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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:PRUNE2-GNA14

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PRUNE2-GNA14
FusionPDB ID: 69354
FusionGDB2.0 ID: 69354
HgeneTgene
Gene symbol

PRUNE2

GNA14

Gene ID

158471

9630

Gene nameprune homolog 2 with BCH domainG protein subunit alpha 14
SynonymsBMCC1|BNIPXL|C9orf65|KIAA0367-
Cytomap

9q21.2

9q21.2

Type of geneprotein-codingprotein-coding
Descriptionprotein prune homolog 2BCH motif-containing molecule at the carboxyl terminal region 1BNIP2 motif containing molecule at the carboxyl terminal region 1BNIP2 motif-containing molecule at the C-terminal region 1olfaxintruncated PRUNE2guanine nucleotide-binding protein subunit alpha-14g alpha-14guanine nucleotide binding protein (G protein), alpha 14guanine nucleotide-binding protein 14
Modification date2020031320200313
UniProtAcc.

O95837

Main function of 5'-partner protein: FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.
Ensembl transtripts involved in fusion geneENST idsENST00000376713, ENST00000376718, 
ENST00000428286, ENST00000223609, 
ENST00000443509, ENST00000466266, 
ENST00000464095, ENST00000341700, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 11 X 6=5947 X 4 X 5=140
# samples 107
** MAII scorelog2(10/594*10)=-2.57046293102604
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/140*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PRUNE2 [Title/Abstract] AND GNA14 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PRUNE2 [Title/Abstract] AND GNA14 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PRUNE2(79438548)-GNA14(80049438), # samples:2
Anticipated loss of major functional domain due to fusion event.PRUNE2-GNA14 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.
PRUNE2-GNA14 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.
PRUNE2-GNA14 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.
PRUNE2-GNA14 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


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/chr9:79438548/chr9:80049438)
- 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 PRUNE2 (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 GNA14 (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)
ENST00000376718PRUNE2chr979438548-ENST00000341700GNA14chr980049438-25398801241638504
ENST00000376713PRUNE2chr979438548-ENST00000341700GNA14chr980049438-25378781221636504

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
ENST00000376718ENST00000341700PRUNE2chr979438548-GNA14chr980049438-0.0014690970.99853086
ENST00000376713ENST00000341700PRUNE2chr979438548-GNA14chr980049438-0.0014692720.99853075

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 PRUNE2-GNA14

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PRUNE2chr979438548GNA14chr980049438878252IKVAISTVSMNLEENAQIIREVEVDK
PRUNE2chr979438548GNA14chr980049438880252IKVAISTVSMNLEENAQIIREVEVDK

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Potential FusionNeoAntigen Information of PRUNE2-GNA14 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.
PRUNE2-GNA14_79438548_80049438.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)
PRUNE2-GNA14chr979438548chr980049438878HLA-B45:01EENAQIIREV0.99830.88541222

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Potential FusionNeoAntigen Information of PRUNE2-GNA14 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.
PRUNE2-GNA14_79438548_80049438.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)
PRUNE2-GNA14chr979438548chr980049438878DRB1-0303SMNLEENAQIIREVE823

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Fusion breakpoint peptide structures of PRUNE2-GNA14

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
9737TVSMNLEENAQIIRPRUNE2GNA14chr979438548chr980049438878

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PRUNE2-GNA14

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-B14:023BVN9737TVSMNLEENAQIIR-5.45575-5.46295
HLA-B52:013W399737TVSMNLEENAQIIR-5.51835-5.52555
HLA-A24:025HGA9737TVSMNLEENAQIIR-7.37668-7.38388
HLA-B44:053DX89737TVSMNLEENAQIIR-4.22448-4.23168

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Vaccine Design for the FusionNeoAntigens of PRUNE2-GNA14

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
PRUNE2-GNA14chr979438548chr9800494381222EENAQIIREVGAGGAAAATGCCCAGATAATCAGAGAAGTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PRUNE2-GNA14chr979438548chr980049438823SMNLEENAQIIREVEAGCATGAACCTTGAGGAAAATGCCCAGATAATCAGAGAAGTGGAA

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Information of the samples that have these potential fusion neoantigens of PRUNE2-GNA14

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
PRADPRUNE2-GNA14chr979438548ENST00000376713chr980049438ENST00000341700TCGA-KK-A5A1-01A

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Potential target of CAR-T therapy development for PRUNE2-GNA14

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 PRUNE2-GNA14

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 PRUNE2-GNA14

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