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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:ITPKB-ZC3HAV1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ITPKB-ZC3HAV1
FusionPDB ID: 40669
FusionGDB2.0 ID: 40669
HgeneTgene
Gene symbol

ITPKB

ZC3HAV1

Gene ID

3707

56829

Gene nameinositol-trisphosphate 3-kinase Bzinc finger CCCH-type containing, antiviral 1
SynonymsIP3-3KB|IP3K|IP3K-B|IP3KB|PIG37ARTD13|FLB6421|PARP13|ZAP|ZC3H2|ZC3HDC2
Cytomap

1q42.12

7q34

Type of geneprotein-codingprotein-coding
Descriptioninositol-trisphosphate 3-kinase BIP3 3-kinase BIP3K Binositol 1,4,5-trisphosphate 3-kinase BinsP 3-kinase Bproliferation-inducing protein 37zinc finger CCCH-type antiviral protein 1ADP-ribosyltransferase diphtheria toxin-like 13inactive Poly [ADP-ribose] polymerase 13zinc finger CCCH domain-containing protein 2zinc finger CCCH-type, antiviral 1
Modification date2020031320200313
UniProtAcc

P27987

Main function of 5'-partner protein:
.
Ensembl transtripts involved in fusion geneENST idsENST00000272117, ENST00000366784, 
ENST00000429204, 
ENST00000242351, 
ENST00000464606, ENST00000471652, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 5 X 3=7513 X 10 X 5=650
# samples 616
** MAII scorelog2(6/75*10)=-0.321928094887362
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/650*10)=-2.02236781302845
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ITPKB [Title/Abstract] AND ZC3HAV1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ITPKB [Title/Abstract] AND ZC3HAV1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ITPKB(226923228)-ZC3HAV1(138749745), # samples:3
ZC3HAV1(138749625)-ITPKB(226836472), # samples:3
Anticipated loss of major functional domain due to fusion event.ITPKB-ZC3HAV1 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.
ITPKB-ZC3HAV1 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.
ITPKB-ZC3HAV1 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.
ITPKB-ZC3HAV1 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.
ZC3HAV1-ITPKB seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
ZC3HAV1-ITPKB seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
ZC3HAV1-ITPKB 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
HgeneITPKB

GO:0032957

inositol trisphosphate metabolic process

1654894

HgeneITPKB

GO:0071277

cellular response to calcium ion

1654894

TgeneZC3HAV1

GO:0006471

protein ADP-ribosylation

25043379

TgeneZC3HAV1

GO:0009615

response to virus

21876179

TgeneZC3HAV1

GO:0045071

negative regulation of viral genome replication

21876179

TgeneZC3HAV1

GO:0061014

positive regulation of mRNA catabolic process

21876179



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/chr1:226923228/chr7:138749745)
- 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 ITPKB (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 ZC3HAV1 (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)
ENST00000272117ITPKBchr1226923228-ENST00000242351ZC3HAV1chr7138749745-6843193202768922
ENST00000272117ITPKBchr1226923228-ENST00000464606ZC3HAV1chr7138749745-4447193202768922
ENST00000272117ITPKBchr1226923228-ENST00000471652ZC3HAV1chr7138749745-2854193202159719
ENST00000429204ITPKBchr1226923228-ENST00000242351ZC3HAV1chr7138749745-717122601843096970
ENST00000429204ITPKBchr1226923228-ENST00000464606ZC3HAV1chr7138749745-477522601843096970
ENST00000429204ITPKBchr1226923228-ENST00000471652ZC3HAV1chr7138749745-318222601842487767
ENST00000366784ITPKBchr1226923228-ENST00000242351ZC3HAV1chr7138749745-733124203443256970
ENST00000366784ITPKBchr1226923228-ENST00000464606ZC3HAV1chr7138749745-493524203443256970
ENST00000366784ITPKBchr1226923228-ENST00000471652ZC3HAV1chr7138749745-334224203442647767
ENST00000272117ITPKBchr1226923227-ENST00000242351ZC3HAV1chr7138749745-6843193202768922
ENST00000272117ITPKBchr1226923227-ENST00000464606ZC3HAV1chr7138749745-4447193202768922
ENST00000272117ITPKBchr1226923227-ENST00000471652ZC3HAV1chr7138749745-2854193202159719
ENST00000429204ITPKBchr1226923227-ENST00000242351ZC3HAV1chr7138749745-717122601843096970
ENST00000429204ITPKBchr1226923227-ENST00000464606ZC3HAV1chr7138749745-477522601843096970
ENST00000429204ITPKBchr1226923227-ENST00000471652ZC3HAV1chr7138749745-318222601842487767
ENST00000366784ITPKBchr1226923227-ENST00000242351ZC3HAV1chr7138749745-733124203443256970
ENST00000366784ITPKBchr1226923227-ENST00000464606ZC3HAV1chr7138749745-493524203443256970
ENST00000366784ITPKBchr1226923227-ENST00000471652ZC3HAV1chr7138749745-334224203442647767

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
ENST00000272117ENST00000242351ITPKBchr1226923228-ZC3HAV1chr7138749745-0.0006815770.9993185
ENST00000272117ENST00000464606ITPKBchr1226923228-ZC3HAV1chr7138749745-0.0020681090.99793184
ENST00000272117ENST00000471652ITPKBchr1226923228-ZC3HAV1chr7138749745-0.037106010.96289396
ENST00000429204ENST00000242351ITPKBchr1226923228-ZC3HAV1chr7138749745-0.0007069510.99929297
ENST00000429204ENST00000464606ITPKBchr1226923228-ZC3HAV1chr7138749745-0.0020622540.99793774
ENST00000429204ENST00000471652ITPKBchr1226923228-ZC3HAV1chr7138749745-0.0338403660.9661597
ENST00000366784ENST00000242351ITPKBchr1226923228-ZC3HAV1chr7138749745-0.0007644340.99923563
ENST00000366784ENST00000464606ITPKBchr1226923228-ZC3HAV1chr7138749745-0.0021845010.9978155
ENST00000366784ENST00000471652ITPKBchr1226923228-ZC3HAV1chr7138749745-0.0355246180.96447545
ENST00000272117ENST00000242351ITPKBchr1226923227-ZC3HAV1chr7138749745-0.0006815770.9993185
ENST00000272117ENST00000464606ITPKBchr1226923227-ZC3HAV1chr7138749745-0.0020681090.99793184
ENST00000272117ENST00000471652ITPKBchr1226923227-ZC3HAV1chr7138749745-0.037106010.96289396
ENST00000429204ENST00000242351ITPKBchr1226923227-ZC3HAV1chr7138749745-0.0007069510.99929297
ENST00000429204ENST00000464606ITPKBchr1226923227-ZC3HAV1chr7138749745-0.0020622540.99793774
ENST00000429204ENST00000471652ITPKBchr1226923227-ZC3HAV1chr7138749745-0.0338403660.9661597
ENST00000366784ENST00000242351ITPKBchr1226923227-ZC3HAV1chr7138749745-0.0007644340.99923563
ENST00000366784ENST00000464606ITPKBchr1226923227-ZC3HAV1chr7138749745-0.0021845010.9978155
ENST00000366784ENST00000471652ITPKBchr1226923227-ZC3HAV1chr7138749745-0.0355246180.96447545

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 ITPKB-ZC3HAV1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ITPKBchr1226923227ZC3HAV1chr71387497451932644AFLHTLDQQKPRVKDKRKNSNVDSSY
ITPKBchr1226923227ZC3HAV1chr71387497452260692AFLHTLDQQKPRVKDKRKNSNVDSSY
ITPKBchr1226923227ZC3HAV1chr71387497452420692AFLHTLDQQKPRVKDKRKNSNVDSSY
ITPKBchr1226923228ZC3HAV1chr71387497451932644AFLHTLDQQKPRVKDKRKNSNVDSSY
ITPKBchr1226923228ZC3HAV1chr71387497452260692AFLHTLDQQKPRVKDKRKNSNVDSSY
ITPKBchr1226923228ZC3HAV1chr71387497452420692AFLHTLDQQKPRVKDKRKNSNVDSSY

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Potential FusionNeoAntigen Information of ITPKB-ZC3HAV1 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.
ITPKB-ZC3HAV1_226923227_138749745.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)
ITPKB-ZC3HAV1chr1226923227chr71387497451932HLA-A30:01RVKDKRKNS0.96450.85481120
ITPKB-ZC3HAV1chr1226923227chr71387497451932HLA-A30:01QQKPRVKDK0.92980.6061716

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Potential FusionNeoAntigen Information of ITPKB-ZC3HAV1 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 ITPKB-ZC3HAV1

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
1356DQQKPRVKDKRKNSITPKBZC3HAV1chr1226923227chr71387497451932

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ITPKB-ZC3HAV1

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-B14:023BVN1356DQQKPRVKDKRKNS-7.4838-7.5956
HLA-B14:023BVN1356DQQKPRVKDKRKNS-3.16066-4.20376
HLA-B52:013W391356DQQKPRVKDKRKNS-6.93679-7.04859
HLA-B52:013W391356DQQKPRVKDKRKNS-6.10064-7.14374
HLA-A11:014UQ21356DQQKPRVKDKRKNS-7.21307-7.32487
HLA-A24:025HGA1356DQQKPRVKDKRKNS-6.56769-6.67949
HLA-A24:025HGA1356DQQKPRVKDKRKNS-4.65311-5.69621
HLA-B44:053DX81356DQQKPRVKDKRKNS-6.68002-6.79182
HLA-B44:053DX81356DQQKPRVKDKRKNS-3.22493-4.26803

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Vaccine Design for the FusionNeoAntigens of ITPKB-ZC3HAV1

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
ITPKB-ZC3HAV1chr1226923227chr71387497451120RVKDKRKNSAGAGTGAAAGACAAACGGAAAAATTCA
ITPKB-ZC3HAV1chr1226923227chr7138749745716QQKPRVKDKCAGCAGAAACCTAGAGTGAAAGACAAA

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 ITPKB-ZC3HAV1

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
BRCAITPKB-ZC3HAV1chr1226923227ENST00000272117chr7138749745ENST00000242351TCGA-AO-A0J2

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Potential target of CAR-T therapy development for ITPKB-ZC3HAV1

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 ITPKB-ZC3HAV1

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 ITPKB-ZC3HAV1

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