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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:MANBA-UBE2D3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MANBA-UBE2D3
FusionPDB ID: 51133
FusionGDB2.0 ID: 51133
HgeneTgene
Gene symbol

MANBA

UBE2D3

Gene ID

4126

7323

Gene namemannosidase betaubiquitin conjugating enzyme E2 D3
SynonymsMANB1E2(17)KB3|UBC4/5|UBCH5C
Cytomap

4q24

4q24

Type of geneprotein-codingprotein-coding
Descriptionbeta-mannosidasebeta-mannosidase Alysosomal beta A mannosidasemannanasemannasemannosidase, beta A, lysosomalubiquitin-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
Modification date2020031320200313
UniProtAcc

Q9NQG1

Main function of 5'-partner protein: 		.
Ensembl transtripts involved in fusion geneENST idsENST00000226578, ENST00000505239, 
ENST00000357194, ENST00000502404, 
ENST00000504211, ENST00000505207, 
ENST00000507845, ENST00000513098, 
ENST00000321805, ENST00000338145, 
ENST00000343106, ENST00000349311, 
ENST00000350435, ENST00000394801, 
ENST00000394803, ENST00000394804, 
ENST00000453744, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 4=648 X 5 X 7=280
# samples 59
** MAII scorelog2(5/64*10)=-0.356143810225275
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(9/280*10)=-1.63742992061529
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

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

Fusion neoantigen context

PubMed: MANBA [Title/Abstract] AND UBE2D3 [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 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.
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
TgeneUBE2D3

GO:0000209

protein polyubiquitination

14765125|16522193

TgeneUBE2D3

GO:0006513

protein monoubiquitination

20347421

TgeneUBE2D3

GO:0016567

protein ubiquitination

9990509|21532592

TgeneUBE2D3

GO:0043161

proteasome-mediated ubiquitin-dependent protein catabolic process

20347421

TgeneUBE2D3

GO:0051865

protein autoubiquitination

21068390

TgeneUBE2D3

GO:0070936

protein K48-linked ubiquitination

20061386

TgeneUBE2D3

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 MANBA (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 UBE2D3 (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)
ENST00000226578MANBAchr4103571694-ENST00000453744UBE2D3chr4103723795-532519691002292730
ENST00000226578MANBAchr4103571694-ENST00000394801UBE2D3chr4103723795-373219691002292730
ENST00000226578MANBAchr4103571694-ENST00000394803UBE2D3chr4103723795-373219691002292730
ENST00000226578MANBAchr4103571694-ENST00000394804UBE2D3chr4103723795-373119691002292730
ENST00000226578MANBAchr4103571694-ENST00000343106UBE2D3chr4103723795-362419691002295731
ENST00000226578MANBAchr4103571694-ENST00000321805UBE2D3chr4103723795-247319691002292730
ENST00000226578MANBAchr4103571694-ENST00000350435UBE2D3chr4103723795-246119691002292730
ENST00000226578MANBAchr4103571694-ENST00000338145UBE2D3chr4103723795-245619691002292730
ENST00000226578MANBAchr4103571694-ENST00000349311UBE2D3chr4103723795-244419691002292730
ENST00000226578MANBAchr4103571694-ENST00000504211UBE2D3chr4103723795-238619691002292730
ENST00000226578MANBAchr4103571694-ENST00000357194UBE2D3chr4103723795-235119691002292730
ENST00000226578MANBAchr4103571694-ENST00000505207UBE2D3chr4103723795-234119691002292730
ENST00000226578MANBAchr4103571694-ENST00000507845UBE2D3chr4103723795-232319691002292730
ENST00000226578MANBAchr4103571694-ENST00000502404UBE2D3chr4103723795-230919691002292730
ENST00000505239MANBAchr4103571694-ENST00000453744UBE2D3chr4103723795-50931737392060673
ENST00000505239MANBAchr4103571694-ENST00000394801UBE2D3chr4103723795-35001737392060673
ENST00000505239MANBAchr4103571694-ENST00000394803UBE2D3chr4103723795-35001737392060673
ENST00000505239MANBAchr4103571694-ENST00000394804UBE2D3chr4103723795-34991737392060673
ENST00000505239MANBAchr4103571694-ENST00000343106UBE2D3chr4103723795-33921737392063674
ENST00000505239MANBAchr4103571694-ENST00000321805UBE2D3chr4103723795-22411737392060673
ENST00000505239MANBAchr4103571694-ENST00000350435UBE2D3chr4103723795-22291737392060673
ENST00000505239MANBAchr4103571694-ENST00000338145UBE2D3chr4103723795-22241737392060673
ENST00000505239MANBAchr4103571694-ENST00000349311UBE2D3chr4103723795-22121737392060673
ENST00000505239MANBAchr4103571694-ENST00000504211UBE2D3chr4103723795-21541737392060673
ENST00000505239MANBAchr4103571694-ENST00000357194UBE2D3chr4103723795-21191737392060673
ENST00000505239MANBAchr4103571694-ENST00000505207UBE2D3chr4103723795-21091737392060673
ENST00000505239MANBAchr4103571694-ENST00000507845UBE2D3chr4103723795-20911737392060673
ENST00000505239MANBAchr4103571694-ENST00000502404UBE2D3chr4103723795-20771737392060673

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
ENST00000226578ENST00000453744MANBAchr4103571694-UBE2D3chr4103723795-0.0002482530.99975175
ENST00000226578ENST00000394801MANBAchr4103571694-UBE2D3chr4103723795-0.0005012970.9994987
ENST00000226578ENST00000394803MANBAchr4103571694-UBE2D3chr4103723795-0.0005012970.9994987
ENST00000226578ENST00000394804MANBAchr4103571694-UBE2D3chr4103723795-0.0005016120.99949837
ENST00000226578ENST00000343106MANBAchr4103571694-UBE2D3chr4103723795-0.0004805180.99951947
ENST00000226578ENST00000321805MANBAchr4103571694-UBE2D3chr4103723795-0.0009919770.999008
ENST00000226578ENST00000350435MANBAchr4103571694-UBE2D3chr4103723795-0.0010510830.998949
ENST00000226578ENST00000338145MANBAchr4103571694-UBE2D3chr4103723795-0.0010474810.9989525
ENST00000226578ENST00000349311MANBAchr4103571694-UBE2D3chr4103723795-0.0009893280.9990107
ENST00000226578ENST00000504211MANBAchr4103571694-UBE2D3chr4103723795-0.0010470740.99895287
ENST00000226578ENST00000357194MANBAchr4103571694-UBE2D3chr4103723795-0.0010864210.99891365
ENST00000226578ENST00000505207MANBAchr4103571694-UBE2D3chr4103723795-0.0011747870.99882525
ENST00000226578ENST00000507845MANBAchr4103571694-UBE2D3chr4103723795-0.0012340110.99876606
ENST00000226578ENST00000502404MANBAchr4103571694-UBE2D3chr4103723795-0.0012153060.9987847
ENST00000505239ENST00000453744MANBAchr4103571694-UBE2D3chr4103723795-0.0002261650.9997738
ENST00000505239ENST00000394801MANBAchr4103571694-UBE2D3chr4103723795-0.0004113160.99958867
ENST00000505239ENST00000394803MANBAchr4103571694-UBE2D3chr4103723795-0.0004113160.99958867
ENST00000505239ENST00000394804MANBAchr4103571694-UBE2D3chr4103723795-0.0004123860.9995876
ENST00000505239ENST00000343106MANBAchr4103571694-UBE2D3chr4103723795-0.0003675780.99963236
ENST00000505239ENST00000321805MANBAchr4103571694-UBE2D3chr4103723795-0.0008998860.9991001
ENST00000505239ENST00000350435MANBAchr4103571694-UBE2D3chr4103723795-0.0009530940.99904686
ENST00000505239ENST00000338145MANBAchr4103571694-UBE2D3chr4103723795-0.0009489770.99905103
ENST00000505239ENST00000349311MANBAchr4103571694-UBE2D3chr4103723795-0.0008856490.99911433
ENST00000505239ENST00000504211MANBAchr4103571694-UBE2D3chr4103723795-0.0009127060.99908733
ENST00000505239ENST00000357194MANBAchr4103571694-UBE2D3chr4103723795-0.0009205040.99907947
ENST00000505239ENST00000505207MANBAchr4103571694-UBE2D3chr4103723795-0.0010193020.9989807
ENST00000505239ENST00000507845MANBAchr4103571694-UBE2D3chr4103723795-0.0010831230.99891686
ENST00000505239ENST00000502404MANBAchr4103571694-UBE2D3chr4103723795-0.0010666160.9989334

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 MANBA-UBE2D3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MANBAchr4103571694UBE2D3chr41037237951737565DPLRTFKDTIYLTQNDSPYQGGVFFL
MANBAchr4103571694UBE2D3chr41037237951969622DPLRTFKDTIYLTQNDSPYQGGVFFL

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Potential FusionNeoAntigen Information of MANBA-UBE2D3 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.
MANBA-UBE2D3_103571694_103723795.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)
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B15:25YLTQNDSPY0.97510.68741019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B15:02YLTQNDSPY0.95350.71361019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B35:08YLTQNDSPY0.88220.63611019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B35:01YLTQNDSPY0.77780.68111019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B13:02TQNDSPYQGGV0.87860.99051223
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B15:21YLTQNDSPY0.94970.70941019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B15:05YLTQNDSPY0.82840.61881019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B15:31YLTQNDSPY0.81170.62271019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B15:27YLTQNDSPY0.9960.78281019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B15:11YLTQNDSPY0.99370.67591019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B15:08YLTQNDSPY0.99260.68471019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B15:39YLTQNDSPY0.97530.56671019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B15:20YLTQNDSPY0.84230.68721019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B35:23YLTQNDSPY0.78790.67871019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B35:77YLTQNDSPY0.77780.68111019
MANBA-UBE2D3chr4103571694chr41037237951969HLA-B35:20YLTQNDSPY0.77570.70671019

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Potential FusionNeoAntigen Information of MANBA-UBE2D3 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.
MANBA-UBE2D3_103571694_103723795.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)
MANBA-UBE2D3chr4103571694chr41037237951969DRB3-0201TIYLTQNDSPYQGGV823
MANBA-UBE2D3chr4103571694chr41037237951969DRB3-0204TIYLTQNDSPYQGGV823
MANBA-UBE2D3chr4103571694chr41037237951969DRB3-0224TIYLTQNDSPYQGGV823

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Fusion breakpoint peptide structures of MANBA-UBE2D3

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
4169KDTIYLTQNDSPYQMANBAUBE2D3chr4103571694chr41037237951969

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MANBA-UBE2D3

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-B14:023BVN4169KDTIYLTQNDSPYQ-7.15543-7.26883
HLA-B14:023BVN4169KDTIYLTQNDSPYQ-4.77435-5.80965
HLA-B52:013W394169KDTIYLTQNDSPYQ-6.80875-6.92215
HLA-B52:013W394169KDTIYLTQNDSPYQ-4.20386-5.23916
HLA-A11:014UQ24169KDTIYLTQNDSPYQ-7.5194-8.5547
HLA-A11:014UQ24169KDTIYLTQNDSPYQ-6.9601-7.0735
HLA-A24:025HGA4169KDTIYLTQNDSPYQ-7.52403-7.63743
HLA-A24:025HGA4169KDTIYLTQNDSPYQ-5.82433-6.85963
HLA-B27:056PYJ4169KDTIYLTQNDSPYQ-3.28285-4.31815
HLA-B44:053DX84169KDTIYLTQNDSPYQ-5.91172-6.94702
HLA-B44:053DX84169KDTIYLTQNDSPYQ-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of MANBA-UBE2D3

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
MANBA-UBE2D3chr4103571694chr41037237951019YLTQNDSPYCTTACTCAGAATGACAGCCCATATCAA
MANBA-UBE2D3chr4103571694chr41037237951223TQNDSPYQGGVCAGAATGACAGCCCATATCAAGGCGGTGTATTC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
MANBA-UBE2D3chr4103571694chr4103723795823TIYLTQNDSPYQGGVATCTACCTTACTCAGAATGACAGCCCATATCAAGGCGGTGTATTC

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Information of the samples that have these potential fusion neoantigens of MANBA-UBE2D3

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
ACCMANBA-UBE2D3chr4103571694ENST00000226578chr4103723795ENST00000321805TCGA-OR-A5J7-01A

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Potential target of CAR-T therapy development for MANBA-UBE2D3

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 MANBA-UBE2D3

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 MANBA-UBE2D3

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