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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:UBE4B-SLC25A33

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: UBE4B-SLC25A33
FusionPDB ID: 96336
FusionGDB2.0 ID: 96336
HgeneTgene
Gene symbol

UBE4B

SLC25A33

Gene ID

10277

84275

Gene nameubiquitination factor E4Bsolute carrier family 25 member 33
SynonymsE4|HDNB1|UBOX3|UFD2|UFD2ABMSC-MCP|PNC1
Cytomap

1p36.22

1p36.22

Type of geneprotein-codingprotein-coding
Descriptionubiquitin conjugation factor E4 BRING-type E3 ubiquitin transferase E4 BUFD2A-III/UBE4B-III splice isoformhomologous to yeast UFD2homozygously deleted in neuroblastoma-1ubiquitin-fusion degradation protein 2ubiquitination factor E4B (UFD2 homolog, ysolute carrier family 25 member 33PNC1 proteinbone marrow stromal cell mitochondrial carrier proteinhuBMSC-MCPmitochondrial carrier proteinnovel mitochondrial carrier proteinsolute carrier family 25 (pyrimidine nucleotide carrier), member 33
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000253251, ENST00000343090, 
ENST00000377157, ENST00000377153, 
ENST00000475795, 
ENST00000302692, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score18 X 13 X 10=23405 X 4 X 5=100
# samples 235
** MAII scorelog2(23/2340*10)=-3.34680276352639
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/100*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: UBE4B [Title/Abstract] AND SLC25A33 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: UBE4B [Title/Abstract] AND SLC25A33 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)UBE4B(10209340)-SLC25A33(9613684), # samples:1
Anticipated loss of major functional domain due to fusion event.UBE4B-SLC25A33 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.
UBE4B-SLC25A33 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
HgeneUBE4B

GO:0008626

granzyme-mediated apoptotic signaling pathway

11802788

HgeneUBE4B

GO:0009411

response to UV

11802788

HgeneUBE4B

GO:0043161

proteasome-mediated ubiquitin-dependent protein catabolic process

23509263

TgeneSLC25A33

GO:0000002

mitochondrial genome maintenance

25320081

TgeneSLC25A33

GO:0006864

pyrimidine nucleotide transport

25320081

TgeneSLC25A33

GO:0007005

mitochondrion organization

25320081

TgeneSLC25A33

GO:0032869

cellular response to insulin stimulus

17596519

TgeneSLC25A33

GO:0051881

regulation of mitochondrial membrane potential

25320081

TgeneSLC25A33

GO:1990314

cellular response to insulin-like growth factor stimulus

17596519



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/chr1:10209340/chr1:9613684)
- 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 UBE4B (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 SLC25A33 (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)
ENST00000253251UBE4Bchr110209340+ENST00000302692SLC25A33chr19613684+6730314283940511070
ENST00000377157UBE4Bchr110209340+ENST00000302692SLC25A33chr19613684+6604301671339251070
ENST00000343090UBE4Bchr110209340+ENST00000302692SLC25A33chr19613684+635327657536741199

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
ENST00000253251ENST00000302692UBE4Bchr110209340+SLC25A33chr19613684+0.0006837580.9993162
ENST00000377157ENST00000302692UBE4Bchr110209340+SLC25A33chr19613684+0.0005608290.9994392
ENST00000343090ENST00000302692UBE4Bchr110209340+SLC25A33chr19613684+0.0005005340.99949944

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 UBE4B-SLC25A33

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
UBE4Bchr110209340SLC25A33chr196136842765897VEDVAEFLFFIVQCGGTVGAIFTCPL
UBE4Bchr110209340SLC25A33chr196136843016768VEDVAEFLFFIVQCGGTVGAIFTCPL
UBE4Bchr110209340SLC25A33chr196136843142768VEDVAEFLFFIVQCGGTVGAIFTCPL

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Potential FusionNeoAntigen Information of UBE4B-SLC25A33 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 UBE4B-SLC25A33 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 UBE4B-SLC25A33

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 UBE4B-SLC25A33

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 UBE4B-SLC25A33

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 UBE4B-SLC25A33

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 UBE4B-SLC25A33

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
TgeneSLC25A33chr1:10209340chr1:9613684ENST0000030269207121_1410322.0TransmembraneHelical%3B Name%3D3
TgeneSLC25A33chr1:10209340chr1:9613684ENST0000030269207190_2100322.0TransmembraneHelical%3B Name%3D4
TgeneSLC25A33chr1:10209340chr1:9613684ENST0000030269207233_2530322.0TransmembraneHelical%3B Name%3D5
TgeneSLC25A33chr1:10209340chr1:9613684ENST0000030269207298_3180322.0TransmembraneHelical%3B Name%3D6
TgeneSLC25A33chr1:10209340chr1:9613684ENST000003026920749_650322.0TransmembraneHelical%3B Name%3D2

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 UBE4B-SLC25A33

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 UBE4B-SLC25A33

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