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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:TEAD2-NOSIP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TEAD2-NOSIP
FusionPDB ID: 89968
FusionGDB2.0 ID: 89968
HgeneTgene
Gene symbol

TEAD2

NOSIP

Gene ID

8463

51070

Gene nameTEA domain transcription factor 2nitric oxide synthase interacting protein
SynonymsETF|TEAD-2|TEF-4|TEF4CGI-25
Cytomap

19q13.33

19q13.33

Type of geneprotein-codingprotein-coding
Descriptiontranscriptional enhancer factor TEF-4TEA domain family member 2nitric oxide synthase-interacting proteinE3 ubiquitin-protein ligase NOSIPRING-type E3 ubiquitin transferase NOSIPeNOS-interacting protein
Modification date2020031320200313
UniProtAcc.

Q9Y314

Main function of 5'-partner protein: FUNCTION: E3 ubiquitin-protein ligase that is essential for proper development of the forebrain, the eye, and the face. Catalyzes monoubiquitination of serine/threonine-protein phosphatase 2A (PP2A) catalytic subunit PPP2CA/PPP2CB (By similarity). Negatively regulates nitric oxide production by inducing NOS1 and NOS3 translocation to actin cytoskeleton and inhibiting their enzymatic activity (PubMed:11149895, PubMed:15548660, PubMed:16135813). {ECO:0000250|UniProtKB:Q9D6T0, ECO:0000269|PubMed:11149895, ECO:0000269|PubMed:15548660, ECO:0000269|PubMed:16135813}.
Ensembl transtripts involved in fusion geneENST idsENST00000598397, ENST00000377214, 
ENST00000539846, ENST00000593945, 
ENST00000598810, ENST00000601519, 
ENST00000311227, 
ENST00000339093, 
ENST00000391853, ENST00000596358, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score2 X 2 X 2=88 X 2 X 5=80
# samples 28
** MAII scorelog2(2/8*10)=1.32192809488736log2(8/80*10)=0
Fusion gene context

PubMed: TEAD2 [Title/Abstract] AND NOSIP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TEAD2 [Title/Abstract] AND NOSIP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TEAD2(49858405)-NOSIP(50060506), # samples:2
Anticipated loss of major functional domain due to fusion event.TEAD2-NOSIP 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.
TEAD2-NOSIP 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.
TEAD2-NOSIP 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.
TEAD2-NOSIP 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.
TEAD2-NOSIP seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
TEAD2-NOSIP seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
TEAD2-NOSIP seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
TEAD2-NOSIP seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneTEAD2

GO:0035329

hippo signaling

18579750|19324877

TgeneNOSIP

GO:0043086

negative regulation of catalytic activity

11149895

TgeneNOSIP

GO:0051001

negative regulation of nitric-oxide synthase activity

11149895



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/chr19:49858405/chr19:50060506)
- 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 TEAD2 (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 NOSIP (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)
ENST00000311227TEAD2chr1949858405-ENST00000339093NOSIPchr1950060506-13156185791274231
ENST00000311227TEAD2chr1949858405-ENST00000596358NOSIPchr1950060506-13066185791265228
ENST00000311227TEAD2chr1949858405-ENST00000391853NOSIPchr1950060506-13046185791265228

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
ENST00000311227ENST00000339093TEAD2chr1949858405-NOSIPchr1950060506-0.55734980.44265026
ENST00000311227ENST00000596358TEAD2chr1949858405-NOSIPchr1950060506-0.567753730.43224624
ENST00000311227ENST00000391853TEAD2chr1949858405-NOSIPchr1950060506-0.555139540.44486043

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 TEAD2-NOSIP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TEAD2chr1949858405NOSIPchr195006050661813MVWRIWAPLECSRAYEKQRGTRREEQ

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Potential FusionNeoAntigen Information of TEAD2-NOSIP 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.
TEAD2-NOSIP_49858405_50060506.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)
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:01APLECSRAY0.9960.7245615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:08APLECSRAY0.99080.7438615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B15:02APLECSRAY0.97110.8704615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:01WAPLECSRAY0.9780.7514515
TEAD2-NOSIPchr1949858405chr1950060506618HLA-A31:02RAYEKQRGTRR0.9850.65861223
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:05IWAPLECSRAY0.96830.5911415
TEAD2-NOSIPchr1949858405chr1950060506618HLA-A31:06RAYEKQRGTRR0.95870.55921223
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B15:31APLECSRAY0.99620.6644615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B15:21APLECSRAY0.96550.8201615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-A31:01RAYEKQRGTRR0.99350.63181223
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:77APLECSRAY0.9960.7245615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:23APLECSRAY0.99570.7278615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:20APLECSRAY0.99550.7911615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:11APLECSRAY0.96750.8093615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:24APLECSRAY0.96480.6292615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B18:04APLECSRAY0.49560.7248615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B15:11APLECSRAY0.23710.6877615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B15:08APLECSRAY0.23550.6856615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:43APLECSRAY0.19190.6934615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B18:07APLECSRAY0.16660.6433615
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B15:11WAPLECSRAY0.98920.71515
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:11WAPLECSRAY0.97820.8247515
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:77WAPLECSRAY0.9780.7514515
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:23WAPLECSRAY0.97790.7803515
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:24WAPLECSRAY0.95310.7042515
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:17WAPLECSRAY0.93950.5767515
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:30WAPLECSRAY0.93950.5767515
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:17IWAPLECSRAY0.9840.716415
TEAD2-NOSIPchr1949858405chr1950060506618HLA-B35:30IWAPLECSRAY0.9840.716415

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Potential FusionNeoAntigen Information of TEAD2-NOSIP 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.
TEAD2-NOSIP_49858405_50060506.msa

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)
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0101SRAYEKQRGTRREEQ1126
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0101CSRAYEKQRGTRREE1025
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0101ECSRAYEKQRGTRRE924
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0102SRAYEKQRGTRREEQ1126
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0103SRAYEKQRGTRREEQ1126
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0104SRAYEKQRGTRREEQ1126
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0104CSRAYEKQRGTRREE1025
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0105SRAYEKQRGTRREEQ1126
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0105CSRAYEKQRGTRREE1025
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0105ECSRAYEKQRGTRRE924
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0108NSRAYEKQRGTRREEQ1126
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0111SRAYEKQRGTRREEQ1126
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0111CSRAYEKQRGTRREE1025
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0111ECSRAYEKQRGTRRE924
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0113SRAYEKQRGTRREEQ1126
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0113CSRAYEKQRGTRREE1025
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0113ECSRAYEKQRGTRRE924
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0114SRAYEKQRGTRREEQ1126
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0114CSRAYEKQRGTRREE1025
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0114ECSRAYEKQRGTRRE924
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0203SRAYEKQRGTRREEQ1126
TEAD2-NOSIPchr1949858405chr1950060506618DRB5-0203CSRAYEKQRGTRREE1025

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Fusion breakpoint peptide structures of TEAD2-NOSIP

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
488APLECSRAYEKQRGTEAD2NOSIPchr1949858405chr1950060506618

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TEAD2-NOSIP

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-B14:023BVN488APLECSRAYEKQRG-7.15543-7.26883
HLA-B14:023BVN488APLECSRAYEKQRG-4.77435-5.80965
HLA-B52:013W39488APLECSRAYEKQRG-6.80875-6.92215
HLA-B52:013W39488APLECSRAYEKQRG-4.20386-5.23916
HLA-A11:014UQ2488APLECSRAYEKQRG-7.5194-8.5547
HLA-A11:014UQ2488APLECSRAYEKQRG-6.9601-7.0735
HLA-A24:025HGA488APLECSRAYEKQRG-7.52403-7.63743
HLA-A24:025HGA488APLECSRAYEKQRG-5.82433-6.85963
HLA-B27:056PYJ488APLECSRAYEKQRG-3.28285-4.31815
HLA-B44:053DX8488APLECSRAYEKQRG-5.91172-6.94702
HLA-B44:053DX8488APLECSRAYEKQRG-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of TEAD2-NOSIP

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
TEAD2-NOSIPchr1949858405chr19500605061223RAYEKQRGTRRAGAGCCTACGAGAAGCAGCGGGGCACCCGGCGC
TEAD2-NOSIPchr1949858405chr1950060506415IWAPLECSRAYATCTGGGCCCCCCTGGAATGTTCCAGAGCCTAC
TEAD2-NOSIPchr1949858405chr1950060506515WAPLECSRAYTGGGCCCCCCTGGAATGTTCCAGAGCCTAC
TEAD2-NOSIPchr1949858405chr1950060506615APLECSRAYGCCCCCCTGGAATGTTCCAGAGCCTAC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TEAD2-NOSIPchr1949858405chr19500605061025CSRAYEKQRGTRREETGTTCCAGAGCCTACGAGAAGCAGCGGGGCACCCGGCGCGAGGAG
TEAD2-NOSIPchr1949858405chr19500605061126SRAYEKQRGTRREEQTCCAGAGCCTACGAGAAGCAGCGGGGCACCCGGCGCGAGGAGCAG
TEAD2-NOSIPchr1949858405chr1950060506924ECSRAYEKQRGTRREGAATGTTCCAGAGCCTACGAGAAGCAGCGGGGCACCCGGCGCGAG

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Information of the samples that have these potential fusion neoantigens of TEAD2-NOSIP

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
STADTEAD2-NOSIPchr1949858405ENST00000311227chr1950060506ENST00000339093TCGA-BR-8060-01A

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Potential target of CAR-T therapy development for TEAD2-NOSIP

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 TEAD2-NOSIP

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 TEAD2-NOSIP

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