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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:GPI-FDPS

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GPI-FDPS
FusionPDB ID: 34287
FusionGDB2.0 ID: 34287
HgeneTgene
Gene symbol

GPI

FDPS

Gene ID

10007

2224

Gene nameglucosamine-6-phosphate deaminase 1farnesyl diphosphate synthase
SynonymsGNP1|GNPDA|GNPI|GPI|HLNFPPS|FPS|POROK9
Cytomap

5q31.3

1q22

Type of geneprotein-codingprotein-coding
Descriptionglucosamine-6-phosphate isomerase 1GNPDA 1glcN6P deaminase 1oscillinfarnesyl pyrophosphate synthase(2E,6E)-farnesyl diphosphate synthaseFPP synthaseFPP synthetasefarnesyl pyrophosphate synthetase, dimethylallyltranstransferase, geranyltranstransferase
Modification date2020031320200329
UniProtAcc

Q8IV16

Main function of 5'-partner protein: FUNCTION: Mediates the transport of lipoprotein lipase LPL from the basolateral to the apical surface of endothelial cells in capillaries (By similarity). Anchors LPL on the surface of endothelial cells in the lumen of blood capillaries (By similarity). Protects LPL against loss of activity, and against ANGPTL4-mediated unfolding (PubMed:27929370, PubMed:29899144). Thereby, plays an important role in lipolytic processing of chylomicrons by LPL, triglyceride metabolism and lipid homeostasis (PubMed:19304573, PubMed:21314738). Binds chylomicrons and phospholipid particles that contain APOA5 (PubMed:17997385, PubMed:19304573). Binds high-density lipoprotein (HDL) and plays a role in the uptake of lipids from HDL (By similarity). {ECO:0000250|UniProtKB:Q9D1N2, ECO:0000269|PubMed:17997385, ECO:0000269|PubMed:19304573, ECO:0000269|PubMed:21314738, ECO:0000269|PubMed:27929370, ECO:0000269|PubMed:29899144}.

P14324

Main function of 5'-partner protein: FUNCTION: Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. FPP also serves as substrate for protein farnesylation and geranylgeranylation. Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate.
Ensembl transtripts involved in fusion geneENST idsENST00000356487, ENST00000415930, 
ENST00000586425, 
ENST00000356657, 
ENST00000487002, ENST00000368356, 
ENST00000447866, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score27 X 23 X 11=68315 X 4 X 2=40
# samples 285
** MAII scorelog2(28/6831*10)=-4.60859805991281
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/40*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: GPI [Title/Abstract] AND FDPS [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GPI [Title/Abstract] AND FDPS [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GPI(34870455)-FDPS(155290342), # samples:1
Anticipated loss of major functional domain due to fusion event.GPI-FDPS 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.
GPI-FDPS 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.
GPI-FDPS seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
GPI-FDPS seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
GPI-FDPS seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
GPI-FDPS seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
GPI-FDPS 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


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/chr19:34870455/chr1:155290342)
- 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 GPI (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 FDPS (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)
ENST00000415930GPIchr1934870455+ENST00000447866FDPSchr1155290342+1035920170982270
ENST00000356487GPIchr1934870455+ENST00000447866FDPSchr1155290342+10739581721020282
ENST00000586425GPIchr1934870455+ENST00000447866FDPSchr1155290342+85774225804259

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
ENST00000415930ENST00000447866GPIchr1934870455+FDPSchr1155290342+0.0050041910.99499583
ENST00000356487ENST00000447866GPIchr1934870455+FDPSchr1155290342+0.0029700480.9970299
ENST00000586425ENST00000447866GPIchr1934870455+FDPSchr1155290342+0.0023423120.99765766

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 GPI-FDPS

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GPIchr1934870455FDPSchr1155290342742238KEWFLQAAKDSTNTPAPSRLSGACAQ
GPIchr1934870455FDPSchr1155290342920249KEWFLQAAKDSTNTPAPSRLSGACAQ
GPIchr1934870455FDPSchr1155290342958261KEWFLQAAKDSTNTPAPSRLSGACAQ

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Potential FusionNeoAntigen Information of GPI-FDPS 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.
GPI-FDPS_34870455_155290342.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)
GPI-FDPSchr1934870455chr1155290342958HLA-A74:09STNTPAPSR0.98720.65631019
GPI-FDPSchr1934870455chr1155290342958HLA-A74:03STNTPAPSR0.98720.65631019
GPI-FDPSchr1934870455chr1155290342958HLA-A74:11STNTPAPSR0.98720.65631019
GPI-FDPSchr1934870455chr1155290342958HLA-A30:08STNTPAPSR0.95070.74441019
GPI-FDPSchr1934870455chr1155290342958HLA-A31:02STNTPAPSR0.93460.66681019
GPI-FDPSchr1934870455chr1155290342958HLA-A66:01DSTNTPAPSR0.99420.5819919
GPI-FDPSchr1934870455chr1155290342958HLA-A74:03KDSTNTPAPSR0.99390.8084819
GPI-FDPSchr1934870455chr1155290342958HLA-A74:11KDSTNTPAPSR0.99390.8084819
GPI-FDPSchr1934870455chr1155290342958HLA-A74:09KDSTNTPAPSR0.99390.8084819
GPI-FDPSchr1934870455chr1155290342958HLA-A31:06KDSTNTPAPSR0.98640.5543819
GPI-FDPSchr1934870455chr1155290342958HLA-C01:17NTPAPSRL0.99760.95881220
GPI-FDPSchr1934870455chr1155290342958HLA-C01:30NTPAPSRL0.96490.96531220
GPI-FDPSchr1934870455chr1155290342958HLA-A31:01STNTPAPSR0.98850.59881019
GPI-FDPSchr1934870455chr1155290342958HLA-A31:01KDSTNTPAPSR0.99650.8005819
GPI-FDPSchr1934870455chr1155290342958HLA-C01:03NTPAPSRL0.99840.9351220
GPI-FDPSchr1934870455chr1155290342958HLA-C01:02NTPAPSRL0.99750.95641220
GPI-FDPSchr1934870455chr1155290342958HLA-A74:01STNTPAPSR0.98720.65631019
GPI-FDPSchr1934870455chr1155290342958HLA-A30:01STNTPAPSR0.95170.88621019
GPI-FDPSchr1934870455chr1155290342958HLA-A74:01KDSTNTPAPSR0.99390.8084819

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Potential FusionNeoAntigen Information of GPI-FDPS 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 GPI-FDPS

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
37AAKDSTNTPAPSRLGPIFDPSchr1934870455chr1155290342958

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GPI-FDPS

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-B14:023BVN37AAKDSTNTPAPSRL-6.00367-7.03897
HLA-B14:023BVN37AAKDSTNTPAPSRL-5.39279-5.50619
HLA-B52:013W3937AAKDSTNTPAPSRL-6.37513-6.48853
HLA-B52:013W3937AAKDSTNTPAPSRL-5.71942-6.75472
HLA-A11:014UQ237AAKDSTNTPAPSRL-11.5708-11.6842
HLA-A11:014UQ237AAKDSTNTPAPSRL-8.11091-9.14621
HLA-A24:025HGA37AAKDSTNTPAPSRL-6.75661-6.87001
HLA-A24:025HGA37AAKDSTNTPAPSRL-5.30147-6.33677
HLA-B27:056PYJ37AAKDSTNTPAPSRL-4.27108-5.30638
HLA-B44:053DX837AAKDSTNTPAPSRL-6.47731-6.59071
HLA-B44:053DX837AAKDSTNTPAPSRL-3.23433-4.26963

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Vaccine Design for the FusionNeoAntigens of GPI-FDPS

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
GPI-FDPSchr1934870455chr11552903421019STNTPAPSRACTAACACACCTGCCCCCAGCCGTCTT
GPI-FDPSchr1934870455chr11552903421220NTPAPSRLACACCTGCCCCCAGCCGTCTTTCT
GPI-FDPSchr1934870455chr1155290342819KDSTNTPAPSRGATTCTACTAACACACCTGCCCCCAGCCGTCTT
GPI-FDPSchr1934870455chr1155290342919DSTNTPAPSRTCTACTAACACACCTGCCCCCAGCCGTCTT

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 GPI-FDPS

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
N/AGPI-FDPSchr1934870455ENST00000356487chr1155290342ENST00000447866CB046420

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Potential target of CAR-T therapy development for GPI-FDPS

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 GPI-FDPS

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 GPI-FDPS

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