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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:BRD9-TPPP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: BRD9-TPPP
FusionPDB ID: 10230
FusionGDB2.0 ID: 10230
HgeneTgene
Gene symbol

BRD9

TPPP

Gene ID

65980

11076

Gene namebromodomain containing 9tubulin polymerization promoting protein
SynonymsLAVS3040|PRO9856TPPP/p25|TPPP1|p24|p25|p25alpha
Cytomap

5p15.33

5p15.33

Type of geneprotein-codingprotein-coding
Descriptionbromodomain-containing protein 9rhabdomyosarcoma antigen MU-RMS-40.8sarcoma antigen NY-SAR-29tubulin polymerization-promoting protein25 kDa brain-specific proteinbrain specific protein p25 alphaglycogen synthase kinase 3 (GSK3) inhibitor p24p25-alpha
Modification date2020031520200322
UniProtAcc

Q9H8M2

Main function of 5'-partner protein: FUNCTION: Plays a role in chromatin remodeling and regulation of transcription (PubMed:22464331, PubMed:26365797). Acts as a chromatin reader that recognizes and binds acylated histones: binds histones that are acetylated and/or butyrylated (PubMed:26365797). Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:29374058). Orchestrates also the RAD51-RAD54 complex formation and thereby plays a role in homologous recombination (HR) (PubMed:32457312). {ECO:0000269|PubMed:22464331, ECO:0000269|PubMed:26365797, ECO:0000269|PubMed:29374058, ECO:0000269|PubMed:32457312}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000494422, ENST00000435709, 
ENST00000323510, ENST00000388890, 
ENST00000467963, ENST00000483173, 
ENST00000360578, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 15 X 7=10504 X 2 X 3=24
# samples 125
** MAII scorelog2(12/1050*10)=-3.12928301694497
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/24*10)=1.05889368905357
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: BRD9 [Title/Abstract] AND TPPP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: BRD9 [Title/Abstract] AND TPPP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TPPP(693393)-BRD9(880004), # samples:5
BRD9(886707)-TPPP(666238), # samples:2
Anticipated loss of major functional domain due to fusion event.BRD9-TPPP 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.
BRD9-TPPP 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.
BRD9-TPPP 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.
BRD9-TPPP 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.
BRD9-TPPP seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
BRD9-TPPP seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
BRD9-TPPP seems lost the major protein functional domain in Hgene 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
TgeneTPPP

GO:0001578

microtubule bundle formation

17105200|26289831

TgeneTPPP

GO:0030953

astral microtubule organization

22328514

TgeneTPPP

GO:0032273

positive regulation of protein polymerization

15590652

TgeneTPPP

GO:0046785

microtubule polymerization

18028908

TgeneTPPP

GO:0051418

microtubule nucleation by microtubule organizing center

31522887

TgeneTPPP

GO:0070507

regulation of microtubule cytoskeleton organization

23093407

TgeneTPPP

GO:1904428

negative regulation of tubulin deacetylation

20308065|23093407



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/chr5:693393/chr5:880004)
- 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 BRD9 (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 TPPP (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)
ENST00000388890BRD9chr5886707-ENST00000360578TPPPchr5666238-51684850833277
ENST00000323510BRD9chr5886707-ENST00000360578TPPPchr5666238-52285450893297
ENST00000483173BRD9chr5886707-ENST00000360578TPPPchr5666238-54978141041162352
ENST00000467963BRD9chr5886707-ENST00000360578TPPPchr5666238-568310001671348393
ENST00000388890BRD9chr5886706-ENST00000360578TPPPchr5666238-51684850833277
ENST00000323510BRD9chr5886706-ENST00000360578TPPPchr5666238-52285450893297
ENST00000483173BRD9chr5886706-ENST00000360578TPPPchr5666238-54978141041162352
ENST00000467963BRD9chr5886706-ENST00000360578TPPPchr5666238-568310001671348393

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
ENST00000388890ENST00000360578BRD9chr5886707-TPPPchr5666238-0.003702770.9962972
ENST00000323510ENST00000360578BRD9chr5886707-TPPPchr5666238-0.002782830.9972172
ENST00000483173ENST00000360578BRD9chr5886707-TPPPchr5666238-0.0248953850.9751047
ENST00000467963ENST00000360578BRD9chr5886707-TPPPchr5666238-0.0028335310.99716645
ENST00000388890ENST00000360578BRD9chr5886706-TPPPchr5666238-0.003702770.9962972
ENST00000323510ENST00000360578BRD9chr5886706-TPPPchr5666238-0.002782830.9972172
ENST00000483173ENST00000360578BRD9chr5886706-TPPPchr5666238-0.0248953850.9751047
ENST00000467963ENST00000360578BRD9chr5886706-TPPPchr5666238-0.0028335310.99716645

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 BRD9-TPPP

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 BRD9-TPPP 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 BRD9-TPPP 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 BRD9-TPPP

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 BRD9-TPPP

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 BRD9-TPPP

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 BRD9-TPPP

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 BRD9-TPPP

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 BRD9-TPPP

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 BRD9-TPPP

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
HgeneBRD9C0036920Sezary Syndrome1CTD_human