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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:EGFR-VOPP1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: EGFR-VOPP1
FusionPDB ID: 25487
FusionGDB2.0 ID: 25487
HgeneTgene
Gene symbol

EGFR

VOPP1

Gene ID

1956

81552

Gene nameepidermal growth factor receptorVOPP1 WW domain binding protein
SynonymsERBB|ERBB1|HER1|NISBD2|PIG61|mENAECOP|GASP|WBP1L2
Cytomap

7p11.2

7p11.2

Type of geneprotein-codingprotein-coding
Descriptionepidermal growth factor receptoravian erythroblastic leukemia viral (v-erb-b) oncogene homologcell growth inhibiting protein 40cell proliferation-inducing protein 61epidermal growth factor receptor tyrosine kinase domainerb-b2 receptor tyrosine kinasvesicular, overexpressed in cancer, prosurvival protein 1EGFR-coamplified and overexpressed proteinGlioblastoma-amplified secreted proteinVOPP1, WBP1/VOPP1 family memberhypothetical protein DKFZp564K0822putative NF-kappa-B-activating protein 055N
Modification date2020032920200313
UniProtAcc

P00533

Main function of 5'-partner protein: FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:2790960, PubMed:10805725, PubMed:27153536). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975, PubMed:15611079, PubMed:12297049, PubMed:27153536, PubMed:20837704, PubMed:17909029). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). {ECO:0000250|UniProtKB:Q01279, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11116146, ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:12297049, ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15374980, ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:15611079, ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:2790960, ECO:0000269|PubMed:7679104, ECO:0000269|PubMed:8144591, ECO:0000269|PubMed:9419975}.; FUNCTION: Isoform 2 may act as an antagonist of EGF action.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000463948, ENST00000275493, 
ENST00000342916, ENST00000344576, 
ENST00000420316, ENST00000442591, 
ENST00000454757, ENST00000455089, 
ENST00000285279, ENST00000433959, 
ENST00000545390, ENST00000418904, 
ENST00000428097, ENST00000428648, 
ENST00000454227, ENST00000471168, 
ENST00000427700, ENST00000453256, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score41 X 25 X 14=1435010 X 6 X 7=420
# samples 5313
** MAII scorelog2(53/14350*10)=-4.75891456699985
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/420*10)=-1.69187770463767
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: EGFR [Title/Abstract] AND VOPP1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: EGFR [Title/Abstract] AND VOPP1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)EGFR(55087058)-VOPP1(55588823), # samples:3
Anticipated loss of major functional domain due to fusion event.EGFR-VOPP1 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.
EGFR-VOPP1 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.
EGFR-VOPP1 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.
EGFR-VOPP1 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.
EGFR-VOPP1 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
EGFR-VOPP1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
EGFR-VOPP1 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted 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
HgeneEGFR

GO:0001934

positive regulation of protein phosphorylation

20551055

HgeneEGFR

GO:0007165

signal transduction

10572067

HgeneEGFR

GO:0007166

cell surface receptor signaling pathway

7736574

HgeneEGFR

GO:0007173

epidermal growth factor receptor signaling pathway

7736574|12435727

HgeneEGFR

GO:0008283

cell proliferation

17115032

HgeneEGFR

GO:0008284

positive regulation of cell proliferation

7736574

HgeneEGFR

GO:0010750

positive regulation of nitric oxide mediated signal transduction

12828935

HgeneEGFR

GO:0018108

peptidyl-tyrosine phosphorylation

22732145

HgeneEGFR

GO:0030307

positive regulation of cell growth

15467833

HgeneEGFR

GO:0042177

negative regulation of protein catabolic process

17115032

HgeneEGFR

GO:0042327

positive regulation of phosphorylation

15082764

HgeneEGFR

GO:0043406

positive regulation of MAP kinase activity

10572067

HgeneEGFR

GO:0045739

positive regulation of DNA repair

17115032

HgeneEGFR

GO:0045740

positive regulation of DNA replication

17115032

HgeneEGFR

GO:0045944

positive regulation of transcription by RNA polymerase II

20551055

HgeneEGFR

GO:0050679

positive regulation of epithelial cell proliferation

10572067

HgeneEGFR

GO:0050999

regulation of nitric-oxide synthase activity

12828935

HgeneEGFR

GO:0070141

response to UV-A

18483258

HgeneEGFR

GO:0070374

positive regulation of ERK1 and ERK2 cascade

20551055

HgeneEGFR

GO:0071392

cellular response to estradiol stimulus

20551055

HgeneEGFR

GO:1900020

positive regulation of protein kinase C activity

22732145

HgeneEGFR

GO:1903078

positive regulation of protein localization to plasma membrane

22732145



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/chr7:55087058/chr7:55588823)
- 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 EGFR (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 VOPP1 (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)
ENST00000455089EGFRchr755268106+ENST00000285279VOPP1chr755588823-5775306825735321091
ENST00000455089EGFRchr755268106+ENST00000433959VOPP1chr755588823-5774306825735321091
ENST00000455089EGFRchr755268106+ENST00000545390VOPP1chr755588823-5774306825735321091
ENST00000275493EGFRchr755268106+ENST00000285279VOPP1chr755588823-5830312317735871136
ENST00000275493EGFRchr755268106+ENST00000433959VOPP1chr755588823-5829312317735871136
ENST00000275493EGFRchr755268106+ENST00000545390VOPP1chr755588823-5829312317735871136
ENST00000454757EGFRchr755268106+ENST00000285279VOPP1chr755588823-5677297014434341096
ENST00000454757EGFRchr755268106+ENST00000433959VOPP1chr755588823-5676297014434341096
ENST00000454757EGFRchr755268106+ENST00000545390VOPP1chr755588823-5676297014434341096

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
ENST00000455089ENST00000285279EGFRchr755268106+VOPP1chr755588823-0.0005963330.9994037
ENST00000455089ENST00000433959EGFRchr755268106+VOPP1chr755588823-0.0005945410.9994055
ENST00000455089ENST00000545390EGFRchr755268106+VOPP1chr755588823-0.0005945410.9994055
ENST00000275493ENST00000285279EGFRchr755268106+VOPP1chr755588823-0.0005113730.9994886
ENST00000275493ENST00000433959EGFRchr755268106+VOPP1chr755588823-0.000509840.99949014
ENST00000275493ENST00000545390EGFRchr755268106+VOPP1chr755588823-0.000509840.99949014
ENST00000454757ENST00000285279EGFRchr755268106+VOPP1chr755588823-0.0004242610.9995758
ENST00000454757ENST00000433959EGFRchr755268106+VOPP1chr755588823-0.0004229750.999577
ENST00000454757ENST00000545390EGFRchr755268106+VOPP1chr755588823-0.0004229750.999577

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 EGFR-VOPP1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
EGFRchr755268106VOPP1chr7555888232970941SKMARDPQRYLVIQCTEAKKHCWYFE
EGFRchr755268106VOPP1chr7555888233068936SKMARDPQRYLVIQCTEAKKHCWYFE
EGFRchr755268106VOPP1chr7555888233123981SKMARDPQRYLVIQCTEAKKHCWYFE

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Potential FusionNeoAntigen Information of EGFR-VOPP1 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.
EGFR-VOPP1_55268106_55588823.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)
EGFR-VOPP1chr755268106chr7555888233123HLA-B27:14QRYLVIQCT0.99860.6828716
EGFR-VOPP1chr755268106chr7555888233123HLA-B73:01QRYLVIQCT0.9920.6622716
EGFR-VOPP1chr755268106chr7555888233123HLA-B73:01QRYLVIQCTEA0.99920.8072718

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Potential FusionNeoAntigen Information of EGFR-VOPP1 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 EGFR-VOPP1

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
6926PQRYLVIQCTEAKKEGFRVOPP1chr755268106chr7555888233123

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of EGFR-VOPP1

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-B14:023BVN6926PQRYLVIQCTEAKK-7.15543-7.26883
HLA-B14:023BVN6926PQRYLVIQCTEAKK-4.77435-5.80965
HLA-B52:013W396926PQRYLVIQCTEAKK-6.80875-6.92215
HLA-B52:013W396926PQRYLVIQCTEAKK-4.20386-5.23916
HLA-A11:014UQ26926PQRYLVIQCTEAKK-7.5194-8.5547
HLA-A11:014UQ26926PQRYLVIQCTEAKK-6.9601-7.0735
HLA-A24:025HGA6926PQRYLVIQCTEAKK-7.52403-7.63743
HLA-A24:025HGA6926PQRYLVIQCTEAKK-5.82433-6.85963
HLA-B27:056PYJ6926PQRYLVIQCTEAKK-3.28285-4.31815
HLA-B44:053DX86926PQRYLVIQCTEAKK-5.91172-6.94702
HLA-B44:053DX86926PQRYLVIQCTEAKK-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of EGFR-VOPP1

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
EGFR-VOPP1chr755268106chr755588823716QRYLVIQCTCGCTACCTTGTCATTCAGTGCACAGAA
EGFR-VOPP1chr755268106chr755588823718QRYLVIQCTEACGCTACCTTGTCATTCAGTGCACAGAAGCCAAA

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 EGFR-VOPP1

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
GBMEGFR-VOPP1chr755268106ENST00000275493chr755588823ENST00000285279TCGA-28-2514-01A

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Potential target of CAR-T therapy development for EGFR-VOPP1

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
HgeneEGFRchr7:55268106chr7:55588823ENST00000275493+2428646_6689821211.0TransmembraneHelical
TgeneVOPP1chr7:55268106chr7:55588823ENST000002852790561_810173.0TransmembraneHelical
TgeneVOPP1chr7:55268106chr7:55588823ENST000004339590561_810164.0TransmembraneHelical
TgeneVOPP1chr7:55268106chr7:55588823ENST000005453900561_810170.0TransmembraneHelical

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 EGFR-VOPP1

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 EGFR-VOPP1

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