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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:HBP1-PIK3CG

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HBP1-PIK3CG
FusionPDB ID: 35714
FusionGDB2.0 ID: 35714
HgeneTgene
Gene symbol

HBP1

PIK3CG

Gene ID

26959

5294

Gene nameHMG-box transcription factor 1phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
Synonyms-PI3CG|PI3K|PI3Kgamma|PIK3|p110gamma|p120-PI3K
Cytomap

7q22.3

7q22.3

Type of geneprotein-codingprotein-coding
DescriptionHMG box-containing protein 1high mobility group box transcription factor 1phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform1-phosphatidylinositol 3-kinasePI3-kinase subunit gammaphosphatidylinositol 3 kinase gamma, p110 gammaphosphatidylinositol 3-kinase catalytic 110-kD gammaphosphatidylinosit
Modification date2020032220200313
UniProtAcc

O60381

Main function of 5'-partner protein: FUNCTION: Transcriptional repressor that binds to the promoter region of target genes. Plays a role in the regulation of the cell cycle and of the Wnt pathway. Binds preferentially to the sequence 5'-TTCATTCATTCA-3'. Binding to the histone H1.0 promoter is enhanced by interaction with RB1. Disrupts the interaction between DNA and TCF4. {ECO:0000269|PubMed:10562551, ECO:0000269|PubMed:10958660, ECO:0000269|PubMed:11500377}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000461963, ENST00000222574, 
ENST00000468410, ENST00000485846, 
ENST00000359195, ENST00000440650, 
ENST00000496166, ENST00000466738, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 9 X 6=5943 X 2 X 3=18
# samples 133
** MAII scorelog2(13/594*10)=-2.19195130777231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: HBP1 [Title/Abstract] AND PIK3CG [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: HBP1 [Title/Abstract] AND PIK3CG [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HBP1(106826917)-PIK3CG(106545554), # samples:1
Anticipated loss of major functional domain due to fusion event.HBP1-PIK3CG 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.
HBP1-PIK3CG 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.
HBP1-PIK3CG 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.
HBP1-PIK3CG 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.
HBP1-PIK3CG seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
HBP1-PIK3CG seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
HBP1-PIK3CG seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
HBP1-PIK3CG seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
TgenePIK3CG

GO:0007186

G protein-coupled receptor signaling pathway

12507995

TgenePIK3CG

GO:0014065

phosphatidylinositol 3-kinase signaling

12507995

TgenePIK3CG

GO:0016310

phosphorylation

25327288

TgenePIK3CG

GO:0043406

positive regulation of MAP kinase activity

12507995

TgenePIK3CG

GO:0051897

positive regulation of protein kinase B signaling

12507995



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/chr7:106826917/chr7:106545554)
- 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 HBP1 (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 PIK3CG (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)
ENST00000468410HBP1chr7106826917+ENST00000440650PIK3CGchr7106545554+144773413747244
ENST00000468410HBP1chr7106826917+ENST00000496166PIK3CGchr7106545554+275873413747244
ENST00000222574HBP1chr7106826917+ENST00000440650PIK3CGchr7106545554+1551838186851221
ENST00000222574HBP1chr7106826917+ENST00000496166PIK3CGchr7106545554+2862838186851221
ENST00000485846HBP1chr7106826917+ENST00000440650PIK3CGchr7106545554+203613235211336271
ENST00000485846HBP1chr7106826917+ENST00000496166PIK3CGchr7106545554+334713235211336271

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
ENST00000468410ENST00000440650HBP1chr7106826917+PIK3CGchr7106545554+0.0047277880.9952722
ENST00000468410ENST00000496166HBP1chr7106826917+PIK3CGchr7106545554+0.0023226410.9976774
ENST00000222574ENST00000440650HBP1chr7106826917+PIK3CGchr7106545554+0.0075784030.99242157
ENST00000222574ENST00000496166HBP1chr7106826917+PIK3CGchr7106545554+0.0044263760.99557364
ENST00000485846ENST00000440650HBP1chr7106826917+PIK3CGchr7106545554+0.011381850.98861814
ENST00000485846ENST00000496166HBP1chr7106826917+PIK3CGchr7106545554+0.0054301050.99456984

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 HBP1-PIK3CG

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

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Potential FusionNeoAntigen Information of HBP1-PIK3CG 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 HBP1-PIK3CG 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 HBP1-PIK3CG

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 HBP1-PIK3CG

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 HBP1-PIK3CG

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

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Information of the samples that have these potential fusion neoantigens of HBP1-PIK3CG

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 HBP1-PIK3CG

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 HBP1-PIK3CG

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 HBP1-PIK3CG

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