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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:GLIS3-CTNNA2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GLIS3-CTNNA2
FusionPDB ID: 33305
FusionGDB2.0 ID: 33305
HgeneTgene
Gene symbol

GLIS3

CTNNA2

Gene ID

169792

1496

Gene nameGLIS family zinc finger 3catenin alpha 2
SynonymsNDH|ZNF515CAP-R|CAPR|CDCBM9|CT114|CTNR
Cytomap

9p24.2

2p12

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein GLIS3GLI-similar 3OK/KNS-cl.4zinc finger protein 515catenin alpha-2alpha-N-cateninalpha-catenin-related proteincadherin-associated protein, relatedcancer/testis antigen 114catenin (cadherin-associated protein), alpha 2
Modification date2020031320200313
UniProtAcc

Q8NEA6

Main function of 5'-partner protein: FUNCTION: Acts as both a repressor and activator of transcription. Binds to the consensus sequence 5'-GACCACCCAC-3' (By similarity). {ECO:0000250}.

P26232

Main function of 5'-partner protein: FUNCTION: May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system (By similarity). Required for proper regulation of cortical neuronal migration and neurite growth (PubMed:30013181). It acts as negative regulator of Arp2/3 complex activity and Arp2/3-mediated actin polymerization (PubMed:30013181). It thereby suppresses excessive actin branching which would impair neurite growth and stability (PubMed:30013181). Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation (By similarity). {ECO:0000250|UniProtKB:Q61301, ECO:0000269|PubMed:30013181}.
Ensembl transtripts involved in fusion geneENST idsENST00000324333, ENST00000381971, 
ENST00000461870, 
ENST00000409266, 
ENST00000496251, ENST00000343114, 
ENST00000361291, ENST00000496558, 
ENST00000540488, ENST00000402739, 
ENST00000466387, ENST00000541047, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 7 X 7=63726 X 24 X 10=6240
# samples 1328
** MAII scorelog2(13/637*10)=-2.29278174922785
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(28/6240*10)=-4.47804729680464
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: GLIS3 [Title/Abstract] AND CTNNA2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GLIS3 [Title/Abstract] AND CTNNA2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GLIS3(4117768)-CTNNA2(80874710), # samples:1
Anticipated loss of major functional domain due to fusion event.GLIS3-CTNNA2 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.
GLIS3-CTNNA2 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.
GLIS3-CTNNA2 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.
GLIS3-CTNNA2 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.
GLIS3-CTNNA2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
GLIS3-CTNNA2 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
GLIS3-CTNNA2 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
GLIS3-CTNNA2 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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


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/chr9:4117768/chr2:80874710)
- 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 GLIS3 (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 CTNNA2 (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)
ENST00000381971GLIS3chr94117768-ENST00000361291CTNNA2chr280874710+259223045942591665
ENST00000381971GLIS3chr94117768-ENST00000540488CTNNA2chr280874710+259223045942591665
ENST00000324333GLIS3chr94117768-ENST00000466387CTNNA2chr280874710+263414391941726510
ENST00000324333GLIS3chr94117768-ENST00000402739CTNNA2chr280874710+254414391941726510
ENST00000324333GLIS3chr94117768-ENST00000541047CTNNA2chr280874710+263414391941726510

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
ENST00000381971ENST00000361291GLIS3chr94117768-CTNNA2chr280874710+0.0382170450.96178293
ENST00000381971ENST00000540488GLIS3chr94117768-CTNNA2chr280874710+0.0382170450.96178293
ENST00000324333ENST00000466387GLIS3chr94117768-CTNNA2chr280874710+0.011092170.98890775
ENST00000324333ENST00000402739GLIS3chr94117768-CTNNA2chr280874710+0.0133737980.9866262
ENST00000324333ENST00000541047GLIS3chr94117768-CTNNA2chr280874710+0.011092170.98890775

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 GLIS3-CTNNA2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GLIS3chr94117768CTNNA2chr2808747101439415MRVHSGEKPNKCTLDSATSLIQAAKN
GLIS3chr94117768CTNNA2chr2808747102304570MRVHSGEKPNKCTLDSATSLIQAAKN

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Potential FusionNeoAntigen Information of GLIS3-CTNNA2 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.
GLIS3-CTNNA2_4117768_80874710.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)
GLIS3-CTNNA2chr94117768chr2808747101439HLA-A02:38TLDSATSLI0.94290.78581221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-A02:27TLDSATSLI0.9210.6731221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-A02:13TLDSATSLI0.9150.78621221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-A02:35TLDSATSLI0.87520.64721221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-A02:19TLDSATSLI0.81290.55811221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C04:10TLDSATSL10.75681220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C08:15TLDSATSL10.9851220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C05:09TLDSATSL10.9241220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C04:07TLDSATSL10.77721220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C04:06TLDSATSL0.99770.88151220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C04:14TLDSATSL0.99330.80211220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C08:13TLDSATSL0.98890.95451220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C08:04TLDSATSL0.98890.95451220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C08:03TLDSATSL0.92740.9911220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C05:09TLDSATSLI0.99980.92241221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C04:10TLDSATSLI0.99970.76391221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C04:07TLDSATSLI0.99970.78221221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C08:15TLDSATSLI0.99880.98461221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C03:07CTLDSATSL0.99840.97611120
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C15:06CTLDSATSL0.99770.93561120
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C03:08CTLDSATSL0.99680.89011120
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C04:06TLDSATSLI0.94550.84921221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-A02:07TLDSATSLI0.93270.60411221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C04:14TLDSATSLI0.88360.79141221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C18:01TLDSATSL10.76531220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C04:01TLDSATSL10.77721220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C04:03TLDSATSL10.80811220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C05:01TLDSATSL10.9241220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C08:02TLDSATSL10.9851220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C01:03TLDSATSL10.96111220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C08:01TLDSATSL0.92740.9911220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-B07:13TLDSATSL0.58080.86911220
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C05:01TLDSATSLI0.99980.92241221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C04:03TLDSATSLI0.99980.81341221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C04:01TLDSATSLI0.99970.78221221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C18:01TLDSATSLI0.99960.77551221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C08:02TLDSATSLI0.99880.98461221
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C03:03CTLDSATSL0.99780.97321120
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C03:04CTLDSATSL0.99780.97321120
GLIS3-CTNNA2chr94117768chr2808747101439HLA-C03:06CTLDSATSL0.97070.9791120

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Potential FusionNeoAntigen Information of GLIS3-CTNNA2 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 GLIS3-CTNNA2

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
1857EKPNKCTLDSATSLGLIS3CTNNA2chr94117768chr2808747101439

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GLIS3-CTNNA2

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-B14:023BVN1857EKPNKCTLDSATSL-6.73939-6.85279
HLA-B14:023BVN1857EKPNKCTLDSATSL-5.8572-6.8925
HLA-B52:013W391857EKPNKCTLDSATSL-6.06811-6.18151
HLA-B52:013W391857EKPNKCTLDSATSL-4.01521-5.05051
HLA-A24:025HGA1857EKPNKCTLDSATSL-6.11611-7.15141
HLA-A24:025HGA1857EKPNKCTLDSATSL-5.72969-5.84309
HLA-B27:056PYJ1857EKPNKCTLDSATSL-6.42433-7.45963
HLA-B44:053DX81857EKPNKCTLDSATSL-5.79012-5.90352
HLA-B44:053DX81857EKPNKCTLDSATSL-3.82099-4.85629

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Vaccine Design for the FusionNeoAntigens of GLIS3-CTNNA2

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
GLIS3-CTNNA2chr94117768chr2808747101120CTLDSATSLTGTACGCTGGACAGTGCCACATCGCTT
GLIS3-CTNNA2chr94117768chr2808747101220TLDSATSLACGCTGGACAGTGCCACATCGCTT
GLIS3-CTNNA2chr94117768chr2808747101221TLDSATSLIACGCTGGACAGTGCCACATCGCTTATC

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 GLIS3-CTNNA2

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
HNSCGLIS3-CTNNA2chr94117768ENST00000324333chr280874710ENST00000402739TCGA-CN-5365-01A

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Potential target of CAR-T therapy development for GLIS3-CTNNA2

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 GLIS3-CTNNA2

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 GLIS3-CTNNA2

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