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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:GRIK2-GPC1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GRIK2-GPC1
FusionPDB ID: 34787
FusionGDB2.0 ID: 34787
HgeneTgene
Gene symbol

GRIK2

GPC1

Gene ID

2901

2817

Gene nameglutamate ionotropic receptor kainate type subunit 5glypican 1
SynonymsEAA2|GRIK2|GluK5|KA2glypican
Cytomap

19q13.2

2q37.3

Type of geneprotein-codingprotein-coding
Descriptionglutamate receptor ionotropic, kainate 5excitatory amino acid receptor 2glutamate receptor KA2glypican-1epididymis secretory sperm binding proteinglypican proteoglycan 1
Modification date2020031320200315
UniProtAcc

Q13002

Main function of 5'-partner protein: FUNCTION: Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist (PubMed:28180184). Modulates cell surface expression of NETO2 (By similarity). {ECO:0000250|UniProtKB:P39087, ECO:0000269|PubMed:28180184}.; FUNCTION: Independent of its ionotropic glutamate receptor activity, acts as a thermoreceptor conferring sensitivity to cold temperatures (PubMed:31474366). Functions in dorsal root ganglion neurons (By similarity). {ECO:0000250|UniProtKB:P39087, ECO:0000269|PubMed:31474366}.

P35052

Main function of 5'-partner protein: FUNCTION: Cell surface proteoglycan that bears heparan sulfate. Binds, via the heparan sulfate side chains, alpha-4 (V) collagen and participates in Schwann cell myelination (By similarity). May act as a catalyst in increasing the rate of conversion of prion protein PRPN(C) to PRNP(Sc) via associating (via the heparan sulfate side chains) with both forms of PRPN, targeting them to lipid rafts and facilitating their interaction. Required for proper skeletal muscle differentiation by sequestering FGF2 in lipid rafts preventing its binding to receptors (FGFRs) and inhibiting the FGF-mediated signaling. {ECO:0000250, ECO:0000269|PubMed:19936054, ECO:0000269|PubMed:21642435}.
Ensembl transtripts involved in fusion geneENST idsENST00000318991, ENST00000358361, 
ENST00000369137, ENST00000369138, 
ENST00000413795, ENST00000421544, 
ENST00000369134, 
ENST00000466624, 
ENST00000264039, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 4 X 6=2162 X 2 X 2=8
# samples 102
** MAII scorelog2(10/216*10)=-1.11103131238874
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: GRIK2 [Title/Abstract] AND GPC1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GRIK2 [Title/Abstract] AND GPC1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GRIK2(101847268)-GPC1(241398447), # samples:3
Anticipated loss of major functional domain due to fusion event.GRIK2-GPC1 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.
GRIK2-GPC1 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
TgeneGPC1

GO:0030200

heparan sulfate proteoglycan catabolic process

12732622



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/chr6:101847268/chr2:241398447)
- 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 GRIK2 (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 GPC1 (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)
ENST00000413795GRIK2chr6101847268+ENST00000264039GPC1chr2241398447+39026053912115574
ENST00000369138GRIK2chr6101847268+ENST00000264039GPC1chr2241398447+39026053912115574
ENST00000421544GRIK2chr6101847268+ENST00000264039GPC1chr2241398447+39026053912115574
ENST00000358361GRIK2chr6101847268+ENST00000264039GPC1chr2241398447+38976003862110574
ENST00000318991GRIK2chr6101847268+ENST00000264039GPC1chr2241398447+341211501625541
ENST00000369137GRIK2chr6101847268+ENST00000264039GPC1chr2241398447+341211501625541

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
ENST00000413795ENST00000264039GRIK2chr6101847268+GPC1chr2241398447+0.0167476870.9832523
ENST00000369138ENST00000264039GRIK2chr6101847268+GPC1chr2241398447+0.0167476870.9832523
ENST00000421544ENST00000264039GRIK2chr6101847268+GPC1chr2241398447+0.0167476870.9832523
ENST00000358361ENST00000264039GRIK2chr6101847268+GPC1chr2241398447+0.0165589680.983441
ENST00000318991ENST00000264039GRIK2chr6101847268+GPC1chr2241398447+0.0167870950.9832129
ENST00000369137ENST00000264039GRIK2chr6101847268+GPC1chr2241398447+0.0167870950.9832129

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 GRIK2-GPC1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GRIK2chr6101847268GPC1chr224139844711538IGYSQGTTHVLRFGEHLRICPQGYTC
GRIK2chr6101847268GPC1chr224139844760071IGYSQGTTHVLRFGEHLRICPQGYTC
GRIK2chr6101847268GPC1chr224139844760571IGYSQGTTHVLRFGEHLRICPQGYTC

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Potential FusionNeoAntigen Information of GRIK2-GPC1 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.
GRIK2-GPC1_101847268_241398447.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)
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:02LRFGEHLRI0.99980.91871019
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:04LRFGEHLRI0.99980.89411019
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:05LRFGEHLRI0.99980.9751019
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:07LRFGEHLRI0.99970.7181019
GRIK2-GPC1chr6101847268chr2241398447115HLA-A74:09VLRFGEHLR0.90650.8131918
GRIK2-GPC1chr6101847268chr2241398447115HLA-A74:03VLRFGEHLR0.90650.8131918
GRIK2-GPC1chr6101847268chr2241398447115HLA-A74:11VLRFGEHLR0.90650.8131918
GRIK2-GPC1chr6101847268chr2241398447115HLA-A31:02VLRFGEHLR0.86430.762918
GRIK2-GPC1chr6101847268chr2241398447115HLA-A31:06VLRFGEHLR0.80330.686918
GRIK2-GPC1chr6101847268chr2241398447115HLA-B15:18THVLRFGEH0.23920.8177716
GRIK2-GPC1chr6101847268chr2241398447115HLA-B39:01THVLRFGEHL0.99750.9713717
GRIK2-GPC1chr6101847268chr2241398447115HLA-B38:01THVLRFGEHL0.99490.9929717
GRIK2-GPC1chr6101847268chr2241398447115HLA-B38:02THVLRFGEHL0.99460.9926717
GRIK2-GPC1chr6101847268chr2241398447115HLA-A68:24HVLRFGEHLR0.99120.6198818
GRIK2-GPC1chr6101847268chr2241398447115HLA-A68:03HVLRFGEHLR0.98940.6053818
GRIK2-GPC1chr6101847268chr2241398447115HLA-B15:10THVLRFGEHL0.98810.7135717
GRIK2-GPC1chr6101847268chr2241398447115HLA-A68:08HVLRFGEHLR0.97730.6381818
GRIK2-GPC1chr6101847268chr2241398447115HLA-A31:02HVLRFGEHLR0.96830.8019818
GRIK2-GPC1chr6101847268chr2241398447115HLA-A31:06HVLRFGEHLR0.950.7619818
GRIK2-GPC1chr6101847268chr2241398447115HLA-A68:05HVLRFGEHLR0.94030.608818
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:07HVLRFGEHLRI0.96340.8902819
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:14LRFGEHLRI0.99980.95261019
GRIK2-GPC1chr6101847268chr2241398447115HLA-C07:95LRFGEHLRI0.99590.91711019
GRIK2-GPC1chr6101847268chr2241398447115HLA-B73:01LRFGEHLRI0.99450.88811019
GRIK2-GPC1chr6101847268chr2241398447115HLA-C07:05LRFGEHLRI0.99260.98921019
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:03LRFGEHLRI0.99240.97641019
GRIK2-GPC1chr6101847268chr2241398447115HLA-C07:27LRFGEHLRI0.99110.98441019
GRIK2-GPC1chr6101847268chr2241398447115HLA-C07:13LRFGEHLRI0.95970.9831019
GRIK2-GPC1chr6101847268chr2241398447115HLA-C07:29LRFGEHLRI0.95180.97511019
GRIK2-GPC1chr6101847268chr2241398447115HLA-B39:12LRFGEHLRI0.94350.98751019
GRIK2-GPC1chr6101847268chr2241398447115HLA-A31:01VLRFGEHLR0.93850.7656918
GRIK2-GPC1chr6101847268chr2241398447115HLA-C07:10LRFGEHLRI0.84650.99091019
GRIK2-GPC1chr6101847268chr2241398447115HLA-C07:46LRFGEHLRI0.84150.97051019
GRIK2-GPC1chr6101847268chr2241398447115HLA-C07:19LRFGEHLRI0.83110.93841019
GRIK2-GPC1chr6101847268chr2241398447115HLA-C12:16LRFGEHLRI0.00670.98411019
GRIK2-GPC1chr6101847268chr2241398447115HLA-B39:09THVLRFGEHL0.99820.9058717
GRIK2-GPC1chr6101847268chr2241398447115HLA-B39:05THVLRFGEHL0.99470.9709717
GRIK2-GPC1chr6101847268chr2241398447115HLA-A68:01HVLRFGEHLR0.99120.6198818
GRIK2-GPC1chr6101847268chr2241398447115HLA-A31:01HVLRFGEHLR0.97550.8013818
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:08LRFGEHLRI0.99980.96121019
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:10LRFGEHLRI0.99980.9441019
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:09LRFGEHLRI0.99970.97211019
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:06LRFGEHLRI0.99970.89861019
GRIK2-GPC1chr6101847268chr2241398447115HLA-C07:01LRFGEHLRI0.99660.90661019
GRIK2-GPC1chr6101847268chr2241398447115HLA-C06:08LRFGEHLRI0.95110.99711019
GRIK2-GPC1chr6101847268chr2241398447115HLA-A74:01VLRFGEHLR0.90650.8131918
GRIK2-GPC1chr6101847268chr2241398447115HLA-C07:22LRFGEHLRI0.65810.92431019
GRIK2-GPC1chr6101847268chr2241398447115HLA-C06:06LRFGEHLRI0.22130.99411019
GRIK2-GPC1chr6101847268chr2241398447115HLA-C06:17LRFGEHLRI0.02720.99771019
GRIK2-GPC1chr6101847268chr2241398447115HLA-C06:02LRFGEHLRI0.02720.99771019
GRIK2-GPC1chr6101847268chr2241398447115HLA-B38:05THVLRFGEHL0.99490.9929717
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:06VLRFGEHLRI0.88340.8914919
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:06HVLRFGEHLRI0.98710.8686819
GRIK2-GPC1chr6101847268chr2241398447115HLA-B27:09HVLRFGEHLRI0.96670.9358819

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Potential FusionNeoAntigen Information of GRIK2-GPC1 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 GRIK2-GPC1

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
9691TTHVLRFGEHLRICGRIK2GPC1chr6101847268chr2241398447115

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GRIK2-GPC1

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-B14:023BVN9691TTHVLRFGEHLRIC-7.15543-7.26883
HLA-B14:023BVN9691TTHVLRFGEHLRIC-4.77435-5.80965
HLA-B52:013W399691TTHVLRFGEHLRIC-6.80875-6.92215
HLA-B52:013W399691TTHVLRFGEHLRIC-4.20386-5.23916
HLA-A11:014UQ29691TTHVLRFGEHLRIC-7.5194-8.5547
HLA-A11:014UQ29691TTHVLRFGEHLRIC-6.9601-7.0735
HLA-A24:025HGA9691TTHVLRFGEHLRIC-7.52403-7.63743
HLA-A24:025HGA9691TTHVLRFGEHLRIC-5.82433-6.85963
HLA-B27:056PYJ9691TTHVLRFGEHLRIC-3.28285-4.31815
HLA-B44:053DX89691TTHVLRFGEHLRIC-5.91172-6.94702
HLA-B44:053DX89691TTHVLRFGEHLRIC-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of GRIK2-GPC1

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
GRIK2-GPC1chr6101847268chr22413984471019LRFGEHLRITAAGATTTGGTGAGCACCTGCGGATCT
GRIK2-GPC1chr6101847268chr2241398447716THVLRFGEHCACATGTATTAAGATTTGGTGAGCACC
GRIK2-GPC1chr6101847268chr2241398447717THVLRFGEHLCACATGTATTAAGATTTGGTGAGCACCTGC
GRIK2-GPC1chr6101847268chr2241398447818HVLRFGEHLRATGTATTAAGATTTGGTGAGCACCTGCGGA
GRIK2-GPC1chr6101847268chr2241398447819HVLRFGEHLRIATGTATTAAGATTTGGTGAGCACCTGCGGATCT
GRIK2-GPC1chr6101847268chr2241398447918VLRFGEHLRTATTAAGATTTGGTGAGCACCTGCGGA
GRIK2-GPC1chr6101847268chr2241398447919VLRFGEHLRITATTAAGATTTGGTGAGCACCTGCGGATCT

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 GRIK2-GPC1

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
SKCMGRIK2-GPC1chr6101847268ENST00000318991chr2241398447ENST00000264039TCGA-D3-A2JP-06A

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Potential target of CAR-T therapy development for GRIK2-GPC1

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 GRIK2-GPC1

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 GRIK2-GPC1

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