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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:TCF7L2-GRK5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TCF7L2-GRK5
FusionPDB ID: 89816
FusionGDB2.0 ID: 89816
HgeneTgene
Gene symbol

TCF7L2

GRK5

Gene ID

6934

2869

Gene nametranscription factor 7 like 2G protein-coupled receptor kinase 5
SynonymsTCF-4|TCF4FP2025|GPRK5
Cytomap

10q25.2-q25.3

10q26.11

Type of geneprotein-codingprotein-coding
Descriptiontranscription factor 7-like 2HMG box transcription factor 4T-cell factor 4T-cell-specific transcription factor 4hTCF-4transcription factor 7-like 2 (T-cell specific, HMG-box)G protein-coupled receptor kinase 5g protein-coupled receptor kinase GRK5
Modification date2020031520200313
UniProtAcc

Q9NQB0

Main function of 5'-partner protein: FUNCTION: Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine. {ECO:0000269|PubMed:12408868, ECO:0000269|PubMed:12727872, ECO:0000269|PubMed:19443654, ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:9727977}.

P34947

Main function of 5'-partner protein: FUNCTION: Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro). {ECO:0000269|PubMed:19661922, ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:20038610, ECO:0000269|PubMed:20124405, ECO:0000269|PubMed:21728385}.
Ensembl transtripts involved in fusion geneENST idsENST00000349937, ENST00000355995, 
ENST00000534894, ENST00000536810, 
ENST00000538897, ENST00000543371, 
ENST00000545257, ENST00000352065, 
ENST00000355717, ENST00000369386, 
ENST00000369389, ENST00000369395, 
ENST00000369397, ENST00000466338, 
ENST00000542695, 
ENST00000473264, 
ENST00000369108, ENST00000392870, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score16 X 11 X 11=193619 X 19 X 6=2166
# samples 2319
** MAII scorelog2(23/1936*10)=-3.07337318633022
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(19/2166*10)=-3.51096191927738
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TCF7L2 [Title/Abstract] AND GRK5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TCF7L2 [Title/Abstract] AND GRK5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TCF7L2(114724383)-GRK5(121207635), # samples:1
Anticipated loss of major functional domain due to fusion event.TCF7L2-GRK5 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.
TCF7L2-GRK5 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.
TCF7L2-GRK5 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.
TCF7L2-GRK5 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
HgeneTCF7L2

GO:0000122

negative regulation of transcription by RNA polymerase II

12799378

HgeneTCF7L2

GO:0006357

regulation of transcription by RNA polymerase II

9727977

HgeneTCF7L2

GO:0032092

positive regulation of protein binding

12799378

HgeneTCF7L2

GO:0032350

regulation of hormone metabolic process

15525634

HgeneTCF7L2

GO:0042593

glucose homeostasis

15525634

HgeneTCF7L2

GO:0043433

negative regulation of DNA-binding transcription factor activity

12799378

HgeneTCF7L2

GO:0045444

fat cell differentiation

10937998

HgeneTCF7L2

GO:0045892

negative regulation of transcription, DNA-templated

12799378|15525634

HgeneTCF7L2

GO:0045944

positive regulation of transcription by RNA polymerase II

9065401|19168596

HgeneTCF7L2

GO:0048625

myoblast fate commitment

10937998

TgeneGRK5

GO:0007217

tachykinin receptor signaling pathway

17986524

TgeneGRK5

GO:0043066

negative regulation of apoptotic process

20124405

TgeneGRK5

GO:0046777

protein autophosphorylation

14976207



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/chr10:114724383/chr10:121207635)
- 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 TCF7L2 (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 GRK5 (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)
ENST00000534894TCF7L2chr10114724383+ENST00000392870GRK5chr10121207635+20169571771463428
ENST00000534894TCF7L2chr10114724383+ENST00000369108GRK5chr10121207635+15159571771463428
ENST00000536810TCF7L2chr10114724383+ENST00000392870GRK5chr10121207635+20169571771463428
ENST00000536810TCF7L2chr10114724383+ENST00000369108GRK5chr10121207635+15159571771463428
ENST00000545257TCF7L2chr10114724383+ENST00000392870GRK5chr10121207635+20169571771463428
ENST00000545257TCF7L2chr10114724383+ENST00000369108GRK5chr10121207635+15159571771463428
ENST00000355995TCF7L2chr10114724383+ENST00000392870GRK5chr10121207635+20169571771463428
ENST00000355995TCF7L2chr10114724383+ENST00000369108GRK5chr10121207635+15159571771463428
ENST00000543371TCF7L2chr10114724383+ENST00000392870GRK5chr10121207635+20169571771463428
ENST00000543371TCF7L2chr10114724383+ENST00000369108GRK5chr10121207635+15159571771463428
ENST00000538897TCF7L2chr10114724383+ENST00000392870GRK5chr10121207635+20169571771463428
ENST00000538897TCF7L2chr10114724383+ENST00000369108GRK5chr10121207635+15159571771463428
ENST00000349937TCF7L2chr10114724383+ENST00000392870GRK5chr10121207635+1814755381261407
ENST00000349937TCF7L2chr10114724383+ENST00000369108GRK5chr10121207635+1313755381261407

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
ENST00000534894ENST00000392870TCF7L2chr10114724383+GRK5chr10121207635+0.0019263990.9980736
ENST00000534894ENST00000369108TCF7L2chr10114724383+GRK5chr10121207635+0.0039740410.9960259
ENST00000536810ENST00000392870TCF7L2chr10114724383+GRK5chr10121207635+0.0019263990.9980736
ENST00000536810ENST00000369108TCF7L2chr10114724383+GRK5chr10121207635+0.0039740410.9960259
ENST00000545257ENST00000392870TCF7L2chr10114724383+GRK5chr10121207635+0.0019263990.9980736
ENST00000545257ENST00000369108TCF7L2chr10114724383+GRK5chr10121207635+0.0039740410.9960259
ENST00000355995ENST00000392870TCF7L2chr10114724383+GRK5chr10121207635+0.0019263990.9980736
ENST00000355995ENST00000369108TCF7L2chr10114724383+GRK5chr10121207635+0.0039740410.9960259
ENST00000543371ENST00000392870TCF7L2chr10114724383+GRK5chr10121207635+0.0019263990.9980736
ENST00000543371ENST00000369108TCF7L2chr10114724383+GRK5chr10121207635+0.0039740410.9960259
ENST00000538897ENST00000392870TCF7L2chr10114724383+GRK5chr10121207635+0.0019263990.9980736
ENST00000538897ENST00000369108TCF7L2chr10114724383+GRK5chr10121207635+0.0039740410.9960259
ENST00000349937ENST00000392870TCF7L2chr10114724383+GRK5chr10121207635+0.001930920.9980691
ENST00000349937ENST00000369108TCF7L2chr10114724383+GRK5chr10121207635+0.0046220510.9953779

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 TCF7L2-GRK5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TCF7L2chr10114724383GRK5chr10121207635755238YSAYKTIEHQIAVQLLTKDAKQRLGC
TCF7L2chr10114724383GRK5chr10121207635957259YSAYKTIEHQIAVQLLTKDAKQRLGC

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Potential FusionNeoAntigen Information of TCF7L2-GRK5 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.
TCF7L2-GRK5_114724383_121207635.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)
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:01EHQIAVQL0.99950.8003715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:06EHQIAVQL0.99940.7311715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:24EHQIAVQL0.99940.6059715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B38:02EHQIAVQL0.99930.867715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B38:01EHQIAVQL0.99930.8478715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B14:02EHQIAVQL0.99780.828715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B14:01EHQIAVQL0.99780.828715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B48:01HQIAVQLL0.99670.6588816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:10EHQIAVQL0.99660.5698715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:37EHQIAVQL0.99340.617715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:13HQIAVQLL0.98120.9127816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B13:02HQIAVQLL0.96970.7361816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B13:01HQIAVQLL0.96770.9709816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:10HQIAVQLL0.95250.6209816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:37HQIAVQLL0.78920.595816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B52:01HQIAVQLL0.74320.9474816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:01EHQIAVQLL0.99890.7844716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B38:02EHQIAVQLL0.99860.8574716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B38:01EHQIAVQLL0.99850.8392716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:24EHQIAVQLL0.99670.5488716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:06EHQIAVQLL0.99640.6677716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B13:01IEHQIAVQL0.99640.7915615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B14:01EHQIAVQLL0.98990.7303716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B14:02EHQIAVQLL0.98990.7303716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B18:01IEHQIAVQL0.93430.9033615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B44:03IEHQIAVQL0.92420.7676615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B45:01IEHQIAVQL0.91780.6818615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:10EHQIAVQLL0.91680.5134716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:37EHQIAVQLL0.88030.5398716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:13IEHQIAVQL0.74420.8469615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:37IEHQIAVQL0.72550.6437615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B13:02HQIAVQLLT0.72530.9467817
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B38:02IEHQIAVQL0.72480.9154615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:18EHQIAVQLL0.69060.5949716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B50:01IEHQIAVQL0.46480.6476615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B41:01IEHQIAVQL0.37650.8109615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B52:01IEHQIAVQL0.28020.7705615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B38:01IEHQIAVQLL0.66880.8597616
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:17KTIEHQIAVQL0.99950.9556415
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B57:03KTIEHQIAVQL0.99940.9925415
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B40:01KTIEHQIAVQL0.64630.5483415
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B38:01TIEHQIAVQLL0.37910.9701516
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:09EHQIAVQL0.99970.6716715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:12EHQIAVQL0.99940.8067715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:05EHQIAVQL0.99910.7836715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B48:03HQIAVQLL0.99070.5134816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:05HQIAVQLL0.9740.9042816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B14:03EHQIAVQL0.86870.8242715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B40:06IEHQIAVQL0.99930.5498615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:09EHQIAVQLL0.9990.6822716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:12EHQIAVQLL0.99870.7916716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:05EHQIAVQLL0.99840.7659716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:09IEHQIAVQL0.77780.7132615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:08IEHQIAVQL0.75280.7954615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:05IEHQIAVQL0.73660.8274615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B14:03EHQIAVQLL0.42470.7944716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B51:07IEHQIAVQL0.2320.7475615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-C15:06KTIEHQIAVQL0.99990.9602415
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B48:03KTIEHQIAVQL0.60350.6418415
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:31EHQIAVQL0.99940.8026715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B38:05EHQIAVQL0.99930.8478715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:73HQIAVQLL0.99610.9297816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:11EHQIAVQL0.99340.7566715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:09EHQIAVQL0.99310.5793715
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B40:12HQIAVQLL0.99070.5134816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:30HQIAVQLL0.99070.8954816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:02HQIAVQLL0.99020.9165816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B40:21HQIAVQLL0.96230.6424816
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B40:04IEHQIAVQL0.99930.6306615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:31EHQIAVQLL0.9990.7864716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B38:05EHQIAVQLL0.99850.8392716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B18:04IEHQIAVQL0.95880.9058615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B18:06IEHQIAVQL0.94210.9158615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B18:08IEHQIAVQL0.94120.9123615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B18:07IEHQIAVQL0.93610.8596615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B18:03IEHQIAVQL0.93470.8944615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B18:05IEHQIAVQL0.93430.9033615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:09EHQIAVQLL0.92670.5787716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B44:07IEHQIAVQL0.92420.7676615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B44:13IEHQIAVQL0.92420.7676615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B44:26IEHQIAVQL0.92420.7676615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:11EHQIAVQLL0.85550.6983716
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:31IEHQIAVQL0.78790.8393615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:02IEHQIAVQL0.78670.8493615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B39:11IEHQIAVQL0.74310.7616615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B18:11IEHQIAVQL0.65890.8059615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B50:04IEHQIAVQL0.46480.6476615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B50:05IEHQIAVQL0.46480.6476615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B48:02IEHQIAVQL0.43710.7831615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B15:53IEHQIAVQL0.19480.7459615
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B40:04IEHQIAVQLL0.9940.6084616
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B38:05IEHQIAVQLL0.66880.8597616
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B41:03TIEHQIAVQL0.45660.5572515
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B40:04TIEHQIAVQL0.42570.7659515
TCF7L2-GRK5chr10114724383chr10121207635755HLA-C15:05KTIEHQIAVQL0.99990.9516415
TCF7L2-GRK5chr10114724383chr10121207635755HLA-C15:02KTIEHQIAVQL0.99980.9435415
TCF7L2-GRK5chr10114724383chr10121207635755HLA-A32:01KTIEHQIAVQL0.99610.9826415
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B40:04KTIEHQIAVQL0.7190.8063415
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B40:36KTIEHQIAVQL0.66320.5248415
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B40:49KTIEHQIAVQL0.63860.5831415
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B40:12KTIEHQIAVQL0.60350.6418415
TCF7L2-GRK5chr10114724383chr10121207635755HLA-B38:05TIEHQIAVQLL0.37910.9701516

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Potential FusionNeoAntigen Information of TCF7L2-GRK5 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.
TCF7L2-GRK5_114724383_121207635.msa

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)
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0102YKTIEHQIAVQLLTK318
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0111YKTIEHQIAVQLLTK318
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0123YKTIEHQIAVQLLTK318
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0301IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0301AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0303IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0303AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0307IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0307AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0310IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0310AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0313IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0313AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0315IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0318IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0318AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0320IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0320AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0322IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0322AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0324IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0326IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0328IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0328AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0330IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0330AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0332IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0332AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0334IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0334AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0336IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0336AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0344IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0344AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0346IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0346AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0348IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0348AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0350IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0350AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0352IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0352AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0354IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-0354AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-1107IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-1107AVQLLTKDAKQRLGC1126
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-1476IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB1-1479IAVQLLTKDAKQRLG1025
TCF7L2-GRK5chr10114724383chr10121207635755DRB4-0101EHQIAVQLLTKDAKQ722
TCF7L2-GRK5chr10114724383chr10121207635755DRB4-0101IEHQIAVQLLTKDAK621
TCF7L2-GRK5chr10114724383chr10121207635755DRB4-0103EHQIAVQLLTKDAKQ722
TCF7L2-GRK5chr10114724383chr10121207635755DRB4-0103IEHQIAVQLLTKDAK621
TCF7L2-GRK5chr10114724383chr10121207635755DRB4-0104EHQIAVQLLTKDAKQ722
TCF7L2-GRK5chr10114724383chr10121207635755DRB4-0106EHQIAVQLLTKDAKQ722
TCF7L2-GRK5chr10114724383chr10121207635755DRB4-0106IEHQIAVQLLTKDAK621
TCF7L2-GRK5chr10114724383chr10121207635755DRB4-0107EHQIAVQLLTKDAKQ722
TCF7L2-GRK5chr10114724383chr10121207635755DRB4-0107IEHQIAVQLLTKDAK621
TCF7L2-GRK5chr10114724383chr10121207635755DRB4-0108EHQIAVQLLTKDAKQ722
TCF7L2-GRK5chr10114724383chr10121207635755DRB4-0108IEHQIAVQLLTKDAK621

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Fusion breakpoint peptide structures of TCF7L2-GRK5

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
3645IEHQIAVQLLTKDATCF7L2GRK5chr10114724383chr10121207635755

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TCF7L2-GRK5

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-B14:023BVN3645IEHQIAVQLLTKDA-7.5588-7.6706
HLA-B14:023BVN3645IEHQIAVQLLTKDA-4.42712-5.47022
HLA-B52:013W393645IEHQIAVQLLTKDA-5.79336-5.90516
HLA-B52:013W393645IEHQIAVQLLTKDA-4.82735-5.87045
HLA-A11:014UQ23645IEHQIAVQLLTKDA-10.3742-10.486
HLA-A24:025HGA3645IEHQIAVQLLTKDA-7.36249-8.40559
HLA-A24:025HGA3645IEHQIAVQLLTKDA-7.07591-7.18771
HLA-B27:056PYJ3645IEHQIAVQLLTKDA-8.75018-8.86198
HLA-B44:053DX83645IEHQIAVQLLTKDA-5.28726-5.39906
HLA-B44:053DX83645IEHQIAVQLLTKDA-4.30205-5.34515
HLA-A02:016TDR3645IEHQIAVQLLTKDA-4.2167-4.3285

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Vaccine Design for the FusionNeoAntigens of TCF7L2-GRK5

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
TCF7L2-GRK5chr10114724383chr10121207635415KTIEHQIAVQLACGATTGAACACCAGATTGCAGTTCAGCTGCTC
TCF7L2-GRK5chr10114724383chr10121207635515TIEHQIAVQLATTGAACACCAGATTGCAGTTCAGCTGCTC
TCF7L2-GRK5chr10114724383chr10121207635516TIEHQIAVQLLATTGAACACCAGATTGCAGTTCAGCTGCTCACG
TCF7L2-GRK5chr10114724383chr10121207635615IEHQIAVQLGAACACCAGATTGCAGTTCAGCTGCTC
TCF7L2-GRK5chr10114724383chr10121207635616IEHQIAVQLLGAACACCAGATTGCAGTTCAGCTGCTCACG
TCF7L2-GRK5chr10114724383chr10121207635715EHQIAVQLCACCAGATTGCAGTTCAGCTGCTC
TCF7L2-GRK5chr10114724383chr10121207635716EHQIAVQLLCACCAGATTGCAGTTCAGCTGCTCACG
TCF7L2-GRK5chr10114724383chr10121207635816HQIAVQLLCAGATTGCAGTTCAGCTGCTCACG
TCF7L2-GRK5chr10114724383chr10121207635817HQIAVQLLTCAGATTGCAGTTCAGCTGCTCACGAAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TCF7L2-GRK5chr10114724383chr101212076351025IAVQLLTKDAKQRLGGCAGTTCAGCTGCTCACGAAAGATGCGAAGCAGAGGCTGGGCTGC
TCF7L2-GRK5chr10114724383chr101212076351126AVQLLTKDAKQRLGCGTTCAGCTGCTCACGAAAGATGCGAAGCAGAGGCTGGGCTGCCAG
TCF7L2-GRK5chr10114724383chr10121207635318YKTIEHQIAVQLLTKAAAACGATTGAACACCAGATTGCAGTTCAGCTGCTCACGAAAGAT
TCF7L2-GRK5chr10114724383chr10121207635621IEHQIAVQLLTKDAKGAACACCAGATTGCAGTTCAGCTGCTCACGAAAGATGCGAAGCAG
TCF7L2-GRK5chr10114724383chr10121207635722EHQIAVQLLTKDAKQCACCAGATTGCAGTTCAGCTGCTCACGAAAGATGCGAAGCAGAGG

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Information of the samples that have these potential fusion neoantigens of TCF7L2-GRK5

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
COADTCF7L2-GRK5chr10114724383ENST00000349937chr10121207635ENST00000369108TCGA-AA-3837-01A

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Potential target of CAR-T therapy development for TCF7L2-GRK5

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 TCF7L2-GRK5

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 TCF7L2-GRK5

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
HgeneTCF7L2C0036341Schizophrenia4PSYGENET
HgeneTCF7L2C0011860Diabetes Mellitus, Non-Insulin-Dependent3CTD_human
HgeneTCF7L2C0009402Colorectal Carcinoma2CTD_human;UNIPROT
HgeneTCF7L2C0009404Colorectal Neoplasms2CTD_human
HgeneTCF7L2C0001418Adenocarcinoma1CTD_human
HgeneTCF7L2C0005586Bipolar Disorder1PSYGENET
HgeneTCF7L2C0007102Malignant tumor of colon1CTD_human
HgeneTCF7L2C0007193Cardiomyopathy, Dilated1CTD_human
HgeneTCF7L2C0009375Colonic Neoplasms1CTD_human
HgeneTCF7L2C0010068Coronary heart disease1CTD_human
HgeneTCF7L2C0020507Hyperplasia1CTD_human
HgeneTCF7L2C0036337Schizoaffective Disorder1PSYGENET
HgeneTCF7L2C0087031Juvenile-Onset Still Disease1CTD_human
HgeneTCF7L2C0151744Myocardial Ischemia1CTD_human
HgeneTCF7L2C0205641Adenocarcinoma, Basal Cell1CTD_human
HgeneTCF7L2C0205642Adenocarcinoma, Oxyphilic1CTD_human
HgeneTCF7L2C0205643Carcinoma, Cribriform1CTD_human
HgeneTCF7L2C0205644Carcinoma, Granular Cell1CTD_human
HgeneTCF7L2C0205645Adenocarcinoma, Tubular1CTD_human
HgeneTCF7L2C0600519Ventricular Remodeling1CTD_human
HgeneTCF7L2C0600520Left Ventricle Remodeling1CTD_human
HgeneTCF7L2C1449563Cardiomyopathy, Familial Idiopathic1CTD_human
HgeneTCF7L2C1535926Neurodevelopmental Disorders1CTD_human
HgeneTCF7L2C2931456Prostate cancer, familial1CTD_human
HgeneTCF7L2C3495559Juvenile arthritis1CTD_human
HgeneTCF7L2C3714758Juvenile psoriatic arthritis1CTD_human
HgeneTCF7L2C4552091Polyarthritis, Juvenile, Rheumatoid Factor Negative1CTD_human
HgeneTCF7L2C4704862Polyarthritis, Juvenile, Rheumatoid Factor Positive1CTD_human
HgeneTCF7L2C4722327PROSTATE CANCER, HEREDITARY, 11CTD_human