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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:HSPG2-IRF8

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HSPG2-IRF8
FusionPDB ID: 38022
FusionGDB2.0 ID: 38022
HgeneTgene
Gene symbol

HSPG2

IRF8

Gene ID

3339

3394

Gene nameheparan sulfate proteoglycan 2interferon regulatory factor 8
SynonymsHSPG|PLC|PRCAN|SJA|SJS|SJS1H-ICSBP|ICSBP|ICSBP1|IMD32A|IMD32B|IRF-8
Cytomap

1p36.12

16q24.1

Type of geneprotein-codingprotein-coding
Descriptionbasement membrane-specific heparan sulfate proteoglycan core proteinendorepellin (domain V region)perlecan proteoglycaninterferon regulatory factor 8interferon consensus sequence binding protein 1
Modification date2020031320200313
UniProtAcc

P98160

Main function of 5'-partner protein: FUNCTION: Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development.; FUNCTION: Endorepellin in an anti-angiogenic and anti-tumor peptide that inhibits endothelial cell migration, collagen-induced endothelial tube morphogenesis and blood vessel growth in the chorioallantoic membrane. Blocks endothelial cell adhesion to fibronectin and type I collagen. Anti-tumor agent in neovascularization. Interaction with its ligand, integrin alpha2/beta1, is required for the anti-angiogenic properties. Evokes a reduction in phosphorylation of receptor tyrosine kinases via alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase, PTPN6.; FUNCTION: The LG3 peptide has anti-angiogenic properties that require binding of calcium ions for full activity.

Q02556

Main function of 5'-partner protein: FUNCTION: Transcription factor that specifically binds to the upstream regulatory region of type I interferon (IFN) and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)) (PubMed:25122610). Can both act as a transcriptional activator or repressor (By similarity). Plays a negative regulatory role in cells of the immune system (By similarity). Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF8 and activation of genes (By similarity). Required for the development of plasmacytoid dendritic cells (pDCs), which produce most of the type I IFN in response to viral infection (By similarity). Positively regulates macroautophagy in dendritic cells (PubMed:29434592). {ECO:0000250|UniProtKB:P23611, ECO:0000269|PubMed:25122610, ECO:0000269|PubMed:29434592}.
Ensembl transtripts involved in fusion geneENST idsENST00000374695, ENST00000430507, 
ENST00000486901, 
ENST00000562492, 
ENST00000563180, ENST00000268638, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score22 X 23 X 12=60724 X 3 X 4=48
# samples 254
** MAII scorelog2(25/6072*10)=-4.60217179075338
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: HSPG2 [Title/Abstract] AND IRF8 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: HSPG2 [Title/Abstract] AND IRF8 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HSPG2(22263648)-IRF8(85942596), # samples:1
Anticipated loss of major functional domain due to fusion event.HSPG2-IRF8 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.
HSPG2-IRF8 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.
HSPG2-IRF8 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
HSPG2-IRF8 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted ORF.
HSPG2-IRF8 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
TgeneIRF8

GO:0000122

negative regulation of transcription by RNA polymerase II

1460054|25122610

TgeneIRF8

GO:0045944

positive regulation of transcription by RNA polymerase II

25122610

TgeneIRF8

GO:0071346

cellular response to interferon-gamma

25122610



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/chr1:22263648/chr16:85942596)
- 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 HSPG2 (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 IRF8 (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)
ENST00000374695HSPG2chr122263648-ENST00000268638IRF8chr1685942596+2577143171249410

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
ENST00000374695ENST00000268638HSPG2chr122263648-IRF8chr1685942596+0.0006142780.9993857

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 HSPG2-IRF8

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
HSPG2chr122263648IRF8chr168594259614340GALLLALLLHGRLLAAWAVFKGKFKE

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Potential FusionNeoAntigen Information of HSPG2-IRF8 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.
HSPG2-IRF8_22263648_85942596.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)
HSPG2-IRF8chr122263648chr1685942596143HLA-B39:06LHGRLLAA0.99940.874816
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:07GRLLAAWAV0.99960.94541019
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:04GRLLAAWAV0.99960.85991019
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:02GRLLAAWAV0.99960.6971019
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:05GRLLAAWAV0.99950.87061019
HSPG2-IRF8chr122263648chr1685942596143HLA-A03:12LLAAWAVFK0.99740.73951221
HSPG2-IRF8chr122263648chr1685942596143HLA-A03:25LLAAWAVFK0.99730.731221
HSPG2-IRF8chr122263648chr1685942596143HLA-B08:09LLHGRLLAA0.99720.7697716
HSPG2-IRF8chr122263648chr1685942596143HLA-A11:04LLAAWAVFK0.99560.56721221
HSPG2-IRF8chr122263648chr1685942596143HLA-B15:01RLLAAWAVF0.98930.84281120
HSPG2-IRF8chr122263648chr1685942596143HLA-A34:02LLAAWAVFK0.98920.60771221
HSPG2-IRF8chr122263648chr1685942596143HLA-A02:13LLHGRLLAA0.98580.6773716
HSPG2-IRF8chr122263648chr1685942596143HLA-A32:13RLLAAWAVF0.97760.97931120
HSPG2-IRF8chr122263648chr1685942596143HLA-A02:27LLHGRLLAA0.97220.5147716
HSPG2-IRF8chr122263648chr1685942596143HLA-B15:25RLLAAWAVF0.93350.97651120
HSPG2-IRF8chr122263648chr1685942596143HLA-A02:38LLHGRLLAA0.91660.6497716
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:05GRLLAAWAVF10.84621020
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:02GRLLAAWAVF10.59841020
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:04GRLLAAWAVF0.99990.74321020
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:07GRLLAAWAVF0.99980.76551020
HSPG2-IRF8chr122263648chr1685942596143HLA-A03:25RLLAAWAVFK0.99910.62521121
HSPG2-IRF8chr122263648chr1685942596143HLA-A03:12RLLAAWAVFK0.99910.6471121
HSPG2-IRF8chr122263648chr1685942596143HLA-A74:09RLLAAWAVFK0.97890.73721121
HSPG2-IRF8chr122263648chr1685942596143HLA-A74:03RLLAAWAVFK0.97890.73721121
HSPG2-IRF8chr122263648chr1685942596143HLA-A74:11RLLAAWAVFK0.97890.73721121
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:05GRLLAAWAVFK0.99990.80121021
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:14GRLLAAWAV0.99960.8781019
HSPG2-IRF8chr122263648chr1685942596143HLA-A03:01LLAAWAVFK0.99730.731221
HSPG2-IRF8chr122263648chr1685942596143HLA-B73:01GRLLAAWAV0.99620.97021019
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:03GRLLAAWAV0.97970.88151019
HSPG2-IRF8chr122263648chr1685942596143HLA-B15:07RLLAAWAVF0.97390.76651120
HSPG2-IRF8chr122263648chr1685942596143HLA-B15:05RLLAAWAVF0.77990.93681120
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:03GRLLAAWAVF0.99930.85621020
HSPG2-IRF8chr122263648chr1685942596143HLA-A03:01RLLAAWAVFK0.99910.62521121
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:14GRLLAAWAVFK0.99990.76831021
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:03GRLLAAWAVFK0.99850.81691021
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:09GRLLAAWAV0.99970.86281019
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:10GRLLAAWAV0.99950.90831019
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:08GRLLAAWAV0.99950.83071019
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:06GRLLAAWAV0.99940.90951019
HSPG2-IRF8chr122263648chr1685942596143HLA-A02:03LLHGRLLAA0.99780.6055716
HSPG2-IRF8chr122263648chr1685942596143HLA-A03:02LLAAWAVFK0.99530.51881221
HSPG2-IRF8chr122263648chr1685942596143HLA-B15:27RLLAAWAVF0.99040.86141120
HSPG2-IRF8chr122263648chr1685942596143HLA-A32:01RLLAAWAVF0.99040.97251120
HSPG2-IRF8chr122263648chr1685942596143HLA-B15:34RLLAAWAVF0.98930.84281120
HSPG2-IRF8chr122263648chr1685942596143HLA-B15:125RLLAAWAVF0.98930.84281120
HSPG2-IRF8chr122263648chr1685942596143HLA-B15:33RLLAAWAVF0.98930.84281120
HSPG2-IRF8chr122263648chr1685942596143HLA-B15:35RLLAAWAVF0.97690.82441120
HSPG2-IRF8chr122263648chr1685942596143HLA-B15:50RLLAAWAVF0.97590.85361120
HSPG2-IRF8chr122263648chr1685942596143HLA-B15:39RLLAAWAVF0.93180.88691120
HSPG2-IRF8chr122263648chr1685942596143HLA-B15:20RLLAAWAVF0.7830.96111120
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:08GRLLAAWAVF10.78391020
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:06GRLLAAWAVF0.99990.79971020
HSPG2-IRF8chr122263648chr1685942596143HLA-B27:09GRLLAAWAVF0.99970.83391020
HSPG2-IRF8chr122263648chr1685942596143HLA-A74:01RLLAAWAVFK0.97890.73721121

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Potential FusionNeoAntigen Information of HSPG2-IRF8 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.
HSPG2-IRF8_22263648_85942596.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)
HSPG2-IRF8chr122263648chr1685942596143DRB1-0437GRLLAAWAVFKGKFK1025
HSPG2-IRF8chr122263648chr1685942596143DRB1-0473GRLLAAWAVFKGKFK1025
HSPG2-IRF8chr122263648chr1685942596143DRB1-1457GRLLAAWAVFKGKFK1025
HSPG2-IRF8chr122263648chr1685942596143DRB5-0103RLLAAWAVFKGKFKE1126

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Fusion breakpoint peptide structures of HSPG2-IRF8

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
5240LLLHGRLLAAWAVFHSPG2IRF8chr122263648chr1685942596143

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HSPG2-IRF8

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-B14:023BVN5240LLLHGRLLAAWAVF-5.68508-5.79848
HLA-B14:023BVN5240LLLHGRLLAAWAVF-4.48181-5.51711
HLA-B52:013W395240LLLHGRLLAAWAVF-6.58333-6.69673
HLA-B52:013W395240LLLHGRLLAAWAVF-5.63259-6.66789
HLA-A11:014UQ25240LLLHGRLLAAWAVF-10.3303-10.4437
HLA-A11:014UQ25240LLLHGRLLAAWAVF-6.29447-7.32977
HLA-A24:025HGA5240LLLHGRLLAAWAVF-7.77035-7.88375
HLA-A24:025HGA5240LLLHGRLLAAWAVF-5.35627-6.39157
HLA-B27:056PYJ5240LLLHGRLLAAWAVF-3.97515-5.01045
HLA-B44:053DX85240LLLHGRLLAAWAVF-5.81963-5.93303
HLA-B44:053DX85240LLLHGRLLAAWAVF-4.86027-5.89557
HLA-A02:016TDR5240LLLHGRLLAAWAVF-5.17978-6.21508
HLA-A02:016TDR5240LLLHGRLLAAWAVF-5.36237-5.47577

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Vaccine Design for the FusionNeoAntigens of HSPG2-IRF8

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
HSPG2-IRF8chr122263648chr16859425961019GRLLAAWAVCTGCTGGCGGCCTGGGCAGTTTTTAAA
HSPG2-IRF8chr122263648chr16859425961020GRLLAAWAVFCTGCTGGCGGCCTGGGCAGTTTTTAAAGGG
HSPG2-IRF8chr122263648chr16859425961021GRLLAAWAVFKCTGCTGGCGGCCTGGGCAGTTTTTAAAGGGAAG
HSPG2-IRF8chr122263648chr16859425961120RLLAAWAVFCTGGCGGCCTGGGCAGTTTTTAAAGGG
HSPG2-IRF8chr122263648chr16859425961121RLLAAWAVFKCTGGCGGCCTGGGCAGTTTTTAAAGGGAAG
HSPG2-IRF8chr122263648chr16859425961221LLAAWAVFKGCGGCCTGGGCAGTTTTTAAAGGGAAG
HSPG2-IRF8chr122263648chr1685942596716LLHGRLLAACACGGGCGGCTGCTGGCGGCCTGGGCA
HSPG2-IRF8chr122263648chr1685942596816LHGRLLAAGGGCGGCTGCTGGCGGCCTGGGCA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
HSPG2-IRF8chr122263648chr16859425961025GRLLAAWAVFKGKFKCTGCTGGCGGCCTGGGCAGTTTTTAAAGGGAAGTTTAAAGAAGGG
HSPG2-IRF8chr122263648chr16859425961126RLLAAWAVFKGKFKECTGGCGGCCTGGGCAGTTTTTAAAGGGAAGTTTAAAGAAGGGGAC

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Information of the samples that have these potential fusion neoantigens of HSPG2-IRF8

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
STADHSPG2-IRF8chr122263648ENST00000374695chr1685942596ENST00000268638TCGA-CD-5799-01A

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Potential target of CAR-T therapy development for HSPG2-IRF8

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 HSPG2-IRF8

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 HSPG2-IRF8

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