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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:IFI6-ATP1B3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: IFI6-ATP1B3
FusionPDB ID: 38334
FusionGDB2.0 ID: 38334
HgeneTgene
Gene symbol

IFI6

ATP1B3

Gene ID

2537

483

Gene nameinterferon alpha inducible protein 6ATPase Na+/K+ transporting subunit beta 3
Synonyms6-16|FAM14C|G1P3|IFI-6-16|IFI616ATPB-3|CD298
Cytomap

1p35.3

3q23

Type of geneprotein-codingprotein-coding
Descriptioninterferon alpha-inducible protein 6interferon, alpha-inducible protein clone IFI-6-16interferon-induced protein 6-16sodium/potassium-transporting ATPase subunit beta-3ATPase, Na+/K+ transporting, beta 3 polypeptideNa, K-ATPase beta-3 polypeptidesodium pump subunit beta-3sodium-potassium ATPase subunit beta 3 (non-catalytic)sodium/potassium-dependent ATPase subunit
Modification date2020031320200313
UniProtAcc

P09912

Main function of 5'-partner protein: FUNCTION: Plays a role in apoptosis, negatively regulating the intrinsinc apoptotic signaling pathway and TNFSF10-induced apoptosis (PubMed:15685448, PubMed:17823654, PubMed:26244642). However, it has also been shown to have a pro-apoptotic activity (PubMed:27673746). Has an antiviral activity towards hepatitis C virus/HCV by inhibiting the EGFR signaling pathway, which activation is required for entry of the virus into cells (PubMed:25757571). {ECO:0000269|PubMed:15685448, ECO:0000269|PubMed:17823654, ECO:0000269|PubMed:25757571, ECO:0000269|PubMed:26244642, ECO:0000269|PubMed:27673746}.

P54709

Main function of 5'-partner protein: FUNCTION: This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-3 subunit is not known.
Ensembl transtripts involved in fusion geneENST idsENST00000339145, ENST00000361157, 
ENST00000362020, 
ENST00000462082, 
ENST00000484727, ENST00000539728, 
ENST00000286371, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 8 X 7=5605 X 3 X 4=60
# samples 105
** MAII scorelog2(10/560*10)=-2.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/60*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: IFI6 [Title/Abstract] AND ATP1B3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: IFI6 [Title/Abstract] AND ATP1B3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)IFI6(27994736)-ATP1B3(141644372), # samples:2
Anticipated loss of major functional domain due to fusion event.IFI6-ATP1B3 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.
IFI6-ATP1B3 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
TgeneATP1B3

GO:0006883

cellular sodium ion homeostasis

10636900|19542013

TgeneATP1B3

GO:0030007

cellular potassium ion homeostasis

10636900|19542013

TgeneATP1B3

GO:0032781

positive regulation of ATPase activity

10636900

TgeneATP1B3

GO:0036376

sodium ion export across plasma membrane

10636900|19542013

TgeneATP1B3

GO:0050821

protein stabilization

10636900

TgeneATP1B3

GO:0072659

protein localization to plasma membrane

18522992

TgeneATP1B3

GO:0086009

membrane repolarization

19542013

TgeneATP1B3

GO:1901018

positive regulation of potassium ion transmembrane transporter activity

10636900

TgeneATP1B3

GO:1903278

positive regulation of sodium ion export across plasma membrane

10636900

TgeneATP1B3

GO:1903288

positive regulation of potassium ion import

10636900

TgeneATP1B3

GO:1990573

potassium ion import across plasma membrane

10636900|19542013



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/chr1:27994736/chr3:141644372)
- 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 IFI6 (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 ATP1B3 (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)
ENST00000361157IFI6chr127994736-ENST00000286371ATP1B3chr3141644372+138042635475146
ENST00000339145IFI6chr127994736-ENST00000286371ATP1B3chr3141644372+136441088459123
ENST00000362020IFI6chr127994736-ENST00000286371ATP1B3chr3141644372+137241815467150

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
ENST00000361157ENST00000286371IFI6chr127994736-ATP1B3chr3141644372+0.320976880.6790231
ENST00000339145ENST00000286371IFI6chr127994736-ATP1B3chr3141644372+0.163447320.8365527
ENST00000362020ENST00000286371IFI6chr127994736-ATP1B3chr3141644372+0.26859620.73140377

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 IFI6-ATP1B3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
IFI6chr127994736ATP1B3chr3141644372410107VPAGGLVATLQSLGWVSTAIGCCSGQ
IFI6chr127994736ATP1B3chr3141644372418134VPAGGLVATLQSLGWVSTAIGCCSGQ
IFI6chr127994736ATP1B3chr3141644372426130VPAGGLVATLQSLGWVSTAIGCCSGQ

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Potential FusionNeoAntigen Information of IFI6-ATP1B3 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.
IFI6-ATP1B3_27994736_141644372.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)
IFI6-ATP1B3chr127994736chr3141644372410HLA-B57:01ATLQSLGW0.99940.9964715
IFI6-ATP1B3chr127994736chr3141644372410HLA-B58:01ATLQSLGW0.99770.9949715
IFI6-ATP1B3chr127994736chr3141644372410HLA-B57:01VATLQSLGW0.99910.9953615
IFI6-ATP1B3chr127994736chr3141644372410HLA-B58:01VATLQSLGW0.99880.9932615
IFI6-ATP1B3chr127994736chr3141644372410HLA-B58:02VATLQSLGW0.99810.9877615
IFI6-ATP1B3chr127994736chr3141644372410HLA-B15:17VATLQSLGW0.99480.9723615
IFI6-ATP1B3chr127994736chr3141644372410HLA-B57:03VATLQSLGW0.99140.9978615
IFI6-ATP1B3chr127994736chr3141644372410HLA-B15:16VATLQSLGW0.98930.984615
IFI6-ATP1B3chr127994736chr3141644372410HLA-B53:01VATLQSLGW0.96040.9301615
IFI6-ATP1B3chr127994736chr3141644372410HLA-B57:01LVATLQSLGW0.99960.9943515
IFI6-ATP1B3chr127994736chr3141644372410HLA-B58:01LVATLQSLGW0.99840.9914515
IFI6-ATP1B3chr127994736chr3141644372410HLA-B57:03LVATLQSLGW0.98270.9977515
IFI6-ATP1B3chr127994736chr3141644372410HLA-B57:10ATLQSLGW0.99940.9964715
IFI6-ATP1B3chr127994736chr3141644372410HLA-B57:04ATLQSLGW0.99890.8952715
IFI6-ATP1B3chr127994736chr3141644372410HLA-B57:10VATLQSLGW0.99910.9953615
IFI6-ATP1B3chr127994736chr3141644372410HLA-B57:04VATLQSLGW0.99890.8405615
IFI6-ATP1B3chr127994736chr3141644372410HLA-B58:06VATLQSLGW0.99690.9812615
IFI6-ATP1B3chr127994736chr3141644372410HLA-B57:02VATLQSLGW0.9850.9762615
IFI6-ATP1B3chr127994736chr3141644372410HLA-B15:13VATLQSLGW0.95830.9787615
IFI6-ATP1B3chr127994736chr3141644372410HLA-B53:02VATLQSLGW0.94730.8668615
IFI6-ATP1B3chr127994736chr3141644372410HLA-B57:10LVATLQSLGW0.99960.9943515
IFI6-ATP1B3chr127994736chr3141644372410HLA-B57:04LVATLQSLGW0.99940.8879515

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Potential FusionNeoAntigen Information of IFI6-ATP1B3 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 IFI6-ATP1B3

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
9807VATLQSLGWVSTAIIFI6ATP1B3chr127994736chr3141644372410

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of IFI6-ATP1B3

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-B14:023BVN9807VATLQSLGWVSTAI-7.79901-8.83431
HLA-B14:023BVN9807VATLQSLGWVSTAI-6.80356-6.91696
HLA-B52:013W399807VATLQSLGWVSTAI-6.53697-6.65037
HLA-B52:013W399807VATLQSLGWVSTAI-3.97996-5.01526
HLA-A24:025HGA9807VATLQSLGWVSTAI-8.69281-8.80621
HLA-A24:025HGA9807VATLQSLGWVSTAI-7.61255-8.64785
HLA-B44:053DX89807VATLQSLGWVSTAI-6.79741-7.83271
HLA-B44:053DX89807VATLQSLGWVSTAI-6.07628-6.18968
HLA-A02:016TDR9807VATLQSLGWVSTAI-5.40972-5.52312

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Vaccine Design for the FusionNeoAntigens of IFI6-ATP1B3

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
IFI6-ATP1B3chr127994736chr3141644372515LVATLQSLGWTAGTGGCCACGCTGCAGAGCCTCGGTTGGG
IFI6-ATP1B3chr127994736chr3141644372615VATLQSLGWTGGCCACGCTGCAGAGCCTCGGTTGGG
IFI6-ATP1B3chr127994736chr3141644372715ATLQSLGWCCACGCTGCAGAGCCTCGGTTGGG

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 IFI6-ATP1B3

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
HNSCIFI6-ATP1B3chr127994736ENST00000339145chr3141644372ENST00000286371TCGA-CR-7372

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Potential target of CAR-T therapy development for IFI6-ATP1B3

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
HgeneIFI6chr1:27994736chr3:141644372ENST00000339145-4541_61107139.0TransmembraneHelical
HgeneIFI6chr1:27994736chr3:141644372ENST00000339145-454_24107139.0TransmembraneHelical
HgeneIFI6chr1:27994736chr3:141644372ENST00000339145-4575_95107139.0TransmembraneHelical
HgeneIFI6chr1:27994736chr3:141644372ENST00000361157-4541_6199131.0TransmembraneHelical
HgeneIFI6chr1:27994736chr3:141644372ENST00000361157-454_2499131.0TransmembraneHelical
HgeneIFI6chr1:27994736chr3:141644372ENST00000361157-4575_9599131.0TransmembraneHelical
HgeneIFI6chr1:27994736chr3:141644372ENST00000362020-4541_61103135.0TransmembraneHelical
HgeneIFI6chr1:27994736chr3:141644372ENST00000362020-454_24103135.0TransmembraneHelical
HgeneIFI6chr1:27994736chr3:141644372ENST00000362020-4575_95103135.0TransmembraneHelical

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 IFI6-ATP1B3

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 IFI6-ATP1B3

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