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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-TERT

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GLIS3-TERT
FusionPDB ID: 33316
FusionGDB2.0 ID: 33316
HgeneTgene
Gene symbol

GLIS3

TERT

Gene ID

169792

7015

Gene nameGLIS family zinc finger 3telomerase reverse transcriptase
SynonymsNDH|ZNF515CMM9|DKCA2|DKCB4|EST2|PFBMFT1|TCS1|TP2|TRT|hEST2|hTRT
Cytomap

9p24.2

5p15.33

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein GLIS3GLI-similar 3OK/KNS-cl.4zinc finger protein 515telomerase reverse transcriptasetelomerase catalytic subunittelomerase-associated protein 2
Modification date2020031320200329
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}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000324333, ENST00000381971, 
ENST00000461870, 
ENST00000522877, 
ENST00000296820, ENST00000310581, 
ENST00000334602, ENST00000508104, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 7 X 7=63722 X 7 X 15=2310
# samples 1331
** MAII scorelog2(13/637*10)=-2.29278174922785
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(31/2310*10)=-2.89755273102918
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

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

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GLIS3(4117768)-TERT(1282739), # samples:2
Anticipated loss of major functional domain due to fusion event.GLIS3-TERT 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-TERT 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-TERT 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-TERT 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-TERT seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
GLIS3-TERT seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
GLIS3-TERT seems lost the major protein functional domain in Tgene partner, which is a CGC 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
TgeneTERT

GO:0001172

transcription, RNA-templated

19701182

TgeneTERT

GO:0006278

RNA-dependent DNA biosynthetic process

9398860

TgeneTERT

GO:0007004

telomere maintenance via telomerase

9443919|16043710|17940095|19701182|21531765|29695869

TgeneTERT

GO:0007005

mitochondrion organization

21937513

TgeneTERT

GO:0010629

negative regulation of gene expression

11927518

TgeneTERT

GO:0022616

DNA strand elongation

16043710

TgeneTERT

GO:0030422

production of siRNA involved in RNA interference

19701182

TgeneTERT

GO:0031647

regulation of protein stability

24415760|26194824

TgeneTERT

GO:0032092

positive regulation of protein binding

24415760

TgeneTERT

GO:0051000

positive regulation of nitric-oxide synthase activity

11927518

TgeneTERT

GO:0070200

establishment of protein localization to telomere

25589350

TgeneTERT

GO:0071897

DNA biosynthetic process

9398860|19701182

TgeneTERT

GO:1903704

negative regulation of production of siRNA involved in RNA interference

19701182

TgeneTERT

GO:1904751

positive regulation of protein localization to nucleolus

24415760

TgeneTERT

GO:2000773

negative regulation of cellular senescence

11927518



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/chr5:1282739)
- 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 TERT (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-ENST00000296820TERTchr51282739-450223045942375593

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
ENST00000381971ENST00000296820GLIS3chr94117768-TERTchr51282739-0.0900291350.9099708

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-TERT

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GLIS3chr94117768TERTchr512827392304570MRVHSGEKPNKCTGLAVFRPQSTVCV

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Potential FusionNeoAntigen Information of GLIS3-TERT 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-TERT_4117768_1282739.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-TERTchr94117768chr512827392304HLA-B15:18NKCTGLAVF0.39240.6277918

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Potential FusionNeoAntigen Information of GLIS3-TERT 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-TERT

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
1856EKPNKCTGLAVFRPGLIS3TERTchr94117768chr512827392304

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

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-B14:023BVN1856EKPNKCTGLAVFRP-7.9962-8.1096
HLA-B14:023BVN1856EKPNKCTGLAVFRP-5.70842-6.74372
HLA-B52:013W391856EKPNKCTGLAVFRP-6.83737-6.95077
HLA-B52:013W391856EKPNKCTGLAVFRP-4.4836-5.5189
HLA-A11:014UQ21856EKPNKCTGLAVFRP-10.0067-10.1201
HLA-A11:014UQ21856EKPNKCTGLAVFRP-9.03915-10.0745
HLA-A24:025HGA1856EKPNKCTGLAVFRP-6.56204-6.67544
HLA-A24:025HGA1856EKPNKCTGLAVFRP-5.42271-6.45801
HLA-B44:053DX81856EKPNKCTGLAVFRP-7.85648-8.89178
HLA-B44:053DX81856EKPNKCTGLAVFRP-5.3978-5.5112
HLA-A02:016TDR1856EKPNKCTGLAVFRP-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of GLIS3-TERT

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-TERTchr94117768chr51282739918NKCTGLAVFAACAAGTGTACGGGGTTGGCTGTGTTC

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-TERT

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
SARCGLIS3-TERTchr94117768ENST00000381971chr51282739ENST00000296820TCGA-DX-A3LS-01A

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

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-TERT

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-TERT

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