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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:PI4KA-ZNF274

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PI4KA-ZNF274
FusionPDB ID: 65089
FusionGDB2.0 ID: 65089
HgeneTgene
Gene symbol

PI4KA

ZNF274

Gene ID

5297

10782

Gene namephosphatidylinositol 4-kinase alphazinc finger protein 274
SynonymsPI4K-ALPHA|PIK4CA|PMGYCHA|pi4K230HFB101|ZF2|ZKSCAN19|ZSCAN51
Cytomap

22q11.21

19q13.43

Type of geneprotein-codingprotein-coding
Descriptionphosphatidylinositol 4-kinase alphaPI4-kinase alphaphosphatidylinositol 4-kinase 230phosphatidylinositol 4-kinase III alphaphosphatidylinositol 4-kinase IIII+/-phosphatidylinositol 4-kinase, catalytic, alphaphosphatidylinositol 4-kinase, type III, aneurotrophin receptor-interacting factor homologKRAB zinc finger protein HFB101zinc finger protein HFB101zinc finger protein with KRAB and SCAN domains 19zinc finger protein zfp2
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000255882, ENST00000572273, 
ENST00000414196, ENST00000466162, 
ENST00000597818, ENST00000424679, 
ENST00000326804, ENST00000345813, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score20 X 14 X 12=33603 X 3 X 3=27
# samples 213
** MAII scorelog2(21/3360*10)=-4
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/27*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: PI4KA [Title/Abstract] AND ZNF274 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PI4KA [Title/Abstract] AND ZNF274 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PI4KA(21101871)-ZNF274(58718087), # samples:3
Anticipated loss of major functional domain due to fusion event.PI4KA-ZNF274 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.
PI4KA-ZNF274 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.
PI4KA-ZNF274 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.
PI4KA-ZNF274 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.
PI4KA-ZNF274 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
PI4KA-ZNF274 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
PI4KA-ZNF274 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
PI4KA-ZNF274 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
PI4KA-ZNF274 seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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
HgenePI4KA

GO:0016310

phosphorylation

25327288



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/chr22:21101871/chr19:58718087)
- 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 PI4KA (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 ZNF274 (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)
ENST00000572273PI4KAchr2221101871-ENST00000345813ZNF274chr1958718087+554134205734791140
ENST00000572273PI4KAchr2221101871-ENST00000326804ZNF274chr1958718087+554134205734791140

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
ENST00000572273ENST00000345813PI4KAchr2221101871-ZNF274chr1958718087+0.0006751770.9993248
ENST00000572273ENST00000326804PI4KAchr2221101871-ZNF274chr1958718087+0.0006751770.9993248

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 PI4KA-ZNF274

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PI4KAchr2221101871ZNF274chr195871808734201119ILHFAGYNKQNTTLGSILSSSWTLNW

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Potential FusionNeoAntigen Information of PI4KA-ZNF274 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.
PI4KA-ZNF274_21101871_58718087.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)
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B48:01KQNTTLGSI0.87970.5423817
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B13:02KQNTTLGSI0.73130.6602817
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B13:01KQNTTLGSI0.53610.9069817
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B52:01KQNTTLGSI0.00930.9526817
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B48:01KQNTTLGSIL0.96090.7091818
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B57:01TTLGSILSSSW0.99980.98571122
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B58:01TTLGSILSSSW0.99910.97571122
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B58:02TTLGSILSSSW0.9990.96641122
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B15:17TTLGSILSSSW0.99830.91351122
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B15:16TTLGSILSSSW0.99690.90511122
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B57:03TTLGSILSSSW0.9960.9941122
PI4KA-ZNF274chr2221101871chr19587180873420HLA-A32:13TTLGSILSSSW0.98170.98071122
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B15:04KQNTTLGSI0.87110.8332817
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C07:05GYNKQNTTL0.53710.9576514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C07:10GYNKQNTTL0.49930.8555514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C07:29GYNKQNTTL0.48010.9483514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C07:13GYNKQNTTL0.47340.8831514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C07:80GYNKQNTTL0.47120.8444514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C07:67GYNKQNTTL0.47120.8444514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C07:19GYNKQNTTL0.46630.6183514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C07:27GYNKQNTTL0.43420.9275514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C07:46GYNKQNTTL0.420.736514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C04:10GYNKQNTTL0.38540.7943514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C04:14GYNKQNTTL0.31770.7883514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B15:73KQNTTLGSI0.79990.8594817
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B15:30KQNTTLGSI0.71160.8547817
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C03:67GYNKQNTTL0.55330.9767514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C07:02GYNKQNTTL0.47120.8444514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C07:17GYNKQNTTL0.45870.9434514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C06:06GYNKQNTTL0.44610.9834514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C18:01GYNKQNTTL0.40970.7975514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C07:04GYNKQNTTL0.39840.956514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C14:03GYNKQNTTL0.2940.9398514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C14:02GYNKQNTTL0.2940.9398514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-C04:04GYNKQNTTL0.22360.8598514
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B15:73KQNTTLGSIL0.97560.9539818
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B15:30KQNTTLGSIL0.9540.9374818
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B15:13TLGSILSSSW0.94590.66721222
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B57:04TTLGSILSSSW0.99980.79221122
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B57:10TTLGSILSSSW0.99980.98571122
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B58:06TTLGSILSSSW0.99840.90951122
PI4KA-ZNF274chr2221101871chr19587180873420HLA-B57:02TTLGSILSSSW0.99770.96221122
PI4KA-ZNF274chr2221101871chr19587180873420HLA-A32:01TTLGSILSSSW0.99540.98661122
PI4KA-ZNF274chr2221101871chr19587180873420HLA-A25:01TTLGSILSSSW0.80060.94781122

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Potential FusionNeoAntigen Information of PI4KA-ZNF274 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 PI4KA-ZNF274

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
10750YNKQNTTLGSILSSPI4KAZNF274chr2221101871chr19587180873420

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PI4KA-ZNF274

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-B14:023BVN10750YNKQNTTLGSILSS-7.15543-7.26883
HLA-B14:023BVN10750YNKQNTTLGSILSS-4.77435-5.80965
HLA-B52:013W3910750YNKQNTTLGSILSS-6.80875-6.92215
HLA-B52:013W3910750YNKQNTTLGSILSS-4.20386-5.23916
HLA-A11:014UQ210750YNKQNTTLGSILSS-7.5194-8.5547
HLA-A11:014UQ210750YNKQNTTLGSILSS-6.9601-7.0735
HLA-A24:025HGA10750YNKQNTTLGSILSS-7.52403-7.63743
HLA-A24:025HGA10750YNKQNTTLGSILSS-5.82433-6.85963
HLA-B27:056PYJ10750YNKQNTTLGSILSS-3.28285-4.31815
HLA-B44:053DX810750YNKQNTTLGSILSS-5.91172-6.94702
HLA-B44:053DX810750YNKQNTTLGSILSS-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of PI4KA-ZNF274

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
PI4KA-ZNF274chr2221101871chr19587180871122TTLGSILSSSWCTTGGGAGTATCCTGAGCTCCAGCTGGACCCTA
PI4KA-ZNF274chr2221101871chr19587180871222TLGSILSSSWGGGAGTATCCTGAGCTCCAGCTGGACCCTA
PI4KA-ZNF274chr2221101871chr1958718087514GYNKQNTTLAACAAGCAGAACACAACTCTTGGGAGT
PI4KA-ZNF274chr2221101871chr1958718087817KQNTTLGSIAACACAACTCTTGGGAGTATCCTGAGC
PI4KA-ZNF274chr2221101871chr1958718087818KQNTTLGSILAACACAACTCTTGGGAGTATCCTGAGCTCC

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 PI4KA-ZNF274

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
LUADPI4KA-ZNF274chr2221101871ENST00000572273chr1958718087ENST00000326804TCGA-05-4434-01A

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Potential target of CAR-T therapy development for PI4KA-ZNF274

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 PI4KA-ZNF274

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 PI4KA-ZNF274

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