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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:MAN1A1-PDSS2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MAN1A1-PDSS2
FusionPDB ID: 51062
FusionGDB2.0 ID: 51062
HgeneTgene
Gene symbol

MAN1A1

PDSS2

Gene ID

4121

57107

Gene namemannosidase alpha class 1A member 1decaprenyl diphosphate synthase subunit 2
SynonymsHUMM3|HUMM9|MAN9C6orf210|COQ10D3|COQ1B|DLP1|bA59I9.3|hDLP1
Cytomap

6q22.31

6q21

Type of geneprotein-codingprotein-coding
Descriptionmannosyl-oligosaccharide 1,2-alpha-mannosidase IAMan9-mannosidasealpha-1,2-mannosidase IAman(9)-alpha-mannosidaseprocessing alpha-1,2-mannosidase IAdecaprenyl-diphosphate synthase subunit 2all-trans-decaprenyl-diphosphate synthase subunit 2decaprenyl pyrophosphate synthase subunit 2decaprenyl pyrophosphate synthetase subunit 2prenyl (decaprenyl) diphosphate synthase, subunit 2subunit 2 of decapr
Modification date2020031320200313
UniProtAcc

P33908

Main function of 5'-partner protein: FUNCTION: Involved in the maturation of Asn-linked oligosaccharides. Progressively trim alpha-1,2-linked mannose residues from Man(9)GlcNAc(2) to produce Man(5)GlcNAc(2).
.
Ensembl transtripts involved in fusion geneENST idsENST00000368466, ENST00000368468, 
ENST00000369031, ENST00000369037, 
ENST00000453874, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 7 X 5=3509 X 7 X 6=378
# samples 810
** MAII scorelog2(8/350*10)=-2.12928301694497
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/378*10)=-1.91838623444635
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MAN1A1 [Title/Abstract] AND PDSS2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MAN1A1 [Title/Abstract] AND PDSS2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MAN1A1(119669628)-PDSS2(107475981), # samples:3
Anticipated loss of major functional domain due to fusion event.MAN1A1-PDSS2 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
MAN1A1-PDSS2 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
MAN1A1-PDSS2 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
TgenePDSS2

GO:0006744

ubiquinone biosynthetic process

16262699

TgenePDSS2

GO:0008299

isoprenoid biosynthetic process

16262699



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/chr6:119669628/chr6:107475981)
- 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 MAN1A1 (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 PDSS2 (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)
ENST00000368466MAN1A1chr6119669628-ENST00000453874PDSS2chr6107475981-135210201531178341

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
ENST00000368466ENST00000453874MAN1A1chr6119669628-PDSS2chr6107475981-0.0080351590.9919648

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 MAN1A1-PDSS2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MAN1A1chr6119669628PDSS2chr61074759811020289DAAIREKRAKIKELRERIKAGKGVTS

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Potential FusionNeoAntigen Information of MAN1A1-PDSS2 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.
MAN1A1-PDSS2_119669628_107475981.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)
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-B08:09ELRERIKA0.99950.5151220
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-B27:05KRAKIKELR0.99880.9289615
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-B45:01KELRERIKA0.99420.53781120
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-B14:01EKRAKIKEL0.99080.6631514
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-B14:02EKRAKIKEL0.99080.6631514
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-B08:09ELRERIKAG0.95220.51741221
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-B08:09EKRAKIKEL0.92290.6024514
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-B41:01KELRERIKA0.67960.63671120
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-C07:05KRAKIKEL0.99890.9784614
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-B27:14KRAKIKELR0.99870.876615
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-B27:03KRAKIKELR0.96720.9426615
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-B14:03EKRAKIKEL0.41070.864514
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-C07:22KRAKIKEL0.99760.8146614
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-C06:17KRAKIKEL0.95030.9957614
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-C06:02KRAKIKEL0.95030.9957614
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-B27:10KRAKIKELR0.99780.9255615
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-B08:12EKRAKIKEL0.92610.5308514
MAN1A1-PDSS2chr6119669628chr61074759811020HLA-A30:01KIKELRERIK0.99380.7892919

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Potential FusionNeoAntigen Information of MAN1A1-PDSS2 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 MAN1A1-PDSS2

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
4548KRAKIKELRERIKAMAN1A1PDSS2chr6119669628chr61074759811020

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MAN1A1-PDSS2

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-B14:023BVN4548KRAKIKELRERIKA-7.9962-8.1096
HLA-B14:023BVN4548KRAKIKELRERIKA-5.70842-6.74372
HLA-B52:013W394548KRAKIKELRERIKA-6.83737-6.95077
HLA-B52:013W394548KRAKIKELRERIKA-4.4836-5.5189
HLA-A11:014UQ24548KRAKIKELRERIKA-10.0067-10.1201
HLA-A11:014UQ24548KRAKIKELRERIKA-9.03915-10.0745
HLA-A24:025HGA4548KRAKIKELRERIKA-6.56204-6.67544
HLA-A24:025HGA4548KRAKIKELRERIKA-5.42271-6.45801
HLA-B44:053DX84548KRAKIKELRERIKA-7.85648-8.89178
HLA-B44:053DX84548KRAKIKELRERIKA-5.3978-5.5112
HLA-A02:016TDR4548KRAKIKELRERIKA-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of MAN1A1-PDSS2

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
MAN1A1-PDSS2chr6119669628chr61074759811120KELRERIKAAAAGAGTTGCGAGAAAGAATCAAAGCT
MAN1A1-PDSS2chr6119669628chr61074759811220ELRERIKAGAGTTGCGAGAAAGAATCAAAGCT
MAN1A1-PDSS2chr6119669628chr61074759811221ELRERIKAGGAGTTGCGAGAAAGAATCAAAGCTGGC
MAN1A1-PDSS2chr6119669628chr6107475981514EKRAKIKELGAGAAAAGGGCAAAGATCAAAGAGTTG
MAN1A1-PDSS2chr6119669628chr6107475981614KRAKIKELAAAAGGGCAAAGATCAAAGAGTTG
MAN1A1-PDSS2chr6119669628chr6107475981615KRAKIKELRAAAAGGGCAAAGATCAAAGAGTTGCGA
MAN1A1-PDSS2chr6119669628chr6107475981919KIKELRERIKAAGATCAAAGAGTTGCGAGAAAGAATCAAA

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 MAN1A1-PDSS2

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
BRCAMAN1A1-PDSS2chr6119669628ENST00000368466chr6107475981ENST00000453874TCGA-E9-A1RF-01A

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Potential target of CAR-T therapy development for MAN1A1-PDSS2

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
HgeneMAN1A1chr6:119669628chr6:107475981ENST00000368468-21342_62201654.0TransmembraneHelical%3B Signal-anchor for type II membrane protein

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 MAN1A1-PDSS2

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 MAN1A1-PDSS2

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