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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:GPC4-GPC3 (FusionGDB2 ID:34179)

Fusion Gene Summary for GPC4-GPC3

check button Fusion gene summary
Fusion gene informationFusion gene name: GPC4-GPC3
Fusion gene ID: 34179
HgeneTgene
Gene symbol

GPC4

GPC3

Gene ID

2239

2719

Gene nameglypican 4glypican 3
SynonymsK-glypican|KPTSDGSX|GTR2-2|MXR7|OCI-5|SDYS|SGB|SGBS|SGBS1
Cytomap

Xq26.2

Xq26.2

Type of geneprotein-codingprotein-coding
Descriptionglypican-4dJ900E8.1 (glypican 4)glypican proteoglycan 4glypican-3glypican proteoglycan 3heparan sulphate proteoglycanintestinal protein OCI-5secreted glypican-3
Modification date2020032720200315
UniProtAcc

O75487

P51654

Ensembl transtripts involved in fusion geneENST00000370828, ENST00000535467, 
ENST00000370818, ENST00000394299, 
ENST00000543339, 
Fusion gene scores* DoF score6 X 4 X 4=9612 X 11 X 6=792
# samples 612
** MAII scorelog2(6/96*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/792*10)=-2.72246602447109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: GPC4 [Title/Abstract] AND GPC3 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointGPC4(132548834)-GPC3(132670321), # samples:2
GPC3(132730468)-GPC4(132473369), # samples:1
Anticipated loss of major functional domain due to fusion event.GPC4-GPC3 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
GPC4-GPC3 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
GPC4-GPC3 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
GPC4-GPC3 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
GPC4-GPC3 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
GPC4-GPC3 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
TgeneGPC3

GO:0060828

regulation of canonical Wnt signaling pathway

14610063

TgeneGPC3

GO:0090263

positive regulation of canonical Wnt signaling pathway

24496449

TgeneGPC3

GO:2000050

regulation of non-canonical Wnt signaling pathway

14610063


check buttonFusion gene breakpoints across GPC4 (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 GPC3 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4BRCATCGA-E9-A1NA-01AGPC4chrX

132548834

-GPC3chrX

132670321

-
ChimerDB4TGCTTCGA-2G-AAKD-01AGPC4chrX

132548834

-GPC3chrX

132670321

-


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Fusion Gene ORF analysis for GPC4-GPC3

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
Frame-shiftENST00000370828ENST00000370818GPC4chrX

132548834

-GPC3chrX

132670321

-
Frame-shiftENST00000370828ENST00000394299GPC4chrX

132548834

-GPC3chrX

132670321

-
In-frameENST00000370828ENST00000543339GPC4chrX

132548834

-GPC3chrX

132670321

-
intron-3CDSENST00000535467ENST00000370818GPC4chrX

132548834

-GPC3chrX

132670321

-
intron-3CDSENST00000535467ENST00000394299GPC4chrX

132548834

-GPC3chrX

132670321

-
intron-3CDSENST00000535467ENST00000543339GPC4chrX

132548834

-GPC3chrX

132670321

-

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000370828GPC4chrX132548834-ENST00000543339GPC3chrX132670321-85568519759246

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
ENST00000370828ENST00000543339GPC4chrX132548834-GPC3chrX132670321-0.0099976440.9900024

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Fusion Genomic Features for GPC4-GPC3


check buttonFusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.
genomic feature

check buttonDistribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for GPC4-GPC3


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/chrX:132548834/chrX:132670321)
- 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 buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
GPC4

O75487

GPC3

P51654

FUNCTION: Cell surface proteoglycan that bears heparan sulfate. May be involved in the development of kidney tubules and of the central nervous system (By similarity). {ECO:0000250}.FUNCTION: Cell surface proteoglycan that bears heparan sulfate (PubMed:14610063). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for binding to hedgehog proteins (By similarity). Binding to the hedgehog protein SHH triggers internalization of the complex by endocytosis and its subsequent lysosomal degradation (By similarity). Positively regulates the canonical Wnt signaling pathway by binding to the Wnt receptor Frizzled and stimulating the binding of the Frizzled receptor to Wnt ligands (PubMed:16227623, PubMed:24496449). Positively regulates the non-canonical Wnt signaling pathway (By similarity). Binds to CD81 which decreases the availability of free CD81 for binding to the transcriptional repressor HHEX, resulting in nuclear translocation of HHEX and transcriptional repression (By similarity). Inhibits the dipeptidyl peptidase activity of DPP4 (PubMed:17549790). Plays a role in limb patterning and skeletal development by controlling the cellular response to BMP4 (By similarity). Modulates the effects of growth factors BMP2, BMP7 and FGF7 on renal branching morphogenesis (By similarity). Required for coronary vascular development (By similarity). Plays a role in regulating cell movements during gastrulation (By similarity). {ECO:0000250|UniProtKB:Q6V9Y8, ECO:0000250|UniProtKB:Q8CFZ4, ECO:0000269|PubMed:14610063, ECO:0000269|PubMed:16227623, ECO:0000269|PubMed:17549790, ECO:0000269|PubMed:24496449}.

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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page


* Minus value of BPloci means that the break pointn is located before the CDS.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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Fusion Gene Sequence for GPC4-GPC3


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>34179_34179_1_GPC4-GPC3_GPC4_chrX_132548834_ENST00000370828_GPC3_chrX_132670321_ENST00000543339_length(transcript)=855nt_BP=685nt
CAGTCAATCAGCGGCAGAGCTGAGAAGGGCACAGCCGCGCGGCGGAGGGCAGAGTCAGCCGAGCCGAGTCCAGCCGGACGAGCGGACCAG
CGCAGGGCAGCCCAAGCAGCGCGCAGCGAACGCCCGCCGCCGCCCACACCCTCTGCGGTCCCCGCGGCGCCTGCCACCCTTCCCTCCTTC
CCCGCGTCCCCGCCTCGCCGGCCAGTCAGCTTGCCGGGTTCGCTGCCCCGCGAAACCCCGAGGTCACCAGCCCGCGCCTCTGCTTCCCTG
GGCCGCGCGCCGCCTCCACGCCCTCCTTCTCCCCTGGCCCGGCGCCTGGCACCGGGGACCGTTGCCTGACGCGAGGCCCAGCTCTACTTT
TCGCCCCGCGTCTCCTCCGCCTGCTCGCCTCTTCCACCAACTCCAACTCCTTCTCCCTCCAGCTCCACTCGCTAGTCCCCGACTCCGCCA
GCCCTCGGCCCGCTGCCGTAGCGCCGCTTCCCGTCCGGTCCCAAAGGTGGGAACGCGTCCGCCCCGGCCCGCACCATGGCACGGTTCGGC
TTGCCCGCGCTTCTCTGCACCCTGGCAGTGCTCAGCGCCGCGCTGCTGGCTGCCGAGCTCAAGTCGAAAAGTTGCTCGGAAGTGCGACGT
CTTTACGTGTCCAAAGGCTTCAACAAGAACGATGCCCCCCTCCACGAGATCAACGAACTGGCCTATGATCTGGATGTGGATGATGCGCCT
GGAAACAGTCAGCAGGCAACTCCGAAGGACAACGAGATAAGCACCTTTCACAACCTCGGGAACGTTCATTCCCCGCTGAAGCTTCTCACC

>34179_34179_1_GPC4-GPC3_GPC4_chrX_132548834_ENST00000370828_GPC3_chrX_132670321_ENST00000543339_length(amino acids)=246AA_BP=222
MRRAQPRGGGQSQPSRVQPDERTSAGQPKQRAANARRRPHPLRSPRRLPPFPPSPRPRLAGQSACRVRCPAKPRGHQPAPLLPWAARRLH
ALLLPWPGAWHRGPLPDARPSSTFRPASPPPARLFHQLQLLLPPAPLASPRLRQPSARCRSAASRPVPKVGTRPPRPAPWHGSACPRFSA

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Fusion Gene PPI Analysis for GPC4-GPC3


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs for GPC4-GPC3


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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Related Diseases for GPC4-GPC3


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource