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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:DPP4-THSD7B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DPP4-THSD7B
FusionPDB ID: 24023
FusionGDB2.0 ID: 24023
HgeneTgene
Gene symbol

DPP4

THSD7B

Gene ID

1803

80731

Gene namedipeptidyl peptidase 4thrombospondin type 1 domain containing 7B
SynonymsADABP|ADCP2|CD26|DPPIV|TP103-
Cytomap

2q24.2

2q22.1

Type of geneprotein-codingprotein-coding
Descriptiondipeptidyl peptidase 4ADCP-2DPP IVT-cell activation antigen CD26adenosine deaminase complexing protein 2dipeptidyl peptidase IVdipeptidylpeptidase 4dipeptidylpeptidase IV (CD26, adenosine deaminase complexing protein 2)thrombospondin type-1 domain-containing protein 7Bthrombospondin, type I, domain containing 7B
Modification date2020032220200313
UniProtAcc

P27487

Main function of 5'-partner protein: FUNCTION: Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation (PubMed:10951221, PubMed:10900005, PubMed:11772392, PubMed:17287217). Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC (PubMed:10951221, PubMed:10900005, PubMed:11772392, PubMed:14691230). Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (PubMed:17287217). Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion (PubMed:11772392). In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM (PubMed:16651416, PubMed:10593948). May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation (PubMed:18708048). When overexpressed, enhanced cell proliferation, a process inhibited by GPC3 (PubMed:17549790). Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones such as brain natriuretic peptide 32 (PubMed:16254193, PubMed:10570924). Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline (PubMed:10593948). {ECO:0000269|PubMed:10570924, ECO:0000269|PubMed:10593948, ECO:0000269|PubMed:10900005, ECO:0000269|PubMed:10951221, ECO:0000269|PubMed:11772392, ECO:0000269|PubMed:14691230, ECO:0000269|PubMed:16254193, ECO:0000269|PubMed:16651416, ECO:0000269|PubMed:17287217, ECO:0000269|PubMed:17549790, ECO:0000269|PubMed:18708048}.; FUNCTION: (Microbial infection) Acts as a receptor for human coronavirus MERS-CoV-2. {ECO:0000269|PubMed:23835475}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000360534, ENST00000491591, 
ENST00000485379, ENST00000543459, 
ENST00000272643, ENST00000409968, 
ENST00000413152, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 5 X 4=1009 X 7 X 4=252
# samples 69
** MAII scorelog2(6/100*10)=-0.736965594166206
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/252*10)=-1.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DPP4 [Title/Abstract] AND THSD7B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DPP4 [Title/Abstract] AND THSD7B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DPP4(162929909)-THSD7B(137813990), # samples:3
Anticipated loss of major functional domain due to fusion event.DPP4-THSD7B 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.
DPP4-THSD7B 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.
DPP4-THSD7B 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.
DPP4-THSD7B 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
HgeneDPP4

GO:0001666

response to hypoxia

16670267

HgeneDPP4

GO:0006508

proteolysis

27198182

HgeneDPP4

GO:0008284

positive regulation of cell proliferation

17549790

HgeneDPP4

GO:0010716

negative regulation of extracellular matrix disassembly

16651416

HgeneDPP4

GO:0031295

T cell costimulation

10900005|17287217

HgeneDPP4

GO:0033632

regulation of cell-cell adhesion mediated by integrin

11772392

HgeneDPP4

GO:0042110

T cell activation

7594462

HgeneDPP4

GO:0043542

endothelial cell migration

16651416



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/chr2:162929909/chr2:137813990)
- 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 DPP4 (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 THSD7B (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)
ENST00000360534DPP4chr2162929909-ENST00000409968THSD7Bchr2137813990+644965556153361591
ENST00000360534DPP4chr2162929909-ENST00000272643THSD7Bchr2137813990+645865556153451594
ENST00000360534DPP4chr2162929909-ENST00000413152THSD7Bchr2137813990+645865556153451594

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
ENST00000360534ENST00000409968DPP4chr2162929909-THSD7Bchr2137813990+0.0019816570.9980184
ENST00000360534ENST00000272643DPP4chr2162929909-THSD7Bchr2137813990+0.0018142770.9981857
ENST00000360534ENST00000413152DPP4chr2162929909-THSD7Bchr2137813990+0.0018142770.9981857

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 DPP4-THSD7B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DPP4chr2162929909THSD7Bchr213781399065532IITVPVVLLNKGSPWGRCTGDCGPGG

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Potential FusionNeoAntigen Information of DPP4-THSD7B 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.
DPP4-THSD7B_162929909_137813990.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)
DPP4-THSD7Bchr2162929909chr2137813990655HLA-A32:13VLLNKGSPW0.85420.9047615
DPP4-THSD7Bchr2162929909chr2137813990655HLA-A74:09VLLNKGSPWGR0.98010.8126617
DPP4-THSD7Bchr2162929909chr2137813990655HLA-A74:03VLLNKGSPWGR0.98010.8126617
DPP4-THSD7Bchr2162929909chr2137813990655HLA-A74:11VLLNKGSPWGR0.98010.8126617
DPP4-THSD7Bchr2162929909chr2137813990655HLA-A31:02VLLNKGSPWGR0.96210.8099617
DPP4-THSD7Bchr2162929909chr2137813990655HLA-A31:06VLLNKGSPWGR0.94430.5275617
DPP4-THSD7Bchr2162929909chr2137813990655HLA-A31:01VLLNKGSPWGR0.98440.7867617
DPP4-THSD7Bchr2162929909chr2137813990655HLA-A32:01VLLNKGSPW0.92920.8392615
DPP4-THSD7Bchr2162929909chr2137813990655HLA-B15:24VLLNKGSPW0.82340.8037615
DPP4-THSD7Bchr2162929909chr2137813990655HLA-B15:13VLLNKGSPW0.74880.7027615
DPP4-THSD7Bchr2162929909chr2137813990655HLA-A74:01VLLNKGSPWGR0.98010.8126617

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Potential FusionNeoAntigen Information of DPP4-THSD7B 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.
DPP4-THSD7B_162929909_137813990.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)
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-0804TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-0828TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-0831TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1104TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1106TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1135TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1138TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1143TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1144TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1146TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1147TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1158TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1160TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1167TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1177TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1178TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1311TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1342TVPVVLLNKGSPWGR217
DPP4-THSD7Bchr2162929909chr2137813990655DRB1-1415TVPVVLLNKGSPWGR217

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Fusion breakpoint peptide structures of DPP4-THSD7B

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
10082VLLNKGSPWGRCTGDPP4THSD7Bchr2162929909chr2137813990655

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DPP4-THSD7B

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-B14:023BVN10082VLLNKGSPWGRCTG-7.9962-8.1096
HLA-B14:023BVN10082VLLNKGSPWGRCTG-5.70842-6.74372
HLA-B52:013W3910082VLLNKGSPWGRCTG-6.83737-6.95077
HLA-B52:013W3910082VLLNKGSPWGRCTG-4.4836-5.5189
HLA-A11:014UQ210082VLLNKGSPWGRCTG-10.0067-10.1201
HLA-A11:014UQ210082VLLNKGSPWGRCTG-9.03915-10.0745
HLA-A24:025HGA10082VLLNKGSPWGRCTG-6.56204-6.67544
HLA-A24:025HGA10082VLLNKGSPWGRCTG-5.42271-6.45801
HLA-B44:053DX810082VLLNKGSPWGRCTG-7.85648-8.89178
HLA-B44:053DX810082VLLNKGSPWGRCTG-5.3978-5.5112
HLA-B35:011A1N10082VLLNKGSPWGRCTG-6.27422-6.38762
HLA-B35:011A1N10082VLLNKGSPWGRCTG-5.27424-6.30954
HLA-A02:016TDR10082VLLNKGSPWGRCTG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of DPP4-THSD7B

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
DPP4-THSD7Bchr2162929909chr2137813990615VLLNKGSPWTGGTTCTGCTGAACAAAGGCAGTCCGT
DPP4-THSD7Bchr2162929909chr2137813990617VLLNKGSPWGRTGGTTCTGCTGAACAAAGGCAGTCCGTGGGGAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
DPP4-THSD7Bchr2162929909chr2137813990217TVPVVLLNKGSPWGRTCACCGTGCCCGTGGTTCTGCTGAACAAAGGCAGTCCGTGGGGAA

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Information of the samples that have these potential fusion neoantigens of DPP4-THSD7B

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
LIHCDPP4-THSD7Bchr2162929909ENST00000360534chr2137813990ENST00000272643TCGA-DD-A3A5-01A

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Potential target of CAR-T therapy development for DPP4-THSD7B

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
HgeneDPP4chr2:162929909chr2:137813990ENST00000360534-2267_2831767.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
TgeneTHSD7Bchr2:162929909chr2:137813990ENST000002726430281556_157601610.0TransmembraneHelical

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
DPP4chr2162929909ENST00000360534THSD7Bchr2137813990ENST00000272643
DPP4chr2162929909ENST00000360534THSD7Bchr2137813990ENST00000409968

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Related Drugs to DPP4-THSD7B

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 DPP4-THSD7B

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