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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:GSTP1-CTSA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GSTP1-CTSA
FusionPDB ID: 35132
FusionGDB2.0 ID: 35132
HgeneTgene
Gene symbol

GSTP1

CTSA

Gene ID

2950

5476

Gene nameglutathione S-transferase pi 1cathepsin A
SynonymsDFN7|FAEES3|GST3|GSTP|HEL-S-22|PIGLB2|GSL|NGBE|PPCA|PPGB
Cytomap

11q13.2

20q13.12

Type of geneprotein-codingprotein-coding
Descriptionglutathione S-transferase PGST class-piGSTP1-1deafness, X-linked 7epididymis secretory protein Li 22fatty acid ethyl ester synthase IIIlysosomal protective proteinbeta-galactosidase 2beta-galactosidase protective proteincarboxypeptidase Ccarboxypeptidase Y-like kininasecarboxypeptidase-Ldeamidaselysosomal carboxypeptidase Aprotective protein cathepsin Aurinary kininase
Modification date2020032920200313
UniProtAcc

P09211

Main function of 5'-partner protein: FUNCTION: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). Participates in the formation of novel hepoxilin regioisomers (PubMed:21046276). Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration. {ECO:0000269|PubMed:21046276, ECO:0000269|PubMed:21668448, ECO:0000269|PubMed:9084911}.

P10619

Main function of 5'-partner protein: FUNCTION: Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins. {ECO:0000269|PubMed:1907282}.
Ensembl transtripts involved in fusion geneENST idsENST00000498765, ENST00000398603, 
ENST00000398606, 
ENST00000191018, 
ENST00000354880, ENST00000372459, 
ENST00000372484, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score16 X 13 X 5=10407 X 6 X 4=168
# samples 167
** MAII scorelog2(16/1040*10)=-2.70043971814109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/168*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: GSTP1 [Title/Abstract] AND CTSA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GSTP1 [Title/Abstract] AND CTSA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GSTP1(67353925)-CTSA(44522704), # samples:1
Anticipated loss of major functional domain due to fusion event.GSTP1-CTSA 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.
GSTP1-CTSA 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.
GSTP1-CTSA seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
GSTP1-CTSA seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
GSTP1-CTSA seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
GSTP1-CTSA seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
GSTP1-CTSA seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
GSTP1-CTSA seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
HgeneGSTP1

GO:0006469

negative regulation of protein kinase activity

16636664

HgeneGSTP1

GO:0006749

glutathione metabolic process

1540159

HgeneGSTP1

GO:0006805

xenobiotic metabolic process

1540159

HgeneGSTP1

GO:0009890

negative regulation of biosynthetic process

18962899

HgeneGSTP1

GO:0032691

negative regulation of interleukin-1 beta production

18962899

HgeneGSTP1

GO:0032720

negative regulation of tumor necrosis factor production

18962899

HgeneGSTP1

GO:0043407

negative regulation of MAP kinase activity

11408560

HgeneGSTP1

GO:0043508

negative regulation of JUN kinase activity

16636664

HgeneGSTP1

GO:0043651

linoleic acid metabolic process

16624487

HgeneGSTP1

GO:0051771

negative regulation of nitric-oxide synthase biosynthetic process

18962899

HgeneGSTP1

GO:0070373

negative regulation of ERK1 and ERK2 cascade

11408560

HgeneGSTP1

GO:0071638

negative regulation of monocyte chemotactic protein-1 production

18962899

HgeneGSTP1

GO:2001237

negative regulation of extrinsic apoptotic signaling pathway

16636664

TgeneCTSA

GO:0006508

proteolysis

12505983



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/chr11:67353925/chr20:44522704)
- 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 GSTP1 (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 CTSA (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)
ENST00000398606GSTP1chr1167353925-ENST00000372484CTSAchr2044522704-194289930815261
ENST00000398606GSTP1chr1167353925-ENST00000354880CTSAchr2044522704-194289930815261
ENST00000398606GSTP1chr1167353925-ENST00000191018CTSAchr2044522704-194289930815261
ENST00000398606GSTP1chr1167353925-ENST00000372459CTSAchr2044522704-190889930815261

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
ENST00000398606ENST00000372484GSTP1chr1167353925-CTSAchr2044522704-0.0048155850.99518436
ENST00000398606ENST00000354880GSTP1chr1167353925-CTSAchr2044522704-0.0048155850.99518436
ENST00000398606ENST00000191018GSTP1chr1167353925-CTSAchr2044522704-0.0048155850.99518436
ENST00000398606ENST00000372459GSTP1chr1167353925-CTSAchr2044522704-0.0047138840.99528617

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 GSTP1-CTSA

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 GSTP1-CTSA 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 GSTP1-CTSA 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 GSTP1-CTSA

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 GSTP1-CTSA

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 GSTP1-CTSA

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 GSTP1-CTSA

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 GSTP1-CTSA

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 GSTP1-CTSA

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 GSTP1-CTSA

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