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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-ERBB3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: EGFR-ERBB3
FusionPDB ID: 25452
FusionGDB2.0 ID: 25452
HgeneTgene
Gene symbol

EGFR

ERBB3

Gene ID

1956

2065

Gene nameepidermal growth factor receptorerb-b2 receptor tyrosine kinase 3
SynonymsERBB|ERBB1|HER1|NISBD2|PIG61|mENAErbB-3|FERLK|HER3|LCCS2|MDA-BF-1|c-erbB-3|c-erbB3|erbB3-S|p180-ErbB3|p45-sErbB3|p85-sErbB3
Cytomap

7p11.2

12q13.2

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 kinasreceptor tyrosine-protein kinase erbB-3human epidermal growth factor receptor 3proto-oncogene-like protein c-ErbB-3tyrosine kinase-type cell surface receptor HER3v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3
Modification date2020032920200327
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}.

P21860

Main function of 5'-partner protein: FUNCTION: Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). May also be activated by CSPG5 (PubMed:15358134). Involved in the regulation of myeloid cell differentiation (PubMed:27416908). {ECO:0000269|PubMed:15358134, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:27416908}.
Ensembl transtripts involved in fusion geneENST idsENST00000463948, ENST00000275493, 
ENST00000342916, ENST00000344576, 
ENST00000420316, ENST00000442591, 
ENST00000455089, ENST00000454757, 
ENST00000267101, ENST00000415288, 
ENST00000450146, ENST00000553131, 
ENST00000411731, ENST00000549832, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score41 X 25 X 14=1435028 X 12 X 14=4704
# samples 5328
** MAII scorelog2(53/14350*10)=-4.75891456699985
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(28/4704*10)=-4.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: EGFR [Title/Abstract] AND ERBB3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: EGFR [Title/Abstract] AND ERBB3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ERBB3(56492359)-EGFR(55266410), # samples:5
EGFR(55087058)-ERBB3(56492542), # samples:1
Anticipated loss of major functional domain due to fusion event.EGFR-ERBB3 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-ERBB3 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-ERBB3 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-ERBB3 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.
ERBB3-EGFR 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.
ERBB3-EGFR 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
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

TgeneERBB3

GO:0007162

negative regulation of cell adhesion

7556068

TgeneERBB3

GO:0007165

signal transduction

10572067

TgeneERBB3

GO:0009968

negative regulation of signal transduction

11389077

TgeneERBB3

GO:0014065

phosphatidylinositol 3-kinase signaling

7556068

TgeneERBB3

GO:0042127

regulation of cell proliferation

11389077

TgeneERBB3

GO:0051048

negative regulation of secretion

10559227



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/chr7:56492359/chr12:55266410)
- 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 ERBB3 (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)
ENST00000455089EGFRchr755087058+ENST00000267101ERBB3chr1256492542+31323452571681474
ENST00000455089EGFRchr755087058+ENST00000450146ERBB3chr1256492542+20013452571681474
ENST00000455089EGFRchr755087058+ENST00000415288ERBB3chr1256492542+19633452571681474
ENST00000455089EGFRchr755087058+ENST00000553131ERBB3chr1256492542+24333452571681474
ENST00000342916EGFRchr755087058+ENST00000267101ERBB3chr1256492542+31213342461670474
ENST00000342916EGFRchr755087058+ENST00000450146ERBB3chr1256492542+19903342461670474
ENST00000342916EGFRchr755087058+ENST00000415288ERBB3chr1256492542+19523342461670474
ENST00000342916EGFRchr755087058+ENST00000553131ERBB3chr1256492542+24223342461670474
ENST00000344576EGFRchr755087058+ENST00000267101ERBB3chr1256492542+31203332451669474
ENST00000344576EGFRchr755087058+ENST00000450146ERBB3chr1256492542+19893332451669474
ENST00000344576EGFRchr755087058+ENST00000415288ERBB3chr1256492542+19513332451669474
ENST00000344576EGFRchr755087058+ENST00000553131ERBB3chr1256492542+24213332451669474
ENST00000420316EGFRchr755087058+ENST00000267101ERBB3chr1256492542+31193322441668474
ENST00000420316EGFRchr755087058+ENST00000450146ERBB3chr1256492542+19883322441668474
ENST00000420316EGFRchr755087058+ENST00000415288ERBB3chr1256492542+19503322441668474
ENST00000420316EGFRchr755087058+ENST00000553131ERBB3chr1256492542+24203322441668474
ENST00000275493EGFRchr755087058+ENST00000267101ERBB3chr1256492542+30522651771601474
ENST00000275493EGFRchr755087058+ENST00000450146ERBB3chr1256492542+19212651771601474
ENST00000275493EGFRchr755087058+ENST00000415288ERBB3chr1256492542+18832651771601474
ENST00000275493EGFRchr755087058+ENST00000553131ERBB3chr1256492542+23532651771601474
ENST00000442591EGFRchr755087058+ENST00000267101ERBB3chr1256492542+30352481601584474
ENST00000442591EGFRchr755087058+ENST00000450146ERBB3chr1256492542+19042481601584474
ENST00000442591EGFRchr755087058+ENST00000415288ERBB3chr1256492542+18662481601584474
ENST00000442591EGFRchr755087058+ENST00000553131ERBB3chr1256492542+23362481601584474

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
ENST00000455089ENST00000267101EGFRchr755087058+ERBB3chr1256492542+0.0010680560.99893194
ENST00000455089ENST00000450146EGFRchr755087058+ERBB3chr1256492542+0.0033167790.9966832
ENST00000455089ENST00000415288EGFRchr755087058+ERBB3chr1256492542+0.0034870880.99651295
ENST00000455089ENST00000553131EGFRchr755087058+ERBB3chr1256492542+0.0023569680.99764305
ENST00000342916ENST00000267101EGFRchr755087058+ERBB3chr1256492542+0.0010502610.9989498
ENST00000342916ENST00000450146EGFRchr755087058+ERBB3chr1256492542+0.0033030790.99669695
ENST00000342916ENST00000415288EGFRchr755087058+ERBB3chr1256492542+0.0034648360.9965352
ENST00000342916ENST00000553131EGFRchr755087058+ERBB3chr1256492542+0.0023355050.9976646
ENST00000344576ENST00000267101EGFRchr755087058+ERBB3chr1256492542+0.0010446260.99895537
ENST00000344576ENST00000450146EGFRchr755087058+ERBB3chr1256492542+0.0032617190.99673826
ENST00000344576ENST00000415288EGFRchr755087058+ERBB3chr1256492542+0.0034157110.9965843
ENST00000344576ENST00000553131EGFRchr755087058+ERBB3chr1256492542+0.002307840.9976922
ENST00000420316ENST00000267101EGFRchr755087058+ERBB3chr1256492542+0.0010485030.99895144
ENST00000420316ENST00000450146EGFRchr755087058+ERBB3chr1256492542+0.0032638160.9967361
ENST00000420316ENST00000415288EGFRchr755087058+ERBB3chr1256492542+0.0034193060.99658066
ENST00000420316ENST00000553131EGFRchr755087058+ERBB3chr1256492542+0.002312410.9976876
ENST00000275493ENST00000267101EGFRchr755087058+ERBB3chr1256492542+0.0009591260.9990409
ENST00000275493ENST00000450146EGFRchr755087058+ERBB3chr1256492542+0.0031129420.996887
ENST00000275493ENST00000415288EGFRchr755087058+ERBB3chr1256492542+0.0032703690.9967296
ENST00000275493ENST00000553131EGFRchr755087058+ERBB3chr1256492542+0.0021427040.9978573
ENST00000442591ENST00000267101EGFRchr755087058+ERBB3chr1256492542+0.0009151180.99908483
ENST00000442591ENST00000450146EGFRchr755087058+ERBB3chr1256492542+0.0030020280.99699795
ENST00000442591ENST00000415288EGFRchr755087058+ERBB3chr1256492542+0.0031227240.9968773
ENST00000442591ENST00000553131EGFRchr755087058+ERBB3chr1256492542+0.0020507940.9979492

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-ERBB3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
EGFRchr755087058ERBB3chr125649254224829ALCPASRALEEKKGVTVWELMTFGAE
EGFRchr755087058ERBB3chr125649254226529ALCPASRALEEKKGVTVWELMTFGAE
EGFRchr755087058ERBB3chr125649254233229ALCPASRALEEKKGVTVWELMTFGAE
EGFRchr755087058ERBB3chr125649254233329ALCPASRALEEKKGVTVWELMTFGAE
EGFRchr755087058ERBB3chr125649254233429ALCPASRALEEKKGVTVWELMTFGAE
EGFRchr755087058ERBB3chr125649254234529ALCPASRALEEKKGVTVWELMTFGAE

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Potential FusionNeoAntigen Information of EGFR-ERBB3 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-ERBB3_55087058_56492542.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-ERBB3chr755087058chr1256492542265HLA-B44:03EEKKGVTVW0.99960.9195918
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:02EEKKGVTVW0.99940.5982918
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:05EEKKGVTVW0.99860.6896918
EGFR-ERBB3chr755087058chr1256492542265HLA-B50:02LEEKKGVTV0.98850.7867817
EGFR-ERBB3chr755087058chr1256492542265HLA-B18:01EEKKGVTVW0.97860.7327918
EGFR-ERBB3chr755087058chr1256492542265HLA-B41:01LEEKKGVTV0.61360.9138817
EGFR-ERBB3chr755087058chr1256492542265HLA-B48:01KKGVTVWEL0.46950.81471120
EGFR-ERBB3chr755087058chr1256492542265HLA-B50:01LEEKKGVTV0.45590.8306817
EGFR-ERBB3chr755087058chr1256492542265HLA-B39:13LEEKKGVTV0.15410.9568817
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:02LEEKKGVTVW0.99710.7907818
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:03LEEKKGVTVW0.99610.9546818
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:05LEEKKGVTVW0.99330.8877818
EGFR-ERBB3chr755087058chr1256492542265HLA-A02:13ALEEKKGVTV0.95980.6129717
EGFR-ERBB3chr755087058chr1256492542265HLA-A02:27ALEEKKGVTV0.94550.5317717
EGFR-ERBB3chr755087058chr1256492542265HLA-B57:01KGVTVWELMTF0.99930.9881223
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:02ALEEKKGVTVW0.99560.9053718
EGFR-ERBB3chr755087058chr1256492542265HLA-B57:03KGVTVWELMTF0.99540.99481223
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:05ALEEKKGVTVW0.99490.9541718
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:03ALEEKKGVTVW0.99260.9738718
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:08EEKKGVTVW0.99930.679918
EGFR-ERBB3chr755087058chr1256492542265HLA-B40:06LEEKKGVTV0.99920.6841817
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:09EEKKGVTVW0.99880.6507918
EGFR-ERBB3chr755087058chr1256492542265HLA-B40:03EEKKGVTVW0.97560.557918
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:10EEKKGVTVW0.92960.7874918
EGFR-ERBB3chr755087058chr1256492542265HLA-B39:08LEEKKGVTV0.4930.8922817
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:04LEEKKGVTVW0.99590.7197818
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:08LEEKKGVTVW0.99570.8469818
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:08ALEEKKGVTVW0.99520.9203718
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:04ALEEKKGVTVW0.99410.7581718
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:09ALEEKKGVTVW0.99290.9043718
EGFR-ERBB3chr755087058chr1256492542265HLA-B18:03EEKKGVTV0.95540.6768917
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:26EEKKGVTVW0.99960.9195918
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:07EEKKGVTVW0.99960.9195918
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:13EEKKGVTVW0.99960.9195918
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:22EEKKGVTVW0.99940.5982918
EGFR-ERBB3chr755087058chr1256492542265HLA-B40:04LEEKKGVTV0.99390.8091817
EGFR-ERBB3chr755087058chr1256492542265HLA-B18:07EEKKGVTVW0.98460.6848918
EGFR-ERBB3chr755087058chr1256492542265HLA-B18:08EEKKGVTVW0.98180.9014918
EGFR-ERBB3chr755087058chr1256492542265HLA-B18:04EEKKGVTVW0.98070.7408918
EGFR-ERBB3chr755087058chr1256492542265HLA-B18:05EEKKGVTVW0.97860.7327918
EGFR-ERBB3chr755087058chr1256492542265HLA-B18:06EEKKGVTVW0.96690.7846918
EGFR-ERBB3chr755087058chr1256492542265HLA-B18:11EEKKGVTVW0.95740.6851918
EGFR-ERBB3chr755087058chr1256492542265HLA-B18:03EEKKGVTVW0.95670.7259918
EGFR-ERBB3chr755087058chr1256492542265HLA-B41:03LEEKKGVTV0.61410.6977817
EGFR-ERBB3chr755087058chr1256492542265HLA-B15:13EEKKGVTVW0.46020.8831918
EGFR-ERBB3chr755087058chr1256492542265HLA-B50:05LEEKKGVTV0.45590.8306817
EGFR-ERBB3chr755087058chr1256492542265HLA-B50:04LEEKKGVTV0.45590.8306817
EGFR-ERBB3chr755087058chr1256492542265HLA-B15:24EEKKGVTVW0.43290.9347918
EGFR-ERBB3chr755087058chr1256492542265HLA-B39:02LEEKKGVTV0.16880.957817
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:22LEEKKGVTVW0.99710.7907818
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:21LEEKKGVTVW0.99620.7056818
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:13LEEKKGVTVW0.99610.9546818
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:07LEEKKGVTVW0.99610.9546818
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:26LEEKKGVTVW0.99610.9546818
EGFR-ERBB3chr755087058chr1256492542265HLA-B41:03ALEEKKGVTV0.26110.7446717
EGFR-ERBB3chr755087058chr1256492542265HLA-B57:10KGVTVWELMTF0.99930.9881223
EGFR-ERBB3chr755087058chr1256492542265HLA-B15:24ALEEKKGVTVW0.99910.9717718
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:21ALEEKKGVTVW0.99850.8669718
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:22ALEEKKGVTVW0.99560.9053718
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:13ALEEKKGVTVW0.99260.9738718
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:26ALEEKKGVTVW0.99260.9738718
EGFR-ERBB3chr755087058chr1256492542265HLA-B44:07ALEEKKGVTVW0.99260.9738718

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Potential FusionNeoAntigen Information of EGFR-ERBB3 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-ERBB3

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
7696RALEEKKGVTVWELEGFRERBB3chr755087058chr1256492542265

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of EGFR-ERBB3

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-B52:013W397696RALEEKKGVTVWEL-7.90165-7.90165
HLA-B44:053DX87696RALEEKKGVTVWEL-5.81679-5.81679

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Vaccine Design for the FusionNeoAntigens of EGFR-ERBB3

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-ERBB3chr755087058chr12564925421120KKGVTVWELAGAAAGGTGTGACAGTTTGGGAGTTGA
EGFR-ERBB3chr755087058chr12564925421223KGVTVWELMTFAAGGTGTGACAGTTTGGGAGTTGATGACCTTCG
EGFR-ERBB3chr755087058chr1256492542717ALEEKKGVTVCTCTGGAGGAAAAGAAAGGTGTGACAGTTT
EGFR-ERBB3chr755087058chr1256492542718ALEEKKGVTVWCTCTGGAGGAAAAGAAAGGTGTGACAGTTTGGG
EGFR-ERBB3chr755087058chr1256492542817LEEKKGVTVTGGAGGAAAAGAAAGGTGTGACAGTTT
EGFR-ERBB3chr755087058chr1256492542818LEEKKGVTVWTGGAGGAAAAGAAAGGTGTGACAGTTTGGG
EGFR-ERBB3chr755087058chr1256492542917EEKKGVTVAGGAAAAGAAAGGTGTGACAGTTT
EGFR-ERBB3chr755087058chr1256492542918EEKKGVTVWAGGAAAAGAAAGGTGTGACAGTTTGGG

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-ERBB3

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
STADEGFR-ERBB3chr755087058ENST00000275493chr1256492542ENST00000267101TCGA-CD-A486

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Potential target of CAR-T therapy development for EGFR-ERBB3

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
TgeneERBB3chr7:55087058chr12:56492542ENST0000041173103644_6640184.0TransmembraneHelical
TgeneERBB3chr7:55087058chr12:56492542ENST00000450146815644_6640700.0TransmembraneHelical

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-ERBB3

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-ERBB3

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