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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:PRR5-ARHGAP8

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PRR5-ARHGAP8
FusionPDB ID: 69171
FusionGDB2.0 ID: 69171
HgeneTgene
Gene symbol

PRR5

ARHGAP8

Gene ID

55615

23779

Gene nameproline rich 5Rho GTPase activating protein 8
SynonymsFLJ20185k|PP610|PROTOR-1|PROTOR1BPGAP1|PP610
Cytomap

22q13.31

22q13.31

Type of geneprotein-codingprotein-coding
Descriptionproline-rich protein 5Rho GTPase activating protein 8proline rich 5 (renal)protein observed with Rictor-1rho GTPase-activating protein 8BCH domain-containing Cdc42GAP-like proteinBNIP-2 and Cdc42GAP homology domain-containing, proline-rich and Cdc42GAP-like protein subtype-1rho-type GTPase-activating protein 8
Modification date2020031320200313
UniProtAcc.

P85298

Main function of 5'-partner protein: FUNCTION: GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000477331, ENST00000006251, 
ENST00000336985, ENST00000403581, 
ENST00000336963, ENST00000356099, 
ENST00000389773, ENST00000389774, 
ENST00000517296, ENST00000469872, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 6 X 3=726 X 9 X 5=270
# samples 57
** MAII scorelog2(5/72*10)=-0.526068811667588
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/270*10)=-1.94753258010586
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PRR5 [Title/Abstract] AND ARHGAP8 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PRR5 [Title/Abstract] AND ARHGAP8 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ARHGAP8(45182486)-PRR5(45098372), # samples:1
PRR5(45110550)-ARHGAP8(45241148), # samples:1
PRR5(45122513)-ARHGAP8(45241148), # samples:1
PRR5(NA)-ARHGAP8(NA), # samples:1
PRR5(45122514)-ARHGAP8(45182337), # samples:1
Anticipated loss of major functional domain due to fusion event.PRR5-ARHGAP8 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.
PRR5-ARHGAP8 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.
PRR5-ARHGAP8 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.
PRR5-ARHGAP8 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.
PRR5-ARHGAP8 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
PRR5-ARHGAP8 seems lost the major protein functional domain in Hgene 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
TgeneARHGAP8

GO:0070374

positive regulation of ERK1 and ERK2 cascade

20179103



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/chr22:45182486/chr22:45098372)
- 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 PRR5 (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 ARHGAP8 (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)
ENST00000006251PRR5chr2245110550+ENST00000517296ARHGAP8chr2245241148+1199382411087348
ENST00000006251PRR5chr2245110550+ENST00000389773ARHGAP8chr2245241148+1277382411087348
ENST00000006251PRR5chr2245110550+ENST00000389774ARHGAP8chr2245241148+1277382411087348
ENST00000006251PRR5chr2245110550+ENST00000336963ARHGAP8chr2245241148+117438241703220
ENST00000006251PRR5chr2245110550+ENST00000356099ARHGAP8chr2245241148+1277382411087348
ENST00000403581PRR5chr2245110550+ENST00000517296ARHGAP8chr2245241148+17108935881598336
ENST00000403581PRR5chr2245110550+ENST00000389773ARHGAP8chr2245241148+17888935881598336
ENST00000403581PRR5chr2245110550+ENST00000389774ARHGAP8chr2245241148+17888935881598336
ENST00000403581PRR5chr2245110550+ENST00000336963ARHGAP8chr2245241148+16858931295627222
ENST00000403581PRR5chr2245110550+ENST00000356099ARHGAP8chr2245241148+17888935881598336
ENST00000336985PRR5chr2245110550+ENST00000517296ARHGAP8chr2245241148+13094922771197306
ENST00000336985PRR5chr2245110550+ENST00000389773ARHGAP8chr2245241148+13874922771197306
ENST00000336985PRR5chr2245110550+ENST00000389774ARHGAP8chr2245241148+13874922771197306
ENST00000336985PRR5chr2245110550+ENST00000336963ARHGAP8chr2245241148+1284492277813178
ENST00000336985PRR5chr2245110550+ENST00000356099ARHGAP8chr2245241148+13874922771197306

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
ENST00000006251ENST00000517296PRR5chr2245110550+ARHGAP8chr2245241148+0.093763340.9062367
ENST00000006251ENST00000389773PRR5chr2245110550+ARHGAP8chr2245241148+0.090124620.9098754
ENST00000006251ENST00000389774PRR5chr2245110550+ARHGAP8chr2245241148+0.090124620.9098754
ENST00000006251ENST00000336963PRR5chr2245110550+ARHGAP8chr2245241148+0.0252681280.9747319
ENST00000006251ENST00000356099PRR5chr2245110550+ARHGAP8chr2245241148+0.090124620.9098754
ENST00000403581ENST00000517296PRR5chr2245110550+ARHGAP8chr2245241148+0.0681790040.93182105
ENST00000403581ENST00000389773PRR5chr2245110550+ARHGAP8chr2245241148+0.062086170.9379139
ENST00000403581ENST00000389774PRR5chr2245110550+ARHGAP8chr2245241148+0.062086170.9379139
ENST00000403581ENST00000336963PRR5chr2245110550+ARHGAP8chr2245241148+0.0271410030.97285897
ENST00000403581ENST00000356099PRR5chr2245110550+ARHGAP8chr2245241148+0.062086170.9379139
ENST00000336985ENST00000517296PRR5chr2245110550+ARHGAP8chr2245241148+0.036384810.96361524
ENST00000336985ENST00000389773PRR5chr2245110550+ARHGAP8chr2245241148+0.033538610.96646136
ENST00000336985ENST00000389774PRR5chr2245110550+ARHGAP8chr2245241148+0.033538610.96646136
ENST00000336985ENST00000336963PRR5chr2245110550+ARHGAP8chr2245241148+0.0156447440.98435533
ENST00000336985ENST00000356099PRR5chr2245110550+ARHGAP8chr2245241148+0.033538610.96646136

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 PRR5-ARHGAP8

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 PRR5-ARHGAP8 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 PRR5-ARHGAP8 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 PRR5-ARHGAP8

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 PRR5-ARHGAP8

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 PRR5-ARHGAP8

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 PRR5-ARHGAP8

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 PRR5-ARHGAP8

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 PRR5-ARHGAP8

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 PRR5-ARHGAP8

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