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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:DVL2-CST6

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DVL2-CST6
FusionPDB ID: 24541
FusionGDB2.0 ID: 24541
HgeneTgene
Gene symbol

DVL2

CST6

Gene ID

1856

1476

Gene namedishevelled segment polarity protein 2cystatin B
Synonyms-CPI-B|CST6|EPM1|EPM1A|PME|STFB|ULD
Cytomap

17p13.1

21q22.3

Type of geneprotein-codingprotein-coding
Descriptionsegment polarity protein dishevelled homolog DVL-2dishevelled 2 (homologous to Drosophila dsh)dishevelled, dsh homolog 2cystatin-Bcystatin B (stefin B)epididymis secretory sperm binding proteinliver thiol proteinase inhibitor
Modification date2020032720200313
UniProtAcc

O14641

Main function of 5'-partner protein: FUNCTION: Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Participates both in canonical and non-canonical Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling. {ECO:0000250|UniProtKB:Q60838, ECO:0000269|PubMed:19252499}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000005340, ENST00000575458, 
ENST00000574642, 
ENST00000312134, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 8 X 4=1922 X 2 X 1=4
# samples 83
** MAII scorelog2(8/192*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/4*10)=2.90689059560852
Fusion gene context

PubMed: DVL2 [Title/Abstract] AND CST6 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DVL2 [Title/Abstract] AND CST6 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DVL2(7134047)-CST6(65779657), # samples:2
Anticipated loss of major functional domain due to fusion event.DVL2-CST6 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.
DVL2-CST6 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.
DVL2-CST6 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.
DVL2-CST6 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
HgeneDVL2

GO:0006366

transcription by RNA polymerase II

11742073

HgeneDVL2

GO:0043507

positive regulation of JUN kinase activity

17593335

HgeneDVL2

GO:0044340

canonical Wnt signaling pathway involved in regulation of cell proliferation

18787224

HgeneDVL2

GO:0045893

positive regulation of transcription, DNA-templated

12805222|17593335

HgeneDVL2

GO:0051091

positive regulation of DNA-binding transcription factor activity

17593335

HgeneDVL2

GO:0060070

canonical Wnt signaling pathway

17593335

HgeneDVL2

GO:0060071

Wnt signaling pathway, planar cell polarity pathway

12805222

TgeneCST6

GO:0010466

negative regulation of peptidase activity

6203523

TgeneCST6

GO:0045861

negative regulation of proteolysis

3488317



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/chr17:7134047/chr11:65779657)
- 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 DVL2 (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 CST6 (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)
ENST00000005340DVL2chr177134047-ENST00000312134CST6chr1165779657+960547283672129
ENST00000575458DVL2chr177134047-ENST00000312134CST6chr1165779657+73332056445129

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
ENST00000005340ENST00000312134DVL2chr177134047-CST6chr1165779657+0.178609830.82139015
ENST00000575458ENST00000312134DVL2chr177134047-CST6chr1165779657+0.102899480.89710045

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 DVL2-CST6

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DVL2chr177134047CST6chr116577965732088ARLPCFNGRVVSWCRRRRRRPWPATT
DVL2chr177134047CST6chr116577965754788ARLPCFNGRVVSWCRRRRRRPWPATT

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Potential FusionNeoAntigen Information of DVL2-CST6 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 DVL2-CST6 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.
DVL2-CST6_7134047_65779657.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)
DVL2-CST6chr177134047chr1165779657547DRB1-1102NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1116NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1121NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1121FNGRVVSWCRRRRRR520
DVL2-CST6chr177134047chr1165779657547DRB1-1121GRVVSWCRRRRRRPW722
DVL2-CST6chr177134047chr1165779657547DRB1-1136NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1165NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1170NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1170FNGRVVSWCRRRRRR520
DVL2-CST6chr177134047chr1165779657547DRB1-1186NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1186FNGRVVSWCRRRRRR520
DVL2-CST6chr177134047chr1165779657547DRB1-1301NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1315NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1315FNGRVVSWCRRRRRR520
DVL2-CST6chr177134047chr1165779657547DRB1-1315GRVVSWCRRRRRRPW722
DVL2-CST6chr177134047chr1165779657547DRB1-1316NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1316FNGRVVSWCRRRRRR520
DVL2-CST6chr177134047chr1165779657547DRB1-1317NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1319NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1320NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1322NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1327NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1327FNGRVVSWCRRRRRR520
DVL2-CST6chr177134047chr1165779657547DRB1-1335NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1351NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1352NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1353NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1357NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1357FNGRVVSWCRRRRRR520
DVL2-CST6chr177134047chr1165779657547DRB1-1357GRVVSWCRRRRRRPW722
DVL2-CST6chr177134047chr1165779657547DRB1-1359NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1361NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1361FNGRVVSWCRRRRRR520
DVL2-CST6chr177134047chr1165779657547DRB1-1364NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1368NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1369NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1371NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1378NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1379NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1380NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1383NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1387NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1391NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1392NGRVVSWCRRRRRRP621
DVL2-CST6chr177134047chr1165779657547DRB1-1398NGRVVSWCRRRRRRP621

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Fusion breakpoint peptide structures of DVL2-CST6

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 DVL2-CST6

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 DVL2-CST6

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
DVL2-CST6chr177134047chr1165779657520FNGRVVSWCRRRRRRTTCAACGGAAGGGTGGTATCCTGGTGCAGAAGGCGGCGCAGGCGG
DVL2-CST6chr177134047chr1165779657621NGRVVSWCRRRRRRPAACGGAAGGGTGGTATCCTGGTGCAGAAGGCGGCGCAGGCGGCCG
DVL2-CST6chr177134047chr1165779657722GRVVSWCRRRRRRPWGGAAGGGTGGTATCCTGGTGCAGAAGGCGGCGCAGGCGGCCGTGG

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Information of the samples that have these potential fusion neoantigens of DVL2-CST6

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 DVL2-CST6

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 DVL2-CST6

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 DVL2-CST6

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