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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:GSTO1-INA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GSTO1-INA
FusionPDB ID: 35120
FusionGDB2.0 ID: 35120
HgeneTgene
Gene symbol

GSTO1

INA

Gene ID

9446

9118

Gene nameglutathione S-transferase omega 1internexin neuronal intermediate filament protein alpha
SynonymsGSTO 1-1|GSTTLp28|HEL-S-21|P28|SPG-RNEF5|NF-66|TXBP-1
Cytomap

10q25.1

10q24.33

Type of geneprotein-codingprotein-coding
Descriptionglutathione S-transferase omega-1MMA(V) reductaseS-(Phenacyl)glutathione reductaseepididymis secretory protein Li 21glutathione S-transferase omega 1-1glutathione-S-transferase likeglutathione-dependent dehydroascorbate reductasemonomethylarsonic aalpha-internexin66 kDa neurofilament proteinalpha-Inxneurofilament 5 (66kD)neurofilament-66, tax-binding protein
Modification date2020031320200313
UniProtAcc

P78417

Main function of 5'-partner protein: FUNCTION: Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities. Has S-(phenacyl)glutathione reductase activity. Has also glutathione S-transferase activity. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA) and dimethylarsonic acid. {ECO:0000269|PubMed:10783391, ECO:0000269|PubMed:11511179, ECO:0000269|PubMed:17226937, ECO:0000269|PubMed:18028863, ECO:0000269|PubMed:21106529}.

Q3KP66

Main function of 5'-partner protein: FUNCTION: Expressed in peripheral macrophages and intestinal myeloid-derived cells, is required for optimal PRR (pattern recognition receptor)-induced signaling, cytokine secretion, and bacterial clearance. Upon stimulation of a broad range of PRRs (pattern recognition receptor) such as NOD2 or TLR2, TLR3, TLR4, TLR5, TLR7 and TLR9, associates with YWHAQ/14-3-3T, which in turn leads to the recruitment and activation of MAP kinases and NF-kappa-B signaling complexes that amplifies PRR-induced downstream signals and cytokine secretion (PubMed:28436939). In the intestine, regulates adherens junction stability by regulating the degradation of CYTH1 and CYTH2, probably acting as substrate cofactor for SCF E3 ubiquitin-protein ligase complexes. Stabilizes adherens junctions by limiting CYTH1-dependent ARF6 activation (PubMed:29420262). {ECO:0000269|PubMed:28436939, ECO:0000269|PubMed:29420262}.
Ensembl transtripts involved in fusion geneENST idsENST00000493946, ENST00000369713, 
ENST00000539281, ENST00000369710, 
ENST00000369849, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 5 X 2=604 X 2 X 3=24
# samples 65
** MAII scorelog2(6/60*10)=0log2(5/24*10)=1.05889368905357
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: GSTO1 [Title/Abstract] AND INA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GSTO1 [Title/Abstract] AND INA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GSTO1(106022835)-INA(105046792), # samples:1
Anticipated loss of major functional domain due to fusion event.GSTO1-INA 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.
GSTO1-INA 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.
GSTO1-INA 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.
GSTO1-INA 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
HgeneGSTO1

GO:0010880

regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum

11035031

HgeneGSTO1

GO:0019852

L-ascorbic acid metabolic process

11511179

HgeneGSTO1

GO:0042178

xenobiotic catabolic process

12928150

HgeneGSTO1

GO:0060315

negative regulation of ryanodine-sensitive calcium-release channel activity

11035031

HgeneGSTO1

GO:0060316

positive regulation of ryanodine-sensitive calcium-release channel activity

11035031

HgeneGSTO1

GO:0071243

cellular response to arsenic-containing substance

11511179



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/chr10:106022835/chr10:105046792)
- 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 GSTO1 (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 INA (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)
ENST00000539281GSTO1chr10106022835+ENST00000369849INAchr10105046792+28547372841171295
ENST00000369713GSTO1chr10106022835+ENST00000369849INAchr10105046792+27766591461093315

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
ENST00000539281ENST00000369849GSTO1chr10106022835+INAchr10105046792+0.000434030.999566
ENST00000369713ENST00000369849GSTO1chr10106022835+INAchr10105046792+0.0004966480.9995034

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 GSTO1-INA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GSTO1chr10106022835INAchr10105046792659171KEEFRKEFTKLEEDSIGQLENDLRNT
GSTO1chr10106022835INAchr10105046792737151KEEFRKEFTKLEEDSIGQLENDLRNT

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Potential FusionNeoAntigen Information of GSTO1-INA 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.
GSTO1-INA_106022835_105046792.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)
GSTO1-INAchr10106022835chr10105046792659HLA-B39:13LEEDSIGQL0.34540.59651019
GSTO1-INAchr10106022835chr10105046792659HLA-B41:01LEEDSIGQL0.26430.70031019
GSTO1-INAchr10106022835chr10105046792659HLA-B39:08LEEDSIGQL0.54350.50621019
GSTO1-INAchr10106022835chr10105046792659HLA-B39:08KLEEDSIGQL0.68140.6541919
GSTO1-INAchr10106022835chr10105046792659HLA-B40:04LEEDSIGQL0.99690.54581019
GSTO1-INAchr10106022835chr10105046792659HLA-B39:02LEEDSIGQL0.42730.61031019
GSTO1-INAchr10106022835chr10105046792659HLA-B40:04KLEEDSIGQL0.43880.5934919

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Potential FusionNeoAntigen Information of GSTO1-INA 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.
GSTO1-INA_106022835_105046792.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)
GSTO1-INAchr10106022835chr10105046792659DRB1-0405KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0409KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0429KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0430KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0445KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0448KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0457KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0462KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0477KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0480KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0483KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0484KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0486KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0487KEEFRKEFTKLEEDS015
GSTO1-INAchr10106022835chr10105046792659DRB1-0489KEEFRKEFTKLEEDS015

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Fusion breakpoint peptide structures of GSTO1-INA

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
1722EFTKLEEDSIGQLEGSTO1INAchr10106022835chr10105046792659

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GSTO1-INA

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-B14:023BVN1722EFTKLEEDSIGQLE-7.9962-8.1096
HLA-B14:023BVN1722EFTKLEEDSIGQLE-5.70842-6.74372
HLA-B52:013W391722EFTKLEEDSIGQLE-6.83737-6.95077
HLA-B52:013W391722EFTKLEEDSIGQLE-4.4836-5.5189
HLA-A11:014UQ21722EFTKLEEDSIGQLE-10.0067-10.1201
HLA-A11:014UQ21722EFTKLEEDSIGQLE-9.03915-10.0745
HLA-A24:025HGA1722EFTKLEEDSIGQLE-6.56204-6.67544
HLA-A24:025HGA1722EFTKLEEDSIGQLE-5.42271-6.45801
HLA-B44:053DX81722EFTKLEEDSIGQLE-7.85648-8.89178
HLA-B44:053DX81722EFTKLEEDSIGQLE-5.3978-5.5112
HLA-A02:016TDR1722EFTKLEEDSIGQLE-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of GSTO1-INA

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
GSTO1-INAchr10106022835chr101050467921019LEEDSIGQLCTAGAGGAGGATAGCATTGGGCAGCTG
GSTO1-INAchr10106022835chr10105046792919KLEEDSIGQLAAGCTAGAGGAGGATAGCATTGGGCAGCTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
GSTO1-INAchr10106022835chr10105046792015KEEFRKEFTKLEEDSAAAGAAGAATTTCGTAAAGAATTTACCAAGCTAGAGGAGGATAGC

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Information of the samples that have these potential fusion neoantigens of GSTO1-INA

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
PRADGSTO1-INAchr10106022835ENST00000369713chr10105046792ENST00000369849TCGA-EJ-8474-01A

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Potential target of CAR-T therapy development for GSTO1-INA

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 GSTO1-INA

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 GSTO1-INA

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