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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:ZC3H8-TIA1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZC3H8-TIA1
FusionPDB ID: 100607
FusionGDB2.0 ID: 100607
HgeneTgene
Gene symbol

ZC3H8

TIA1

Gene ID

84524

7072

Gene namezinc finger CCCH-type containing 8TIA1 cytotoxic granule associated RNA binding protein
SynonymsFliz1|ZC3HDC8TIA-1|WDM
Cytomap

2q14.1

2p13.3

Type of geneprotein-codingprotein-coding
Descriptionzinc finger CCCH domain-containing protein 8zinc finger CCCH-type domain containing 8nucleolysin TIA-1 isoform p40nucleolysin TIA-1T-cell-restricted intracellular antigen-1p40-TIA-1 (containing p15-TIA-1)
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000272570, ENST00000409573, 
ENST00000476902, 
ENST00000416149, 
ENST00000482876, ENST00000282574, 
ENST00000415783, ENST00000433529, 
ENST00000445587, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 4=6411 X 6 X 6=396
# samples 411
** MAII scorelog2(4/64*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/396*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ZC3H8 [Title/Abstract] AND TIA1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZC3H8 [Title/Abstract] AND TIA1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZC3H8(112991697)-TIA1(70444126), # samples:1
Anticipated loss of major functional domain due to fusion event.ZC3H8-TIA1 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.
ZC3H8-TIA1 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.
ZC3H8-TIA1 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.
ZC3H8-TIA1 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
HgeneZC3H8

GO:0045892

negative regulation of transcription, DNA-templated

12077251

HgeneZC3H8

GO:0046677

response to antibiotic

12153508

TgeneTIA1

GO:0048024

regulation of mRNA splicing, via spliceosome

11106748



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/chr2:112991697/chr2:70444126)
- 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 ZC3H8 (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 TIA1 (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)
ENST00000409573ZC3H8chr2112991697-ENST00000433529TIA1chr270444126-47137511301437435
ENST00000409573ZC3H8chr2112991697-ENST00000415783TIA1chr270444126-47137511301437435
ENST00000409573ZC3H8chr2112991697-ENST00000282574TIA1chr270444126-39507511301434434
ENST00000409573ZC3H8chr2112991697-ENST00000445587TIA1chr270444126-15707511301167345
ENST00000272570ZC3H8chr2112991697-ENST00000433529TIA1chr270444126-46897271061413435
ENST00000272570ZC3H8chr2112991697-ENST00000415783TIA1chr270444126-46897271061413435
ENST00000272570ZC3H8chr2112991697-ENST00000282574TIA1chr270444126-39267271061410434
ENST00000272570ZC3H8chr2112991697-ENST00000445587TIA1chr270444126-15467271061143345

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
ENST00000409573ENST00000433529ZC3H8chr2112991697-TIA1chr270444126-0.000115950.999884
ENST00000409573ENST00000415783ZC3H8chr2112991697-TIA1chr270444126-0.000115950.999884
ENST00000409573ENST00000282574ZC3H8chr2112991697-TIA1chr270444126-0.0001577150.9998423
ENST00000409573ENST00000445587ZC3H8chr2112991697-TIA1chr270444126-0.0007587240.99924135
ENST00000272570ENST00000433529ZC3H8chr2112991697-TIA1chr270444126-0.0001156840.99988425
ENST00000272570ENST00000415783ZC3H8chr2112991697-TIA1chr270444126-0.0001156840.99988425
ENST00000272570ENST00000282574ZC3H8chr2112991697-TIA1chr270444126-0.0001573190.99984264
ENST00000272570ENST00000445587ZC3H8chr2112991697-TIA1chr270444126-0.0007607230.9992393

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 ZC3H8-TIA1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZC3H8chr2112991697TIA1chr270444126727207QICKYFLERKCIKDAENAIQQMGGQW
ZC3H8chr2112991697TIA1chr270444126751207QICKYFLERKCIKDAENAIQQMGGQW

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Potential FusionNeoAntigen Information of ZC3H8-TIA1 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.

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)

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Potential FusionNeoAntigen Information of ZC3H8-TIA1 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.
ZC3H8-TIA1_112991697_70444126.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)
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0403RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0413RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0427RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0439RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0440RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0441RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0442RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0446RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0449RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0450RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0451RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0452RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0455RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0456RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0459RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0460RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0465RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0468RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0470RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0471RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0478RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0485RKCIKDAENAIQQMG823
ZC3H8-TIA1chr2112991697chr270444126727DRB1-0488RKCIKDAENAIQQMG823

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Fusion breakpoint peptide structures of ZC3H8-TIA1

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZC3H8-TIA1

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

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Vaccine Design for the FusionNeoAntigens of ZC3H8-TIA1

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

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ZC3H8-TIA1chr2112991697chr270444126823RKCIKDAENAIQQMGAGGAAATGTATTAAGGATGCTGAAAACGCCATTCAACAGATGGGT

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Information of the samples that have these potential fusion neoantigens of ZC3H8-TIA1

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

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Potential target of CAR-T therapy development for ZC3H8-TIA1

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 ZC3H8-TIA1

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 ZC3H8-TIA1

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