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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:EPHB2-ZBTB40

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: EPHB2-ZBTB40
FusionPDB ID: 26998
FusionGDB2.0 ID: 26998
HgeneTgene
Gene symbol

EPHB2

ZBTB40

Gene ID

2048

9923

Gene nameEPH receptor B2zinc finger and BTB domain containing 40
SynonymsBDPLT22|CAPB|DRT|EK5|EPHT3|ERK|Hek5|PCBC|Tyro5ZNF923
Cytomap

1p36.12

1p36.12

Type of geneprotein-codingprotein-coding
Descriptionephrin type-B receptor 2EPH-like kinase 5developmentally-regulated Eph-related tyrosine kinaseelk-related tyrosine kinaseeph tyrosine kinase 3protein-tyrosine kinase HEK5renal carcinoma antigen NY-REN-47tyrosine-protein kinase TYRO5tyrosine-proteizinc finger and BTB domain-containing protein 40
Modification date2020031320200313
UniProtAcc

P29323

Main function of 5'-partner protein: FUNCTION: Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. May be involved in the regulation of platelet activation and blood coagulation (PubMed:30213874). {ECO:0000269|PubMed:15300251, ECO:0000269|PubMed:30213874}.		.
Ensembl transtripts involved in fusion geneENST idsENST00000374630, ENST00000374632, 
ENST00000400191, ENST00000544305, 
ENST00000374627, ENST00000465676, 
ENST00000374651, ENST00000375647, 
ENST00000404138, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 6 X 7=3783 X 5 X 4=60
# samples 135
** MAII scorelog2(13/378*10)=-1.53987461119262
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(5/60*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: EPHB2 [Title/Abstract] AND ZBTB40 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: EPHB2 [Title/Abstract] AND ZBTB40 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)EPHB2(23111569)-ZBTB40(22843792), # samples:2
Anticipated loss of major functional domain due to fusion event.EPHB2-ZBTB40 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.
EPHB2-ZBTB40 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.
EPHB2-ZBTB40 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.
EPHB2-ZBTB40 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
TgeneZBTB40

GO:0006974

cellular response to DNA damage stimulus

17525332



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/chr1:23111569/chr1:22843792)
- 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 EPHB2 (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 ZBTB40 (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)
ENST00000544305EPHB2chr123111569+ENST00000404138ZBTB40chr122843793+676895532006667
ENST00000544305EPHB2chr123111569+ENST00000375647ZBTB40chr122843793+676595532006667
ENST00000544305EPHB2chr123111569+ENST00000374651ZBTB40chr122843793+297395532006667
ENST00000374630EPHB2chr123111569+ENST00000404138ZBTB40chr122843793+6642829181880620
ENST00000374630EPHB2chr123111569+ENST00000375647ZBTB40chr122843793+6639829181880620
ENST00000374630EPHB2chr123111569+ENST00000374651ZBTB40chr122843793+2847829181880620
ENST00000400191EPHB2chr123111569+ENST00000404138ZBTB40chr122843793+6642829181880620
ENST00000400191EPHB2chr123111569+ENST00000375647ZBTB40chr122843793+6639829181880620
ENST00000400191EPHB2chr123111569+ENST00000374651ZBTB40chr122843793+2847829181880620
ENST00000374632EPHB2chr123111569+ENST00000404138ZBTB40chr122843793+6637824131875620
ENST00000374632EPHB2chr123111569+ENST00000375647ZBTB40chr122843793+6634824131875620
ENST00000374632EPHB2chr123111569+ENST00000374651ZBTB40chr122843793+2842824131875620
ENST00000374627EPHB2chr123111569+ENST00000404138ZBTB40chr122843793+6630817241868614
ENST00000374627EPHB2chr123111569+ENST00000375647ZBTB40chr122843793+6627817241868614
ENST00000374627EPHB2chr123111569+ENST00000374651ZBTB40chr122843793+2835817241868614
ENST00000544305EPHB2chr123111569+ENST00000404138ZBTB40chr122843792+676895532006667
ENST00000544305EPHB2chr123111569+ENST00000375647ZBTB40chr122843792+676595532006667
ENST00000544305EPHB2chr123111569+ENST00000374651ZBTB40chr122843792+297395532006667
ENST00000374630EPHB2chr123111569+ENST00000404138ZBTB40chr122843792+6642829181880620
ENST00000374630EPHB2chr123111569+ENST00000375647ZBTB40chr122843792+6639829181880620
ENST00000374630EPHB2chr123111569+ENST00000374651ZBTB40chr122843792+2847829181880620
ENST00000400191EPHB2chr123111569+ENST00000404138ZBTB40chr122843792+6642829181880620
ENST00000400191EPHB2chr123111569+ENST00000375647ZBTB40chr122843792+6639829181880620
ENST00000400191EPHB2chr123111569+ENST00000374651ZBTB40chr122843792+2847829181880620
ENST00000374632EPHB2chr123111569+ENST00000404138ZBTB40chr122843792+6637824131875620
ENST00000374632EPHB2chr123111569+ENST00000375647ZBTB40chr122843792+6634824131875620
ENST00000374632EPHB2chr123111569+ENST00000374651ZBTB40chr122843792+2842824131875620
ENST00000374627EPHB2chr123111569+ENST00000404138ZBTB40chr122843792+6630817241868614
ENST00000374627EPHB2chr123111569+ENST00000375647ZBTB40chr122843792+6627817241868614
ENST00000374627EPHB2chr123111569+ENST00000374651ZBTB40chr122843792+2835817241868614

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
ENST00000544305ENST00000404138EPHB2chr123111569+ZBTB40chr122843793+0.0017565610.99824345
ENST00000544305ENST00000375647EPHB2chr123111569+ZBTB40chr122843793+0.0017670730.99823284
ENST00000544305ENST00000374651EPHB2chr123111569+ZBTB40chr122843793+0.0118292240.98817074
ENST00000374630ENST00000404138EPHB2chr123111569+ZBTB40chr122843793+0.0017867370.9982133
ENST00000374630ENST00000375647EPHB2chr123111569+ZBTB40chr122843793+0.0017968710.99820316
ENST00000374630ENST00000374651EPHB2chr123111569+ZBTB40chr122843793+0.012739670.98726034
ENST00000400191ENST00000404138EPHB2chr123111569+ZBTB40chr122843793+0.0017867370.9982133
ENST00000400191ENST00000375647EPHB2chr123111569+ZBTB40chr122843793+0.0017968710.99820316
ENST00000400191ENST00000374651EPHB2chr123111569+ZBTB40chr122843793+0.012739670.98726034
ENST00000374632ENST00000404138EPHB2chr123111569+ZBTB40chr122843793+0.0017884620.9982115
ENST00000374632ENST00000375647EPHB2chr123111569+ZBTB40chr122843793+0.0017989480.998201
ENST00000374632ENST00000374651EPHB2chr123111569+ZBTB40chr122843793+0.0128048510.9871952
ENST00000374627ENST00000404138EPHB2chr123111569+ZBTB40chr122843793+0.0010658240.9989342
ENST00000374627ENST00000375647EPHB2chr123111569+ZBTB40chr122843793+0.0010719570.998928
ENST00000374627ENST00000374651EPHB2chr123111569+ZBTB40chr122843793+0.0069254190.99307454
ENST00000544305ENST00000404138EPHB2chr123111569+ZBTB40chr122843792+0.0017565610.99824345
ENST00000544305ENST00000375647EPHB2chr123111569+ZBTB40chr122843792+0.0017670730.99823284
ENST00000544305ENST00000374651EPHB2chr123111569+ZBTB40chr122843792+0.0118292240.98817074
ENST00000374630ENST00000404138EPHB2chr123111569+ZBTB40chr122843792+0.0017867370.9982133
ENST00000374630ENST00000375647EPHB2chr123111569+ZBTB40chr122843792+0.0017968710.99820316
ENST00000374630ENST00000374651EPHB2chr123111569+ZBTB40chr122843792+0.012739670.98726034
ENST00000400191ENST00000404138EPHB2chr123111569+ZBTB40chr122843792+0.0017867370.9982133
ENST00000400191ENST00000375647EPHB2chr123111569+ZBTB40chr122843792+0.0017968710.99820316
ENST00000400191ENST00000374651EPHB2chr123111569+ZBTB40chr122843792+0.012739670.98726034
ENST00000374632ENST00000404138EPHB2chr123111569+ZBTB40chr122843792+0.0017884620.9982115
ENST00000374632ENST00000375647EPHB2chr123111569+ZBTB40chr122843792+0.0017989480.998201
ENST00000374632ENST00000374651EPHB2chr123111569+ZBTB40chr122843792+0.0128048510.9871952
ENST00000374627ENST00000404138EPHB2chr123111569+ZBTB40chr122843792+0.0010658240.9989342
ENST00000374627ENST00000375647EPHB2chr123111569+ZBTB40chr122843792+0.0010719570.998928
ENST00000374627ENST00000374651EPHB2chr123111569+ZBTB40chr122843792+0.0069254190.99307454

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 EPHB2-ZBTB40

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
EPHB2chr123111569ZBTB40chr122843792817264AGFEAVENGTVCRGKMYACQYCDAVF
EPHB2chr123111569ZBTB40chr122843792824270AGFEAVENGTVCRGKMYACQYCDAVF
EPHB2chr123111569ZBTB40chr122843792829270AGFEAVENGTVCRGKMYACQYCDAVF
EPHB2chr123111569ZBTB40chr122843792955317AGFEAVENGTVCRGKMYACQYCDAVF
EPHB2chr123111569ZBTB40chr122843793817264AGFEAVENGTVCRGKMYACQYCDAVF
EPHB2chr123111569ZBTB40chr122843793824270AGFEAVENGTVCRGKMYACQYCDAVF
EPHB2chr123111569ZBTB40chr122843793829270AGFEAVENGTVCRGKMYACQYCDAVF
EPHB2chr123111569ZBTB40chr122843793955317AGFEAVENGTVCRGKMYACQYCDAVF

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Potential FusionNeoAntigen Information of EPHB2-ZBTB40 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 EPHB2-ZBTB40 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 EPHB2-ZBTB40

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 EPHB2-ZBTB40

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 EPHB2-ZBTB40

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

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Information of the samples that have these potential fusion neoantigens of EPHB2-ZBTB40

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 EPHB2-ZBTB40

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 EPHB2-ZBTB40

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 EPHB2-ZBTB40

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