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Fusion Protein:GPC4-GPC3 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: GPC4-GPC3 | FusionPDB ID: 34179 | FusionGDB2.0 ID: 34179 | Hgene | Tgene | Gene symbol | GPC4 | GPC3 | Gene ID | 2239 | 2719 |
| Gene name | glypican 4 | glypican 3 | |
| Synonyms | K-glypican|KPTS | DGSX|GTR2-2|MXR7|OCI-5|SDYS|SGB|SGBS|SGBS1 | |
| Cytomap | Xq26.2 | Xq26.2 | |
| Type of gene | protein-coding | protein-coding | |
| Description | glypican-4dJ900E8.1 (glypican 4)glypican proteoglycan 4 | glypican-3glypican proteoglycan 3heparan sulphate proteoglycanintestinal protein OCI-5secreted glypican-3 | |
| Modification date | 20200327 | 20200315 | |
| UniProtAcc | O75487 | P51654 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000370828, ENST00000535467, | ENST00000370818, ENST00000394299, ENST00000543339, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 6 X 4 X 4=96 | 12 X 11 X 6=792 |
| # samples | 6 | 12 | |
| ** MAII score | log2(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 (manual curation of fusion genes in FusionPDB) | PubMed: GPC4 [Title/Abstract] AND GPC3 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | GPC4(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) |
| Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Tgene | GPC3 | GO:0060828 | regulation of canonical Wnt signaling pathway | 14610063 |
| Tgene | GPC3 | GO:0090263 | positive regulation of canonical Wnt signaling pathway | 24496449 |
| Tgene | GPC3 | GO:2000050 | regulation of non-canonical Wnt signaling pathway | 14610063 |
| Fusion 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. |
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| Fusion 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. |
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Fusion Gene Sample Information |
| Fusion gene information from FusionGDB2.0. |
| 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. |
| Source | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| ChimerDB4 | BRCA | TCGA-E9-A1NA-01A | GPC4 | chrX | 132548834 | - | GPC3 | chrX | 132670321 | - |
| ChimerDB4 | TGCT | TCGA-2G-AAKD-01A | GPC4 | chrX | 132548834 | - | GPC3 | chrX | 132670321 | - |
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Fusion ORF Analysis |
| Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
| ENST00000370828 | GPC4 | chrX | 132548834 | - | ENST00000543339 | GPC3 | chrX | 132670321 | - | 855 | 685 | 19 | 759 | 246 |
| DeepORF 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. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
| ENST00000370828 | ENST00000543339 | GPC4 | chrX | 132548834 | - | GPC3 | chrX | 132670321 | - | 0.009997644 | 0.9900024 |
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Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP >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 Protein Functional Features |
| 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. |
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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| GPC4 | GPC3 |
| 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}. |
| Retention 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 * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| - Not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
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Fusion Protein Structures |
| PDB and CIF files of the predicted fusion proteins * Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| Fusion protein PDB link (fusion AA seq ID in FusionPDB) | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | AA seq | Len(AA seq) |
| PDB file >>>402_GPC4_132548834_GPC3_132670321_ranked_0.pdb | GPC4 | 132548834 | 132548834 | ENST00000543339 | GPC3 | chrX | 132670321 | - | MRRAQPRGGGQSQPSRVQPDERTSAGQPKQRAANARRRPHPLRSPRRLPPFPPSPRPRLAGQSACRVRCPAKPRGHQPAPLLPWAARRLH ALLLPWPGAWHRGPLPDARPSSTFRPASPPPARLFHQLQLLLPPAPLASPRLRQPSARCRSAASRPVPKVGTRPPRPAPWHGSACPRFSA | 246 |
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pLDDT score distribution |
| pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
GPC4_pLDDT.png  |
GPC3_pLDDT.png  |
| pLDDT score distribution of the predicted fusion protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
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Ramachandran Plot of Fusion Protein Structure |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide. |
| Fusion AA seq ID in FusionPDB and their Ramachandran plots |
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Fusion Protein-Protein Interaction |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
| Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160) |
| Gene | PPI interactors |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| GPC4 | |
| GPC3 |
| - Retained interactions in fusion protein (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost interactions due to fusion (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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Related Drugs to GPC4-GPC3 |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to GPC4-GPC3 |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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