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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:EPHA7-PTPRK

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: EPHA7-PTPRK
FusionPDB ID: 26982
FusionGDB2.0 ID: 26982
HgeneTgene
Gene symbol

EPHA7

PTPRK

Gene ID

2045

5796

Gene nameEPH receptor A7protein tyrosine phosphatase receptor type K
SynonymsEHK-3|EHK3|EK11|HEK11R-PTP-kappa
Cytomap

6q16.1

6q22.33

Type of geneprotein-codingprotein-coding
Descriptionephrin type-A receptor 7EPH homology kinase 3EPH-like kinase 11Eph homology kinase-3receptor protein-tyrosine kinase HEK11tyrosine-protein kinase receptor EHK-3receptor-type tyrosine-protein phosphatase kappadJ480J14.2.1 (protein tyrosine phosphatase, receptor type, K (R-PTP-KAPPA, protein tyrosine phosphatase kappa , protein tyrosine phosphatase kappaprotein-tyrosine phosphatase kappaprotein-tyrosine phospha
Modification date2020031320200322
UniProtAcc

Q15375

Main function of 5'-partner protein: FUNCTION: Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A 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. Among GPI-anchored ephrin-A ligands, EFNA5 is a cognate/functional ligand for EPHA7 and their interaction regulates brain development modulating cell-cell adhesion and repulsion. Has a repellent activity on axons and is for instance involved in the guidance of corticothalamic axons and in the proper topographic mapping of retinal axons to the colliculus. May also regulate brain development through a caspase(CASP3)-dependent proapoptotic activity. Forward signaling may result in activation of components of the ERK signaling pathway including MAP2K1, MAP2K2, MAPK1 AND MAPK3 which are phosphorylated upon activation of EPHA7. {ECO:0000269|PubMed:17726105}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000369303, ENST00000369297, 
ENST00000524481, ENST00000525459, 
ENST00000368207, ENST00000368210, 
ENST00000368213, ENST00000368215, 
ENST00000368226, ENST00000368227, 
ENST00000532331, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 5 X 4=12017 X 12 X 9=1836
# samples 621
** MAII scorelog2(6/120*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(21/1836*10)=-3.12810482574769
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: EPHA7 [Title/Abstract] AND PTPRK [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: EPHA7 [Title/Abstract] AND PTPRK [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)EPHA7(94066435)-PTPRK(128718833), # samples:1
Anticipated loss of major functional domain due to fusion event.EPHA7-PTPRK 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.
EPHA7-PTPRK 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.
EPHA7-PTPRK 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.
EPHA7-PTPRK 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
HgeneEPHA7

GO:0048013

ephrin receptor signaling pathway

17726105

HgeneEPHA7

GO:0050730

regulation of peptidyl-tyrosine phosphorylation

17726105

HgeneEPHA7

GO:0070372

regulation of ERK1 and ERK2 cascade

17726105

TgenePTPRK

GO:0006470

protein dephosphorylation

16263724

TgenePTPRK

GO:0007165

signal transduction

16849327

TgenePTPRK

GO:0007179

transforming growth factor beta receptor signaling pathway

15899872

TgenePTPRK

GO:0008285

negative regulation of cell proliferation

15899872|18276111

TgenePTPRK

GO:0010839

negative regulation of keratinocyte proliferation

16263724

TgenePTPRK

GO:0030336

negative regulation of cell migration

18276111

TgenePTPRK

GO:0034394

protein localization to cell surface

18276111

TgenePTPRK

GO:0034614

cellular response to reactive oxygen species

16849327

TgenePTPRK

GO:0034644

cellular response to UV

16849327

TgenePTPRK

GO:0045786

negative regulation of cell cycle

15899872

TgenePTPRK

GO:0045892

negative regulation of transcription, DNA-templated

18276111



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/chr6:94066435/chr6:128718833)
- 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 EPHA7 (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 PTPRK (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)
ENST00000369303EPHA7chr694066435-ENST00000368226PTPRKchr6128718833-7180150918557311848
ENST00000369303EPHA7chr694066435-ENST00000368227PTPRKchr6128718833-7230150918557821865
ENST00000369303EPHA7chr694066435-ENST00000532331PTPRKchr6128718833-7048150918557971870
ENST00000369303EPHA7chr694066435-ENST00000368213PTPRKchr6128718833-7000150918557491854
ENST00000369303EPHA7chr694066435-ENST00000368210PTPRKchr6128718833-6176150918557851866
ENST00000369303EPHA7chr694066435-ENST00000368215PTPRKchr6128718833-6060150918557281847
ENST00000369303EPHA7chr694066435-ENST00000368207PTPRKchr6128718833-5942150918558271880

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
ENST00000369303ENST00000368226EPHA7chr694066435-PTPRKchr6128718833-0.0002558810.9997441
ENST00000369303ENST00000368227EPHA7chr694066435-PTPRKchr6128718833-0.0005725090.99942756
ENST00000369303ENST00000532331EPHA7chr694066435-PTPRKchr6128718833-0.0005702960.99942964
ENST00000369303ENST00000368213EPHA7chr694066435-PTPRKchr6128718833-0.0004311220.9995689
ENST00000369303ENST00000368210EPHA7chr694066435-PTPRKchr6128718833-0.0009249720.99907506
ENST00000369303ENST00000368215EPHA7chr694066435-PTPRKchr6128718833-0.000566210.9994338
ENST00000369303ENST00000368207EPHA7chr694066435-PTPRKchr6128718833-0.000867150.99913293

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 EPHA7-PTPRK

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
EPHA7chr694066435PTPRKchr61287188331509441RLFAAVSITTGQAGGCTFDDGPGACD

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Potential FusionNeoAntigen Information of EPHA7-PTPRK 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.
EPHA7-PTPRK_94066435_128718833.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)
EPHA7-PTPRKchr694066435chr61287188331509HLA-B15:03GQAGGCTF0.95130.93431018
EPHA7-PTPRKchr694066435chr61287188331509HLA-B15:54GQAGGCTF0.99750.94131018

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Potential FusionNeoAntigen Information of EPHA7-PTPRK 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 EPHA7-PTPRK

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
8674SITTGQAGGCTFDDEPHA7PTPRKchr694066435chr61287188331509

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of EPHA7-PTPRK

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-B14:023BVN8674SITTGQAGGCTFDD-6.69561-6.80901
HLA-B14:023BVN8674SITTGQAGGCTFDD-4.57314-5.60844
HLA-B52:013W398674SITTGQAGGCTFDD-8.26982-8.38322
HLA-B52:013W398674SITTGQAGGCTFDD-4.20619-5.24149
HLA-A11:014UQ28674SITTGQAGGCTFDD-6.38936-6.50276
HLA-A11:014UQ28674SITTGQAGGCTFDD-5.4102-6.4455
HLA-A24:025HGA8674SITTGQAGGCTFDD-7.10684-7.22024
HLA-A24:025HGA8674SITTGQAGGCTFDD-5.37582-6.41112
HLA-B44:053DX88674SITTGQAGGCTFDD-5.61918-5.73258
HLA-B44:053DX88674SITTGQAGGCTFDD-4.56468-5.59998

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Vaccine Design for the FusionNeoAntigens of EPHA7-PTPRK

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
EPHA7-PTPRKchr694066435chr61287188331018GQAGGCTFGTCAAGCAGGTGGCTGTACTTTTG

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 EPHA7-PTPRK

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
BRCAEPHA7-PTPRKchr694066435ENST00000369303chr6128718833ENST00000368207TCGA-A7-A3IZ-01A

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Potential target of CAR-T therapy development for EPHA7-PTPRK

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
TgenePTPRKchr6:94066435chr6:128718833ENST00000368213031753_77401447.0TransmembraneHelical
TgenePTPRKchr6:94066435chr6:128718833ENST00000368215030753_77401440.0TransmembraneHelical
TgenePTPRKchr6:94066435chr6:128718833ENST00000368226030753_77401441.0TransmembraneHelical

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 EPHA7-PTPRK

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 EPHA7-PTPRK

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