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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:SDHA-VDAC3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SDHA-VDAC3
FusionPDB ID: 79911
FusionGDB2.0 ID: 79911
HgeneTgene
Gene symbol

SDHA

VDAC3

Gene ID

6389

7419

Gene namesuccinate dehydrogenase complex flavoprotein subunit Avoltage dependent anion channel 3
SynonymsCMD1GG|FP|PGL5|SDH1|SDH2|SDHFHD-VDAC3|VDAC-3
Cytomap

5p15.33

8p11.21

Type of geneprotein-codingprotein-coding
Descriptionsuccinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrialflavoprotein subunit of complex IIsuccinate dehydrogenase complex, subunit A, flavoprotein (Fp)voltage-dependent anion-selective channel protein 3outer mitochondrial membrane protein porin 3
Modification date2020031320200313
UniProtAcc

Q5VUM1

Main function of 5'-partner protein: FUNCTION: Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol (PubMed:24954416). Binds to the flavoprotein subunit SDHA in its FAD-bound form, blocking the generation of excess reactive oxigen species (ROS) and facilitating its assembly with the iron-sulfur protein subunit SDHB into the SDH catalytic dimer (By similarity). {ECO:0000250|UniProtKB:P38345, ECO:0000269|PubMed:24954416}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000264932, ENST00000504309, 
ENST00000510361, ENST00000507522, 
ENST00000022615, ENST00000392935, 
ENST00000521158, ENST00000522572, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 7 X 6=4208 X 8 X 6=384
# samples 118
** MAII scorelog2(11/420*10)=-1.93288580414146
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/384*10)=-2.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SDHA [Title/Abstract] AND VDAC3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SDHA [Title/Abstract] AND VDAC3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SDHA(233760)-VDAC3(42259306), # samples:1
Anticipated loss of major functional domain due to fusion event.
* 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
HgeneSDHA

GO:0006105

succinate metabolic process

7550341

HgeneSDHA

GO:0022904

respiratory electron transport chain

7550341

HgeneSDHA

GO:0055114

oxidation-reduction process

7550341



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/chr5:233760/chr8:42259306)
- 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 SDHA (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 VDAC3 (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)
ENST00000264932SDHAchr5233760+ENST00000392935VDAC3chr842259306+21391179731707544
ENST00000264932SDHAchr5233760+ENST00000522572VDAC3chr842259306+15451179731257394
ENST00000264932SDHAchr5233760+ENST00000521158VDAC3chr842259306+17341179731707544
ENST00000264932SDHAchr5233760+ENST00000022615VDAC3chr842259306+21431179731707544
ENST00000504309SDHAchr5233760+ENST00000392935VDAC3chr842259306+20771117111645544
ENST00000504309SDHAchr5233760+ENST00000522572VDAC3chr842259306+14831117111195394
ENST00000504309SDHAchr5233760+ENST00000521158VDAC3chr842259306+16721117111645544
ENST00000504309SDHAchr5233760+ENST00000022615VDAC3chr842259306+20811117111645544
ENST00000510361SDHAchr5233760+ENST00000392935VDAC3chr842259306+1918958381486482
ENST00000510361SDHAchr5233760+ENST00000522572VDAC3chr842259306+1324958381036332
ENST00000510361SDHAchr5233760+ENST00000521158VDAC3chr842259306+1513958381486482
ENST00000510361SDHAchr5233760+ENST00000022615VDAC3chr842259306+1922958381486482

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
ENST00000264932ENST00000392935SDHAchr5233760+VDAC3chr842259306+0.0020798260.9979202
ENST00000264932ENST00000522572SDHAchr5233760+VDAC3chr842259306+0.0041334520.99586654
ENST00000264932ENST00000521158SDHAchr5233760+VDAC3chr842259306+0.0055759270.99442405
ENST00000264932ENST00000022615SDHAchr5233760+VDAC3chr842259306+0.0020285790.99797136
ENST00000504309ENST00000392935SDHAchr5233760+VDAC3chr842259306+0.0020417510.9979583
ENST00000504309ENST00000522572SDHAchr5233760+VDAC3chr842259306+0.0043067760.99569327
ENST00000504309ENST00000521158SDHAchr5233760+VDAC3chr842259306+0.0058970810.9941029
ENST00000504309ENST00000022615SDHAchr5233760+VDAC3chr842259306+0.0019969960.99800295
ENST00000510361ENST00000392935SDHAchr5233760+VDAC3chr842259306+0.0012473830.9987526
ENST00000510361ENST00000522572SDHAchr5233760+VDAC3chr842259306+0.002428860.9975712
ENST00000510361ENST00000521158SDHAchr5233760+VDAC3chr842259306+0.0038288390.9961712
ENST00000510361ENST00000022615SDHAchr5233760+VDAC3chr842259306+0.0012094910.99879056

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 SDHA-VDAC3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SDHAchr5233760VDAC3chr8422593061117368VVSRSMTLEIREGRKKSGKLKASYKR
SDHAchr5233760VDAC3chr8422593061179368VVSRSMTLEIREGRKKSGKLKASYKR
SDHAchr5233760VDAC3chr842259306958306VVSRSMTLEIREGRKKSGKLKASYKR

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Potential FusionNeoAntigen Information of SDHA-VDAC3 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.
SDHA-VDAC3_233760_42259306.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)
SDHA-VDAC3chr5233760chr8422593061179HLA-B08:01EGRKKSGKL0.91590.58051120
SDHA-VDAC3chr5233760chr8422593061179HLA-B27:10GRKKSGKLK0.97210.91931221
SDHA-VDAC3chr5233760chr8422593061179HLA-B08:18EGRKKSGKL0.91590.58051120

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Potential FusionNeoAntigen Information of SDHA-VDAC3 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.
SDHA-VDAC3_233760_42259306.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)
SDHA-VDAC3chr5233760chr8422593061179DRB1-0307SRSMTLEIREGRKKS217
SDHA-VDAC3chr5233760chr8422593061179DRB1-1107SRSMTLEIREGRKKS217

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Fusion breakpoint peptide structures of SDHA-VDAC3

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
9452TLEIREGRKKSGKLSDHAVDAC3chr5233760chr8422593061179

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SDHA-VDAC3

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-B14:023BVN9452TLEIREGRKKSGKL-7.15543-7.26883
HLA-B14:023BVN9452TLEIREGRKKSGKL-4.77435-5.80965
HLA-B52:013W399452TLEIREGRKKSGKL-6.80875-6.92215
HLA-B52:013W399452TLEIREGRKKSGKL-4.20386-5.23916
HLA-A11:014UQ29452TLEIREGRKKSGKL-7.5194-8.5547
HLA-A11:014UQ29452TLEIREGRKKSGKL-6.9601-7.0735
HLA-A24:025HGA9452TLEIREGRKKSGKL-7.52403-7.63743
HLA-A24:025HGA9452TLEIREGRKKSGKL-5.82433-6.85963
HLA-B27:056PYJ9452TLEIREGRKKSGKL-3.28285-4.31815
HLA-B44:053DX89452TLEIREGRKKSGKL-5.91172-6.94702
HLA-B44:053DX89452TLEIREGRKKSGKL-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of SDHA-VDAC3

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
SDHA-VDAC3chr5233760chr8422593061120EGRKKSGKLAGGAAGAAAGAAGAGTGGGAAATTGAA
SDHA-VDAC3chr5233760chr8422593061221GRKKSGKLKAAGAAAGAAGAGTGGGAAATTGAAGGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
SDHA-VDAC3chr5233760chr842259306217SRSMTLEIREGRKKSTCGGTCCATGACTCTGGAGATCCGAGAAGGAAGAAAGAAGAGTGG

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Information of the samples that have these potential fusion neoantigens of SDHA-VDAC3

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
STADSDHA-VDAC3chr5233760ENST00000264932chr842259306ENST00000022615TCGA-BR-A4PD-01A

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Potential target of CAR-T therapy development for SDHA-VDAC3

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
TgeneVDAC3chr5:233760chr8:42259306ENST00000022615510111_1200284.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000022615510123_1300284.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000022615510137_1450284.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000022615510150_1580284.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000022615510163_1750284.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000022615510178_1850284.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000022615510189_1980284.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000022615510202_2110284.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000022615510218_2270284.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000022615510231_2380284.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000022615510242_2510284.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000022615510254_2630284.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000022615510273_2820284.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000521158611111_1200285.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000521158611123_1300285.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000521158611137_1450285.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000521158611150_1580285.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000521158611163_1750285.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000521158611178_1850285.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000521158611189_1980285.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000521158611202_2110285.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000521158611218_2270285.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000521158611231_2380285.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000521158611242_2510285.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000521158611254_2630285.0TransmembraneBeta stranded
TgeneVDAC3chr5:233760chr8:42259306ENST00000521158611273_2820285.0TransmembraneBeta stranded

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 SDHA-VDAC3

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 SDHA-VDAC3

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