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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:CACNA2D3-DAP3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CACNA2D3-DAP3
FusionPDB ID: 12362
FusionGDB2.0 ID: 12362
HgeneTgene
Gene symbol

CACNA2D3

DAP3

Gene ID

55799

58512

Gene namecalcium voltage-gated channel auxiliary subunit alpha2delta 3DLG associated protein 3
SynonymsHSA272268DAP3|SAPAP3
Cytomap

3p21.1-p14.3

1p34.3

Type of geneprotein-codingprotein-coding
Descriptionvoltage-dependent calcium channel subunit alpha-2/delta-3calcium channel alpha2-delta3 subunitcalcium channel, voltage-dependent, alpha 2/delta 3 subunitcalcium channel, voltage-dependent, alpha 2/delta subunit 3voltage-gated calcium channel subunit adisks large-associated protein 3DAP-3PSD-95/SAP90-binding protein 3SAP90/PSD-95-associated protein 3discs large homolog associated protein 3
Modification date2020031320200313
UniProtAcc

Q8IZS8

Main function of 5'-partner protein: FUNCTION: The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) but not T-type (CACNA1G) (By similarity). {ECO:0000250}.

P51398

Main function of 5'-partner protein: FUNCTION: Involved in mediating interferon-gamma-induced cell death.
Ensembl transtripts involved in fusion geneENST idsENST00000288197, ENST00000415676, 
ENST00000474759, ENST00000490478, 
ENST00000478261, 
ENST00000421487, 
ENST00000465375, ENST00000496863, 
ENST00000535183, ENST00000343043, 
ENST00000471642, ENST00000368336, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 12 X 6=100816 X 12 X 6=1152
# samples 1518
** MAII scorelog2(15/1008*10)=-2.74846123300404
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(18/1152*10)=-2.67807190511264
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CACNA2D3 [Title/Abstract] AND DAP3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CACNA2D3 [Title/Abstract] AND DAP3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CACNA2D3(54676268)-DAP3(155707948), # samples:2
Anticipated loss of major functional domain due to fusion event.CACNA2D3-DAP3 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.
CACNA2D3-DAP3 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.
CACNA2D3-DAP3 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.
CACNA2D3-DAP3 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.
CACNA2D3-DAP3 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
CACNA2D3-DAP3 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
CACNA2D3-DAP3 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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


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/chr3:54676268/chr1:155707948)
- 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 CACNA2D3 (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 DAP3 (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)
ENST00000415676CACNA2D3chr354676268+ENST00000368336DAP3chr1155707948+213912851181323401
ENST00000288197CACNA2D3chr354676268+ENST00000368336DAP3chr1155707948+20691215481253401
ENST00000474759CACNA2D3chr354676268+ENST00000368336DAP3chr1155707948+20691215481253401
ENST00000490478CACNA2D3chr354676268+ENST00000368336DAP3chr1155707948+195110971251135336
ENST00000415676CACNA2D3chr354676268+ENST00000368336DAP3chr1155707947+213912851181323401
ENST00000288197CACNA2D3chr354676268+ENST00000368336DAP3chr1155707947+20691215481253401
ENST00000474759CACNA2D3chr354676268+ENST00000368336DAP3chr1155707947+20691215481253401
ENST00000490478CACNA2D3chr354676268+ENST00000368336DAP3chr1155707947+195110971251135336
ENST00000415676CACNA2D3chr354676268+ENST00000471642DAP3chr1155706737+177312851181488456
ENST00000415676CACNA2D3chr354676268+ENST00000368336DAP3chr1155706737+225712851181488456
ENST00000415676CACNA2D3chr354676268+ENST00000343043DAP3chr1155706737+177312851181488456
ENST00000288197CACNA2D3chr354676268+ENST00000471642DAP3chr1155706737+17031215481418456
ENST00000288197CACNA2D3chr354676268+ENST00000368336DAP3chr1155706737+21871215481418456
ENST00000288197CACNA2D3chr354676268+ENST00000343043DAP3chr1155706737+17031215481418456
ENST00000474759CACNA2D3chr354676268+ENST00000471642DAP3chr1155706737+17031215481418456
ENST00000474759CACNA2D3chr354676268+ENST00000368336DAP3chr1155706737+21871215481418456
ENST00000474759CACNA2D3chr354676268+ENST00000343043DAP3chr1155706737+17031215481418456
ENST00000490478CACNA2D3chr354676268+ENST00000471642DAP3chr1155706737+158510971251300391
ENST00000490478CACNA2D3chr354676268+ENST00000368336DAP3chr1155706737+206910971251300391
ENST00000490478CACNA2D3chr354676268+ENST00000343043DAP3chr1155706737+158510971251300391

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
ENST00000415676ENST00000368336CACNA2D3chr354676268+DAP3chr1155707948+0.001041830.9989581
ENST00000288197ENST00000368336CACNA2D3chr354676268+DAP3chr1155707948+0.0008518910.99914813
ENST00000474759ENST00000368336CACNA2D3chr354676268+DAP3chr1155707948+0.0008518910.99914813
ENST00000490478ENST00000368336CACNA2D3chr354676268+DAP3chr1155707948+0.0008371630.9991628
ENST00000415676ENST00000368336CACNA2D3chr354676268+DAP3chr1155707947+0.001041830.9989581
ENST00000288197ENST00000368336CACNA2D3chr354676268+DAP3chr1155707947+0.0008518910.99914813
ENST00000474759ENST00000368336CACNA2D3chr354676268+DAP3chr1155707947+0.0008518910.99914813
ENST00000490478ENST00000368336CACNA2D3chr354676268+DAP3chr1155707947+0.0008371630.9991628
ENST00000415676ENST00000471642CACNA2D3chr354676268+DAP3chr1155706737+0.0008876460.9991123
ENST00000415676ENST00000368336CACNA2D3chr354676268+DAP3chr1155706737+0.0009201790.9990798
ENST00000415676ENST00000343043CACNA2D3chr354676268+DAP3chr1155706737+0.0008876460.9991123
ENST00000288197ENST00000471642CACNA2D3chr354676268+DAP3chr1155706737+0.0006615220.99933845
ENST00000288197ENST00000368336CACNA2D3chr354676268+DAP3chr1155706737+0.0007583130.9992417
ENST00000288197ENST00000343043CACNA2D3chr354676268+DAP3chr1155706737+0.0006615220.99933845
ENST00000474759ENST00000471642CACNA2D3chr354676268+DAP3chr1155706737+0.0006615220.99933845
ENST00000474759ENST00000368336CACNA2D3chr354676268+DAP3chr1155706737+0.0007583130.9992417
ENST00000474759ENST00000343043CACNA2D3chr354676268+DAP3chr1155706737+0.0006615220.99933845
ENST00000490478ENST00000471642CACNA2D3chr354676268+DAP3chr1155706737+0.0004338280.99956614
ENST00000490478ENST00000368336CACNA2D3chr354676268+DAP3chr1155706737+0.0005542250.99944574
ENST00000490478ENST00000343043CACNA2D3chr354676268+DAP3chr1155706737+0.0004338280.99956614

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 CACNA2D3-DAP3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CACNA2D3chr354676268DAP3chr11557067371097324DTIFAKYNWPDRKEGFDALDPFIPIL
CACNA2D3chr354676268DAP3chr11557067371215389DTIFAKYNWPDRKEGFDALDPFIPIL
CACNA2D3chr354676268DAP3chr11557067371285389DTIFAKYNWPDRKEGFDALDPFIPIL

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Potential FusionNeoAntigen Information of CACNA2D3-DAP3 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.
CACNA2D3-DAP3_54676268_155706737.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)
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B14:02DRKEGFDAL0.99830.86561019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B14:01DRKEGFDAL0.99830.86561019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B39:24DRKEGFDAL0.99710.56951019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B39:01DRKEGFDAL0.99610.90681019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B39:06DRKEGFDAL0.99410.91091019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B38:02DRKEGFDAL0.99030.95441019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B15:10DRKEGFDAL0.9310.58261019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B15:37DRKEGFDAL0.90430.56591019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-A24:31NWPDRKEGF0.85520.5909716
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B15:18DRKEGFDAL0.60080.7381019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B08:09DRKEGFDAL0.31870.77211019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B07:10DRKEGFDAL0.00740.56771019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-A24:25KYNWPDRKEGF0.99810.5773516
CACNA2D3-DAP3chr354676268chr11557067371215HLA-A24:10KYNWPDRKEGF0.99790.5679516
CACNA2D3-DAP3chr354676268chr11557067371215HLA-A24:20KYNWPDRKEGF0.99780.5764516
CACNA2D3-DAP3chr354676268chr11557067371215HLA-A24:15KYNWPDRKEGF0.99750.5811516
CACNA2D3-DAP3chr354676268chr11557067371215HLA-A24:31KYNWPDRKEGF0.99670.5335516
CACNA2D3-DAP3chr354676268chr11557067371215HLA-A31:08KYNWPDRKEGF0.99620.5267516
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B35:03WPDRKEGFDAL0.99540.809819
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B35:02WPDRKEGFDAL0.98550.914819
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B35:04WPDRKEGFDAL0.98550.914819
CACNA2D3-DAP3chr354676268chr11557067371215HLA-A24:14KYNWPDRKEGF0.98360.5806516
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B81:01WPDRKEGFDAL0.97110.606819
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B82:01WPDRKEGFDAL0.95260.6597819
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B39:09DRKEGFDAL0.99580.74031019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B39:12DRKEGFDAL0.99490.91321019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B39:05DRKEGFDAL0.9910.89031019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B73:01DRKEGFDAL0.81480.78821019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B14:03DRKEGFDAL0.74630.85451019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-C12:16DRKEGFDAL0.10950.97381019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B42:02WPDRKEGFDAL0.99830.6656819
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B42:01WPDRKEGFDAL0.99790.6595819
CACNA2D3-DAP3chr354676268chr11557067371215HLA-A24:02KYNWPDRKEGF0.99780.5764516
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B39:10WPDRKEGFDAL0.9880.932819
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B35:12WPDRKEGFDAL0.98550.914819
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B39:31DRKEGFDAL0.99640.91051019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B39:11DRKEGFDAL0.89560.80461019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B15:09DRKEGFDAL0.87590.63321019
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B67:01WPDRKEGFDAL0.99020.8759819
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B35:09WPDRKEGFDAL0.98550.914819
CACNA2D3-DAP3chr354676268chr11557067371215HLA-B82:02WPDRKEGFDAL0.95260.6597819

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Potential FusionNeoAntigen Information of CACNA2D3-DAP3 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.
CACNA2D3-DAP3_54676268_155706737.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)
CACNA2D3-DAP3chr354676268chr11557067371215DRB1-1457DTIFAKYNWPDRKEG015

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Fusion breakpoint peptide structures of CACNA2D3-DAP3

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
10756YNWPDRKEGFDALDCACNA2D3DAP3chr354676268chr11557067371215

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CACNA2D3-DAP3

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-B14:023BVN10756YNWPDRKEGFDALD-7.99449-8.10789
HLA-B14:023BVN10756YNWPDRKEGFDALD-4.19364-5.22894
HLA-B52:013W3910756YNWPDRKEGFDALD-5.8571-6.8924
HLA-B52:013W3910756YNWPDRKEGFDALD-5.03914-5.15254
HLA-A24:025HGA10756YNWPDRKEGFDALD-5.78302-5.89642
HLA-A24:025HGA10756YNWPDRKEGFDALD-5.66991-6.70521
HLA-B44:053DX810756YNWPDRKEGFDALD-5.96708-6.08048
HLA-B44:053DX810756YNWPDRKEGFDALD-3.40973-4.44503
HLA-A02:016TDR10756YNWPDRKEGFDALD-6.12518-7.16048

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Vaccine Design for the FusionNeoAntigens of CACNA2D3-DAP3

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
CACNA2D3-DAP3chr354676268chr11557067371019DRKEGFDALGATCGAAAGGAAGGATTTGATGCCCTG
CACNA2D3-DAP3chr354676268chr1155706737516KYNWPDRKEGFAAATACAATTGGCCAGATCGAAAGGAAGGATTT
CACNA2D3-DAP3chr354676268chr1155706737716NWPDRKEGFAATTGGCCAGATCGAAAGGAAGGATTT
CACNA2D3-DAP3chr354676268chr1155706737819WPDRKEGFDALTGGCCAGATCGAAAGGAAGGATTTGATGCCCTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CACNA2D3-DAP3chr354676268chr1155706737015DTIFAKYNWPDRKEGGATACAATCTTTGCAAAATACAATTGGCCAGATCGAAAGGAAGGA

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Information of the samples that have these potential fusion neoantigens of CACNA2D3-DAP3

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
OVCACNA2D3-DAP3chr354676268ENST00000288197chr1155706737ENST00000343043TCGA-20-1684-01A

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Potential target of CAR-T therapy development for CACNA2D3-DAP3

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 CACNA2D3-DAP3

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 CACNA2D3-DAP3

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