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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:ATP11B-IVNS1ABP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ATP11B-IVNS1ABP
FusionPDB ID: 7731
FusionGDB2.0 ID: 7731
HgeneTgene
Gene symbol

ATP11B

IVNS1ABP

Gene ID

23200

10625

Gene nameATPase phospholipid transporting 11B (putative)influenza virus NS1A binding protein
SynonymsATPIF|ATPIRARA3|FLARA3|HSPC068|KLHL39|ND1|NS-1|NS1-BP|NS1BP
Cytomap

3q26.33

1q25.3

Type of geneprotein-codingprotein-coding
Descriptionprobable phospholipid-transporting ATPase IFATPase IRATPase, class VI, type 11BP4-ATPase flippase complex alpha subunit ATP11Btruncated ATPase 11B proteininfluenza virus NS1A-binding proteinNCX downstream gene 1NS1-binding proteinaryl hydrocarbon receptor-associated 3aryl hydrocarbon receptor-associated protein 3kelch-like family member 39kelch-like protein 39
Modification date2020031320200320
UniProtAcc

Q9Y2G3

Main function of 5'-partner protein: FUNCTION: Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of intracellular membranes (PubMed:30018401). May contribute to the maintenance of membrane lipid asymmetry in endosome compartment (PubMed:30018401). {ECO:0000269|PubMed:30018401}.

Q9Y6Y0

Main function of 5'-partner protein: FUNCTION: Involved in many cell functions, including pre-mRNA splicing, the aryl hydrocarbon receptor (AHR) pathway, F-actin organization and protein ubiquitination. Plays a role in the dynamic organization of the actin skeleton as a stabilizer of actin filaments by association with F-actin through Kelch repeats (By similarity). Protects cells from cell death induced by actin destabilization (By similarity). Functions as modifier of the AHR/Aryl hydrocarbon receptor pathway increasing the concentration of AHR available to activate transcription (PubMed:16582008). In addition, functions as a negative regulator of BCR(KLHL20) E3 ubiquitin ligase complex to prevent ubiquitin-mediated proteolysis of PML and DAPK1, two tumor suppressors (PubMed:25619834). Inhibits pre-mRNA splicing (in vitro) (PubMed:9696811). {ECO:0000250|UniProtKB:Q920Q8, ECO:0000269|PubMed:16582008, ECO:0000269|PubMed:25619834, ECO:0000269|PubMed:9696811}.; FUNCTION: (Microbial infection) Involved in the alternative splicing of influenza A virus M1 mRNA through interaction with HNRNPK, thereby facilitating the generation of viral M2 protein. {ECO:0000269|PubMed:23825951, ECO:0000269|PubMed:9696811}.
Ensembl transtripts involved in fusion geneENST idsENST00000482794, ENST00000323116, 
ENST00000493826, 
ENST00000367498, 
ENST00000392007, ENST00000459929, 
ENST00000367497, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score20 X 15 X 10=300017 X 9 X 9=1377
# samples 2218
** MAII scorelog2(22/3000*10)=-3.76938707185858
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(18/1377*10)=-2.93545974780529
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ATP11B [Title/Abstract] AND IVNS1ABP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ATP11B [Title/Abstract] AND IVNS1ABP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ATP11B(182554258)-IVNS1ABP(185270695), # samples:1
Anticipated loss of major functional domain due to fusion event.ATP11B-IVNS1ABP 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.
ATP11B-IVNS1ABP 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.
ATP11B-IVNS1ABP seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
ATP11B-IVNS1ABP seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
ATP11B-IVNS1ABP seems lost the major protein functional domain in Tgene partner, which is a essential gene 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


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/chr3:182554258/chr1:185270695)
- 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 ATP11B (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 IVNS1ABP (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)
ENST00000323116ATP11Bchr3182554258+ENST00000367498IVNS1ABPchr1185270695-36238122061975589

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
ENST00000323116ENST00000367498ATP11Bchr3182554258+IVNS1ABPchr1185270695-0.0003210580.99967897

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 ATP11B-IVNS1ABP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ATP11Bchr3182554258IVNS1ABPchr1185270695812200CHVTTASLDGETNLKKKPPRENGHKQ

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Potential FusionNeoAntigen Information of ATP11B-IVNS1ABP 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.
ATP11B-IVNS1ABP_182554258_185270695.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)
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-B45:01GETNLKKKP0.97930.8562918
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-B41:01GETNLKKKP0.24690.8921918
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-B50:01GETNLKKKP0.09350.507918
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-C04:10SLDGETNL10.7793614
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-C04:07SLDGETNL10.7931614
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-C08:15SLDGETNL10.9486614
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-C05:09SLDGETNL10.9063614
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-C03:07ASLDGETNL0.99930.9895514
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-C15:06ASLDGETNL0.99860.9557514
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-C08:02SLDGETNL10.9486614
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-C05:01SLDGETNL10.9063614
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-C04:01SLDGETNL10.7931614
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-C04:03SLDGETNL10.8213614
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-C15:05ASLDGETNL0.99840.8557514
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-C03:06ASLDGETNL0.99180.9944514
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-B35:13ASLDGETNL0.60960.9514514
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-C17:01ASLDGETNL0.57870.8892514
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-B50:05GETNLKKKP0.09350.507918
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-B50:04GETNLKKKP0.09350.507918
ATP11B-IVNS1ABPchr3182554258chr1185270695812HLA-B07:13ASLDGETNL0.02350.7183514

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Potential FusionNeoAntigen Information of ATP11B-IVNS1ABP 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 ATP11B-IVNS1ABP

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
8730SLDGETNLKKKPPRATP11BIVNS1ABPchr3182554258chr1185270695812

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ATP11B-IVNS1ABP

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-B14:023BVN8730SLDGETNLKKKPPR-7.14368-7.25548
HLA-B14:023BVN8730SLDGETNLKKKPPR-6.90724-7.95034
HLA-B52:013W398730SLDGETNLKKKPPR-7.67666-8.71976
HLA-B52:013W398730SLDGETNLKKKPPR-5.5221-5.6339
HLA-A11:014UQ28730SLDGETNLKKKPPR-8.37369-9.41679
HLA-A11:014UQ28730SLDGETNLKKKPPR-6.26273-6.37453
HLA-A24:025HGA8730SLDGETNLKKKPPR-7.6158-8.6589
HLA-A24:025HGA8730SLDGETNLKKKPPR-5.36701-5.47881
HLA-B44:053DX88730SLDGETNLKKKPPR-8.09865-8.21045
HLA-B44:053DX88730SLDGETNLKKKPPR-5.97829-7.02139

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Vaccine Design for the FusionNeoAntigens of ATP11B-IVNS1ABP

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
ATP11B-IVNS1ABPchr3182554258chr1185270695514ASLDGETNLTTGGACGGAGAAACTAACCTGAAGAAA
ATP11B-IVNS1ABPchr3182554258chr1185270695614SLDGETNLGACGGAGAAACTAACCTGAAGAAA
ATP11B-IVNS1ABPchr3182554258chr1185270695918GETNLKKKPACTAACCTGAAGAAAAAGCCACCACGT

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 ATP11B-IVNS1ABP

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
Non-CancerATP11B-IVNS1ABPchr3182554258ENST00000323116chr1185270695ENST00000367498135N

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Potential target of CAR-T therapy development for ATP11B-IVNS1ABP

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
HgeneATP11Bchr3:182554258chr1:185270695ENST00000323116+63056_771841178.0TransmembraneHelical
HgeneATP11Bchr3:182554258chr1:185270695ENST00000323116+63083_1041841178.0TransmembraneHelical

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 ATP11B-IVNS1ABP

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 ATP11B-IVNS1ABP

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