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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:SEPT9-MPO

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SEPT9-MPO
FusionPDB ID: 80525
FusionGDB2.0 ID: 80525
HgeneTgene
Gene symbol

SEPT9

MPO

Gene ID

10801

4353

Gene nameseptin 9myeloperoxidase
SynonymsAF17q25|MSF|MSF1|NAPB|PNUTL4|SEPT9|SINT1|SeptD1-
Cytomap

17q25.3

17q22

Type of geneprotein-codingprotein-coding
Descriptionseptin-9MLL septin-like fusion protein MSF-AOv/Br septinovarian/breast septinseptin D1myeloperoxidase
Modification date2020032820200329
UniProtAcc.

P05164

Main function of 5'-partner protein: FUNCTION: Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity. {ECO:0000269|PubMed:9922160}.
Ensembl transtripts involved in fusion geneENST idsENST00000427177, ENST00000431235, 
ENST00000449803, ENST00000329047, 
ENST00000423034, ENST00000427180, 
ENST00000427674, ENST00000541152, 
ENST00000585930, ENST00000588690, 
ENST00000590294, ENST00000590917, 
ENST00000591088, ENST00000591198, 
ENST00000592420, ENST00000592481, 
ENST00000592951, 
ENST00000578493, 
ENST00000225275, ENST00000340482, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score31 X 14 X 18=781212 X 18 X 3=648
# samples 4112
** MAII scorelog2(41/7812*10)=-4.25199613438135
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/648*10)=-2.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SEPT9 [Title/Abstract] AND MPO [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SEPT9 [Title/Abstract] AND MPO [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SEPT9(75303279)-MPO(56351030), # samples:1
SEPT9(75303279)-MPO(56353063), # samples:1
Anticipated loss of major functional domain due to fusion event.SEPT9-MPO 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.
SEPT9-MPO 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.
SEPT9-MPO seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
TgeneMPO

GO:0034374

low-density lipoprotein particle remodeling

10772654

TgeneMPO

GO:0042744

hydrogen peroxide catabolic process

10772654|11907569

TgeneMPO

GO:0055114

oxidation-reduction process

10772654



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/chr17:75303279/chr17:56351030)
- 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 SEPT9 (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 MPO (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)
ENST00000427177SEPT9chr1775303279-ENST00000340482MPOchr1756353063-20362021261235369
ENST00000427177SEPT9chr1775303279-ENST00000225275MPOchr1756353063-20362021261235369

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
ENST00000427177ENST00000340482SEPT9chr1775303279-MPOchr1756353063-0.0126343680.9873656
ENST00000427177ENST00000225275SEPT9chr1775303279-MPOchr1756353063-0.0126343680.9873656

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 SEPT9-MPO

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SEPT9chr1775303279MPOchr175635306320225SGRLRRLGDSSGPGDTRSSEMPELTS

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Potential FusionNeoAntigen Information of SEPT9-MPO 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.
SEPT9-MPO_75303279_56353063.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)
SEPT9-MPOchr1775303279chr1756353063202HLA-A66:01DSSGPGDTR0.98270.5961817
SEPT9-MPOchr1775303279chr1756353063202HLA-A68:24DSSGPGDTR0.98230.5244817
SEPT9-MPOchr1775303279chr1756353063202HLA-A68:03DSSGPGDTR0.97790.5315817
SEPT9-MPOchr1775303279chr1756353063202HLA-A26:03DSSGPGDTR0.93620.6468817
SEPT9-MPOchr1775303279chr1756353063202HLA-A68:05DSSGPGDTR0.83090.5297817
SEPT9-MPOchr1775303279chr1756353063202HLA-A34:01DSSGPGDTR0.64040.5571817
SEPT9-MPOchr1775303279chr1756353063202HLA-A34:05DSSGPGDTR0.64040.5571817
SEPT9-MPOchr1775303279chr1756353063202HLA-A68:08DSSGPGDTR0.44650.5668817
SEPT9-MPOchr1775303279chr1756353063202HLA-A66:03DSSGPGDTR0.23610.5122817
SEPT9-MPOchr1775303279chr1756353063202HLA-B07:02GPGDTRSSEM0.99730.64741121
SEPT9-MPOchr1775303279chr1756353063202HLA-B07:05GPGDTRSSEM0.99690.53581121
SEPT9-MPOchr1775303279chr1756353063202HLA-B82:01GPGDTRSSEM0.49480.50911121
SEPT9-MPOchr1775303279chr1756353063202HLA-A68:01DSSGPGDTR0.98230.5244817
SEPT9-MPOchr1775303279chr1756353063202HLA-B07:12GPGDTRSSEM0.98190.79221121
SEPT9-MPOchr1775303279chr1756353063202HLA-B07:04GPGDTRSSEM0.94110.60271121
SEPT9-MPOchr1775303279chr1756353063202HLA-B42:01GPGDTRSSEM0.81920.51411121
SEPT9-MPOchr1775303279chr1756353063202HLA-A66:02DSSGPGDTR0.29310.5179817
SEPT9-MPOchr1775303279chr1756353063202HLA-B07:22GPGDTRSSEM0.99730.64741121
SEPT9-MPOchr1775303279chr1756353063202HLA-B07:09GPGDTRSSEM0.99730.63931121
SEPT9-MPOchr1775303279chr1756353063202HLA-B82:02GPGDTRSSEM0.49480.50911121
SEPT9-MPOchr1775303279chr1756353063202HLA-B67:01GPGDTRSSEM0.43350.79941121

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Potential FusionNeoAntigen Information of SEPT9-MPO 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.
SEPT9-MPO_75303279_56353063.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)
SEPT9-MPOchr1775303279chr1756353063202DRB1-0413SGRLRRLGDSSGPGD015
SEPT9-MPOchr1775303279chr1756353063202DRB1-0415SGRLRRLGDSSGPGD015
SEPT9-MPOchr1775303279chr1756353063202DRB1-0436SGRLRRLGDSSGPGD015
SEPT9-MPOchr1775303279chr1756353063202DRB1-0440SGRLRRLGDSSGPGD015
SEPT9-MPOchr1775303279chr1756353063202DRB1-0442SGRLRRLGDSSGPGD015
SEPT9-MPOchr1775303279chr1756353063202DRB1-0451SGRLRRLGDSSGPGD015
SEPT9-MPOchr1775303279chr1756353063202DRB1-0453SGRLRRLGDSSGPGD015
SEPT9-MPOchr1775303279chr1756353063202DRB1-0455SGRLRRLGDSSGPGD015
SEPT9-MPOchr1775303279chr1756353063202DRB1-0456SGRLRRLGDSSGPGD015
SEPT9-MPOchr1775303279chr1756353063202DRB1-0458SGRLRRLGDSSGPGD015
SEPT9-MPOchr1775303279chr1756353063202DRB1-0468SGRLRRLGDSSGPGD015
SEPT9-MPOchr1775303279chr1756353063202DRB1-0470SGRLRRLGDSSGPGD015
SEPT9-MPOchr1775303279chr1756353063202DRB1-0479SGRLRRLGDSSGPGD015

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Fusion breakpoint peptide structures of SEPT9-MPO

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
4989LGDSSGPGDTRSSESEPT9MPOchr1775303279chr1756353063202

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SEPT9-MPO

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-B14:023BVN4989LGDSSGPGDTRSSE-6.46878-6.66328
HLA-B14:023BVN4989LGDSSGPGDTRSSE-4.33704-5.09154
HLA-B52:013W394989LGDSSGPGDTRSSE-6.45088-7.20538
HLA-B52:013W394989LGDSSGPGDTRSSE-6.08714-6.28164
HLA-A11:014UQ24989LGDSSGPGDTRSSE-7.67344-8.42794
HLA-A24:025HGA4989LGDSSGPGDTRSSE-7.49907-7.69357
HLA-A24:025HGA4989LGDSSGPGDTRSSE-4.36357-5.11807
HLA-B27:056PYJ4989LGDSSGPGDTRSSE-8.53231-9.28681
HLA-B44:053DX84989LGDSSGPGDTRSSE-5.69992-5.89442
HLA-B44:053DX84989LGDSSGPGDTRSSE-3.58931-4.34381
HLA-A02:016TDR4989LGDSSGPGDTRSSE-7.78181-7.97631

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Vaccine Design for the FusionNeoAntigens of SEPT9-MPO

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
SEPT9-MPOchr1775303279chr17563530631121GPGDTRSSEMGCCCAGGGGACACCCGTTCCAGTGAGATGC
SEPT9-MPOchr1775303279chr1756353063817DSSGPGDTRACTCCAGTGGCCCAGGGGACACCCGTT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
SEPT9-MPOchr1775303279chr1756353063015SGRLRRLGDSSGPGDGTGGCCGGCTCCGGAGGCTTGGTGACTCCAGTGGCCCAGGGGACA

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Information of the samples that have these potential fusion neoantigens of SEPT9-MPO

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
LUADSEPT9-MPOchr1775303279ENST00000427177chr1756353063ENST00000225275TCGA-05-5429-01A

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Potential target of CAR-T therapy development for SEPT9-MPO

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 SEPT9-MPO

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 SEPT9-MPO

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