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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:EZR-ANP32B

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: EZR-ANP32B
FusionPDB ID: 28109
FusionGDB2.0 ID: 28109
HgeneTgene
Gene symbol

EZR

ANP32B

Gene ID

7430

10541

Gene nameezrinacidic nuclear phosphoprotein 32 family member B
SynonymsCVIL|CVL|HEL-S-105|VIL2APRIL|PHAPI2|SSP29
Cytomap

6q25.3

9q22.33

Type of geneprotein-codingprotein-coding
Descriptionezrincytovillin 2epididymis secretory protein Li 105p81villin 2 (ezrin)acidic leucine-rich nuclear phosphoprotein 32 family member Bacidic (leucine-rich) nuclear phosphoprotein 32 family, member Bacidic protein rich in leucinesputative HLA-DR-associated protein I-2silver-stainable protein SSP29
Modification date2020032220200313
UniProtAcc

P15311

Main function of 5'-partner protein: FUNCTION: Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis. {ECO:0000269|PubMed:17881735, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19111582}.

Q92688

Main function of 5'-partner protein: FUNCTION: Multifunctional protein that is involved in the regulation of many processes including cell proliferation, apoptosis, cell cycle progression or transcription (PubMed:20015864, PubMed:18039846). Regulates the proliferation of neuronal stem cells, differentiation of leukemic cells and progression from G1 to S phase of the cell cycle. As negative regulator of caspase-3-dependent apoptosis, may act as an antagonist of ANP32A in regulating tissue homeostasis (PubMed:20015864). Exhibits histone chaperone properties, able to recruit histones to certain promoters, thus regulating the transcription of specific genes (PubMed:20538007, PubMed:18039846). Plays also an essential role in the nucleocytoplasmic transport of specific mRNAs via the uncommon nuclear mRNA export receptor XPO1/CRM1 (PubMed:17178712). Participates in the regulation of adequate adaptive immune responses by acting on mRNA expression and cell proliferation (By similarity). {ECO:0000250|UniProtKB:Q9EST5, ECO:0000269|PubMed:17178712, ECO:0000269|PubMed:18039846, ECO:0000269|PubMed:20015864, ECO:0000269|PubMed:20538007}.; FUNCTION: (Microbial infection) Plays an essential role in influenza A and B viral genome replication (PubMed:33045004, PubMed:31217244). Plays also a role in foamy virus mRNA export from the nucleus to the cytoplasm (PubMed:21159877). {ECO:0000269|PubMed:21159877, ECO:0000269|PubMed:31217244, ECO:0000269|PubMed:33045004}.
Ensembl transtripts involved in fusion geneENST idsENST00000337147, ENST00000367075, 
ENST00000392177, ENST00000476189, 
ENST00000473205, ENST00000339399, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score26 X 22 X 10=572019 X 20 X 7=2660
# samples 3221
** MAII scorelog2(32/5720*10)=-4.15987133677839
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(21/2660*10)=-3.66296501272243
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: EZR [Title/Abstract] AND ANP32B [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: EZR [Title/Abstract] AND ANP32B [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)EZR(159204556)-ANP32B(100773628), # samples:1
Anticipated loss of major functional domain due to fusion event.EZR-ANP32B 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.
EZR-ANP32B 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.
EZR-ANP32B 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.
EZR-ANP32B 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.
EZR-ANP32B seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
EZR-ANP32B seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
EZR-ANP32B seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF.
EZR-ANP32B 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
HgeneEZR

GO:0048015

phosphatidylinositol-mediated signaling

25591774

HgeneEZR

GO:0051017

actin filament bundle assembly

10793131

TgeneANP32B

GO:0006334

nucleosome assembly

20538007

TgeneANP32B

GO:0045596

negative regulation of cell differentiation

22705300



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/chr6:159204556/chr9:100773628)
- 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 EZR (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 ANP32B (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)
ENST00000367075EZRchr6159204556-ENST00000339399ANP32Bchr9100773628+1542867971029310

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
ENST00000367075ENST00000339399EZRchr6159204556-ANP32Bchr9100773628+0.0004071240.99959284

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 EZR-ANP32B

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
EZRchr6159204556ANP32Bchr9100773628867255GVDALGLNIYEKDDKDVEGDEDDDEV

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Potential FusionNeoAntigen Information of EZR-ANP32B 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.

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)

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Potential FusionNeoAntigen Information of EZR-ANP32B 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.
EZR-ANP32B_159204556_100773628.msa

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)
EZR-ANP32Bchr6159204556chr9100773628867DRB1-0305LNIYEKDDKDVEGDE621
EZR-ANP32Bchr6159204556chr9100773628867DRB1-0840LNIYEKDDKDVEGDE621
EZR-ANP32Bchr6159204556chr9100773628867DRB1-1303LNIYEKDDKDVEGDE621
EZR-ANP32Bchr6159204556chr9100773628867DRB1-1303GLNIYEKDDKDVEGD520
EZR-ANP32Bchr6159204556chr9100773628867DRB1-13101LNIYEKDDKDVEGDE621
EZR-ANP32Bchr6159204556chr9100773628867DRB1-13101GLNIYEKDDKDVEGD520
EZR-ANP32Bchr6159204556chr9100773628867DRB1-1310LNIYEKDDKDVEGDE621
EZR-ANP32Bchr6159204556chr9100773628867DRB1-1310GLNIYEKDDKDVEGD520
EZR-ANP32Bchr6159204556chr9100773628867DRB1-1333LNIYEKDDKDVEGDE621
EZR-ANP32Bchr6159204556chr9100773628867DRB1-1333GLNIYEKDDKDVEGD520
EZR-ANP32Bchr6159204556chr9100773628867DRB1-1333NIYEKDDKDVEGDED722
EZR-ANP32Bchr6159204556chr9100773628867DRB1-1388LNIYEKDDKDVEGDE621
EZR-ANP32Bchr6159204556chr9100773628867DRB1-1388GLNIYEKDDKDVEGD520
EZR-ANP32Bchr6159204556chr9100773628867DRB1-1390LNIYEKDDKDVEGDE621
EZR-ANP32Bchr6159204556chr9100773628867DRB1-1390GLNIYEKDDKDVEGD520
EZR-ANP32Bchr6159204556chr9100773628867DRB1-1395LNIYEKDDKDVEGDE621
EZR-ANP32Bchr6159204556chr9100773628867DRB1-1395GLNIYEKDDKDVEGD520

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Fusion breakpoint peptide structures of EZR-ANP32B

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of EZR-ANP32B

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

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Vaccine Design for the FusionNeoAntigens of EZR-ANP32B

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

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
EZR-ANP32Bchr6159204556chr9100773628520GLNIYEKDDKDVEGDGAATATTTATGAGAAAGATGATAAAGATGTAGAAGGGGATGAGGA
EZR-ANP32Bchr6159204556chr9100773628621LNIYEKDDKDVEGDETATTTATGAGAAAGATGATAAAGATGTAGAAGGGGATGAGGACGA
EZR-ANP32Bchr6159204556chr9100773628722NIYEKDDKDVEGDEDTTATGAGAAAGATGATAAAGATGTAGAAGGGGATGAGGACGACGA

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Information of the samples that have these potential fusion neoantigens of EZR-ANP32B

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

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Potential target of CAR-T therapy development for EZR-ANP32B

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 EZR-ANP32B

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 EZR-ANP32B

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
HgeneEZRC0033578Prostatic Neoplasms3CTD_human
HgeneEZRC0376358Malignant neoplasm of prostate3CTD_human
HgeneEZRC0007097Carcinoma1CTD_human
HgeneEZRC0023893Liver Cirrhosis, Experimental1CTD_human
HgeneEZRC0024667Animal Mammary Neoplasms1CTD_human
HgeneEZRC0024668Mammary Neoplasms, Experimental1CTD_human
HgeneEZRC0027627Neoplasm Metastasis1CTD_human
HgeneEZRC0029408Degenerative polyarthritis1CTD_human
HgeneEZRC0086743Osteoarthrosis Deformans1CTD_human
HgeneEZRC0205696Anaplastic carcinoma1CTD_human
HgeneEZRC0205697Carcinoma, Spindle-Cell1CTD_human
HgeneEZRC0205698Undifferentiated carcinoma1CTD_human
HgeneEZRC0205699Carcinomatosis1CTD_human
HgeneEZRC1257925Mammary Carcinoma, Animal1CTD_human