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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-VAV1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SEPT9-VAV1
FusionPDB ID: 80538
FusionGDB2.0 ID: 80538
HgeneTgene
Gene symbol

SEPT9

VAV1

Gene ID

10801

7409

Gene nameseptin 9vav guanine nucleotide exchange factor 1
SynonymsAF17q25|MSF|MSF1|NAPB|PNUTL4|SEPT9|SINT1|SeptD1VAV
Cytomap

17q25.3

19p13.3

Type of geneprotein-codingprotein-coding
Descriptionseptin-9MLL septin-like fusion protein MSF-AOv/Br septinovarian/breast septinseptin D1proto-oncogene vavvav 1 guanine nucleotide exchange factorvav 1 oncogene
Modification date2020032820200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000423034, ENST00000329047, 
ENST00000427177, ENST00000427180, 
ENST00000427674, ENST00000431235, 
ENST00000449803, ENST00000541152, 
ENST00000585930, ENST00000588690, 
ENST00000590294, ENST00000590917, 
ENST00000591088, ENST00000591198, 
ENST00000592420, ENST00000592481, 
ENST00000592951, 
ENST00000304076, 
ENST00000539284, ENST00000596764, 
ENST00000599806, ENST00000602142, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score31 X 14 X 18=781210 X 11 X 8=880
# samples 4112
** MAII scorelog2(41/7812*10)=-4.25199613438135
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/880*10)=-2.87446911791614
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SEPT9 [Title/Abstract] AND VAV1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SEPT9 [Title/Abstract] AND VAV1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SEPT9(75369634)-VAV1(6836443), # samples:1
Anticipated loss of major functional domain due to fusion event.SEPT9-VAV1 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-VAV1 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-VAV1 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-VAV1 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.
* 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


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/chr17:75369634/chr19:6836443)
- 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 VAV1 (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)
ENST00000423034SEPT9chr1775369634-ENST00000304076VAV1chr196836443+13173633081057249
ENST00000423034SEPT9chr1775369634-ENST00000602142VAV1chr196836443+11243633081123272
ENST00000423034SEPT9chr1775369634-ENST00000596764VAV1chr196836443+13773633081123271
ENST00000423034SEPT9chr1775369634-ENST00000539284VAV1chr196836443+13773633081123271
ENST00000423034SEPT9chr1775369634-ENST00000599806VAV1chr196836443+13833633081123271

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
ENST00000423034ENST00000304076SEPT9chr1775369634-VAV1chr196836443+0.0069093520.9930906
ENST00000423034ENST00000602142SEPT9chr1775369634-VAV1chr196836443+0.0049150750.99508494
ENST00000423034ENST00000596764SEPT9chr1775369634-VAV1chr196836443+0.0044744440.99552554
ENST00000423034ENST00000539284SEPT9chr1775369634-VAV1chr196836443+0.0044744440.99552554
ENST00000423034ENST00000599806SEPT9chr1775369634-VAV1chr196836443+0.0045937420.99540627

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-VAV1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SEPT9chr1775369634VAV1chr19683644336318VNAQLDGIISDFEGLPKMEVFQEYYG

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Potential FusionNeoAntigen Information of SEPT9-VAV1 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-VAV1_75369634_6836443.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-VAV1chr1775369634chr196836443363HLA-B13:01SDFEGLPKM0.93390.8584918
SEPT9-VAV1chr1775369634chr196836443363HLA-A02:21GIISDFEGL0.89330.86615
SEPT9-VAV1chr1775369634chr196836443363HLA-B47:01SDFEGLPKM0.88070.7834918
SEPT9-VAV1chr1775369634chr196836443363HLA-B41:01FEGLPKMEV0.73520.97291120
SEPT9-VAV1chr1775369634chr196836443363HLA-B50:01FEGLPKMEV0.73510.86171120
SEPT9-VAV1chr1775369634chr196836443363HLA-B39:13FEGLPKMEV0.31490.97981120
SEPT9-VAV1chr1775369634chr196836443363HLA-B39:13SDFEGLPKM0.26760.8993918
SEPT9-VAV1chr1775369634chr196836443363HLA-B15:16ISDFEGLPKM0.92240.824818
SEPT9-VAV1chr1775369634chr196836443363HLA-B40:06FEGLPKMEV0.99960.63251120
SEPT9-VAV1chr1775369634chr196836443363HLA-B40:03SDFEGLPKM0.98940.5514918
SEPT9-VAV1chr1775369634chr196836443363HLA-B39:08SDFEGLPKM0.72060.6766918
SEPT9-VAV1chr1775369634chr196836443363HLA-C05:09ISDFEGLPKM10.8968818
SEPT9-VAV1chr1775369634chr196836443363HLA-C08:15ISDFEGLPKM0.99990.9256818
SEPT9-VAV1chr1775369634chr196836443363HLA-B40:04FEGLPKMEV0.99320.78831120
SEPT9-VAV1chr1775369634chr196836443363HLA-B40:04SDFEGLPKM0.96780.7223918
SEPT9-VAV1chr1775369634chr196836443363HLA-B18:11SDFEGLPKM0.90690.9531918
SEPT9-VAV1chr1775369634chr196836443363HLA-A02:14GIISDFEGL0.89580.7599615
SEPT9-VAV1chr1775369634chr196836443363HLA-A02:06GIISDFEGL0.89330.86615
SEPT9-VAV1chr1775369634chr196836443363HLA-B18:04SDFEGLPKM0.80990.9811918
SEPT9-VAV1chr1775369634chr196836443363HLA-B18:06SDFEGLPKM0.76750.9818918
SEPT9-VAV1chr1775369634chr196836443363HLA-B41:03FEGLPKMEV0.75280.86821120
SEPT9-VAV1chr1775369634chr196836443363HLA-B50:04FEGLPKMEV0.73510.86171120
SEPT9-VAV1chr1775369634chr196836443363HLA-B50:05FEGLPKMEV0.73510.86171120
SEPT9-VAV1chr1775369634chr196836443363HLA-B18:08SDFEGLPKM0.69780.9644918
SEPT9-VAV1chr1775369634chr196836443363HLA-B39:02SDFEGLPKM0.29880.9092918
SEPT9-VAV1chr1775369634chr196836443363HLA-C05:01ISDFEGLPKM10.8968818
SEPT9-VAV1chr1775369634chr196836443363HLA-C04:03ISDFEGLPKM10.7425818
SEPT9-VAV1chr1775369634chr196836443363HLA-C08:02ISDFEGLPKM0.99990.9256818

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Potential FusionNeoAntigen Information of SEPT9-VAV1 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-VAV1_75369634_6836443.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-VAV1chr1775369634chr196836443363DRB1-0807ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB1-0825ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB1-1172ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB1-13100ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB1-13100IISDFEGLPKMEVFQ722
SEPT9-VAV1chr1775369634chr196836443363DRB1-1346ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB1-1346IISDFEGLPKMEVFQ722
SEPT9-VAV1chr1775369634chr196836443363DRB1-1386ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB1-1402ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB1-1409ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB1-1430ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB1-1441ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB1-1449ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB1-1453ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB1-1469ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB1-1494ISDFEGLPKMEVFQE823
SEPT9-VAV1chr1775369634chr196836443363DRB5-0106DGIISDFEGLPKMEV520
SEPT9-VAV1chr1775369634chr196836443363DRB5-0106LDGIISDFEGLPKME419
SEPT9-VAV1chr1775369634chr196836443363DRB5-0202DGIISDFEGLPKMEV520
SEPT9-VAV1chr1775369634chr196836443363DRB5-0202LDGIISDFEGLPKME419
SEPT9-VAV1chr1775369634chr196836443363DRB5-0204DGIISDFEGLPKMEV520
SEPT9-VAV1chr1775369634chr196836443363DRB5-0204LDGIISDFEGLPKME419
SEPT9-VAV1chr1775369634chr196836443363DRB5-0205DGIISDFEGLPKMEV520
SEPT9-VAV1chr1775369634chr196836443363DRB5-0205LDGIISDFEGLPKME419

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Fusion breakpoint peptide structures of SEPT9-VAV1

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
2870GIISDFEGLPKMEVSEPT9VAV1chr1775369634chr196836443363

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SEPT9-VAV1

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-B14:023BVN2870GIISDFEGLPKMEV-7.9962-8.1096
HLA-B14:023BVN2870GIISDFEGLPKMEV-5.70842-6.74372
HLA-B52:013W392870GIISDFEGLPKMEV-6.83737-6.95077
HLA-B52:013W392870GIISDFEGLPKMEV-4.4836-5.5189
HLA-A11:014UQ22870GIISDFEGLPKMEV-10.0067-10.1201
HLA-A11:014UQ22870GIISDFEGLPKMEV-9.03915-10.0745
HLA-A24:025HGA2870GIISDFEGLPKMEV-6.56204-6.67544
HLA-A24:025HGA2870GIISDFEGLPKMEV-5.42271-6.45801
HLA-B44:053DX82870GIISDFEGLPKMEV-7.85648-8.89178
HLA-B44:053DX82870GIISDFEGLPKMEV-5.3978-5.5112
HLA-A02:016TDR2870GIISDFEGLPKMEV-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of SEPT9-VAV1

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-VAV1chr1775369634chr1968364431120FEGLPKMEVTCGAAGGTCTGCCCAAGATGGAGGTGT
SEPT9-VAV1chr1775369634chr196836443615GIISDFEGLGGATCATTTCGGACTTCGAAGGTCTGC
SEPT9-VAV1chr1775369634chr196836443818ISDFEGLPKMTTTCGGACTTCGAAGGTCTGCCCAAGATGG
SEPT9-VAV1chr1775369634chr196836443918SDFEGLPKMCGGACTTCGAAGGTCTGCCCAAGATGG

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-VAV1chr1775369634chr196836443419LDGIISDFEGLPKMETGGATGGGATCATTTCGGACTTCGAAGGTCTGCCCAAGATGGAGG
SEPT9-VAV1chr1775369634chr196836443520DGIISDFEGLPKMEVATGGGATCATTTCGGACTTCGAAGGTCTGCCCAAGATGGAGGTGT
SEPT9-VAV1chr1775369634chr196836443722IISDFEGLPKMEVFQTCATTTCGGACTTCGAAGGTCTGCCCAAGATGGAGGTGTTTCAGG
SEPT9-VAV1chr1775369634chr196836443823ISDFEGLPKMEVFQETTTCGGACTTCGAAGGTCTGCCCAAGATGGAGGTGTTTCAGGAAT

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Information of the samples that have these potential fusion neoantigens of SEPT9-VAV1

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
ACCSEPT9-VAV1chr1775369634ENST00000423034chr196836443ENST00000304076TCGA-OR-A5JA-01A

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Potential target of CAR-T therapy development for SEPT9-VAV1

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-VAV1

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-VAV1

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