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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:GLRX3-PPM1G

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GLRX3-PPM1G
FusionPDB ID: 33348
FusionGDB2.0 ID: 33348
HgeneTgene
Gene symbol

GLRX3

PPM1G

Gene ID

10539

5496

Gene nameglutaredoxin 3protein phosphatase, Mg2+/Mn2+ dependent 1G
SynonymsGLRX4|GRX3|GRX4|PICOT|TXNL2|TXNL3PP2CG|PP2CGAMMA|PPP2CG
Cytomap

10q26.3

2p23.3

Type of geneprotein-codingprotein-coding
Descriptionglutaredoxin-3PKC-interacting cousin of thioredoxinPKC-theta-interacting proteinPKCq-interacting proteinglutaredoxin 4testicular tissue protein Li 75thioredoxin-like protein 2protein phosphatase 1GPP2C-gammaprotein phosphatase 1Cprotein phosphatase 1G (formerly 2C), magnesium-dependent, gamma isoformprotein phosphatase 2, catalytic subunit, gamma isoformprotein phosphatase 2C gamma isoformprotein phosphatase 2C isoform g
Modification date2020032720200313
UniProtAcc

O76003

Main function of 5'-partner protein: FUNCTION: Together with BOLA2, acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins (PubMed:26613676, PubMed:27519415). Acts as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator (By similarity). Required for hemoglobin maturation (PubMed:23615448). Does not possess any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity. {ECO:0000250|UniProtKB:Q9CQM9, ECO:0000269|PubMed:23615448, ECO:0000269|PubMed:26613676, ECO:0000269|PubMed:27519415}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000331244, ENST00000368644, 
ENST00000496195, 
ENST00000344034, 
ENST00000350803, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 5 X 4=12010 X 10 X 2=200
# samples 610
** MAII scorelog2(6/120*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/200*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: GLRX3 [Title/Abstract] AND PPM1G [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GLRX3 [Title/Abstract] AND PPM1G [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GLRX3(131943583)-PPM1G(27610025), # samples:1
Anticipated loss of major functional domain due to fusion event.GLRX3-PPM1G 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.
GLRX3-PPM1G 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.
GLRX3-PPM1G 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.
GLRX3-PPM1G 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
HgeneGLRX3

GO:0044571

[2Fe-2S] cluster assembly

27519415

HgeneGLRX3

GO:0097428

protein maturation by iron-sulfur cluster transfer

27519415

TgenePPM1G

GO:0035970

peptidyl-threonine dephosphorylation

20801214



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/chr10:131943583/chr2:27610025)
- 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 GLRX3 (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 PPM1G (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)
ENST00000331244GLRX3chr10131943583+ENST00000344034PPM1Gchr227610025-214922341743579
ENST00000331244GLRX3chr10131943583+ENST00000350803PPM1Gchr227610025-214222341743579
ENST00000368644GLRX3chr10131943583+ENST00000344034PPM1Gchr227610025-214922341743579
ENST00000368644GLRX3chr10131943583+ENST00000350803PPM1Gchr227610025-214222341743579

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
ENST00000331244ENST00000344034GLRX3chr10131943583+PPM1Gchr227610025-0.0036586350.9963413
ENST00000331244ENST00000350803GLRX3chr10131943583+PPM1Gchr227610025-0.0036936810.9963063
ENST00000368644ENST00000344034GLRX3chr10131943583+PPM1Gchr227610025-0.0036586350.9963413
ENST00000368644ENST00000350803GLRX3chr10131943583+PPM1Gchr227610025-0.0036936810.9963063

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 GLRX3-PPM1G

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GLRX3chr10131943583PPM1Gchr22761002522373ELAKELPQVSFVKDAHNCIPELDSET

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Potential FusionNeoAntigen Information of GLRX3-PPM1G 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.
GLRX3-PPM1G_131943583_27610025.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)
GLRX3-PPM1Gchr10131943583chr227610025223HLA-C06:03FVKDAHNCI0.96240.96791019
GLRX3-PPM1Gchr10131943583chr227610025223HLA-C12:04FVKDAHNCI0.95970.97371019
GLRX3-PPM1Gchr10131943583chr227610025223HLA-C12:12FVKDAHNCI0.91890.79721019
GLRX3-PPM1Gchr10131943583chr227610025223HLA-C02:06FVKDAHNCI0.24670.92541019
GLRX3-PPM1Gchr10131943583chr227610025223HLA-C12:03FVKDAHNCI0.9460.90921019
GLRX3-PPM1Gchr10131943583chr227610025223HLA-C12:02FVKDAHNCI0.89580.89511019

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Potential FusionNeoAntigen Information of GLRX3-PPM1G 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.
GLRX3-PPM1G_131943583_27610025.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)
GLRX3-PPM1Gchr10131943583chr227610025223DRB1-0338PQVSFVKDAHNCIPE621
GLRX3-PPM1Gchr10131943583chr227610025223DRB1-0338QVSFVKDAHNCIPEL722
GLRX3-PPM1Gchr10131943583chr227610025223DRB3-0114PQVSFVKDAHNCIPE621
GLRX3-PPM1Gchr10131943583chr227610025223DRB3-0114QVSFVKDAHNCIPEL722

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Fusion breakpoint peptide structures of GLRX3-PPM1G

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
6931PQVSFVKDAHNCIPGLRX3PPM1Gchr10131943583chr227610025223

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GLRX3-PPM1G

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-B14:023BVN6931PQVSFVKDAHNCIP-7.15543-7.26883
HLA-B14:023BVN6931PQVSFVKDAHNCIP-4.77435-5.80965
HLA-B52:013W396931PQVSFVKDAHNCIP-6.80875-6.92215
HLA-B52:013W396931PQVSFVKDAHNCIP-4.20386-5.23916
HLA-A11:014UQ26931PQVSFVKDAHNCIP-7.5194-8.5547
HLA-A11:014UQ26931PQVSFVKDAHNCIP-6.9601-7.0735
HLA-A24:025HGA6931PQVSFVKDAHNCIP-7.52403-7.63743
HLA-A24:025HGA6931PQVSFVKDAHNCIP-5.82433-6.85963
HLA-B27:056PYJ6931PQVSFVKDAHNCIP-3.28285-4.31815
HLA-B44:053DX86931PQVSFVKDAHNCIP-5.91172-6.94702
HLA-B44:053DX86931PQVSFVKDAHNCIP-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of GLRX3-PPM1G

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
GLRX3-PPM1Gchr10131943583chr2276100251019FVKDAHNCITTTGTGAAGGATGCTCACAACTGTATT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
GLRX3-PPM1Gchr10131943583chr227610025621PQVSFVKDAHNCIPECCTCAAGTTTCATTTGTGAAGGATGCTCACAACTGTATTCCTGAG
GLRX3-PPM1Gchr10131943583chr227610025722QVSFVKDAHNCIPELCAAGTTTCATTTGTGAAGGATGCTCACAACTGTATTCCTGAGCTG

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Information of the samples that have these potential fusion neoantigens of GLRX3-PPM1G

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
STADGLRX3-PPM1Gchr10131943583ENST00000331244chr227610025ENST00000344034TCGA-BR-4267

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Potential target of CAR-T therapy development for GLRX3-PPM1G

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 GLRX3-PPM1G

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 GLRX3-PPM1G

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