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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:MGAT5-SP100

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MGAT5-SP100
FusionPDB ID: 53360
FusionGDB2.0 ID: 53360
HgeneTgene
Gene symbol

MGAT5

SP100

Gene ID

4249

6672

Gene namealpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferaseSP100 nuclear antigen
SynonymsGNT-V|GNT-VA|MGAT5A|glcNAc-T Vlysp100b
Cytomap

2q21.2-q21.3

2q37.1

Type of geneprotein-codingprotein-coding
Descriptionalpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase AN-acetylglucosaminyl-transferase Valpha-mannoside beta-1,6-N-acetylglucosaminyltransferasealpha-mannoside beta-1,6-N-acetylglucosaminyltransferase Vmannoside acetylglucosaminyltrannuclear autoantigen Sp-100SP100-HMG nuclear autoantigennuclear dot-associated Sp100 proteinspeckled 100 kDa
Modification date2020031320200313
UniProtAcc

Q3V5L5

Main function of 5'-partner protein: FUNCTION: Glycosyltransferase that acts on alpha-linked mannose of N-glycans and O-mannosyl glycans. Catalyzes the transfer of N-acetylglucosamine (GlcNAc) to the beta 1-6 linkage of the mannose residue of GlcNAc-beta1,2-Man-alpha on both the alpha1,3- and alpha1,6-linked mannose arms in the core structure of N-glycan. Also acts on the GlcNAc-beta1,2-Man-alpha1-Ser/Thr moiety, forming a 2,6-branched structure in brain O-mannosyl glycan. Plays an active role in modulating integrin and laminin-dependent adhesion and migration of neuronal cells via its activity in the O-mannosyl glycan pathway. {ECO:0000269|PubMed:12941944, ECO:0000269|PubMed:14617637, ECO:0000269|PubMed:14623122, ECO:0000269|PubMed:16606368, ECO:0000269|PubMed:16857188, ECO:0000269|PubMed:19846580}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000468758, ENST00000281923, 
ENST00000409645, 
ENST00000264052, 
ENST00000340126, ENST00000341950, 
ENST00000409112, ENST00000409341, 
ENST00000409824, ENST00000409897, 
ENST00000427101, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 12 X 3=3963 X 3 X 2=18
# samples 144
** MAII scorelog2(14/396*10)=-1.50007360313464
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/18*10)=1.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: MGAT5 [Title/Abstract] AND SP100 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MGAT5 [Title/Abstract] AND SP100 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MGAT5(135012215)-SP100(231327150), # samples:1
Anticipated loss of major functional domain due to fusion event.MGAT5-SP100 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.
MGAT5-SP100 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.
MGAT5-SP100 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.
MGAT5-SP100 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.
MGAT5-SP100 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
MGAT5-SP100 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
MGAT5-SP100 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF.
MGAT5-SP100 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
MGAT5-SP100 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted ORF.
MGAT5-SP100 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
HgeneMGAT5

GO:0006487

protein N-linked glycosylation

24846175

HgeneMGAT5

GO:0018279

protein N-linked glycosylation via asparagine

10395745|30140003

HgeneMGAT5

GO:0030335

positive regulation of cell migration

24846175

HgeneMGAT5

GO:1903614

negative regulation of protein tyrosine phosphatase activity

24846175

HgeneMGAT5

GO:1904894

positive regulation of STAT cascade

24846175

TgeneSP100

GO:0000122

negative regulation of transcription by RNA polymerase II

15247905

TgeneSP100

GO:0006978

DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator

14647468

TgeneSP100

GO:0034340

response to type I interferon

9230084|15247905

TgeneSP100

GO:0034341

response to interferon-gamma

9230084

TgeneSP100

GO:0043392

negative regulation of DNA binding

15247905

TgeneSP100

GO:0043433

negative regulation of DNA-binding transcription factor activity

15247905

TgeneSP100

GO:0045185

maintenance of protein location

12470659



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/chr2:135012215/chr2:231327150)
- 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 MGAT5 (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 SP100 (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)
ENST00000409645MGAT5chr2135012215+ENST00000264052SP100chr2231327150+30474932522159635
ENST00000409645MGAT5chr2135012215+ENST00000409112SP100chr2231327150+16874932521586444
ENST00000409645MGAT5chr2135012215+ENST00000340126SP100chr2231327150+24154932522177641
ENST00000409645MGAT5chr2135012215+ENST00000427101SP100chr2231327150+1363493252953233
ENST00000409645MGAT5chr2135012215+ENST00000409824SP100chr2231327150+1340493252962236
ENST00000409645MGAT5chr2135012215+ENST00000409341SP100chr2231327150+1368493252962236
ENST00000409645MGAT5chr2135012215+ENST00000341950SP100chr2231327150+942493252941229
ENST00000409645MGAT5chr2135012215+ENST00000409897SP100chr2231327150+1381493252962236
ENST00000281923MGAT5chr2135012215+ENST00000264052SP100chr2231327150+29403861452052635
ENST00000281923MGAT5chr2135012215+ENST00000409112SP100chr2231327150+15803861451479444
ENST00000281923MGAT5chr2135012215+ENST00000340126SP100chr2231327150+23083861452070641
ENST00000281923MGAT5chr2135012215+ENST00000427101SP100chr2231327150+1256386145846233
ENST00000281923MGAT5chr2135012215+ENST00000409824SP100chr2231327150+1233386145855236
ENST00000281923MGAT5chr2135012215+ENST00000409341SP100chr2231327150+1261386145855236
ENST00000281923MGAT5chr2135012215+ENST00000341950SP100chr2231327150+835386145834230
ENST00000281923MGAT5chr2135012215+ENST00000409897SP100chr2231327150+1274386145855236

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
ENST00000409645ENST00000264052MGAT5chr2135012215+SP100chr2231327150+0.00098970.9990103
ENST00000409645ENST00000409112MGAT5chr2135012215+SP100chr2231327150+0.0089769280.99102306
ENST00000409645ENST00000340126MGAT5chr2135012215+SP100chr2231327150+0.0035459540.9964541
ENST00000409645ENST00000427101MGAT5chr2135012215+SP100chr2231327150+0.0032963660.9967037
ENST00000409645ENST00000409824MGAT5chr2135012215+SP100chr2231327150+0.0043651320.99563485
ENST00000409645ENST00000409341MGAT5chr2135012215+SP100chr2231327150+0.0041859620.995814
ENST00000409645ENST00000341950MGAT5chr2135012215+SP100chr2231327150+0.0072660830.99273396
ENST00000409645ENST00000409897MGAT5chr2135012215+SP100chr2231327150+0.0040681440.9959319
ENST00000281923ENST00000264052MGAT5chr2135012215+SP100chr2231327150+0.0008523390.99914765
ENST00000281923ENST00000409112MGAT5chr2135012215+SP100chr2231327150+0.0073576120.99264234
ENST00000281923ENST00000340126MGAT5chr2135012215+SP100chr2231327150+0.0033146680.9966853
ENST00000281923ENST00000427101MGAT5chr2135012215+SP100chr2231327150+0.003689840.9963102
ENST00000281923ENST00000409824MGAT5chr2135012215+SP100chr2231327150+0.0051556840.9948443
ENST00000281923ENST00000409341MGAT5chr2135012215+SP100chr2231327150+0.0051139110.9948861
ENST00000281923ENST00000341950MGAT5chr2135012215+SP100chr2231327150+0.0098909410.9901091
ENST00000281923ENST00000409897MGAT5chr2135012215+SP100chr2231327150+0.0051448920.99485505

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 MGAT5-SP100

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MGAT5chr2135012215SP100chr223132715038680VVDGPYAGVMTAYVISSEDSEGSTDV
MGAT5chr2135012215SP100chr223132715049380VVDGPYAGVMTAYVISSEDSEGSTDV

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Potential FusionNeoAntigen Information of MGAT5-SP100 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 MGAT5-SP100 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.
MGAT5-SP100_135012215_231327150.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)
MGAT5-SP100chr2135012215chr2231327150386DRB1-0413TAYVISSEDSEGSTD1025
MGAT5-SP100chr2135012215chr2231327150386DRB1-0413AYVISSEDSEGSTDV1126
MGAT5-SP100chr2135012215chr2231327150386DRB1-0422TAYVISSEDSEGSTD1025
MGAT5-SP100chr2135012215chr2231327150386DRB1-0451TAYVISSEDSEGSTD1025
MGAT5-SP100chr2135012215chr2231327150386DRB1-0469DGPYAGVMTAYVISS217
MGAT5-SP100chr2135012215chr2231327150386DRB1-0469VDGPYAGVMTAYVIS116

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Fusion breakpoint peptide structures of MGAT5-SP100

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 MGAT5-SP100

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 MGAT5-SP100

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
MGAT5-SP100chr2135012215chr2231327150116VDGPYAGVMTAYVISTGGATGGGCCATACGCTGGAGTCATGACAGCTTATGTCATCAGCA
MGAT5-SP100chr2135012215chr22313271501025TAYVISSEDSEGSTDCAGCTTATGTCATCAGCAGTGAGGACTCTGAAGGATCCACTGACG
MGAT5-SP100chr2135012215chr22313271501126AYVISSEDSEGSTDVCTTATGTCATCAGCAGTGAGGACTCTGAAGGATCCACTGACGTTG
MGAT5-SP100chr2135012215chr2231327150217DGPYAGVMTAYVISSATGGGCCATACGCTGGAGTCATGACAGCTTATGTCATCAGCAGTG

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Information of the samples that have these potential fusion neoantigens of MGAT5-SP100

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 MGAT5-SP100

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
HgeneMGAT5chr2:135012215chr2:231327150ENST00000281923+11614_3080742.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
HgeneMGAT5chr2:135012215chr2:231327150ENST00000409645+21714_3080742.0TransmembraneHelical%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 MGAT5-SP100

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 MGAT5-SP100

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