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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:CYTH1-CUX1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CYTH1-CUX1
FusionPDB ID: 21133
FusionGDB2.0 ID: 21133
HgeneTgene
Gene symbol

CYTH1

CUX1

Gene ID

9267

1523

Gene namecytohesin 1cut like homeobox 1
SynonymsB2-1|CYTOHESIN-1|D17S811E|PSCD1|SEC7CASP|CDP|CDP/Cut|CDP1|COY1|CUTL1|CUX|Clox|Cux/CDP|GDDI|GOLIM6|Nbla10317|p100|p110|p200|p75
Cytomap

17q25.3

7q22.1

Type of geneprotein-codingprotein-coding
Descriptioncytohesin-1PH, SEC7 and coiled-coil domain-containing protein 1SEC7 homolog B2-1cytoadhesin 1homolog of secretory protein SEC7pleckstrin homology, Sec7 and coiled-coil domains 1protein 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

Q15438

Main function of 5'-partner protein: FUNCTION: Promotes guanine-nucleotide exchange on ARF1, ARF5 and ARF6. Promotes the activation of ARF factors through replacement of GDP with GTP. Plays an important role in membrane trafficking, during junctional remodeling and epithelial polarization, through regulation of ARF6 activity. {ECO:0000250|UniProtKB:Q9QX11, ECO:0000269|PubMed:10652308, ECO:0000269|PubMed:29420262, ECO:0000269|PubMed:9653114}.

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 idsENST00000361101, ENST00000446868, 
ENST00000585509, ENST00000589297, 
ENST00000591455, ENST00000586175, 
ENST00000589296, 
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 score18 X 13 X 7=163826 X 23 X 9=5382
# samples 1929
** MAII scorelog2(19/1638*10)=-3.10786403331006
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
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: CYTH1 [Title/Abstract] AND CUX1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CYTH1 [Title/Abstract] AND CUX1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CYTH1(76696412)-CUX1(101916636), # samples:2
Anticipated loss of major functional domain due to fusion event.CYTH1-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.
CYTH1-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.
CYTH1-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.
CYTH1-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.
CYTH1-CUX1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
CYTH1-CUX1 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
CYTH1-CUX1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
CYTH1-CUX1 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted ORF.
CYTH1-CUX1 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
HgeneCYTH1

GO:0030155

regulation of cell adhesion

12606567



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/chr17:76696412/chr7:101916636)
- 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 CYTH1 (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)
ENST00000589297CYTH1chr1776696412-ENST00000437600CUX1chr7101916636+271510664951847450
ENST00000589297CYTH1chr1776696412-ENST00000292538CUX1chr7101916636+271510664951847450
ENST00000589297CYTH1chr1776696412-ENST00000393824CUX1chr7101916636+223610664951847450
ENST00000589297CYTH1chr1776696412-ENST00000547394CUX1chr7101916636+271510664951847450
ENST00000591455CYTH1chr1776696412-ENST00000437600CUX1chr7101916636+2248599491380443
ENST00000591455CYTH1chr1776696412-ENST00000292538CUX1chr7101916636+2248599491380443
ENST00000591455CYTH1chr1776696412-ENST00000393824CUX1chr7101916636+1769599491380443
ENST00000591455CYTH1chr1776696412-ENST00000547394CUX1chr7101916636+2248599491380443
ENST00000446868CYTH1chr1776696412-ENST00000437600CUX1chr7101916636+2270621711402443
ENST00000446868CYTH1chr1776696412-ENST00000292538CUX1chr7101916636+2270621711402443
ENST00000446868CYTH1chr1776696412-ENST00000393824CUX1chr7101916636+1791621711402443
ENST00000446868CYTH1chr1776696412-ENST00000547394CUX1chr7101916636+2270621711402443
ENST00000361101CYTH1chr1776696412-ENST00000437600CUX1chr7101916636+2270621711402443
ENST00000361101CYTH1chr1776696412-ENST00000292538CUX1chr7101916636+2270621711402443
ENST00000361101CYTH1chr1776696412-ENST00000393824CUX1chr7101916636+1791621711402443
ENST00000361101CYTH1chr1776696412-ENST00000547394CUX1chr7101916636+2270621711402443

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
ENST00000589297ENST00000437600CYTH1chr1776696412-CUX1chr7101916636+0.0097506190.99024934
ENST00000589297ENST00000292538CYTH1chr1776696412-CUX1chr7101916636+0.0097506190.99024934
ENST00000589297ENST00000393824CYTH1chr1776696412-CUX1chr7101916636+0.0094980870.9905019
ENST00000589297ENST00000547394CYTH1chr1776696412-CUX1chr7101916636+0.0097506190.99024934
ENST00000591455ENST00000437600CYTH1chr1776696412-CUX1chr7101916636+0.0140178160.9859822
ENST00000591455ENST00000292538CYTH1chr1776696412-CUX1chr7101916636+0.0140178160.9859822
ENST00000591455ENST00000393824CYTH1chr1776696412-CUX1chr7101916636+0.0142805530.9857195
ENST00000591455ENST00000547394CYTH1chr1776696412-CUX1chr7101916636+0.0140178160.9859822
ENST00000446868ENST00000437600CYTH1chr1776696412-CUX1chr7101916636+0.0137719720.98622805
ENST00000446868ENST00000292538CYTH1chr1776696412-CUX1chr7101916636+0.0137719720.98622805
ENST00000446868ENST00000393824CYTH1chr1776696412-CUX1chr7101916636+0.014185510.9858145
ENST00000446868ENST00000547394CYTH1chr1776696412-CUX1chr7101916636+0.0137719720.98622805
ENST00000361101ENST00000437600CYTH1chr1776696412-CUX1chr7101916636+0.0137719720.98622805
ENST00000361101ENST00000292538CYTH1chr1776696412-CUX1chr7101916636+0.0137719720.98622805
ENST00000361101ENST00000393824CYTH1chr1776696412-CUX1chr7101916636+0.014185510.9858145
ENST00000361101ENST00000547394CYTH1chr1776696412-CUX1chr7101916636+0.0137719720.98622805

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 CYTH1-CUX1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CYTH1chr1776696412CUX1chr71019166361066189QRYCQCNNGVFQSTGRCAELQVRITE
CYTH1chr1776696412CUX1chr7101916636599182QRYCQCNNGVFQSTGRCAELQVRITE
CYTH1chr1776696412CUX1chr7101916636621182QRYCQCNNGVFQSTGRCAELQVRITE

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Potential FusionNeoAntigen Information of CYTH1-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.

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 CYTH1-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 CYTH1-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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CYTH1-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

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Vaccine Design for the FusionNeoAntigens of CYTH1-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

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 CYTH1-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

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Potential target of CAR-T therapy development for CYTH1-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
TgeneCUX1chr17:76696412chr7:101916636ENST000002925381323620_6400679.0TransmembraneHelical%3B Anchor for type IV membrane protein
TgeneCUX1chr17:76696412chr7:101916636ENST000003938241222620_6400640.0TransmembraneHelical%3B Anchor for type IV membrane protein
TgeneCUX1chr17:76696412chr7:101916636ENST000004376001323620_6400677.0TransmembraneHelical%3B Anchor for type IV membrane protein
TgeneCUX1chr17:76696412chr7:101916636ENST000005473941222620_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 CYTH1-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 CYTH1-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