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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:ZSCAN25-CUX1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZSCAN25-CUX1
FusionPDB ID: 103228
FusionGDB2.0 ID: 103228
HgeneTgene
Gene symbol

ZSCAN25

CUX1

Gene ID

221785

1523

Gene namezinc finger and SCAN domain containing 25cut like homeobox 1
SynonymsZNF498CASP|CDP|CDP/Cut|CDP1|COY1|CUTL1|CUX|Clox|Cux/CDP|GDDI|GOLIM6|Nbla10317|p100|p110|p200|p75
Cytomap

7q22.1

7q22.1

Type of geneprotein-codingprotein-coding
Descriptionzinc finger and SCAN domain-containing protein 25zinc finger protein 498protein CASPHomeobox protein cut-like 1CCAAT displacement proteinCUX1 gene Alternatively Spliced Productcut homologgolgi integral membrane protein 6homeobox protein cux-1putative protein product of Nbla10317
Modification date2020031320200320
UniProtAcc.

P39880

Main function of 5'-partner protein: FUNCTION: Transcription factor involved in the control of neuronal differentiation in the brain. Regulates dendrite development and branching, and dendritic spine formation in cortical layers II-III. Also involved in the control of synaptogenesis. In addition, it has probably a broad role in mammalian development as a repressor of developmentally regulated gene expression. May act by preventing binding of positively-activing CCAAT factors to promoters. Component of nf-munr repressor; binds to the matrix attachment regions (MARs) (5' and 3') of the immunoglobulin heavy chain enhancer. Represses T-cell receptor (TCR) beta enhancer function by binding to MARbeta, an ATC-rich DNA sequence located upstream of the TCR beta enhancer. Binds to the TH enhancer; may require the basic helix-loop-helix protein TCF4 as a coactivator. {ECO:0000250|UniProtKB:P53564}.; FUNCTION: [CDP/Cux p110]: Plays a role in cell cycle progression, in particular at the G1/S transition. As cells progress into S phase, a fraction of CUX1 molecules is proteolytically processed into N-terminally truncated proteins of 110 kDa. While CUX1 only transiently binds to DNA and carries the CCAAT-displacement activity, CDP/Cux p110 makes a stable interaction with DNA and stimulates expression of genes such as POLA1. {ECO:0000269|PubMed:15099520}.
Ensembl transtripts involved in fusion geneENST idsENST00000334715, ENST00000394152, 
ENST00000262941, ENST00000466948, 
ENST00000560541, ENST00000292535, 
ENST00000360264, ENST00000425244, 
ENST00000546411, ENST00000549414, 
ENST00000550008, ENST00000556210, 
ENST00000292538, ENST00000393824, 
ENST00000437600, ENST00000547394, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 2=1826 X 23 X 9=5382
# samples 329
** MAII scorelog2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(29/5382*10)=-4.21401758562548
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ZSCAN25 [Title/Abstract] AND CUX1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZSCAN25 [Title/Abstract] AND CUX1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZSCAN25(99221804)-CUX1(101916634), # samples:1
Anticipated loss of major functional domain due to fusion event.ZSCAN25-CUX1 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.
ZSCAN25-CUX1 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.
ZSCAN25-CUX1 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.
ZSCAN25-CUX1 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/chr7:99221804/chr7:101916634)
- 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 ZSCAN25 (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 CUX1 (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)
ENST00000394152ZSCAN25chr799221804+ENST00000437600CUX1chr7101916634+278111323211913530
ENST00000394152ZSCAN25chr799221804+ENST00000292538CUX1chr7101916634+278111323211913530
ENST00000394152ZSCAN25chr799221804+ENST00000393824CUX1chr7101916634+230211323211913530
ENST00000394152ZSCAN25chr799221804+ENST00000547394CUX1chr7101916634+278111323211913530
ENST00000334715ZSCAN25chr799221804+ENST00000437600CUX1chr7101916634+2511862511643530
ENST00000334715ZSCAN25chr799221804+ENST00000292538CUX1chr7101916634+2511862511643530
ENST00000334715ZSCAN25chr799221804+ENST00000393824CUX1chr7101916634+2032862511643530
ENST00000334715ZSCAN25chr799221804+ENST00000547394CUX1chr7101916634+2511862511643530

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
ENST00000394152ENST00000437600ZSCAN25chr799221804+CUX1chr7101916634+0.0310545770.9689454
ENST00000394152ENST00000292538ZSCAN25chr799221804+CUX1chr7101916634+0.0310545770.9689454
ENST00000394152ENST00000393824ZSCAN25chr799221804+CUX1chr7101916634+0.0300355610.9699644
ENST00000394152ENST00000547394ZSCAN25chr799221804+CUX1chr7101916634+0.0310545770.9689454
ENST00000334715ENST00000437600ZSCAN25chr799221804+CUX1chr7101916634+0.0324482470.96755177
ENST00000334715ENST00000292538ZSCAN25chr799221804+CUX1chr7101916634+0.0324482470.96755177
ENST00000334715ENST00000393824ZSCAN25chr799221804+CUX1chr7101916634+0.0320766530.9679233
ENST00000334715ENST00000547394ZSCAN25chr799221804+CUX1chr7101916634+0.0324482620.96755177

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 ZSCAN25-CUX1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZSCAN25chr799221804CUX1chr71019166341132270GEYVEPQDCRVSPGRCAELQVRITEA
ZSCAN25chr799221804CUX1chr7101916634862270GEYVEPQDCRVSPGRCAELQVRITEA

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Potential FusionNeoAntigen Information of ZSCAN25-CUX1 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.
ZSCAN25-CUX1_99221804_101916634.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)
ZSCAN25-CUX1chr799221804chr7101916634862HLA-C01:30VSPGRCAEL0.77850.95381019
ZSCAN25-CUX1chr799221804chr7101916634862HLA-C01:17VSPGRCAEL0.77070.9561019
ZSCAN25-CUX1chr799221804chr7101916634862HLA-C01:17RVSPGRCAEL0.95630.9499919
ZSCAN25-CUX1chr799221804chr7101916634862HLA-C03:17VSPGRCAEL0.99680.96031019
ZSCAN25-CUX1chr799221804chr7101916634862HLA-C01:02VSPGRCAEL0.74640.9521019
ZSCAN25-CUX1chr799221804chr7101916634862HLA-C01:03VSPGRCAEL0.71410.95591019
ZSCAN25-CUX1chr799221804chr7101916634862HLA-C01:02RVSPGRCAEL0.96570.9487919

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Potential FusionNeoAntigen Information of ZSCAN25-CUX1 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 ZSCAN25-CUX1

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
7175QDCRVSPGRCAELQZSCAN25CUX1chr799221804chr7101916634862

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZSCAN25-CUX1

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-B51:011E287175QDCRVSPGRCAELQ-2.66736-2.78076
HLA-A03:012XPG7175QDCRVSPGRCAELQ-1.51105-2.54635
HLA-B14:023BVN7175QDCRVSPGRCAELQ-5.83247-5.94587
HLA-B14:023BVN7175QDCRVSPGRCAELQ-3.51703-4.55233
HLA-B52:013W397175QDCRVSPGRCAELQ-5.64143-6.67673
HLA-B52:013W397175QDCRVSPGRCAELQ-5.35834-5.47174
HLA-B18:014JQV7175QDCRVSPGRCAELQ-4.10602-5.14132
HLA-B18:014JQV7175QDCRVSPGRCAELQ-3.86802-3.98142
HLA-A11:014UQ27175QDCRVSPGRCAELQ-9.64733-9.76073
HLA-A11:014UQ27175QDCRVSPGRCAELQ-2.23117-3.26647
HLA-A24:025HGA7175QDCRVSPGRCAELQ-5.71077-5.82417
HLA-A24:025HGA7175QDCRVSPGRCAELQ-3.6538-4.6891
HLA-C08:026JTP7175QDCRVSPGRCAELQ-5.36916-5.48256
HLA-B27:056PYJ7175QDCRVSPGRCAELQ-6.42081-7.45611
HLA-B27:056PYJ7175QDCRVSPGRCAELQ-5.71384-5.82724
HLA-B27:036PZ57175QDCRVSPGRCAELQ-3.23395-3.34735
HLA-B27:036PZ57175QDCRVSPGRCAELQ-2.07721-3.11251
HLA-B44:053DX87175QDCRVSPGRCAELQ-5.14294-5.25634
HLA-B44:053DX87175QDCRVSPGRCAELQ-3.98213-5.01743
HLA-A02:016TDR7175QDCRVSPGRCAELQ-4.77803-5.81333

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Vaccine Design for the FusionNeoAntigens of ZSCAN25-CUX1

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
ZSCAN25-CUX1chr799221804chr71019166341019VSPGRCAELTCTCTCCAGGACGCTGTGCAGAGCTGC
ZSCAN25-CUX1chr799221804chr7101916634919RVSPGRCAELGGGTCTCTCCAGGACGCTGTGCAGAGCTGC

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 ZSCAN25-CUX1

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
N/AZSCAN25-CUX1chr799221804ENST00000334715chr7101916634ENST00000292538BC036852

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Potential target of CAR-T therapy development for ZSCAN25-CUX1

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
TgeneCUX1chr7:99221804chr7:101916634ENST000002925381323620_6400679.0TransmembraneHelical%3B Anchor for type IV membrane protein
TgeneCUX1chr7:99221804chr7:101916634ENST000003938241222620_6400640.0TransmembraneHelical%3B Anchor for type IV membrane protein
TgeneCUX1chr7:99221804chr7:101916634ENST000004376001323620_6400677.0TransmembraneHelical%3B Anchor for type IV membrane protein
TgeneCUX1chr7:99221804chr7:101916634ENST000005473941222620_6400663.0TransmembraneHelical%3B Anchor for type IV membrane protein

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 ZSCAN25-CUX1

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 ZSCAN25-CUX1

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