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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:PPP2R4-GLUL

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PPP2R4-GLUL
FusionPDB ID: 68052
FusionGDB2.0 ID: 68052
HgeneTgene
Gene symbol

PPP2R4

GLUL

Gene ID

5524

2752

Gene nameprotein phosphatase 2 phosphatase activatorglutamate-ammonia ligase
SynonymsPP2A|PPP2R4|PR53GLNS|GS|PIG43|PIG59
Cytomap

9q34.11

1q25.3

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein phosphatase 2A activatorPP2A phosphatase activatorPP2A subunit B' isoform PR53phosphotyrosyl phosphatase activatorprotein phosphatase 2 regulatory subunit 4protein phosphatase 2A activator, regulatory subunit 4protein phosphglutamine synthetasecell proliferation-inducing protein 59glutamate decarboxylaseglutamine synthasepalmitoyltransferase GLULproliferation-inducing protein 43
Modification date2020032920200313
UniProtAcc.

P15104

Main function of 5'-partner protein: FUNCTION: Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine (PubMed:30158707, PubMed:16267323). Its role depends on tissue localization: in the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, it is one of the enzymes responsible for the removal of ammonia (By similarity). Essential for proliferation of fetal skin fibroblasts (PubMed:18662667). Independently of its glutamine synthetase activity, required for endothelial cell migration during vascular development: acts by regulating membrane localization and activation of the GTPase RHOJ, possibly by promoting RHOJ palmitoylation (PubMed:30158707). May act as a palmitoyltransferase for RHOJ: able to autopalmitoylate and then transfer the palmitoyl group to RHOJ (PubMed:30158707). Plays a role in ribosomal 40S subunit biogenesis (PubMed:26711351). {ECO:0000250|UniProtKB:P15105, ECO:0000269|PubMed:16267323, ECO:0000269|PubMed:18662667, ECO:0000269|PubMed:26711351, ECO:0000269|PubMed:30158707}.
Ensembl transtripts involved in fusion geneENST idsENST00000337738, ENST00000348141, 
ENST00000357197, ENST00000358994, 
ENST00000393370, ENST00000452489, 
ENST00000347048, ENST00000355007, 
ENST00000414510, ENST00000419582, 
ENST00000423100, ENST00000432124, 
ENST00000432651, ENST00000434095, 
ENST00000435132, ENST00000435305, 
ENST00000436883, ENST00000524946, 
ENST00000339526, ENST00000491322, 
ENST00000311223, ENST00000331872, 
ENST00000417584, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 9 X 8=72018 X 16 X 6=1728
# samples 1220
** MAII scorelog2(12/720*10)=-2.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(20/1728*10)=-3.11103131238874
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PPP2R4 [Title/Abstract] AND GLUL [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PPP2R4 [Title/Abstract] AND GLUL [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PPP2R4(131891278)-GLUL(182354526), # samples:1
Anticipated loss of major functional domain due to fusion event.PPP2R4-GLUL 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.
PPP2R4-GLUL 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
HgenePPP2R4

GO:0032515

negative regulation of phosphoprotein phosphatase activity

16916641

HgenePPP2R4

GO:0032516

positive regulation of phosphoprotein phosphatase activity

16916641

HgenePPP2R4

GO:0035307

positive regulation of protein dephosphorylation

16916641

HgenePPP2R4

GO:0035308

negative regulation of protein dephosphorylation

16916641

HgenePPP2R4

GO:0043065

positive regulation of apoptotic process

17333320

HgenePPP2R4

GO:0043666

regulation of phosphoprotein phosphatase activity

16916641

TgeneGLUL

GO:0008283

cell proliferation

18662667

TgeneGLUL

GO:0010594

regulation of endothelial cell migration

30158707

TgeneGLUL

GO:0018345

protein palmitoylation

30158707

TgeneGLUL

GO:1903670

regulation of sprouting angiogenesis

30158707



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/chr9:131891278/chr1:182354526)
- 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 PPP2R4 (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 GLUL (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)
ENST00000358994PPP2R4chr9131891278+ENST00000331872GLULchr1182354526-35945398559183
ENST00000358994PPP2R4chr9131891278+ENST00000417584GLULchr1182354526-35935398559183
ENST00000358994PPP2R4chr9131891278+ENST00000311223GLULchr1182354526-35935398559183
ENST00000393370PPP2R4chr9131891278+ENST00000331872GLULchr1182354526-3665610169630153
ENST00000393370PPP2R4chr9131891278+ENST00000417584GLULchr1182354526-3664610169630153
ENST00000393370PPP2R4chr9131891278+ENST00000311223GLULchr1182354526-3664610169630153
ENST00000337738PPP2R4chr9131891278+ENST00000331872GLULchr1182354526-3754699153719188
ENST00000337738PPP2R4chr9131891278+ENST00000417584GLULchr1182354526-3753699153719188
ENST00000337738PPP2R4chr9131891278+ENST00000311223GLULchr1182354526-3753699153719188
ENST00000348141PPP2R4chr9131891278+ENST00000331872GLULchr1182354526-3665610151630159
ENST00000348141PPP2R4chr9131891278+ENST00000417584GLULchr1182354526-3664610151630159
ENST00000348141PPP2R4chr9131891278+ENST00000311223GLULchr1182354526-3664610151630159
ENST00000452489PPP2R4chr9131891278+ENST00000331872GLULchr1182354526-370064599665188
ENST00000452489PPP2R4chr9131891278+ENST00000417584GLULchr1182354526-369964599665188
ENST00000452489PPP2R4chr9131891278+ENST00000311223GLULchr1182354526-369964599665188
ENST00000357197PPP2R4chr9131891278+ENST00000331872GLULchr1182354526-3487432178750190
ENST00000357197PPP2R4chr9131891278+ENST00000417584GLULchr1182354526-3486432178750190
ENST00000357197PPP2R4chr9131891278+ENST00000311223GLULchr1182354526-3486432178750190

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
ENST00000358994ENST00000331872PPP2R4chr9131891278+GLULchr1182354526-0.0021089570.997891
ENST00000358994ENST00000417584PPP2R4chr9131891278+GLULchr1182354526-0.002736070.9972639
ENST00000358994ENST00000311223PPP2R4chr9131891278+GLULchr1182354526-0.002736070.9972639
ENST00000393370ENST00000331872PPP2R4chr9131891278+GLULchr1182354526-0.0083374220.9916626
ENST00000393370ENST00000417584PPP2R4chr9131891278+GLULchr1182354526-0.0124305790.9875694
ENST00000393370ENST00000311223PPP2R4chr9131891278+GLULchr1182354526-0.0124305790.9875694
ENST00000337738ENST00000331872PPP2R4chr9131891278+GLULchr1182354526-0.0147279490.98527205
ENST00000337738ENST00000417584PPP2R4chr9131891278+GLULchr1182354526-0.0187670180.981233
ENST00000337738ENST00000311223PPP2R4chr9131891278+GLULchr1182354526-0.0187670180.981233
ENST00000348141ENST00000331872PPP2R4chr9131891278+GLULchr1182354526-0.0081616190.9918384
ENST00000348141ENST00000417584PPP2R4chr9131891278+GLULchr1182354526-0.0121412210.9878588
ENST00000348141ENST00000311223PPP2R4chr9131891278+GLULchr1182354526-0.0121412210.9878588
ENST00000452489ENST00000331872PPP2R4chr9131891278+GLULchr1182354526-0.0150893280.98491067
ENST00000452489ENST00000417584PPP2R4chr9131891278+GLULchr1182354526-0.019201860.9807982
ENST00000452489ENST00000311223PPP2R4chr9131891278+GLULchr1182354526-0.019201860.9807982
ENST00000357197ENST00000331872PPP2R4chr9131891278+GLULchr1182354526-0.008559670.9914403
ENST00000357197ENST00000417584PPP2R4chr9131891278+GLULchr1182354526-0.0126077820.98739225
ENST00000357197ENST00000311223PPP2R4chr9131891278+GLULchr1182354526-0.0126077820.98739225

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 PPP2R4-GLUL

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 PPP2R4-GLUL 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 PPP2R4-GLUL 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 PPP2R4-GLUL

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 PPP2R4-GLUL

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 PPP2R4-GLUL

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 PPP2R4-GLUL

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 PPP2R4-GLUL

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 PPP2R4-GLUL

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 PPP2R4-GLUL

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