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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:DUS2-UNC5C

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DUS2-UNC5C
FusionPDB ID: 24448
FusionGDB2.0 ID: 24448
HgeneTgene
Gene symbol

DUS2

UNC5C

Gene ID

54920

8633

Gene namedihydrouridine synthase 2unc-5 netrin receptor C
SynonymsDUS2L|SMM1|URLC8UNC5H3
Cytomap

16q22.1

4q22.3

Type of geneprotein-codingprotein-coding
DescriptiontRNA-dihydrouridine(20) synthase [NAD(P)+]-likeSMM1 homologdihydrouridine synthase 2-like, SMM1 homologtRNA-dihydrouridine(20) synthase (NAD(P)(+))up-regulated in lung cancer protein 8netrin receptor UNC5Cprotein unc-5 homolog 3protein unc-5 homolog Cunc-5 homolog 3unc-5 homolog Cunc5 (C.elegans homolog) c
Modification date2020031320200313
UniProtAcc

Q9NX74

Main function of 5'-partner protein: FUNCTION: Dihydrouridine synthase. Catalyzes the NADPH-dependent synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs (PubMed:15994936, PubMed:26429968, PubMed:30149704). Negatively regulates the activation of EIF2AK2/PKR (PubMed:18096616). {ECO:0000269|PubMed:15994936, ECO:0000269|PubMed:18096616, ECO:0000269|PubMed:26429968, ECO:0000269|PubMed:30149704}.

UNC5CL

Main function of 5'-partner protein: 518
Ensembl transtripts involved in fusion geneENST idsENST00000358896, ENST00000432752, 
ENST00000565263, 
ENST00000453304, 
ENST00000504962, ENST00000506749, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 2 X 2=84 X 4 X 3=48
# samples 24
** MAII scorelog2(2/8*10)=1.32192809488736log2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DUS2 [Title/Abstract] AND UNC5C [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DUS2 [Title/Abstract] AND UNC5C [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DUS2(68072052)-UNC5C(96171818), # samples:1
Anticipated loss of major functional domain due to fusion event.DUS2-UNC5C 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.
DUS2-UNC5C 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.
DUS2-UNC5C 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.
DUS2-UNC5C 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
HgeneDUS2

GO:0002943

tRNA dihydrouridine synthesis

26429968

HgeneDUS2

GO:0060548

negative regulation of cell death

18096616

TgeneUNC5C

GO:1990791

dorsal root ganglion development

28483977



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/chr16:68072052/chr4:96171818)
- 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 DUS2 (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 UNC5C (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)
ENST00000565263DUS2chr1668072052+ENST00000453304UNC5Cchr496171818-95526204942821775
ENST00000565263DUS2chr1668072052+ENST00000506749UNC5Cchr496171818-18976204941819441
ENST00000565263DUS2chr1668072052+ENST00000504962UNC5Cchr496171818-147262092448118
ENST00000358896DUS2chr1668072052+ENST00000453304UNC5Cchr496171818-91752431172444775
ENST00000358896DUS2chr1668072052+ENST00000506749UNC5Cchr496171818-15202431171442441
ENST00000358896DUS2chr1668072052+ENST00000504962UNC5Cchr496171818-1095243117431104
ENST00000432752DUS2chr1668072052+ENST00000453304UNC5Cchr496171818-92162841582485775
ENST00000432752DUS2chr1668072052+ENST00000506749UNC5Cchr496171818-15612841581483441
ENST00000432752DUS2chr1668072052+ENST00000504962UNC5Cchr496171818-1136284158472104

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
ENST00000565263ENST00000453304DUS2chr1668072052+UNC5Cchr496171818-0.0004304080.9995696
ENST00000565263ENST00000506749DUS2chr1668072052+UNC5Cchr496171818-0.001820840.9981792
ENST00000565263ENST00000504962DUS2chr1668072052+UNC5Cchr496171818-0.52972090.4702791
ENST00000358896ENST00000453304DUS2chr1668072052+UNC5Cchr496171818-0.0003780830.99962187
ENST00000358896ENST00000506749DUS2chr1668072052+UNC5Cchr496171818-0.0010674350.99893254
ENST00000358896ENST00000504962DUS2chr1668072052+UNC5Cchr496171818-0.0489088260.9510912
ENST00000432752ENST00000453304DUS2chr1668072052+UNC5Cchr496171818-0.0003902620.99960977
ENST00000432752ENST00000506749DUS2chr1668072052+UNC5Cchr496171818-0.0009219240.99907804
ENST00000432752ENST00000504962DUS2chr1668072052+UNC5Cchr496171818-0.0299570520.9700429

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 DUS2-UNC5C

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DUS2chr1668072052UNC5Cchr49617181824342LALDYGADIVYCEVEWLKNEDIIDPV
DUS2chr1668072052UNC5Cchr49617181828442LALDYGADIVYCEVEWLKNEDIIDPV
DUS2chr1668072052UNC5Cchr49617181862042LALDYGADIVYCEVEWLKNEDIIDPV

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Potential FusionNeoAntigen Information of DUS2-UNC5C 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.
DUS2-UNC5C_68072052_96171818.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)
DUS2-UNC5Cchr1668072052chr496171818243HLA-C05:09GADIVYCEV0.99960.9872514
DUS2-UNC5Cchr1668072052chr496171818243HLA-C05:01GADIVYCEV0.99960.9872514
DUS2-UNC5Cchr1668072052chr496171818243HLA-A25:01DIVYCEVEW0.99270.9635716

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Potential FusionNeoAntigen Information of DUS2-UNC5C 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 DUS2-UNC5C

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
121ADIVYCEVEWLKNEDUS2UNC5Cchr1668072052chr496171818243

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DUS2-UNC5C

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-B14:023BVN121ADIVYCEVEWLKNE-8.79968-8.91308
HLA-B14:023BVN121ADIVYCEVEWLKNE-2.93446-3.96976
HLA-B52:013W39121ADIVYCEVEWLKNE-5.96997-6.08337
HLA-B52:013W39121ADIVYCEVEWLKNE-4.23042-5.26572
HLA-A11:014UQ2121ADIVYCEVEWLKNE-8.20522-8.31862
HLA-A11:014UQ2121ADIVYCEVEWLKNE-4.67476-5.71006
HLA-A24:025HGA121ADIVYCEVEWLKNE-9.05525-9.16865
HLA-A24:025HGA121ADIVYCEVEWLKNE-6.47443-7.50973
HLA-B44:053DX8121ADIVYCEVEWLKNE-6.9286-7.042
HLA-B44:053DX8121ADIVYCEVEWLKNE-2.31135-3.34665
HLA-A02:016TDR121ADIVYCEVEWLKNE-4.18158-5.21688

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Vaccine Design for the FusionNeoAntigens of DUS2-UNC5C

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
DUS2-UNC5Cchr1668072052chr496171818514GADIVYCEVGGAGCGGACATTGTTTACTGTGAGGTG
DUS2-UNC5Cchr1668072052chr496171818716DIVYCEVEWGACATTGTTTACTGTGAGGTGGAATGG

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 DUS2-UNC5C

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
BRCADUS2-UNC5Cchr1668072052ENST00000358896chr496171818ENST00000453304TCGA-E2-A15T-01A

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Potential target of CAR-T therapy development for DUS2-UNC5C

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
TgeneUNC5Cchr16:68072052chr4:96171818ENST00000453304316381_4010932.0TransmembraneHelical
TgeneUNC5Cchr16:68072052chr4:96171818ENST00000506749311381_4010598.0TransmembraneHelical

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 DUS2-UNC5C

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 DUS2-UNC5C

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