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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:HLCS-GRIK1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: HLCS-GRIK1
FusionPDB ID: 36718
FusionGDB2.0 ID: 36718
HgeneTgene
Gene symbol

HLCS

GRIK1

Gene ID

3141

2897

Gene nameholocarboxylase synthetaseglutamate ionotropic receptor kainate type subunit 1
SynonymsHCSEAA3|EEA3|GLR5|GLUR5|GluK1|gluR-5
Cytomap

21q22.13

21q21.3

Type of geneprotein-codingprotein-coding
Descriptionbiotin--protein ligasebiotin apo-protein ligasebiotin--[acetyl-CoA-carboxylase] ligasebiotin--[methylcrotonoyl-CoA-carboxylase] ligasebiotin--[methylmalonyl-CoA-carboxytransferase] ligaseholocarboxylase synthetase (biotin-(proprionyl-CoA-carboxylase glutamate receptor ionotropic, kainate 1excitatory amino acid receptor 3glutamate receptor 5
Modification date2020031320200320
UniProtAcc

P50747

Main function of 5'-partner protein: FUNCTION: Biotin--protein ligase catalyzing the biotinylation of the 4 biotin-dependent carboxylases acetyl-CoA-carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase. {ECO:0000269|PubMed:10590022, ECO:0000269|PubMed:7753853, ECO:0000269|PubMed:7842009}.

P39086

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. May be involved in the transmission of light information from the retina to the hypothalamus.
Ensembl transtripts involved in fusion geneENST idsENST00000336648, ENST00000399120, 
ENST00000482273, 
ENST00000472429, 
ENST00000309434, ENST00000327783, 
ENST00000389124, ENST00000389125, 
ENST00000399907, ENST00000399909, 
ENST00000399913, ENST00000399914, 
ENST00000535441, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score17 X 9 X 9=137712 X 9 X 6=648
# samples 1712
** MAII scorelog2(17/1377*10)=-3.01792190799726
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/648*10)=-2.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: HLCS [Title/Abstract] AND GRIK1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: HLCS [Title/Abstract] AND GRIK1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HLCS(38269160)-GRIK1(30971257), # samples:3
Anticipated loss of major functional domain due to fusion event.HLCS-GRIK1 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.
HLCS-GRIK1 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.
HLCS-GRIK1 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.
HLCS-GRIK1 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.
HLCS-GRIK1 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
HLCS-GRIK1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
HLCS-GRIK1 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
HgeneHLCS

GO:0009305

protein biotinylation

7842009

HgeneHLCS

GO:0016570

histone modification

14613969

HgeneHLCS

GO:0070781

response to biotin

17904341

HgeneHLCS

GO:0071110

histone biotinylation

14613969



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/chr21:38269160/chr21:30971257)
- 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 HLCS (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 GRIK1 (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)
ENST00000336648HLCSchr2138269160-ENST00000327783GRIK1chr2130971257-3971192217753673632
ENST00000336648HLCSchr2138269160-ENST00000389125GRIK1chr2130971257-3839192217753541588
ENST00000336648HLCSchr2138269160-ENST00000399913GRIK1chr2130971257-3884192217753586603
ENST00000336648HLCSchr2138269160-ENST00000399914GRIK1chr2130971257-3926192217753628617
ENST00000336648HLCSchr2138269160-ENST00000535441GRIK1chr2130971257-3587192217753586604
ENST00000336648HLCSchr2138269160-ENST00000389124GRIK1chr2130971257-3504192217753439554
ENST00000336648HLCSchr2138269160-ENST00000399907GRIK1chr2130971257-3884192217753580601
ENST00000336648HLCSchr2138269160-ENST00000399909GRIK1chr2130971257-3839192217753535586
ENST00000336648HLCSchr2138269160-ENST00000309434GRIK1chr2130971257-3581192217753580602

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
ENST00000336648ENST00000327783HLCSchr2138269160-GRIK1chr2130971257-0.0010224460.99897754
ENST00000336648ENST00000389125HLCSchr2138269160-GRIK1chr2130971257-0.0010214660.9989786
ENST00000336648ENST00000399913HLCSchr2138269160-GRIK1chr2130971257-0.0009949060.99900514
ENST00000336648ENST00000399914HLCSchr2138269160-GRIK1chr2130971257-0.0010646530.9989354
ENST00000336648ENST00000535441HLCSchr2138269160-GRIK1chr2130971257-0.0016922620.9983077
ENST00000336648ENST00000389124HLCSchr2138269160-GRIK1chr2130971257-0.0016133170.99838674
ENST00000336648ENST00000399907HLCSchr2138269160-GRIK1chr2130971257-0.0009007510.99909925
ENST00000336648ENST00000399909HLCSchr2138269160-GRIK1chr2130971257-0.0009378580.9990621
ENST00000336648ENST00000309434HLCSchr2138269160-GRIK1chr2130971257-0.0013276490.99867237

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 HLCS-GRIK1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
HLCSchr2138269160GRIK1chr2130971257192249CRSDPHNDASPGWARWDGLTGHITFN

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Potential FusionNeoAntigen Information of HLCS-GRIK1 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.
HLCS-GRIK1_38269160_30971257.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)
HLCS-GRIK1chr2138269160chr21309712571922HLA-B58:02ASPGWARW0.99920.9881816
HLCS-GRIK1chr2138269160chr21309712571922HLA-A33:05DASPGWAR0.99720.8235715
HLCS-GRIK1chr2138269160chr21309712571922HLA-A33:01DASPGWAR0.99720.8235715
HLCS-GRIK1chr2138269160chr21309712571922HLA-B58:01DASPGWARW0.9750.9841716
HLCS-GRIK1chr2138269160chr21309712571922HLA-B53:01DASPGWARW0.97350.8107716
HLCS-GRIK1chr2138269160chr21309712571922HLA-B58:02DASPGWARW0.95470.9805716
HLCS-GRIK1chr2138269160chr21309712571922HLA-B44:02NDASPGWARW0.990.7117616
HLCS-GRIK1chr2138269160chr21309712571922HLA-B57:01HNDASPGWARW10.995516
HLCS-GRIK1chr2138269160chr21309712571922HLA-B58:02HNDASPGWARW0.99980.9901516
HLCS-GRIK1chr2138269160chr21309712571922HLA-B57:03HNDASPGWARW0.99960.9978516
HLCS-GRIK1chr2138269160chr21309712571922HLA-B58:01HNDASPGWARW0.99960.9924516
HLCS-GRIK1chr2138269160chr21309712571922HLA-B27:05GWARWDGLTGH0.99890.59711122
HLCS-GRIK1chr2138269160chr21309712571922HLA-B27:04GWARWDGLTGH0.99830.79681122
HLCS-GRIK1chr2138269160chr21309712571922HLA-B44:06DASPGWARW0.33370.6644716
HLCS-GRIK1chr2138269160chr21309712571922HLA-B44:04NDASPGWARW0.98920.6304616
HLCS-GRIK1chr2138269160chr21309712571922HLA-B44:08NDASPGWARW0.98090.7744616
HLCS-GRIK1chr2138269160chr21309712571922HLA-B44:06NDASPGWARW0.97420.5112616
HLCS-GRIK1chr2138269160chr21309712571922HLA-B27:14GWARWDGLTGH0.99880.68531122
HLCS-GRIK1chr2138269160chr21309712571922HLA-B27:03GWARWDGLTGH0.98240.63281122
HLCS-GRIK1chr2138269160chr21309712571922HLA-B53:02DASPGWARW0.98530.8202716
HLCS-GRIK1chr2138269160chr21309712571922HLA-A25:01DASPGWARW0.98290.9775716
HLCS-GRIK1chr2138269160chr21309712571922HLA-B57:04DASPGWARW0.97010.804716
HLCS-GRIK1chr2138269160chr21309712571922HLA-B58:06DASPGWARW0.9540.9879716
HLCS-GRIK1chr2138269160chr21309712571922HLA-B15:13DASPGWARW0.9450.9677716
HLCS-GRIK1chr2138269160chr21309712571922HLA-B51:06DASPGWARW0.66070.9318716
HLCS-GRIK1chr2138269160chr21309712571922HLA-B44:22NDASPGWARW0.990.7117616
HLCS-GRIK1chr2138269160chr21309712571922HLA-B44:21NDASPGWARW0.98730.6125616
HLCS-GRIK1chr2138269160chr21309712571922HLA-B27:08WARWDGLTGH0.90620.62431222
HLCS-GRIK1chr2138269160chr21309712571922HLA-B57:10HNDASPGWARW10.995516
HLCS-GRIK1chr2138269160chr21309712571922HLA-B57:04HNDASPGWARW0.99990.8315516
HLCS-GRIK1chr2138269160chr21309712571922HLA-B58:06HNDASPGWARW0.99980.9905516
HLCS-GRIK1chr2138269160chr21309712571922HLA-B57:02HNDASPGWARW0.99950.9807516
HLCS-GRIK1chr2138269160chr21309712571922HLA-B27:10GWARWDGLTGH0.99880.81891122
HLCS-GRIK1chr2138269160chr21309712571922HLA-B27:08GWARWDGLTGH0.99870.55981122

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Potential FusionNeoAntigen Information of HLCS-GRIK1 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 HLCS-GRIK1

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
6107NDASPGWARWDGLTHLCSGRIK1chr2138269160chr21309712571922

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HLCS-GRIK1

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-B14:023BVN6107NDASPGWARWDGLT-3.90988-6.26068
HLA-B14:023BVN6107NDASPGWARWDGLT-3.53569-3.54699
HLA-B52:013W396107NDASPGWARWDGLT-5.89258-5.90388
HLA-B52:013W396107NDASPGWARWDGLT-4.54668-6.89748
HLA-A11:014UQ26107NDASPGWARWDGLT-8.08338-8.09468
HLA-A11:014UQ26107NDASPGWARWDGLT-4.42539-6.77619
HLA-A24:025HGA6107NDASPGWARWDGLT-7.0067-9.3575
HLA-A24:025HGA6107NDASPGWARWDGLT-5.79664-5.80794
HLA-B27:056PYJ6107NDASPGWARWDGLT-3.03787-5.38867
HLA-B27:056PYJ6107NDASPGWARWDGLT-2.63644-2.64774
HLA-B44:053DX86107NDASPGWARWDGLT-6.98104-6.99234
HLA-B44:053DX86107NDASPGWARWDGLT-5.37115-7.72195
HLA-A02:016TDR6107NDASPGWARWDGLT-2.16303-2.17433

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Vaccine Design for the FusionNeoAntigens of HLCS-GRIK1

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
HLCS-GRIK1chr2138269160chr21309712571122GWARWDGLTGHGGATGGGCCCGGTGGGATGGCTTGACTGGGCAT
HLCS-GRIK1chr2138269160chr21309712571222WARWDGLTGHTGGGCCCGGTGGGATGGCTTGACTGGGCAT
HLCS-GRIK1chr2138269160chr2130971257516HNDASPGWARWCACAACGATGCGTCTCCTGGATGGGCCCGGTGG
HLCS-GRIK1chr2138269160chr2130971257616NDASPGWARWAACGATGCGTCTCCTGGATGGGCCCGGTGG
HLCS-GRIK1chr2138269160chr2130971257715DASPGWARGATGCGTCTCCTGGATGGGCCCGG
HLCS-GRIK1chr2138269160chr2130971257716DASPGWARWGATGCGTCTCCTGGATGGGCCCGGTGG
HLCS-GRIK1chr2138269160chr2130971257816ASPGWARWGCGTCTCCTGGATGGGCCCGGTGG

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 HLCS-GRIK1

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
LUADHLCS-GRIK1chr2138269160ENST00000336648chr2130971257ENST00000309434TCGA-50-5944-01A

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Potential target of CAR-T therapy development for HLCS-GRIK1

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
TgeneGRIK1chr21:38269160chr21:30971257ENST00000389125616577_5970906.0TransmembraneHelical
TgeneGRIK1chr21:38269160chr21:30971257ENST00000389125616654_6740906.0TransmembraneHelical
TgeneGRIK1chr21:38269160chr21:30971257ENST00000389125616835_8550906.0TransmembraneHelical
TgeneGRIK1chr21:38269160chr21:30971257ENST00000399907617577_5970919.0TransmembraneHelical
TgeneGRIK1chr21:38269160chr21:30971257ENST00000399907617654_6740919.0TransmembraneHelical
TgeneGRIK1chr21:38269160chr21:30971257ENST00000399907617835_8550919.0TransmembraneHelical

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 HLCS-GRIK1

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 HLCS-GRIK1

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