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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:GSK3B-CDC5L

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GSK3B-CDC5L
FusionPDB ID: 35037
FusionGDB2.0 ID: 35037
HgeneTgene
Gene symbol

GSK3B

CDC5L

Gene ID

2932

988

Gene nameglycogen synthase kinase 3 betacell division cycle 5 like
Synonyms-CDC5|CDC5-LIKE|CEF1|PCDC5RP|dJ319D22.1
Cytomap

3q13.33

6p21.1

Type of geneprotein-codingprotein-coding
Descriptionglycogen synthase kinase-3 betaGSK-3 betaGSK3beta isoformserine/threonine-protein kinase GSK3Bcell division cycle 5-like proteinCDC5 cell division cycle 5-likeCdc5-related proteindJ319D22.1 (CDC5-like protein)pombe cdc5-related protein
Modification date2020031520200313
UniProtAcc

C14orf129

Main function of 5'-partner protein: 139

Q99459

Main function of 5'-partner protein: FUNCTION: DNA-binding protein involved in cell cycle control. May act as a transcription activator. Plays role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:11991638, PubMed:20176811, PubMed:28502770, PubMed:28076346, PubMed:29361316, PubMed:29360106, PubMed:29301961, PubMed:30728453, PubMed:30705154). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR) (PubMed:20176811). {ECO:0000269|PubMed:10570151, ECO:0000269|PubMed:11082045, ECO:0000269|PubMed:11101529, ECO:0000269|PubMed:11544257, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12927788, ECO:0000269|PubMed:18583928, ECO:0000269|PubMed:20176811, ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:30728453, ECO:0000269|PubMed:9038199, ECO:0000269|PubMed:9468527, ECO:0000269|PubMed:9632794}.
Ensembl transtripts involved in fusion geneENST idsENST00000264235, ENST00000316626, 
ENST00000473886, 
ENST00000371477, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score31 X 22 X 12=81848 X 6 X 6=288
# samples 368
** MAII scorelog2(36/8184*10)=-4.50673733341565
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/288*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: GSK3B [Title/Abstract] AND CDC5L [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GSK3B [Title/Abstract] AND CDC5L [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GSK3B(119812193)-CDC5L(44413391), # samples:1
Anticipated loss of major functional domain due to fusion event.GSK3B-CDC5L 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.
GSK3B-CDC5L 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.
GSK3B-CDC5L 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.
GSK3B-CDC5L 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
HgeneGSK3B

GO:0005977

glycogen metabolic process

8638126

HgeneGSK3B

GO:0006468

protein phosphorylation

11035810|16315267|20937854

HgeneGSK3B

GO:0006983

ER overload response

14744935

HgeneGSK3B

GO:0018105

peptidyl-serine phosphorylation

8638126|11104755|11955436|14744935|17139249

HgeneGSK3B

GO:0018107

peptidyl-threonine phosphorylation

11955436|17139249|25897075

HgeneGSK3B

GO:0031175

neuron projection development

19830702

HgeneGSK3B

GO:0031334

positive regulation of protein complex assembly

8638126

HgeneGSK3B

GO:0032091

negative regulation of protein binding

16890161

HgeneGSK3B

GO:0032436

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

19364825

HgeneGSK3B

GO:0035556

intracellular signal transduction

14749367

HgeneGSK3B

GO:0043066

negative regulation of apoptotic process

14744935

HgeneGSK3B

GO:0046777

protein autophosphorylation

23184662

HgeneGSK3B

GO:0046827

positive regulation of protein export from nucleus

14744935

HgeneGSK3B

GO:1901215

negative regulation of neuron death

19830702

HgeneGSK3B

GO:1901216

positive regulation of neuron death

18508033

HgeneGSK3B

GO:2000300

regulation of synaptic vesicle exocytosis

17989287

TgeneCDC5L

GO:0000398

mRNA splicing, via spliceosome

28076346

TgeneCDC5L

GO:0045944

positive regulation of transcription by RNA polymerase II

11082045



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/chr3:119812193/chr6:44413391)
- 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 GSK3B (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 CDC5L (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)
ENST00000264235GSK3Bchr3119812193-ENST00000371477CDC5Lchr644413391+510410716421214
ENST00000316626GSK3Bchr3119812193-ENST00000371477CDC5Lchr644413391+4353320335637100

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
ENST00000264235ENST00000371477GSK3Bchr3119812193-CDC5Lchr644413391+0.0419642630.95803577
ENST00000316626ENST00000371477GSK3Bchr3119812193-CDC5Lchr644413391+0.057202080.94279796

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 GSK3B-CDC5L

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

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Potential FusionNeoAntigen Information of GSK3B-CDC5L 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 GSK3B-CDC5L 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 GSK3B-CDC5L

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 GSK3B-CDC5L

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 GSK3B-CDC5L

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 GSK3B-CDC5L

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 GSK3B-CDC5L

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 GSK3B-CDC5L

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 GSK3B-CDC5L

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