-8.1096
HLA-B14:023BVN9947VGGVAESELLDKYL-5.70842-6.74372
HLA-B52:013W399947VGGVAESELLDKYL-6.83737-6.95077
HLA-B52:013W399947VGGVAESELLDKYL-4.4836-5.5189
HLA-A11:014UQ29947VGGVAESELLDKYL-10.0067-10.1201
HLA-A11:014UQ29947VGGVAESELLDKYL-9.03915-10.0745
HLA-A24:025HGA9947VGGVAESELLDKYL-6.56204-6.67544
HLA-A24:025HGA9947VGGVAESELLDKYL-5.42271-6.45801
HLA-B44:053DX89947VGGVAESELLDKYL-7.85648-8.89178
HLA-B44:053DX89947VGGVAESELLDKYL-5.3978-5.5112
HLA-A02:016TDR9947VGGVAESELLDKYL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of SDC4-YWHAB

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
SDC4-YWHABchr2043976964chr20435326331019AESELLDKYGCCGAGTCGGAGCTGTTGGACAAATAT
SDC4-YWHABchr2043976964chr20435326331020AESELLDKYLGCCGAGTCGGAGCTGTTGGACAAATATCTT
SDC4-YWHABchr2043976964chr20435326331220SELLDKYLTCGGAGCTGTTGGACAAATATCTT
SDC4-YWHABchr2043976964chr20435326331221SELLDKYLITCGGAGCTGTTGGACAAATATCTTATT
SDC4-YWHABchr2043976964chr2043532633819GVAESELLDKYGGAGTCGCCGAGTCGGAGCTGTTGGACAAATAT
SDC4-YWHABchr2043976964chr2043532633919VAESELLDKYGTCGCCGAGTCGGAGCTGTTGGACAAATAT

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 SDC4-YWHAB

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
LUADSDC4-YWHABchr2043976964ENST00000372733chr2043532633ENST00000353703TCGA-97-8177

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Potential target of CAR-T therapy development for SDC4-YWHAB

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 SDC4-YWHAB

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 SDC4-YWHAB

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
HgeneSDC4C0007131Non-Small Cell Lung Carcinoma1CTD_human