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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:UBE2D3-MANBA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: UBE2D3-MANBA
FusionPDB ID: 96032
FusionGDB2.0 ID: 96032
HgeneTgene
Gene symbol

UBE2D3

MANBA

Gene ID

7323

4126

Gene nameubiquitin conjugating enzyme E2 D3mannosidase beta
SynonymsE2(17)KB3|UBC4/5|UBCH5CMANB1
Cytomap

4q24

4q24

Type of geneprotein-codingprotein-coding
Descriptionubiquitin-conjugating enzyme E2 D3(E3-independent) E2 ubiquitin-conjugating enzyme D3E2 ubiquitin-conjugating enzyme D3ubiquitin carrier protein D3ubiquitin conjugating enzyme E2D 3ubiquitin-conjugating enzyme E2(17)KB 3ubiquitin-conjugating enzyme beta-mannosidasebeta-mannosidase Alysosomal beta A mannosidasemannanasemannasemannosidase, beta A, lysosomal
Modification date2020031320200313
UniProtAcc.

Q9NQG1

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000343106, ENST00000394801, 
ENST00000394803, ENST00000453744, 
ENST00000502404, ENST00000504211, 
ENST00000505207, ENST00000507845, 
ENST00000321805, ENST00000338145, 
ENST00000349311, ENST00000350435, 
ENST00000357194, ENST00000394804, 
ENST00000513098, 
ENST00000226578, 
ENST00000505239, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 14 X 7=11767 X 6 X 7=294
# samples 177
** MAII scorelog2(17/1176*10)=-2.79028140869866
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/294*10)=-2.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: UBE2D3 [Title/Abstract] AND MANBA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: UBE2D3 [Title/Abstract] AND MANBA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MANBA(103571694)-UBE2D3(103723795), # samples:1
MANBA(103681875)-UBE2D3(103731012), # samples:1
UBE2D3(103722611)-MANBA(103611928), # samples:1
Anticipated loss of major functional domain due to fusion event.MANBA-UBE2D3 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.
MANBA-UBE2D3 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.
UBE2D3-MANBA 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.
UBE2D3-MANBA 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.
UBE2D3-MANBA seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
UBE2D3-MANBA seems lost the major protein functional domain in Hgene 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
HgeneUBE2D3

GO:0000209

protein polyubiquitination

14765125|16522193

HgeneUBE2D3

GO:0006513

protein monoubiquitination

20347421

HgeneUBE2D3

GO:0016567

protein ubiquitination

9990509|21532592

HgeneUBE2D3

GO:0043161

proteasome-mediated ubiquitin-dependent protein catabolic process

20347421

HgeneUBE2D3

GO:0051865

protein autoubiquitination

21068390

HgeneUBE2D3

GO:0070936

protein K48-linked ubiquitination

20061386

HgeneUBE2D3

GO:0070979

protein K11-linked ubiquitination

20061386



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/chr4:103571694/chr4:103723795)
- 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 UBE2D3 (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 MANBA (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)
ENST00000394804UBE2D3chr4103722611-ENST00000226578MANBAchr4103611928-31289976932963756
ENST00000394804UBE2D3chr4103722611-ENST00000505239MANBAchr4103611928-30339976932963756
ENST00000321805UBE2D3chr4103722611-ENST00000226578MANBAchr4103611928-28987674632733756
ENST00000321805UBE2D3chr4103722611-ENST00000505239MANBAchr4103611928-28037674632733756
ENST00000350435UBE2D3chr4103722611-ENST00000226578MANBAchr4103611928-2534403842369761
ENST00000350435UBE2D3chr4103722611-ENST00000505239MANBAchr4103611928-2439403842369761
ENST00000338145UBE2D3chr4103722611-ENST00000226578MANBAchr4103611928-27245932892559756
ENST00000338145UBE2D3chr4103722611-ENST00000505239MANBAchr4103611928-26295932892559756
ENST00000349311UBE2D3chr4103722611-ENST00000226578MANBAchr4103611928-26785472432513756
ENST00000349311UBE2D3chr4103722611-ENST00000505239MANBAchr4103611928-25835472432513756
ENST00000357194UBE2D3chr4103722611-ENST00000226578MANBAchr4103611928-25934621522428758
ENST00000357194UBE2D3chr4103722611-ENST00000505239MANBAchr4103611928-24984621522428758

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
ENST00000394804ENST00000226578UBE2D3chr4103722611-MANBAchr4103611928-0.0008455340.99915445
ENST00000394804ENST00000505239UBE2D3chr4103722611-MANBAchr4103611928-0.0007921470.9992079
ENST00000321805ENST00000226578UBE2D3chr4103722611-MANBAchr4103611928-0.0010616690.9989384
ENST00000321805ENST00000505239UBE2D3chr4103722611-MANBAchr4103611928-0.0009746870.99902534
ENST00000350435ENST00000226578UBE2D3chr4103722611-MANBAchr4103611928-0.0013371190.9986628
ENST00000350435ENST00000505239UBE2D3chr4103722611-MANBAchr4103611928-0.0012018980.99879813
ENST00000338145ENST00000226578UBE2D3chr4103722611-MANBAchr4103611928-0.0009756150.9990244
ENST00000338145ENST00000505239UBE2D3chr4103722611-MANBAchr4103611928-0.0008779320.9991221
ENST00000349311ENST00000226578UBE2D3chr4103722611-MANBAchr4103611928-0.0010780370.998922
ENST00000349311ENST00000505239UBE2D3chr4103722611-MANBAchr4103611928-0.0009661850.9990338
ENST00000357194ENST00000226578UBE2D3chr4103722611-MANBAchr4103611928-0.0026579340.99734205
ENST00000357194ENST00000505239UBE2D3chr4103722611-MANBAchr4103611928-0.0024551770.9975448

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 UBE2D3-MANBA

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 UBE2D3-MANBA 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 UBE2D3-MANBA 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 UBE2D3-MANBA

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 UBE2D3-MANBA

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 UBE2D3-MANBA

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 UBE2D3-MANBA

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 UBE2D3-MANBA

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 UBE2D3-MANBA

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 UBE2D3-MANBA

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