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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:C2CD5-PBX4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: C2CD5-PBX4
FusionPDB ID: 11622
FusionGDB2.0 ID: 11622
HgeneTgene
Gene symbol

C2CD5

PBX4

Gene ID

9847

80714

Gene nameC2 calcium dependent domain containing 5PBX homeobox 4
SynonymsCDP138|KIAA0528-
Cytomap

12p12.1

19p13.11

Type of geneprotein-codingprotein-coding
DescriptionC2 domain-containing protein 5138 kDa C2 domain-containing phosphoproteinpre-B-cell leukemia transcription factor 4homeobox protein PBX4pre-B-cell leukemia homeobox 4
Modification date2020031320200327
UniProtAcc

Q86YS7

Main function of 5'-partner protein: FUNCTION: Required for insulin-stimulated glucose transport and glucose transporter SLC2A4/GLUT4 translocation from intracellular glucose storage vesicle (GSV) to the plasma membrane (PM) in adipocytes. Binds phospholipid membranes in a calcium-dependent manner and is necessary for the optimal membrane fusion between SLC2A4/GLUT4 GSV and the PM. {ECO:0000269|PubMed:21907143}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000544930, ENST00000333957, 
ENST00000396028, ENST00000446597, 
ENST00000536386, ENST00000545552, 
ENST00000542676, ENST00000540703, 
ENST00000251203, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 8 X 6=4807 X 5 X 4=140
# samples 97
** MAII scorelog2(9/480*10)=-2.41503749927884
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/140*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: C2CD5 [Title/Abstract] AND PBX4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: C2CD5 [Title/Abstract] AND PBX4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)C2CD5(22696995)-PBX4(19675898), # samples:1
Anticipated loss of major functional domain due to fusion event.C2CD5-PBX4 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.
C2CD5-PBX4 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.
C2CD5-PBX4 seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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
HgeneC2CD5

GO:0032869

cellular response to insulin stimulus

21907143



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/chr12:22696995/chr19:19675898)
- 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 C2CD5 (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 PBX4 (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)
ENST00000542676C2CD5chr1222696995-ENST00000251203PBX4chr1919675898-86219358549163

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
ENST00000542676ENST00000251203C2CD5chr1222696995-PBX4chr1919675898-0.040810590.95918936

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 C2CD5-PBX4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
C2CD5chr1222696995PBX4chr191967589819345MDRASDLTDAFVEVSNWFGNKRIRYK

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Potential FusionNeoAntigen Information of C2CD5-PBX4 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.
C2CD5-PBX4_22696995_19675898.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)
C2CD5-PBX4chr1222696995chr1919675898193HLA-B57:01TDAFVEVSNW0.99860.9668717
C2CD5-PBX4chr1222696995chr1919675898193HLA-B58:01TDAFVEVSNW0.99320.8965717
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:21SDLTDAFVEV0.88490.5928414
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:35SDLTDAFVEV0.83460.518414
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:38SDLTDAFVEV0.82040.6982414
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:11SDLTDAFVEV0.80420.5072414
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:27SDLTDAFVEV0.63150.5407414
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:13SDLTDAFVEV0.59810.67414
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:19SDLTDAFVEV0.53030.5146414
C2CD5-PBX4chr1222696995chr1919675898193HLA-B57:01LTDAFVEVSNW0.99990.9782617
C2CD5-PBX4chr1222696995chr1919675898193HLA-B58:01LTDAFVEVSNW0.99950.9116617
C2CD5-PBX4chr1222696995chr1919675898193HLA-B57:03LTDAFVEVSNW0.99780.9862617
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:60ASDLTDAFVEV0.92240.5063314
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:24ASDLTDAFVEV0.91910.5006314
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:30ASDLTDAFVEV0.91910.5006314
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:67ASDLTDAFVEV0.91910.5006314
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:11ASDLTDAFVEV0.90020.5067314
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:29ASDLTDAFVEV0.89530.5003314
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:22ASDLTDAFVEV0.83260.5014314
C2CD5-PBX4chr1222696995chr1919675898193HLA-C05:09LTDAFVEV10.9821614
C2CD5-PBX4chr1222696995chr1919675898193HLA-C08:15LTDAFVEV0.99990.9919614
C2CD5-PBX4chr1222696995chr1919675898193HLA-B51:07DAFVEVSNW0.85090.8079817
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:01ASDLTDAFVEV0.91910.5006314
C2CD5-PBX4chr1222696995chr1919675898193HLA-C05:01LTDAFVEV10.9821614
C2CD5-PBX4chr1222696995chr1919675898193HLA-C04:03LTDAFVEV10.9538614
C2CD5-PBX4chr1222696995chr1919675898193HLA-C08:02LTDAFVEV0.99990.9919614
C2CD5-PBX4chr1222696995chr1919675898193HLA-B35:24DAFVEVSNW0.99270.9349817
C2CD5-PBX4chr1222696995chr1919675898193HLA-A68:02DLTDAFVEV0.99260.5663514
C2CD5-PBX4chr1222696995chr1919675898193HLA-A69:01DLTDAFVEV0.97830.6252514
C2CD5-PBX4chr1222696995chr1919675898193HLA-A25:01DAFVEVSNW0.93640.8672817
C2CD5-PBX4chr1222696995chr1919675898193HLA-B15:13DAFVEVSNW0.93210.7369817
C2CD5-PBX4chr1222696995chr1919675898193HLA-C14:02AFVEVSNWF0.02550.9563918
C2CD5-PBX4chr1222696995chr1919675898193HLA-C14:03AFVEVSNWF0.02550.9563918
C2CD5-PBX4chr1222696995chr1919675898193HLA-B57:10TDAFVEVSNW0.99860.9668717
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:06SDLTDAFVEV0.88490.5928414
C2CD5-PBX4chr1222696995chr1919675898193HLA-A02:03SDLTDAFVEV0.72080.5965414
C2CD5-PBX4chr1222696995chr1919675898193HLA-B57:04LTDAFVEVSNW0.99990.7515617
C2CD5-PBX4chr1222696995chr1919675898193HLA-B57:10LTDAFVEVSNW0.99990.9782617
C2CD5-PBX4chr1222696995chr1919675898193HLA-B57:02LTDAFVEVSNW0.99960.932617

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Potential FusionNeoAntigen Information of C2CD5-PBX4 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.
C2CD5-PBX4_22696995_19675898.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)
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0401TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0407TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0419TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0419LTDAFVEVSNWFGNK621
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0431TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0431LTDAFVEVSNWFGNK621
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0433TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0435TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0438TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0443TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0443LTDAFVEVSNWFGNK621
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0447TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0454TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0461TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0461LTDAFVEVSNWFGNK621
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0463TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0474TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0475TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0476TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-0482TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1331VEVSNWFGNKRIRYK1126
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1396VEVSNWFGNKRIRYK1126
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1515TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1527TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1534TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1601TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1602TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1603TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1604TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1605TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1605LTDAFVEVSNWFGNK621
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1607TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1607LTDAFVEVSNWFGNK621
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1608TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1609TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1609LTDAFVEVSNWFGNK621
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1610TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1611TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1612TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1614TDAFVEVSNWFGNKR722
C2CD5-PBX4chr1222696995chr1919675898193DRB1-1616TDAFVEVSNWFGNKR722

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Fusion breakpoint peptide structures of C2CD5-PBX4

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
5683LTDAFVEVSNWFGNC2CD5PBX4chr1222696995chr1919675898193

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of C2CD5-PBX4

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-B14:023BVN5683LTDAFVEVSNWFGN-7.9962-8.1096
HLA-B14:023BVN5683LTDAFVEVSNWFGN-5.70842-6.74372
HLA-B52:013W395683LTDAFVEVSNWFGN-6.83737-6.95077
HLA-B52:013W395683LTDAFVEVSNWFGN-4.4836-5.5189
HLA-A11:014UQ25683LTDAFVEVSNWFGN-10.0067-10.1201
HLA-A11:014UQ25683LTDAFVEVSNWFGN-9.03915-10.0745
HLA-A24:025HGA5683LTDAFVEVSNWFGN-6.56204-6.67544
HLA-A24:025HGA5683LTDAFVEVSNWFGN-5.42271-6.45801
HLA-B44:053DX85683LTDAFVEVSNWFGN-7.85648-8.89178
HLA-B44:053DX85683LTDAFVEVSNWFGN-5.3978-5.5112
HLA-A02:016TDR5683LTDAFVEVSNWFGN-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of C2CD5-PBX4

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
C2CD5-PBX4chr1222696995chr1919675898314ASDLTDAFVEVGCTAGTGACCTGACTGATGCCTTCGTGGAGGTC
C2CD5-PBX4chr1222696995chr1919675898414SDLTDAFVEVAGTGACCTGACTGATGCCTTCGTGGAGGTC
C2CD5-PBX4chr1222696995chr1919675898514DLTDAFVEVGACCTGACTGATGCCTTCGTGGAGGTC
C2CD5-PBX4chr1222696995chr1919675898614LTDAFVEVCTGACTGATGCCTTCGTGGAGGTC
C2CD5-PBX4chr1222696995chr1919675898617LTDAFVEVSNWCTGACTGATGCCTTCGTGGAGGTCTCTAACTGG
C2CD5-PBX4chr1222696995chr1919675898717TDAFVEVSNWACTGATGCCTTCGTGGAGGTCTCTAACTGG
C2CD5-PBX4chr1222696995chr1919675898817DAFVEVSNWGATGCCTTCGTGGAGGTCTCTAACTGG
C2CD5-PBX4chr1222696995chr1919675898918AFVEVSNWFGCCTTCGTGGAGGTCTCTAACTGGTTT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
C2CD5-PBX4chr1222696995chr19196758981126VEVSNWFGNKRIRYKGTGGAGGTCTCTAACTGGTTTGGCAACAAAAGAATCCGGTATAAA
C2CD5-PBX4chr1222696995chr1919675898621LTDAFVEVSNWFGNKCTGACTGATGCCTTCGTGGAGGTCTCTAACTGGTTTGGCAACAAA
C2CD5-PBX4chr1222696995chr1919675898722TDAFVEVSNWFGNKRACTGATGCCTTCGTGGAGGTCTCTAACTGGTTTGGCAACAAAAGA

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Information of the samples that have these potential fusion neoantigens of C2CD5-PBX4

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
STADC2CD5-PBX4chr1222696995ENST00000542676chr1919675898ENST00000251203TCGA-CD-A48C-01A

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Potential target of CAR-T therapy development for C2CD5-PBX4

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 C2CD5-PBX4

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 C2CD5-PBX4

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