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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:ESYT2-CNTNAP2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ESYT2-CNTNAP2
FusionPDB ID: 27600
FusionGDB2.0 ID: 27600
HgeneTgene
Gene symbol

ESYT2

CNTNAP2

Gene ID

57488

26047

Gene nameextended synaptotagmin 2contactin associated protein 2
SynonymsCHR2SYT|E-Syt2|FAM62BAUTS15|CASPR2|CDFE|NRXN4|PTHSL1
Cytomap

7q36.3

7q35-q36.1

Type of geneprotein-codingprotein-coding
Descriptionextended synaptotagmin-2chr2 synaptotagminextended synaptotagmin like protein 2extended synaptotagmin protein 2family with sequence similarity 62 (C2 domain containing), member Bcontactin-associated protein-like 2cell recognition molecule Caspr2contactin associated protein like 2homolog of Drosophila neurexin IV
Modification date2020031320200313
UniProtAcc

A0FGR8

Main function of 5'-partner protein: FUNCTION: Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. Plays a role in FGF signaling via its role in the rapid internalization of FGFR1 that has been activated by FGF1 binding; this occurs most likely via the AP-2 complex. Promotes the localization of SACM1L at endoplasmic reticulum-plasma membrane contact sites (EPCS) (PubMed:27044890). {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:20833364, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:24847877, ECO:0000269|PubMed:27044890}.

Q9UHC6

Main function of 5'-partner protein: FUNCTION: Required for gap junction formation (Probable). Required, with CNTNAP1, for radial and longitudinal organization of myelinated axons. Plays a role in the formation of functional distinct domains critical for saltatory conduction of nerve impulses in myelinated nerve fibers. Demarcates the juxtaparanodal region of the axo-glial junction. {ECO:0000250|UniProtKB:Q9CPW0, ECO:0000305|PubMed:33238150}.
Ensembl transtripts involved in fusion geneENST idsENST00000251527, ENST00000435514, 
ENST00000497111, 
ENST00000463592, 
ENST00000538075, ENST00000361727, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 11 X 10=143030 X 34 X 9=9180
# samples 1636
** MAII scorelog2(16/1430*10)=-3.15987133677839
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(36/9180*10)=-4.6724253419715
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ESYT2 [Title/Abstract] AND CNTNAP2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ESYT2 [Title/Abstract] AND CNTNAP2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ESYT2(158540885)-CNTNAP2(146740999), # samples:1
Anticipated loss of major functional domain due to fusion event.ESYT2-CNTNAP2 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.
ESYT2-CNTNAP2 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.
ESYT2-CNTNAP2 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.
ESYT2-CNTNAP2 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


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/chr7:158540885/chr7:146740999)
- 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 ESYT2 (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 CNTNAP2 (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)
ENST00000251527ESYT2chr7158540885-ENST00000361727CNTNAP2chr7146740999+1076717916653841772

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
ENST00000251527ENST00000361727ESYT2chr7158540885-CNTNAP2chr7146740999+0.0002308220.99976915

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 ESYT2-CNTNAP2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ESYT2chr7158540885CNTNAP2chr71467409991791575FIHNPKRQDLEVEAFPGNINSDGVVR

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Potential FusionNeoAntigen Information of ESYT2-CNTNAP2 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.
ESYT2-CNTNAP2_158540885_146740999.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)
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B48:01RQDLEVEAF0.9790.7868615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B39:06KRQDLEVEA0.9770.7896514
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B47:01RQDLEVEAF0.77270.5344615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B13:01RQDLEVEAF0.67440.9719615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B15:03RQDLEVEAF0.66580.9359615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B39:13RQDLEVEAF0.41210.9833615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B38:01RQDLEVEAF0.40010.9762615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B38:02RQDLEVEAF0.35720.9773615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B27:05KRQDLEVEAF0.99990.5425515
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B27:04KRQDLEVEAF0.99990.6443515
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B27:07KRQDLEVEAF0.99950.512515
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C05:09RQDLEVEAF0.99950.9711615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C04:10RQDLEVEAF0.99940.9594615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C04:07RQDLEVEAF0.99940.9662615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C08:15RQDLEVEAF0.99890.9876615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B73:01KRQDLEVEA0.99560.7638514
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B48:03RQDLEVEAF0.91150.5837615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B15:05RQDLEVEAF0.66110.9606615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B39:08RQDLEVEAF0.57270.9437615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B27:14KRQDLEVEAF0.99990.5226515
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B27:03KRQDLEVEAF0.99820.5708515
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C07:95KRQDLEVEAF0.9980.6642515
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C07:27KRQDLEVEAF0.99330.9369515
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C07:46KRQDLEVEAF0.99320.9184515
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B73:01NPKRQDLEVEA0.98390.6631314
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C05:01RQDLEVEAF0.99950.9711615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C04:03RQDLEVEAF0.99940.9665615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C04:01RQDLEVEAF0.99940.9662615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C18:01RQDLEVEAF0.99910.9654615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C08:02RQDLEVEAF0.99890.9876615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B15:50RQDLEVEAF0.98360.9175615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B15:12RQDLEVEAF0.96950.9116615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B40:12RQDLEVEAF0.91150.5837615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B15:53RQDLEVEAF0.81870.9181615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B40:49RQDLEVEAF0.80580.5632615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B15:39RQDLEVEAF0.79170.9487615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B40:21RQDLEVEAF0.78860.7203615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B15:54RQDLEVEAF0.75040.9104615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B15:20RQDLEVEAF0.65230.9795615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B35:28RQDLEVEAF0.62590.9849615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B15:73RQDLEVEAF0.62210.9765615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B48:02RQDLEVEAF0.58080.982615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B39:02RQDLEVEAF0.5170.9827615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B15:68RQDLEVEAF0.51370.8436615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B39:11RQDLEVEAF0.50420.9059615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B35:20RQDLEVEAF0.48450.9872615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B15:30RQDLEVEAF0.40110.9637615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B38:05RQDLEVEAF0.40010.9762615
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B27:10KRQDLEVEAF0.99990.7503515
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B27:06KRQDLEVEAF0.99980.7068515
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-B27:09KRQDLEVEAF0.99950.5469515
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C07:01KRQDLEVEAF0.99830.6397515
ESYT2-CNTNAP2chr7158540885chr71467409991791HLA-C07:22KRQDLEVEAF0.99660.6515515

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Potential FusionNeoAntigen Information of ESYT2-CNTNAP2 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 ESYT2-CNTNAP2

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
8119RQDLEVEAFPGNINESYT2CNTNAP2chr7158540885chr71467409991791

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ESYT2-CNTNAP2

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-B14:023BVN8119RQDLEVEAFPGNIN-7.15543-7.26883
HLA-B14:023BVN8119RQDLEVEAFPGNIN-4.77435-5.80965
HLA-B52:013W398119RQDLEVEAFPGNIN-6.80875-6.92215
HLA-B52:013W398119RQDLEVEAFPGNIN-4.20386-5.23916
HLA-A11:014UQ28119RQDLEVEAFPGNIN-7.5194-8.5547
HLA-A11:014UQ28119RQDLEVEAFPGNIN-6.9601-7.0735
HLA-A24:025HGA8119RQDLEVEAFPGNIN-7.52403-7.63743
HLA-A24:025HGA8119RQDLEVEAFPGNIN-5.82433-6.85963
HLA-B27:056PYJ8119RQDLEVEAFPGNIN-3.28285-4.31815
HLA-B44:053DX88119RQDLEVEAFPGNIN-5.91172-6.94702
HLA-B44:053DX88119RQDLEVEAFPGNIN-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ESYT2-CNTNAP2

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
ESYT2-CNTNAP2chr7158540885chr7146740999314NPKRQDLEVEAAATCCCAAGCGCCAGGACCTTGAAGTTGAGGCA
ESYT2-CNTNAP2chr7158540885chr7146740999514KRQDLEVEAAAGCGCCAGGACCTTGAAGTTGAGGCA
ESYT2-CNTNAP2chr7158540885chr7146740999515KRQDLEVEAFAAGCGCCAGGACCTTGAAGTTGAGGCATTT
ESYT2-CNTNAP2chr7158540885chr7146740999615RQDLEVEAFCGCCAGGACCTTGAAGTTGAGGCATTT

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 ESYT2-CNTNAP2

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
HNSCESYT2-CNTNAP2chr7158540885ENST00000251527chr7146740999ENST00000361727TCGA-CV-5444-01A

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Potential target of CAR-T therapy development for ESYT2-CNTNAP2

check button Predicted 3D structure. We used RoseTTAFold.
166_ESYT2-CNTNAP2_t000_.e2e.pdb


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
HgeneESYT2chr7:158540885chr7:146740999ENST00000251527-1522104_124575894.0TransmembraneHelical
HgeneESYT2chr7:158540885chr7:146740999ENST00000251527-1522128_148575894.0TransmembraneHelical
TgeneCNTNAP2chr7:158540885chr7:146740999ENST000003617272241263_128301332.0TransmembraneHelical

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
ESYT2chr7158540885ENST00000251527CNTNAP2chr7146740999ENST00000361727

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Related Drugs to ESYT2-CNTNAP2

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 ESYT2-CNTNAP2

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