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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:ZFP90-CBFB

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZFP90-CBFB
FusionPDB ID: 101085
FusionGDB2.0 ID: 101085
HgeneTgene
Gene symbol

ZFP90

CBFB

Gene ID

146198

865

Gene nameZFP90 zinc finger proteincore-binding factor subunit beta
SynonymsFIK|NK10|ZNF756|zfp-90PEBP2B
Cytomap

16q22.1

16q22.1

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein 90 homologFOXP3-interacting KRAB domain-containing proteinzinc finger protein 476zinc finger protein 756core-binding factor subunit betaCBF-betaPEA2-betaPEBP2-betaSL3-3 enhancer factor 1 beta subunitSL3-3 enhancer factor 1 subunit betaSL3/AKV core-binding factor beta subunitcore-binding factor beta subunitpolyomavirus enhancer binding protein 2, bet
Modification date2020031320200320
UniProtAcc.

Q13951

Main function of 5'-partner protein: FUNCTION: Forms the heterodimeric complex core-binding factor (CBF) with RUNX family proteins (RUNX1, RUNX2, and RUNX3). RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters. CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation. {ECO:0000250|UniProtKB:Q08024}.
Ensembl transtripts involved in fusion geneENST idsENST00000398253, ENST00000563169, 
ENST00000564323, ENST00000570495, 
ENST00000570884, 
ENST00000568858, 
ENST00000290858, ENST00000412916, 
ENST00000561924, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 9 X 8=7203 X 3 X 3=27
# samples 123
** MAII scorelog2(12/720*10)=-2.58496250072116
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: ZFP90 [Title/Abstract] AND CBFB [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZFP90 [Title/Abstract] AND CBFB [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZFP90(68573728)-CBFB(67116116), # samples:2
Anticipated loss of major functional domain due to fusion event.ZFP90-CBFB 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.
ZFP90-CBFB 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


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/chr16:68573728/chr16:67116116)
- 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 ZFP90 (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 CBFB (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)
ENST00000570495ZFP90chr1668573728+ENST00000561924CBFBchr1667116116+5543257474155
ENST00000570495ZFP90chr1668573728+ENST00000290858CBFBchr1667116116+28013257474155
ENST00000570495ZFP90chr1668573728+ENST00000412916CBFBchr1667116116+27343257489160
ENST00000563169ZFP90chr1668573728+ENST00000561924CBFBchr1667116116+4932644051135
ENST00000563169ZFP90chr1668573728+ENST00000290858CBFBchr1667116116+27402644051135
ENST00000563169ZFP90chr1668573728+ENST00000412916CBFBchr1667116116+26732643372112
ENST00000564323ZFP90chr1668573728+ENST00000561924CBFBchr1667116116+47624710396128
ENST00000564323ZFP90chr1668573728+ENST00000290858CBFBchr1667116116+272324710396128
ENST00000564323ZFP90chr1668573728+ENST00000412916CBFBchr1667116116+265624710411133
ENST00000398253ZFP90chr1668573728+ENST00000561924CBFBchr1667116116+29768209070
ENST00000398253ZFP90chr1668573728+ENST00000290858CBFBchr1667116116+254468209070
ENST00000398253ZFP90chr1668573728+ENST00000412916CBFBchr1667116116+2477681512130369

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
ENST00000570495ENST00000561924ZFP90chr1668573728+CBFBchr1667116116+0.16748320.8325168
ENST00000570495ENST00000290858ZFP90chr1668573728+CBFBchr1667116116+0.720444260.27955574
ENST00000570495ENST00000412916ZFP90chr1668573728+CBFBchr1667116116+0.323871730.67612827
ENST00000563169ENST00000561924ZFP90chr1668573728+CBFBchr1667116116+0.176469010.82353103
ENST00000563169ENST00000290858ZFP90chr1668573728+CBFBchr1667116116+0.369919360.6300807
ENST00000563169ENST00000412916ZFP90chr1668573728+CBFBchr1667116116+0.413723440.58627653
ENST00000564323ENST00000561924ZFP90chr1668573728+CBFBchr1667116116+0.229833740.7701663
ENST00000564323ENST00000290858ZFP90chr1668573728+CBFBchr1667116116+0.45172590.5482741
ENST00000564323ENST00000412916ZFP90chr1668573728+CBFBchr1667116116+0.73612070.2638793
ENST00000398253ENST00000561924ZFP90chr1668573728+CBFBchr1667116116+0.136275960.86372405
ENST00000398253ENST00000290858ZFP90chr1668573728+CBFBchr1667116116+0.70325060.29674935
ENST00000398253ENST00000412916ZFP90chr1668573728+CBFBchr1667116116+0.65753530.3424647

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 ZFP90-CBFB

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZFP90chr1668573728CBFBchr166711611624778EAGMAPRPPTAAPQQEDALAQQAFEE
ZFP90chr1668573728CBFBchr1667116116325105EAGMAPRPPTAAPQQEDALAQQAFEE

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Potential FusionNeoAntigen Information of ZFP90-CBFB 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.
ZFP90-CBFB_68573728_67116116.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)
ZFP90-CBFBchr1668573728chr1667116116247HLA-B07:05APRPPTAAPQ0.9970.7336414
ZFP90-CBFBchr1668573728chr1667116116247HLA-B07:02APRPPTAAPQ0.99690.7605414
ZFP90-CBFBchr1668573728chr1667116116247HLA-B55:01APRPPTAAPQ0.85310.6376414
ZFP90-CBFBchr1668573728chr1667116116247HLA-B07:02APRPPTAAPQQ0.99960.7364415
ZFP90-CBFBchr1668573728chr1667116116247HLA-B39:10APQQEDAL0.50270.93841119
ZFP90-CBFBchr1668573728chr1667116116247HLA-C01:17AAPQQEDAL0.97260.97841019
ZFP90-CBFBchr1668573728chr1667116116247HLA-C01:30AAPQQEDAL0.89060.96961019
ZFP90-CBFBchr1668573728chr1667116116247HLA-B07:04APRPPTAAPQ0.95860.7577414
ZFP90-CBFBchr1668573728chr1667116116247HLA-C01:03AAPQQEDAL0.97360.96631019
ZFP90-CBFBchr1668573728chr1667116116247HLA-C01:02AAPQQEDAL0.96790.97711019
ZFP90-CBFBchr1668573728chr1667116116247HLA-C03:06AAPQQEDAL0.91370.99251019
ZFP90-CBFBchr1668573728chr1667116116247HLA-B35:13AAPQQEDAL0.74810.94781019
ZFP90-CBFBchr1668573728chr1667116116247HLA-B07:22APRPPTAAPQ0.99690.7605414
ZFP90-CBFBchr1668573728chr1667116116247HLA-B07:09APRPPTAAPQ0.99630.7492414
ZFP90-CBFBchr1668573728chr1667116116247HLA-B35:13TAAPQQEDAL0.9260.9319919
ZFP90-CBFBchr1668573728chr1667116116247HLA-B07:22APRPPTAAPQQ0.99960.7364415
ZFP90-CBFBchr1668573728chr1667116116247HLA-B07:09APRPPTAAPQQ0.99950.7189415

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Potential FusionNeoAntigen Information of ZFP90-CBFB 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 ZFP90-CBFB

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
8100RPPTAAPQQEDALAZFP90CBFBchr1668573728chr1667116116247

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZFP90-CBFB

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-B14:023BVN8100RPPTAAPQQEDALA-7.15543-7.26883
HLA-B14:023BVN8100RPPTAAPQQEDALA-4.77435-5.80965
HLA-B52:013W398100RPPTAAPQQEDALA-6.80875-6.92215
HLA-B52:013W398100RPPTAAPQQEDALA-4.20386-5.23916
HLA-A11:014UQ28100RPPTAAPQQEDALA-7.5194-8.5547
HLA-A11:014UQ28100RPPTAAPQQEDALA-6.9601-7.0735
HLA-A24:025HGA8100RPPTAAPQQEDALA-7.52403-7.63743
HLA-A24:025HGA8100RPPTAAPQQEDALA-5.82433-6.85963
HLA-B27:056PYJ8100RPPTAAPQQEDALA-3.28285-4.31815
HLA-B44:053DX88100RPPTAAPQQEDALA-5.91172-6.94702
HLA-B44:053DX88100RPPTAAPQQEDALA-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ZFP90-CBFB

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
ZFP90-CBFBchr1668573728chr16671161161019AAPQQEDALGCGCCCCAGCAGGAGGATGCATTAGCA
ZFP90-CBFBchr1668573728chr16671161161119APQQEDALCCCCAGCAGGAGGATGCATTAGCA
ZFP90-CBFBchr1668573728chr1667116116414APRPPTAAPQCCGAGGCCTCCGACCGCCGCGCCCCAGCAG
ZFP90-CBFBchr1668573728chr1667116116415APRPPTAAPQQCCGAGGCCTCCGACCGCCGCGCCCCAGCAGGAG
ZFP90-CBFBchr1668573728chr1667116116919TAAPQQEDALGCCGCGCCCCAGCAGGAGGATGCATTAGCA

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 ZFP90-CBFB

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
SKCMZFP90-CBFBchr1668573728ENST00000564323chr1667116116ENST00000290858TCGA-WE-A8ZQ-06A

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Potential target of CAR-T therapy development for ZFP90-CBFB

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 ZFP90-CBFB

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 ZFP90-CBFB

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
TgeneCBFBC0023467Leukemia, Myelocytic, Acute2CTD_human
TgeneCBFBC0023479Acute myelomonocytic leukemia2CTD_human;ORPHANET
TgeneCBFBC0026998Acute Myeloid Leukemia, M12CTD_human
TgeneCBFBC1879321Acute Myeloid Leukemia (AML-M2)2CTD_human
TgeneCBFBC0005941Bone Diseases, Developmental1CTD_human
TgeneCBFBC0008925Cleft Palate1CTD_human
TgeneCBFBC0018798Congenital Heart Defects1CTD_human
TgeneCBFBC0029396Heterotopic Ossification1CTD_human
TgeneCBFBC1837218Cleft palate, isolated1CTD_human