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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:ZNF823-VAV1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZNF823-VAV1
FusionPDB ID: 103020
FusionGDB2.0 ID: 103020
HgeneTgene
Gene symbol

ZNF823

VAV1

Gene ID

55552

7409

Gene namezinc finger protein 823vav guanine nucleotide exchange factor 1
SynonymsHSZFP36VAV
Cytomap

19p13.2

19p13.3

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein 823ZFP 36 for a zinc finger proteinzinc finger protein ZFP-36proto-oncogene vavvav 1 guanine nucleotide exchange factorvav 1 oncogene
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000545749, ENST00000341191, 
ENST00000440527, 
ENST00000304076, 
ENST00000539284, ENST00000596764, 
ENST00000599806, ENST00000602142, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 3=4810 X 11 X 8=880
# samples 512
** MAII scorelog2(5/48*10)=0.0588936890535686
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
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: ZNF823 [Title/Abstract] AND VAV1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZNF823 [Title/Abstract] AND VAV1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZNF823(11849632)-VAV1(6820713), # samples:3
Anticipated loss of major functional domain due to fusion event.ZNF823-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.
ZNF823-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.
ZNF823-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.
ZNF823-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/chr19:11849632/chr19:6820713)
- 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 ZNF823 (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)
ENST00000341191ZNF823chr1911849632-ENST00000304076VAV1chr196820713+2684157432424793
ENST00000341191ZNF823chr1911849632-ENST00000602142VAV1chr196820713+2491157432490816
ENST00000341191ZNF823chr1911849632-ENST00000596764VAV1chr196820713+2648157432394783
ENST00000341191ZNF823chr1911849632-ENST00000539284VAV1chr196820713+2648157432394783
ENST00000341191ZNF823chr1911849632-ENST00000599806VAV1chr196820713+2750157432490815
ENST00000440527ZNF823chr1911849632-ENST00000304076VAV1chr196820713+2720193792460793
ENST00000440527ZNF823chr1911849632-ENST00000602142VAV1chr196820713+2527193792526816
ENST00000440527ZNF823chr1911849632-ENST00000596764VAV1chr196820713+2684193792430783
ENST00000440527ZNF823chr1911849632-ENST00000539284VAV1chr196820713+2684193792430783
ENST00000440527ZNF823chr1911849632-ENST00000599806VAV1chr196820713+2786193792526815

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
ENST00000341191ENST00000304076ZNF823chr1911849632-VAV1chr196820713+0.010350450.98964953
ENST00000341191ENST00000602142ZNF823chr1911849632-VAV1chr196820713+0.0102534260.9897466
ENST00000341191ENST00000596764ZNF823chr1911849632-VAV1chr196820713+0.0076671080.99233294
ENST00000341191ENST00000539284ZNF823chr1911849632-VAV1chr196820713+0.0076671080.99233294
ENST00000341191ENST00000599806ZNF823chr1911849632-VAV1chr196820713+0.0086194170.9913805
ENST00000440527ENST00000304076ZNF823chr1911849632-VAV1chr196820713+0.0104294390.9895705
ENST00000440527ENST00000602142ZNF823chr1911849632-VAV1chr196820713+0.0103290930.98967093
ENST00000440527ENST00000596764ZNF823chr1911849632-VAV1chr196820713+0.0078290110.99217093
ENST00000440527ENST00000539284ZNF823chr1911849632-VAV1chr196820713+0.0078290110.99217093
ENST00000440527ENST00000599806ZNF823chr1911849632-VAV1chr196820713+0.0087343870.9912656

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 ZNF823-VAV1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZNF823chr1911849632VAV1chr19682071315738FKEDTRTPGSWEMFLCLKNIRTFLST
ZNF823chr1911849632VAV1chr19682071319338FKEDTRTPGSWEMFLCLKNIRTFLST

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Potential FusionNeoAntigen Information of ZNF823-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.
ZNF823-VAV1_11849632_6820713.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)
ZNF823-VAV1chr1911849632chr196820713157HLA-B57:03RTPGSWEMF0.96670.9953514
ZNF823-VAV1chr1911849632chr196820713157HLA-B58:02RTPGSWEMF0.96620.9795514
ZNF823-VAV1chr1911849632chr196820713157HLA-A24:20RTPGSWEMF0.95610.5538514
ZNF823-VAV1chr1911849632chr196820713157HLA-A24:15RTPGSWEMF0.95430.567514
ZNF823-VAV1chr1911849632chr196820713157HLA-A24:25RTPGSWEMF0.95090.5555514
ZNF823-VAV1chr1911849632chr196820713157HLA-A32:13RTPGSWEMF0.94730.9765514
ZNF823-VAV1chr1911849632chr196820713157HLA-A24:31RTPGSWEMF0.93860.5492514
ZNF823-VAV1chr1911849632chr196820713157HLA-B35:03TPGSWEMFL0.89670.9266615
ZNF823-VAV1chr1911849632chr196820713157HLA-B35:04TPGSWEMFL0.73530.9818615
ZNF823-VAV1chr1911849632chr196820713157HLA-B35:02TPGSWEMFL0.73530.9818615
ZNF823-VAV1chr1911849632chr196820713157HLA-A24:14RTPGSWEMF0.63450.6639514
ZNF823-VAV1chr1911849632chr196820713157HLA-B81:01TPGSWEMFL0.0860.516615
ZNF823-VAV1chr1911849632chr196820713157HLA-B27:05TRTPGSWEMF0.99990.7398414
ZNF823-VAV1chr1911849632chr196820713157HLA-B27:02TRTPGSWEMF0.99990.5066414
ZNF823-VAV1chr1911849632chr196820713157HLA-B27:04TRTPGSWEMF0.99980.8171414
ZNF823-VAV1chr1911849632chr196820713157HLA-B27:07TRTPGSWEMF0.99910.7627414
ZNF823-VAV1chr1911849632chr196820713157HLA-B15:18TRTPGSWEMF0.96860.8796414
ZNF823-VAV1chr1911849632chr196820713157HLA-B38:01TRTPGSWEMF0.94110.9795414
ZNF823-VAV1chr1911849632chr196820713157HLA-B38:02TRTPGSWEMF0.92930.9762414
ZNF823-VAV1chr1911849632chr196820713157HLA-B27:07TRTPGSWEMFL0.99980.6691415
ZNF823-VAV1chr1911849632chr196820713157HLA-B39:24TRTPGSWEMFL0.99860.6918415
ZNF823-VAV1chr1911849632chr196820713157HLA-B39:01TRTPGSWEMFL0.99690.924415
ZNF823-VAV1chr1911849632chr196820713157HLA-A24:02RTPGSWEMF0.95610.5538514
ZNF823-VAV1chr1911849632chr196820713157HLA-B35:12TPGSWEMFL0.73530.9818615
ZNF823-VAV1chr1911849632chr196820713157HLA-B39:10TPGSWEMFL0.39960.9745615
ZNF823-VAV1chr1911849632chr196820713157HLA-C07:05TRTPGSWEMF0.99870.9475414
ZNF823-VAV1chr1911849632chr196820713157HLA-C07:95TRTPGSWEMF0.99850.7811414
ZNF823-VAV1chr1911849632chr196820713157HLA-B27:03TRTPGSWEMF0.99840.7571414
ZNF823-VAV1chr1911849632chr196820713157HLA-C07:27TRTPGSWEMF0.99810.9565414
ZNF823-VAV1chr1911849632chr196820713157HLA-C07:19TRTPGSWEMF0.99330.8119414
ZNF823-VAV1chr1911849632chr196820713157HLA-C07:80TRTPGSWEMF0.9920.9481414
ZNF823-VAV1chr1911849632chr196820713157HLA-C07:67TRTPGSWEMF0.9920.9481414
ZNF823-VAV1chr1911849632chr196820713157HLA-C07:10TRTPGSWEMF0.99010.9576414
ZNF823-VAV1chr1911849632chr196820713157HLA-C07:46TRTPGSWEMF0.99010.9129414
ZNF823-VAV1chr1911849632chr196820713157HLA-C07:95TRTPGSWEMFL0.99910.7693415
ZNF823-VAV1chr1911849632chr196820713157HLA-B39:12TRTPGSWEMFL0.99690.9315415
ZNF823-VAV1chr1911849632chr196820713157HLA-B58:06RTPGSWEMF0.9680.9738514
ZNF823-VAV1chr1911849632chr196820713157HLA-B57:02RTPGSWEMF0.96190.9777514
ZNF823-VAV1chr1911849632chr196820713157HLA-B35:09TPGSWEMFL0.73530.9818615
ZNF823-VAV1chr1911849632chr196820713157HLA-B67:01TPGSWEMFL0.4730.8544615
ZNF823-VAV1chr1911849632chr196820713157HLA-B51:06TPGSWEMFL0.2420.7514615
ZNF823-VAV1chr1911849632chr196820713157HLA-B27:08TRTPGSWEMF0.99990.6394414
ZNF823-VAV1chr1911849632chr196820713157HLA-C07:01TRTPGSWEMF0.99880.7788414
ZNF823-VAV1chr1911849632chr196820713157HLA-B27:09TRTPGSWEMF0.99860.7301414
ZNF823-VAV1chr1911849632chr196820713157HLA-C07:22TRTPGSWEMF0.99730.7629414
ZNF823-VAV1chr1911849632chr196820713157HLA-C07:02TRTPGSWEMF0.9920.9481414
ZNF823-VAV1chr1911849632chr196820713157HLA-B38:05TRTPGSWEMF0.94110.9795414
ZNF823-VAV1chr1911849632chr196820713157HLA-B27:09TRTPGSWEMFL0.99980.6793415
ZNF823-VAV1chr1911849632chr196820713157HLA-C07:22TRTPGSWEMFL0.99840.7484415
ZNF823-VAV1chr1911849632chr196820713157HLA-B39:31TRTPGSWEMFL0.99710.9264415

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Potential FusionNeoAntigen Information of ZNF823-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.

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 ZNF823-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
9541TPGSWEMFLCLKNIZNF823VAV1chr1911849632chr196820713157

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZNF823-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-B14:023BVN9541TPGSWEMFLCLKNI-7.15543-7.26883
HLA-B14:023BVN9541TPGSWEMFLCLKNI-4.77435-5.80965
HLA-B52:013W399541TPGSWEMFLCLKNI-6.80875-6.92215
HLA-B52:013W399541TPGSWEMFLCLKNI-4.20386-5.23916
HLA-A11:014UQ29541TPGSWEMFLCLKNI-7.5194-8.5547
HLA-A11:014UQ29541TPGSWEMFLCLKNI-6.9601-7.0735
HLA-A24:025HGA9541TPGSWEMFLCLKNI-7.52403-7.63743
HLA-A24:025HGA9541TPGSWEMFLCLKNI-5.82433-6.85963
HLA-B27:056PYJ9541TPGSWEMFLCLKNI-3.28285-4.31815
HLA-B44:053DX89541TPGSWEMFLCLKNI-5.91172-6.94702
HLA-B44:053DX89541TPGSWEMFLCLKNI-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ZNF823-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
ZNF823-VAV1chr1911849632chr196820713414TRTPGSWEMFACCCGGACACCTGGAAGCTGGGAAATGTTC
ZNF823-VAV1chr1911849632chr196820713415TRTPGSWEMFLACCCGGACACCTGGAAGCTGGGAAATGTTCCTG
ZNF823-VAV1chr1911849632chr196820713514RTPGSWEMFCGGACACCTGGAAGCTGGGAAATGTTC
ZNF823-VAV1chr1911849632chr196820713615TPGSWEMFLACACCTGGAAGCTGGGAAATGTTCCTG

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 ZNF823-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
BRCAZNF823-VAV1chr1911849632ENST00000341191chr196820713ENST00000304076TCGA-B6-A0IQ-01A

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Potential target of CAR-T therapy development for ZNF823-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 ZNF823-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 ZNF823-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