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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:TRAF2-CACNA1B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TRAF2-CACNA1B
FusionPDB ID: 93643
FusionGDB2.0 ID: 93643
HgeneTgene
Gene symbol

TRAF2

CACNA1B

Gene ID

10010

774

Gene nameTRAF family member associated NFKB activatorcalcium voltage-gated channel subunit alpha1 B
SynonymsI-TRAF|ITRAF|TRAF2BIII|CACNL1A5|CACNN|Cav2.2|DYT23|NEDNEH
Cytomap

2q24.2

9q34.3

Type of geneprotein-codingprotein-coding
DescriptionTRAF family member-associated NF-kappa-B activatorTRAF-interacting proteinvoltage-dependent N-type calcium channel subunit alpha-1BCav2.2 voltage-gated Ca2+ channelbrain calcium channel IIIcalcium channel alpha12.2 subunitcalcium channel, L type, alpha-1 polypeptidecalcium channel, voltage-dependent, L type, alpha 1B subun
Modification date2020031320200313
UniProtAcc

TNIK

Main function of 5'-partner protein: 1360

Q00975

Main function of 5'-partner protein: FUNCTION: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are specifically blocked by omega-conotoxin-GVIA (AC P01522) (AC P01522) (By similarity). They are however insensitive to dihydropyridines (DHP). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons. {ECO:0000250|UniProtKB:Q02294}.
Ensembl transtripts involved in fusion geneENST idsENST00000247668, ENST00000359662, 
ENST00000536468, ENST00000482854, 
ENST00000277550, ENST00000371365, 
ENST00000371367, ENST00000545473, 
ENST00000277549, ENST00000277551, 
ENST00000371355, ENST00000371357, 
ENST00000371363, ENST00000371372, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 6 X 6=2527 X 8 X 4=224
# samples 77
** MAII scorelog2(7/252*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/224*10)=-1.67807190511264
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TRAF2 [Title/Abstract] AND CACNA1B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TRAF2 [Title/Abstract] AND CACNA1B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TRAF2(139794972)-CACNA1B(140970271), # samples:1
TRAF2(139794972)-CACNA1B(140967940), # samples:1
Anticipated loss of major functional domain due to fusion event.TRAF2-CACNA1B 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.
TRAF2-CACNA1B 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.
TRAF2-CACNA1B 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.
TRAF2-CACNA1B 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
TgeneCACNA1B

GO:0050804

modulation of chemical synaptic transmission

23376566

TgeneCACNA1B

GO:1904645

response to amyloid-beta

23376566



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/chr9:139794972/chr9:140970271)
- 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 TRAF2 (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 CACNA1B (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)
ENST00000536468TRAF2chr9139794972+ENST00000277551CACNA1Bchr9140970271+26955391492395748
ENST00000536468TRAF2chr9139794972+ENST00000371372CACNA1Bchr9140970271+53275391492701850
ENST00000536468TRAF2chr9139794972+ENST00000277549CACNA1Bchr9140970271+53275391492701850
ENST00000536468TRAF2chr9139794972+ENST00000371363CACNA1Bchr9140970271+53275391492701850
ENST00000536468TRAF2chr9139794972+ENST00000371355CACNA1Bchr9140970271+53275391492701850
ENST00000536468TRAF2chr9139794972+ENST00000371357CACNA1Bchr9140970271+53275391492701850
ENST00000247668TRAF2chr9139794972+ENST00000277551CACNA1Bchr9140970271+2574418282274748
ENST00000247668TRAF2chr9139794972+ENST00000371372CACNA1Bchr9140970271+5206418282580850
ENST00000247668TRAF2chr9139794972+ENST00000277549CACNA1Bchr9140970271+5206418282580850
ENST00000247668TRAF2chr9139794972+ENST00000371363CACNA1Bchr9140970271+5206418282580850
ENST00000247668TRAF2chr9139794972+ENST00000371355CACNA1Bchr9140970271+5206418282580850
ENST00000247668TRAF2chr9139794972+ENST00000371357CACNA1Bchr9140970271+5206418282580850
ENST00000359662TRAF2chr9139794972+ENST00000277551CACNA1Bchr9140970271+2624468212324767
ENST00000359662TRAF2chr9139794972+ENST00000371372CACNA1Bchr9140970271+5256468212630869
ENST00000359662TRAF2chr9139794972+ENST00000277549CACNA1Bchr9140970271+5256468212630869
ENST00000359662TRAF2chr9139794972+ENST00000371363CACNA1Bchr9140970271+5256468212630869
ENST00000359662TRAF2chr9139794972+ENST00000371355CACNA1Bchr9140970271+5256468212630869
ENST00000359662TRAF2chr9139794972+ENST00000371357CACNA1Bchr9140970271+5256468212630869
ENST00000536468TRAF2chr9139794972-ENST00000277551CACNA1Bchr9140967940+28785391492578809
ENST00000536468TRAF2chr9139794972-ENST00000371372CACNA1Bchr9140967940+55105391492884911
ENST00000536468TRAF2chr9139794972-ENST00000277549CACNA1Bchr9140967940+55105391492884911
ENST00000536468TRAF2chr9139794972-ENST00000371363CACNA1Bchr9140967940+55105391492884911
ENST00000536468TRAF2chr9139794972-ENST00000371355CACNA1Bchr9140967940+55105391492884911
ENST00000536468TRAF2chr9139794972-ENST00000371357CACNA1Bchr9140967940+55105391492884911
ENST00000247668TRAF2chr9139794972-ENST00000277551CACNA1Bchr9140967940+2757418282457809
ENST00000247668TRAF2chr9139794972-ENST00000371372CACNA1Bchr9140967940+5389418282763911
ENST00000247668TRAF2chr9139794972-ENST00000277549CACNA1Bchr9140967940+5389418282763911
ENST00000247668TRAF2chr9139794972-ENST00000371363CACNA1Bchr9140967940+5389418282763911
ENST00000247668TRAF2chr9139794972-ENST00000371355CACNA1Bchr9140967940+5389418282763911
ENST00000247668TRAF2chr9139794972-ENST00000371357CACNA1Bchr9140967940+5389418282763911
ENST00000359662TRAF2chr9139794972-ENST00000277551CACNA1Bchr9140967940+2807468212507828
ENST00000359662TRAF2chr9139794972-ENST00000371372CACNA1Bchr9140967940+5439468212813930
ENST00000359662TRAF2chr9139794972-ENST00000277549CACNA1Bchr9140967940+5439468212813930
ENST00000359662TRAF2chr9139794972-ENST00000371363CACNA1Bchr9140967940+5439468212813930
ENST00000359662TRAF2chr9139794972-ENST00000371355CACNA1Bchr9140967940+5439468212813930
ENST00000359662TRAF2chr9139794972-ENST00000371357CACNA1Bchr9140967940+5439468212813930

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
ENST00000536468ENST00000277551TRAF2chr9139794972+CACNA1Bchr9140970271+0.066958250.93304175
ENST00000536468ENST00000371372TRAF2chr9139794972+CACNA1Bchr9140970271+0.008950220.99104977
ENST00000536468ENST00000277549TRAF2chr9139794972+CACNA1Bchr9140970271+0.008950220.99104977
ENST00000536468ENST00000371363TRAF2chr9139794972+CACNA1Bchr9140970271+0.008950220.99104977
ENST00000536468ENST00000371355TRAF2chr9139794972+CACNA1Bchr9140970271+0.008950220.99104977
ENST00000536468ENST00000371357TRAF2chr9139794972+CACNA1Bchr9140970271+0.008950220.99104977
ENST00000247668ENST00000277551TRAF2chr9139794972+CACNA1Bchr9140970271+0.063740060.9362599
ENST00000247668ENST00000371372TRAF2chr9139794972+CACNA1Bchr9140970271+0.0083153620.9916847
ENST00000247668ENST00000277549TRAF2chr9139794972+CACNA1Bchr9140970271+0.0083153620.9916847
ENST00000247668ENST00000371363TRAF2chr9139794972+CACNA1Bchr9140970271+0.0083153620.9916847
ENST00000247668ENST00000371355TRAF2chr9139794972+CACNA1Bchr9140970271+0.0083153620.9916847
ENST00000247668ENST00000371357TRAF2chr9139794972+CACNA1Bchr9140970271+0.0083153620.9916847
ENST00000359662ENST00000277551TRAF2chr9139794972+CACNA1Bchr9140970271+0.0478164440.9521836
ENST00000359662ENST00000371372TRAF2chr9139794972+CACNA1Bchr9140970271+0.0051951390.9948048
ENST00000359662ENST00000277549TRAF2chr9139794972+CACNA1Bchr9140970271+0.0051951390.9948048
ENST00000359662ENST00000371363TRAF2chr9139794972+CACNA1Bchr9140970271+0.0051951390.9948048
ENST00000359662ENST00000371355TRAF2chr9139794972+CACNA1Bchr9140970271+0.0051951390.9948048
ENST00000359662ENST00000371357TRAF2chr9139794972+CACNA1Bchr9140970271+0.0051951390.9948048
ENST00000536468ENST00000277551TRAF2chr9139794972-CACNA1Bchr9140967940+0.0451950360.95480496
ENST00000536468ENST00000371372TRAF2chr9139794972-CACNA1Bchr9140967940+0.0051293790.99487066
ENST00000536468ENST00000277549TRAF2chr9139794972-CACNA1Bchr9140967940+0.0051293790.99487066
ENST00000536468ENST00000371363TRAF2chr9139794972-CACNA1Bchr9140967940+0.0051293790.99487066
ENST00000536468ENST00000371355TRAF2chr9139794972-CACNA1Bchr9140967940+0.0051293790.99487066
ENST00000536468ENST00000371357TRAF2chr9139794972-CACNA1Bchr9140967940+0.0051293790.99487066
ENST00000247668ENST00000277551TRAF2chr9139794972-CACNA1Bchr9140967940+0.0432942660.9567057
ENST00000247668ENST00000371372TRAF2chr9139794972-CACNA1Bchr9140967940+0.0047670440.995233
ENST00000247668ENST00000277549TRAF2chr9139794972-CACNA1Bchr9140967940+0.0047670440.995233
ENST00000247668ENST00000371363TRAF2chr9139794972-CACNA1Bchr9140967940+0.0047670440.995233
ENST00000247668ENST00000371355TRAF2chr9139794972-CACNA1Bchr9140967940+0.0047670440.995233
ENST00000247668ENST00000371357TRAF2chr9139794972-CACNA1Bchr9140967940+0.0047670440.995233
ENST00000359662ENST00000277551TRAF2chr9139794972-CACNA1Bchr9140967940+0.0357055330.9642945
ENST00000359662ENST00000371372TRAF2chr9139794972-CACNA1Bchr9140967940+0.0039151880.9960848
ENST00000359662ENST00000277549TRAF2chr9139794972-CACNA1Bchr9140967940+0.0039151880.9960848
ENST00000359662ENST00000371363TRAF2chr9139794972-CACNA1Bchr9140967940+0.0039151880.9960848
ENST00000359662ENST00000371355TRAF2chr9139794972-CACNA1Bchr9140967940+0.0039151880.9960848
ENST00000359662ENST00000371357TRAF2chr9139794972-CACNA1Bchr9140967940+0.0039151880.9960848

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 TRAF2-CACNA1B

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

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Potential FusionNeoAntigen Information of TRAF2-CACNA1B 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.

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)

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Potential FusionNeoAntigen Information of TRAF2-CACNA1B in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of TRAF2-CACNA1B

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TRAF2-CACNA1B

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

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Vaccine Design for the FusionNeoAntigens of TRAF2-CACNA1B

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

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

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Information of the samples that have these potential fusion neoantigens of TRAF2-CACNA1B

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

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Potential target of CAR-T therapy development for TRAF2-CACNA1B

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
TgeneCACNA1Bchr9:139794972chr9:140967940ENST0000037137231471564_158202340.0TransmembraneHelical%3B Name%3DS4 of repeat IV
TgeneCACNA1Bchr9:139794972chr9:140967940ENST0000037137231471602_162102340.0TransmembraneHelical%3B Name%3DS5 of repeat IV
TgeneCACNA1Bchr9:139794972chr9:140967940ENST0000037137231471684_170802340.0TransmembraneHelical%3B Name%3DS6 of repeat IV
TgeneCACNA1Bchr9:139794972chr9:140970271ENST0000037137233471684_170802340.0TransmembraneHelical%3B Name%3DS6 of repeat IV

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 TRAF2-CACNA1B

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 TRAF2-CACNA1B

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