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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:VTI1A-GLS

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: VTI1A-GLS
FusionPDB ID: 98587
FusionGDB2.0 ID: 98587
HgeneTgene
Gene symbol

VTI1A

GLS

Gene ID

143187

27165

Gene namevesicle transport through interaction with t-SNAREs 1Aglutaminase 2
SynonymsMMDS3|MVti1|VTI1RP2|Vti1-rp2GA|GLS|LGA|hLGA
Cytomap

10q25.2

12q13.3

Type of geneprotein-codingprotein-coding
Descriptionvesicle transport through interaction with t-SNAREs homolog 1ASNARE Vti1a-beta proteinvesicle transport v-SNARE protein Vti1-like 2glutaminase liver isoform, mitochondrialL-glutamine amidohydrolasebreast cell glutaminaseglutaminase 2 (liver, mitochondrial)glutaminase Iphosphate-activated glutaminasephosphate-dependent glutaminase
Modification date2020031320200313
UniProtAcc

Q96AJ9

Main function of 5'-partner protein: FUNCTION: V-SNARE that mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane. These interactions are proposed to mediate aspects of the specificity of vesicle trafficking and to promote fusion of the lipid bilayers. Involved in vesicular transport from the late endosomes to the trans-Golgi network. Along with VAMP7, involved in an non-conventional RAB1-dependent traffic route to the cell surface used by KCNIP1 and KCND2. May be involved in increased cytokine secretion associated with cellular senescence. {ECO:0000269|PubMed:18195106, ECO:0000269|PubMed:19138172}.

Q9UI32

Main function of 5'-partner protein: FUNCTION: Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketoglutarate. Increases cellular anti-oxidant function via NADH and glutathione production. May play a role in preventing tumor proliferation. {ECO:0000269|PubMed:20378837}.
Ensembl transtripts involved in fusion geneENST idsENST00000393077, ENST00000432306, 
ENST00000483122, 
ENST00000409626, 
ENST00000409215, ENST00000409428, 
ENST00000471443, ENST00000320717, 
ENST00000338435, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 12 X 12=216012 X 9 X 5=540
# samples 2412
** MAII scorelog2(24/2160*10)=-3.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/540*10)=-2.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: VTI1A [Title/Abstract] AND GLS [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: VTI1A [Title/Abstract] AND GLS [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)VTI1A(114224416)-GLS(191792032), # samples:1
Anticipated loss of major functional domain due to fusion event.VTI1A-GLS 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.
VTI1A-GLS 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
HgeneVTI1A

GO:0042147

retrograde transport, endosome to Golgi

15215310|18195106



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/chr10:114224416/chr2:191792032)
- 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 VTI1A (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 GLS (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)
ENST00000432306VTI1Achr10114224416+ENST00000320717GLSchr2191792032+3708380861141351
ENST00000432306VTI1Achr10114224416+ENST00000338435GLSchr2191792032+335638086928280
ENST00000393077VTI1Achr10114224416+ENST00000320717GLSchr2191792032+3708380861141351
ENST00000393077VTI1Achr10114224416+ENST00000338435GLSchr2191792032+335638086928280

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
ENST00000432306ENST00000320717VTI1Achr10114224416+GLSchr2191792032+0.0002019350.9997981
ENST00000432306ENST00000338435VTI1Achr10114224416+GLSchr2191792032+0.0002050370.999795
ENST00000393077ENST00000320717VTI1Achr10114224416+GLSchr2191792032+0.0002019350.9997981
ENST00000393077ENST00000338435VTI1Achr10114224416+GLSchr2191792032+0.0002050370.999795

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 VTI1A-GLS

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
VTI1Achr10114224416GLSchr219179203238098SYKQEMGKLETDFLCSIEVTCESASV

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Potential FusionNeoAntigen Information of VTI1A-GLS 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.
VTI1A-GLS_114224416_191792032.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)
VTI1A-GLSchr10114224416chr2191792032380HLA-B44:10QEMGKLETDFL0.9980.5145314
VTI1A-GLSchr10114224416chr2191792032380HLA-B40:04QEMGKLETDFL0.99860.7441314
VTI1A-GLSchr10114224416chr2191792032380HLA-B41:03QEMGKLETDFL0.97780.6974314

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Potential FusionNeoAntigen Information of VTI1A-GLS 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 VTI1A-GLS

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
2901GKLETDFLCSIEVTVTI1AGLSchr10114224416chr2191792032380

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of VTI1A-GLS

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-B14:023BVN2901GKLETDFLCSIEVT-7.9962-8.1096
HLA-B14:023BVN2901GKLETDFLCSIEVT-5.70842-6.74372
HLA-B52:013W392901GKLETDFLCSIEVT-6.83737-6.95077
HLA-B52:013W392901GKLETDFLCSIEVT-4.4836-5.5189
HLA-A11:014UQ22901GKLETDFLCSIEVT-10.0067-10.1201
HLA-A11:014UQ22901GKLETDFLCSIEVT-9.03915-10.0745
HLA-A24:025HGA2901GKLETDFLCSIEVT-6.56204-6.67544
HLA-A24:025HGA2901GKLETDFLCSIEVT-5.42271-6.45801
HLA-B44:053DX82901GKLETDFLCSIEVT-7.85648-8.89178
HLA-B44:053DX82901GKLETDFLCSIEVT-5.3978-5.5112
HLA-A02:016TDR2901GKLETDFLCSIEVT-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of VTI1A-GLS

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
VTI1A-GLSchr10114224416chr2191792032314QEMGKLETDFLCAAGAAATGGGAAAACTCGAAACAGATTTTCTG

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 VTI1A-GLS

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
STADVTI1A-GLSchr10114224416ENST00000393077chr2191792032ENST00000320717TCGA-D7-8574-01A

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Potential target of CAR-T therapy development for VTI1A-GLS

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 VTI1A-GLS

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 VTI1A-GLS

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
HgeneVTI1AC0001418Adenocarcinoma1CTD_human
HgeneVTI1AC0009402Colorectal Carcinoma1CTD_human
HgeneVTI1AC0009404Colorectal Neoplasms1CTD_human
HgeneVTI1AC0205641Adenocarcinoma, Basal Cell1CTD_human
HgeneVTI1AC0205642Adenocarcinoma, Oxyphilic1CTD_human
HgeneVTI1AC0205643Carcinoma, Cribriform1CTD_human
HgeneVTI1AC0205644Carcinoma, Granular Cell1CTD_human
HgeneVTI1AC0205645Adenocarcinoma, Tubular1CTD_human