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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:TSC2-RBP1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TSC2-RBP1
FusionPDB ID: 94521
FusionGDB2.0 ID: 94521
HgeneTgene
Gene symbol

TSC2

RBP1

Gene ID

7249

5947

Gene nameTSC complex subunit 2retinol binding protein 1
SynonymsLAM|PPP1R160|TSC4CRABP-I|CRBP|CRBP1|CRBPI|RBPC
Cytomap

16p13.3

3q23

Type of geneprotein-codingprotein-coding
Descriptiontuberinprotein phosphatase 1, regulatory subunit 160tuberous sclerosis 2 proteinretinol-binding protein 1CRBP-Icellular retinol binding protein 1cellular retinol-binding protein Iretinol-binding protein 1, cellular
Modification date2020031320200313
UniProtAcc

TSC22D4

Main function of 5'-partner protein: 395
.
Ensembl transtripts involved in fusion geneENST idsENST00000219476, ENST00000350773, 
ENST00000353929, ENST00000382538, 
ENST00000401874, ENST00000439673, 
ENST00000568454, ENST00000568366, 
ENST00000483943, ENST00000492918, 
ENST00000232219, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 12 X 6=7204 X 3 X 3=36
# samples 126
** MAII scorelog2(12/720*10)=-2.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/36*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: TSC2 [Title/Abstract] AND RBP1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TSC2 [Title/Abstract] AND RBP1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TSC2(2108874)-RBP1(139258671), # samples:1
TSC2(2108874)-RBP1(139258674), # samples:1
Anticipated loss of major functional domain due to fusion event.TSC2-RBP1 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.
TSC2-RBP1 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.
TSC2-RBP1 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.
TSC2-RBP1 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/chr16:2108874/chr3:139258671)
- 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 TSC2 (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 RBP1 (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)
ENST00000219476TSC2chr162108874+ENST00000232219RBP1chr3139258671-25031605572309750
ENST00000382538TSC2chr162108874+ENST00000232219RBP1chr3139258671-1821923891627512
ENST00000401874TSC2chr162108874+ENST00000232219RBP1chr3139258671-197910811061785559
ENST00000353929TSC2chr162108874+ENST00000232219RBP1chr3139258671-197910811061785559
ENST00000439673TSC2chr162108874+ENST00000232219RBP1chr3139258671-1843945811649522
ENST00000350773TSC2chr162108874+ENST00000232219RBP1chr3139258671-19481050751754559
ENST00000568454TSC2chr162108874+ENST00000232219RBP1chr3139258671-19741076591780573
ENST00000219476TSC2chr162108874+ENST00000232219RBP1chr3139258674-25031605572309750
ENST00000382538TSC2chr162108874+ENST00000232219RBP1chr3139258674-1821923891627512
ENST00000401874TSC2chr162108874+ENST00000232219RBP1chr3139258674-197910811061785559
ENST00000353929TSC2chr162108874+ENST00000232219RBP1chr3139258674-197910811061785559
ENST00000439673TSC2chr162108874+ENST00000232219RBP1chr3139258674-1843945811649522
ENST00000350773TSC2chr162108874+ENST00000232219RBP1chr3139258674-19481050751754559
ENST00000568454TSC2chr162108874+ENST00000232219RBP1chr3139258674-19741076591780573

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
ENST00000219476ENST00000232219TSC2chr162108874+RBP1chr3139258671-0.029652120.9703479
ENST00000382538ENST00000232219TSC2chr162108874+RBP1chr3139258671-0.005794620.9942054
ENST00000401874ENST00000232219TSC2chr162108874+RBP1chr3139258671-0.0083987380.9916013
ENST00000353929ENST00000232219TSC2chr162108874+RBP1chr3139258671-0.0083987380.9916013
ENST00000439673ENST00000232219TSC2chr162108874+RBP1chr3139258671-0.0081263960.99187356
ENST00000350773ENST00000232219TSC2chr162108874+RBP1chr3139258671-0.0089880960.991012
ENST00000568454ENST00000232219TSC2chr162108874+RBP1chr3139258671-0.0074460960.9925539
ENST00000219476ENST00000232219TSC2chr162108874+RBP1chr3139258674-0.029652120.9703479
ENST00000382538ENST00000232219TSC2chr162108874+RBP1chr3139258674-0.005794620.9942054
ENST00000401874ENST00000232219TSC2chr162108874+RBP1chr3139258674-0.0083987380.9916013
ENST00000353929ENST00000232219TSC2chr162108874+RBP1chr3139258674-0.0083987380.9916013
ENST00000439673ENST00000232219TSC2chr162108874+RBP1chr3139258674-0.0081263960.99187356
ENST00000350773ENST00000232219TSC2chr162108874+RBP1chr3139258674-0.0089880960.991012
ENST00000568454ENST00000232219TSC2chr162108874+RBP1chr3139258674-0.0074460960.9925539

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 TSC2-RBP1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TSC2chr162108874RBP1chr31392586711050325RNSPTSVLPSFYQKRTERLKRRWRGL
TSC2chr162108874RBP1chr31392586711076339RNSPTSVLPSFYQKRTERLKRRWRGL
TSC2chr162108874RBP1chr31392586711081325RNSPTSVLPSFYQKRTERLKRRWRGL
TSC2chr162108874RBP1chr31392586711605516RNSPTSVLPSFYQKRTERLKRRWRGL
TSC2chr162108874RBP1chr3139258671923278RNSPTSVLPSFYQKRTERLKRRWRGL
TSC2chr162108874RBP1chr3139258671945288RNSPTSVLPSFYQKRTERLKRRWRGL
TSC2chr162108874RBP1chr31392586741050325RNSPTSVLPSFYQKRTERLKRRWRGL
TSC2chr162108874RBP1chr31392586741076339RNSPTSVLPSFYQKRTERLKRRWRGL
TSC2chr162108874RBP1chr31392586741081325RNSPTSVLPSFYQKRTERLKRRWRGL
TSC2chr162108874RBP1chr31392586741605516RNSPTSVLPSFYQKRTERLKRRWRGL
TSC2chr162108874RBP1chr3139258674923278RNSPTSVLPSFYQKRTERLKRRWRGL
TSC2chr162108874RBP1chr3139258674945288RNSPTSVLPSFYQKRTERLKRRWRGL

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Potential FusionNeoAntigen Information of TSC2-RBP1 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.
TSC2-RBP1_2108874_139258671.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)
TSC2-RBP1chr162108874chr31392586711605HLA-A74:03VLPSFYQKR0.94370.6092615
TSC2-RBP1chr162108874chr31392586711605HLA-A74:11VLPSFYQKR0.94370.6092615
TSC2-RBP1chr162108874chr31392586711605HLA-A74:09VLPSFYQKR0.94370.6092615
TSC2-RBP1chr162108874chr31392586711605HLA-A31:02VLPSFYQKR0.92110.5516615
TSC2-RBP1chr162108874chr31392586711605HLA-A74:03SVLPSFYQKR0.98180.5128515
TSC2-RBP1chr162108874chr31392586711605HLA-A74:11SVLPSFYQKR0.98180.5128515
TSC2-RBP1chr162108874chr31392586711605HLA-A74:09SVLPSFYQKR0.98180.5128515
TSC2-RBP1chr162108874chr31392586711605HLA-C12:16FYQKRTERL0.49750.94691019
TSC2-RBP1chr162108874chr31392586711605HLA-B14:03FYQKRTERL0.3790.5551019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:19FYQKRTERL0.35060.57911019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:05FYQKRTERL0.34650.91051019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:29FYQKRTERL0.32910.89131019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:10FYQKRTERL0.32540.94821019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:67FYQKRTERL0.32520.9171019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:80FYQKRTERL0.32520.9171019
TSC2-RBP1chr162108874chr31392586711605HLA-B39:12FYQKRTERL0.31310.76911019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:13FYQKRTERL0.29230.87431019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:46FYQKRTERL0.29180.81381019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:27FYQKRTERL0.21080.91411019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:95FYQKRTERL0.1720.57811019
TSC2-RBP1chr162108874chr31392586711605HLA-C04:14FYQKRTERL0.16790.73961019
TSC2-RBP1chr162108874chr31392586711605HLA-C04:10FYQKRTERL0.06230.58651019
TSC2-RBP1chr162108874chr31392586711605HLA-C04:07FYQKRTERL0.05520.60121019
TSC2-RBP1chr162108874chr31392586711605HLA-A30:01SVLPSFYQK0.98530.6552514
TSC2-RBP1chr162108874chr31392586711605HLA-A74:01VLPSFYQKR0.94370.6092615
TSC2-RBP1chr162108874chr31392586711605HLA-A30:01SFYQKRTER0.88320.754918
TSC2-RBP1chr162108874chr31392586711605HLA-C07:22FYQKRTERL0.58140.64231019
TSC2-RBP1chr162108874chr31392586711605HLA-C03:67FYQKRTERL0.55440.95191019
TSC2-RBP1chr162108874chr31392586711605HLA-C06:02FYQKRTERL0.41460.98391019
TSC2-RBP1chr162108874chr31392586711605HLA-C06:17FYQKRTERL0.41460.98391019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:04FYQKRTERL0.36080.81411019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:02FYQKRTERL0.32520.9171019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:17FYQKRTERL0.28450.95161019
TSC2-RBP1chr162108874chr31392586711605HLA-C07:01FYQKRTERL0.18750.56281019
TSC2-RBP1chr162108874chr31392586711605HLA-C14:03FYQKRTERL0.15950.93141019
TSC2-RBP1chr162108874chr31392586711605HLA-C14:02FYQKRTERL0.15950.93141019
TSC2-RBP1chr162108874chr31392586711605HLA-C06:06FYQKRTERL0.14930.97571019
TSC2-RBP1chr162108874chr31392586711605HLA-C04:04FYQKRTERL0.09590.75671019
TSC2-RBP1chr162108874chr31392586711605HLA-C18:01FYQKRTERL0.07170.62131019
TSC2-RBP1chr162108874chr31392586711605HLA-C04:01FYQKRTERL0.05520.60121019
TSC2-RBP1chr162108874chr31392586711605HLA-C06:08FYQKRTERL0.03340.97911019
TSC2-RBP1chr162108874chr31392586711605HLA-A74:01SVLPSFYQKR0.98180.5128515
TSC2-RBP1chr162108874chr31392586711605HLA-C14:02SFYQKRTERL0.74830.9291919
TSC2-RBP1chr162108874chr31392586711605HLA-C14:03SFYQKRTERL0.74830.9291919

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Potential FusionNeoAntigen Information of TSC2-RBP1 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.
TSC2-RBP1_2108874_139258671.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)
TSC2-RBP1chr162108874chr31392586711605DRB1-0103LPSFYQKRTERLKRR722
TSC2-RBP1chr162108874chr31392586711605DRB1-0103VLPSFYQKRTERLKR621
TSC2-RBP1chr162108874chr31392586711605DRB1-0103PSFYQKRTERLKRRW823
TSC2-RBP1chr162108874chr31392586711605DRB1-1367LPSFYQKRTERLKRR722
TSC2-RBP1chr162108874chr31392586711605DRB1-1367VLPSFYQKRTERLKR621
TSC2-RBP1chr162108874chr31392586711605DRB1-1367PSFYQKRTERLKRRW823
TSC2-RBP1chr162108874chr31392586711605DRB1-1467LPSFYQKRTERLKRR722
TSC2-RBP1chr162108874chr31392586711605DRB1-1498LPSFYQKRTERLKRR722
TSC2-RBP1chr162108874chr31392586711605DRB5-0103LPSFYQKRTERLKRR722

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Fusion breakpoint peptide structures of TSC2-RBP1

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
10094VLPSFYQKRTERLKTSC2RBP1chr162108874chr31392586711605

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TSC2-RBP1

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-B14:023BVN10094VLPSFYQKRTERLK-7.9962-8.1096
HLA-B14:023BVN10094VLPSFYQKRTERLK-5.70842-6.74372
HLA-B52:013W3910094VLPSFYQKRTERLK-6.83737-6.95077
HLA-B52:013W3910094VLPSFYQKRTERLK-4.4836-5.5189
HLA-A11:014UQ210094VLPSFYQKRTERLK-10.0067-10.1201
HLA-A11:014UQ210094VLPSFYQKRTERLK-9.03915-10.0745
HLA-A24:025HGA10094VLPSFYQKRTERLK-6.56204-6.67544
HLA-A24:025HGA10094VLPSFYQKRTERLK-5.42271-6.45801
HLA-B44:053DX810094VLPSFYQKRTERLK-7.85648-8.89178
HLA-B44:053DX810094VLPSFYQKRTERLK-5.3978-5.5112
HLA-B35:011A1N10094VLPSFYQKRTERLK-6.27422-6.38762
HLA-B35:011A1N10094VLPSFYQKRTERLK-5.27424-6.30954
HLA-A02:016TDR10094VLPSFYQKRTERLK-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of TSC2-RBP1

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
TSC2-RBP1chr162108874chr31392586711019FYQKRTERLTTTTACCAGAAACGAACTGAACGTCTG
TSC2-RBP1chr162108874chr3139258671514SVLPSFYQKTCTGTGTTGCCATCATTTTACCAGAAA
TSC2-RBP1chr162108874chr3139258671515SVLPSFYQKRTCTGTGTTGCCATCATTTTACCAGAAACGA
TSC2-RBP1chr162108874chr3139258671615VLPSFYQKRGTGTTGCCATCATTTTACCAGAAACGA
TSC2-RBP1chr162108874chr3139258671918SFYQKRTERTCATTTTACCAGAAACGAACTGAACGT
TSC2-RBP1chr162108874chr3139258671919SFYQKRTERLTCATTTTACCAGAAACGAACTGAACGTCTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TSC2-RBP1chr162108874chr3139258671621VLPSFYQKRTERLKRGTGTTGCCATCATTTTACCAGAAACGAACTGAACGTCTGAAACGA
TSC2-RBP1chr162108874chr3139258671722LPSFYQKRTERLKRRTTGCCATCATTTTACCAGAAACGAACTGAACGTCTGAAACGAAGG
TSC2-RBP1chr162108874chr3139258671823PSFYQKRTERLKRRWCCATCATTTTACCAGAAACGAACTGAACGTCTGAAACGAAGGTGG

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Information of the samples that have these potential fusion neoantigens of TSC2-RBP1

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
OVTSC2-RBP1chr162108874ENST00000219476chr3139258671ENST00000232219TCGA-24-1552

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Potential target of CAR-T therapy development for TSC2-RBP1

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 TSC2-RBP1

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 TSC2-RBP1

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