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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-EYS

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GRIK2-EYS
FusionPDB ID: 34786
FusionGDB2.0 ID: 34786
HgeneTgene
Gene symbol

GRIK2

EYS

Gene ID

2901

346007

Gene nameglutamate ionotropic receptor kainate type subunit 5eyes shut homolog
SynonymsEAA2|GRIK2|GluK5|KA2C6orf178|C6orf179|C6orf180|EGFL10|EGFL11|RP25|SPAM|bA166P24.2|bA307F22.3|bA74E24.1|dJ1018A4.2|dJ22I17.2|dJ303F19.1
Cytomap

19q13.2

6q12

Type of geneprotein-codingprotein-coding
Descriptionglutamate receptor ionotropic, kainate 5excitatory amino acid receptor 2glutamate receptor KA2protein eyes shut homologEGF-like-domain, multiple 10EGF-like-domain, multiple 11epidermal growth factor-like protein 10epidermal growth factor-like protein 11protein spacemaker homolog
Modification date2020031320200313
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}.

Q5T1H1

Main function of 5'-partner protein: FUNCTION: Required to maintain the integrity of photoreceptor cells (PubMed:18836446). Specifically required for normal morphology of the photoreceptor ciliary pocket, and might thus facilitate protein trafficking between the photoreceptor inner and outer segments via the transition zone (By similarity). {ECO:0000250|UniProtKB:B8JI71, ECO:0000269|PubMed:18836446}.
Ensembl transtripts involved in fusion geneENST idsENST00000318991, ENST00000358361, 
ENST00000369137, ENST00000369138, 
ENST00000413795, ENST00000421544, 
ENST00000369134, 
ENST00000342421, 
ENST00000370618, ENST00000393380, 
ENST00000486069, ENST00000370616, 
ENST00000370621, ENST00000503581, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 4 X 6=21636 X 24 X 15=12960
# samples 1038
** MAII scorelog2(10/216*10)=-1.11103131238874
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(38/12960*10)=-5.09192248944104
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

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

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GRIK2(101847268)-EYS(65767620), # samples:1
Anticipated loss of major functional domain due to fusion event.GRIK2-EYS 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-EYS 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-EYS 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.
GRIK2-EYS 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


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/chr6:65767620)
- 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 EYS (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-ENST00000503581EYSchr665767620-863360539180162541
ENST00000413795GRIK2chr6101847268-ENST00000370621EYSchr665767620-854060539180792562
ENST00000413795GRIK2chr6101847268-ENST00000370616EYSchr665767620-808060539180792563
ENST00000369138GRIK2chr6101847268-ENST00000503581EYSchr665767620-863360539180162541
ENST00000369138GRIK2chr6101847268-ENST00000370621EYSchr665767620-854060539180792562
ENST00000369138GRIK2chr6101847268-ENST00000370616EYSchr665767620-808060539180792563
ENST00000421544GRIK2chr6101847268-ENST00000503581EYSchr665767620-863360539180162541
ENST00000421544GRIK2chr6101847268-ENST00000370621EYSchr665767620-854060539180792562
ENST00000421544GRIK2chr6101847268-ENST00000370616EYSchr665767620-808060539180792563
ENST00000358361GRIK2chr6101847268-ENST00000503581EYSchr665767620-862860038680112541
ENST00000358361GRIK2chr6101847268-ENST00000370621EYSchr665767620-853560038680742562
ENST00000358361GRIK2chr6101847268-ENST00000370616EYSchr665767620-807560038680742563
ENST00000318991GRIK2chr6101847268-ENST00000503581EYSchr665767620-8143115075262508
ENST00000318991GRIK2chr6101847268-ENST00000370621EYSchr665767620-8050115075892529
ENST00000318991GRIK2chr6101847268-ENST00000370616EYSchr665767620-7590115075892529
ENST00000369137GRIK2chr6101847268-ENST00000503581EYSchr665767620-8143115075262508
ENST00000369137GRIK2chr6101847268-ENST00000370621EYSchr665767620-8050115075892529
ENST00000369137GRIK2chr6101847268-ENST00000370616EYSchr665767620-7590115075892529

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
ENST00000413795ENST00000503581GRIK2chr6101847268-EYSchr665767620-0.0002575830.99974245
ENST00000413795ENST00000370621GRIK2chr6101847268-EYSchr665767620-0.0004754930.9995245
ENST00000413795ENST00000370616GRIK2chr6101847268-EYSchr665767620-0.0006152070.99938476
ENST00000369138ENST00000503581GRIK2chr6101847268-EYSchr665767620-0.0002575830.99974245
ENST00000369138ENST00000370621GRIK2chr6101847268-EYSchr665767620-0.0004754930.9995245
ENST00000369138ENST00000370616GRIK2chr6101847268-EYSchr665767620-0.0006152070.99938476
ENST00000421544ENST00000503581GRIK2chr6101847268-EYSchr665767620-0.0002575830.99974245
ENST00000421544ENST00000370621GRIK2chr6101847268-EYSchr665767620-0.0004754930.9995245
ENST00000421544ENST00000370616GRIK2chr6101847268-EYSchr665767620-0.0006152070.99938476
ENST00000358361ENST00000503581GRIK2chr6101847268-EYSchr665767620-0.0002547650.9997452
ENST00000358361ENST00000370621GRIK2chr6101847268-EYSchr665767620-0.0004710260.999529
ENST00000358361ENST00000370616GRIK2chr6101847268-EYSchr665767620-0.0006084320.99939156
ENST00000318991ENST00000503581GRIK2chr6101847268-EYSchr665767620-0.0001342710.9998658
ENST00000318991ENST00000370621GRIK2chr6101847268-EYSchr665767620-0.0002522420.9997478
ENST00000318991ENST00000370616GRIK2chr6101847268-EYSchr665767620-0.0003270080.999673
ENST00000369137ENST00000503581GRIK2chr6101847268-EYSchr665767620-0.0001342710.9998658
ENST00000369137ENST00000370621GRIK2chr6101847268-EYSchr665767620-0.0002522420.9997478
ENST00000369137ENST00000370616GRIK2chr6101847268-EYSchr665767620-0.0003270080.999673

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-EYS

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GRIK2chr6101847268EYSchr66576762011538IGYSQGTTHVLRFGTQCEIDIDECAS
GRIK2chr6101847268EYSchr66576762060071IGYSQGTTHVLRFGTQCEIDIDECAS
GRIK2chr6101847268EYSchr66576762060571IGYSQGTTHVLRFGTQCEIDIDECAS

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Potential FusionNeoAntigen Information of GRIK2-EYS 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-EYS_101847268_65767620.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-EYSchr6101847268chr665767620115HLA-B27:04LRFGTQCEI0.99950.89731019
GRIK2-EYSchr6101847268chr665767620115HLA-B27:07LRFGTQCEI0.99920.85881019
GRIK2-EYSchr6101847268chr665767620115HLA-B27:14LRFGTQCEI0.99960.89191019
GRIK2-EYSchr6101847268chr665767620115HLA-B73:01LRFGTQCEI0.97240.92141019
GRIK2-EYSchr6101847268chr665767620115HLA-B27:08LRFGTQCEI0.99950.85481019
GRIK2-EYSchr6101847268chr665767620115HLA-B27:06LRFGTQCEI0.99930.9071019
GRIK2-EYSchr6101847268chr665767620115HLA-B27:09LRFGTQCEI0.99910.91751019
GRIK2-EYSchr6101847268chr665767620115HLA-C06:08LRFGTQCEI0.98080.99731019
GRIK2-EYSchr6101847268chr665767620115HLA-C07:22LRFGTQCEI0.77660.87371019
GRIK2-EYSchr6101847268chr665767620115HLA-C06:02LRFGTQCEI0.04870.9981019
GRIK2-EYSchr6101847268chr665767620115HLA-C06:17LRFGTQCEI0.04870.9981019

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Potential FusionNeoAntigen Information of GRIK2-EYS 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-EYS

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
9692TTHVLRFGTQCEIDGRIK2EYSchr6101847268chr665767620115

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

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-B14:023BVN9692TTHVLRFGTQCEID-7.15543-7.26883
HLA-B14:023BVN9692TTHVLRFGTQCEID-4.77435-5.80965
HLA-B52:013W399692TTHVLRFGTQCEID-6.80875-6.92215
HLA-B52:013W399692TTHVLRFGTQCEID-4.20386-5.23916
HLA-A11:014UQ29692TTHVLRFGTQCEID-7.5194-8.5547
HLA-A11:014UQ29692TTHVLRFGTQCEID-6.9601-7.0735
HLA-A24:025HGA9692TTHVLRFGTQCEID-7.52403-7.63743
HLA-A24:025HGA9692TTHVLRFGTQCEID-5.82433-6.85963
HLA-B27:056PYJ9692TTHVLRFGTQCEID-3.28285-4.31815
HLA-B44:053DX89692TTHVLRFGTQCEID-5.91172-6.94702
HLA-B44:053DX89692TTHVLRFGTQCEID-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of GRIK2-EYS

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-EYSchr6101847268chr6657676201019LRFGTQCEITAAGATTTGGTACGCAATGTGAAATTG

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-EYS

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
LGGGRIK2-EYSchr6101847268ENST00000318991chr665767620ENST00000370616TCGA-TM-A7CF-01A

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

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
GRIK2chr6101847268ENST00000318991EYSchr665767620ENST00000370616
GRIK2chr6101847268ENST00000318991EYSchr665767620ENST00000503581
GRIK2chr6101847268ENST00000358361EYSchr665767620ENST00000370616
GRIK2chr6101847268ENST00000358361EYSchr665767620ENST00000370621
GRIK2chr6101847268ENST00000358361EYSchr665767620ENST00000503581

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Related Drugs to GRIK2-EYS

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-EYS

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