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Fusion Protein:GSK3A-ZNF564 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: GSK3A-ZNF564 | FusionPDB ID: 35027 | FusionGDB2.0 ID: 35027 | Hgene | Tgene | Gene symbol | GSK3A | ZNF564 | Gene ID | 2931 | 163050 |
| Gene name | glycogen synthase kinase 3 alpha | zinc finger protein 564 | |
| Synonyms | - | - | |
| Cytomap | 19q13.2 | 19p13.2 | |
| Type of gene | protein-coding | protein-coding | |
| Description | glycogen synthase kinase-3 alphaGSK-3 alphaserine/threonine-protein kinase GSK3A | zinc finger protein 564 | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | P49840 | . | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000222330, ENST00000398249, | ENST00000416136, ENST00000339282, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 7 X 5 X 5=175 | 4 X 1 X 4=16 |
| # samples | 7 | 4 | |
| ** MAII score | log2(7/175*10)=-1.32192809488736 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(4/16*10)=1.32192809488736 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: GSK3A [Title/Abstract] AND ZNF564 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | GSK3A(42744107)-ZNF564(12639510), # samples:2 | ||
| Anticipated loss of major functional domain due to fusion event. | GSK3A-ZNF564 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. GSK3A-ZNF564 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. GSK3A-ZNF564 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. GSK3A-ZNF564 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) |
| 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 |
| Hgene | GSK3A | GO:0006468 | protein phosphorylation | 11035810 |
| Hgene | GSK3A | GO:0018107 | peptidyl-threonine phosphorylation | 25897075 |
| Fusion gene breakpoints across GSK3A (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 ZNF564 (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 | PRAD | TCGA-KK-A8IH-01A | GSK3A | chr19 | 42744107 | - | ZNF564 | chr19 | 12639510 | - |
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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) |
| ENST00000222330 | GSK3A | chr19 | 42744107 | - | ENST00000339282 | ZNF564 | chr19 | 12639510 | - | 3334 | 599 | 128 | 2257 | 709 |
| ENST00000398249 | GSK3A | chr19 | 42744107 | - | ENST00000339282 | ZNF564 | chr19 | 12639510 | - | 4674 | 1939 | 1714 | 3597 | 627 |
| 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 |
| ENST00000222330 | ENST00000339282 | GSK3A | chr19 | 42744107 | - | ZNF564 | chr19 | 12639510 | - | 0.000880514 | 0.99911946 |
| ENST00000398249 | ENST00000339282 | GSK3A | chr19 | 42744107 | - | ZNF564 | chr19 | 12639510 | - | 0.000185032 | 0.99981505 |
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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 >35027_35027_1_GSK3A-ZNF564_GSK3A_chr19_42744107_ENST00000222330_ZNF564_chr19_12639510_ENST00000339282_length(amino acids)=709AA_BP=292 MSGGGPSGGGPGGSGRARTSSFAEPGGGGGGGGGGPGGSASGPGGTGGGKASVGAMGGGVGASSSGGGPGGSGGGGSGGPGAGTSFPPPG VKLGRDSGKVTTVVATLGQGPERSQEVAYTDIKVIGNGSFGVVYQARLAETRELVAIKKVLQDKRFKDSVASEDVAVNFTLEEWALLDPS QKKLYRDVMRETFRNLACVGKKWEDQSIEDWYKNQGRILRNHMEEGLSESKEYDQCGEAFSQILNLNLNKKIPTIVRPCECSLCGKVFMH HSSLSRHIRSHLGHKPYDYQEYGEKPYKCKQCGKAFSSCQSFRRHERTHTGEKPYACPECGKAFISLPSVRRHMIKHTGDGPYKCQECGK AFDRPSLFQIHERTHTGEKPYECQECAKAFISLPSFQRHMIRHTGDGPYKCQECGKAFDRPSLFRIHERTHTGEKPHECKQCGKAFISFT NFQSHMIRHTGDGPYKCKVCGRAFIFPSYVRKHERTHTGEKPYECNKCGKTFSSSSNVRTHERTHTGEKPYECKECGKAFISLPSVRRHM IKHTGDGPYKCQVCGRAFDCPSSFQIHERTHTGEKPYECQVCGKAFISLKRIRKHMILHTGDGPYKCQVCGKAFDCPSSVRTHERTHTGE -------------------------------------------------------------- >35027_35027_2_GSK3A-ZNF564_GSK3A_chr19_42744107_ENST00000398249_ZNF564_chr19_12639510_ENST00000339282_length(amino acids)=627AA_BP=210 MGQWIVYPLCSPGDSGKVTTVVATLGQGPERSQEVAYTDIKVIGNGSFGVVYQARLAETRELVAIKKVLQDKRFKDSVASEDVAVNFTLE EWALLDPSQKKLYRDVMRETFRNLACVGKKWEDQSIEDWYKNQGRILRNHMEEGLSESKEYDQCGEAFSQILNLNLNKKIPTIVRPCECS LCGKVFMHHSSLSRHIRSHLGHKPYDYQEYGEKPYKCKQCGKAFSSCQSFRRHERTHTGEKPYACPECGKAFISLPSVRRHMIKHTGDGP YKCQECGKAFDRPSLFQIHERTHTGEKPYECQECAKAFISLPSFQRHMIRHTGDGPYKCQECGKAFDRPSLFRIHERTHTGEKPHECKQC GKAFISFTNFQSHMIRHTGDGPYKCKVCGRAFIFPSYVRKHERTHTGEKPYECNKCGKTFSSSSNVRTHERTHTGEKPYECKECGKAFIS LPSVRRHMIKHTGDGPYKCQVCGRAFDCPSSFQIHERTHTGEKPYECQVCGKAFISLKRIRKHMILHTGDGPYKCQVCGKAFDCPSSVRT -------------------------------------------------------------- |
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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/chr19:42744107/chr19:12639510) - 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 |
| GSK3A | . |
| FUNCTION: Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1 (PubMed:11749387, PubMed:17478001, PubMed:19366350). Requires primed phosphorylation of the majority of its substrates (PubMed:11749387, PubMed:17478001, PubMed:19366350). Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:11749387, PubMed:17478001, PubMed:19366350). Regulates glycogen metabolism in liver, but not in muscle (By similarity). May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:10868943, PubMed:17478001). In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin (PubMed:17229088). Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease (PubMed:12761548). May be involved in the regulation of replication in pancreatic beta-cells (By similarity). Is necessary for the establishment of neuronal polarity and axon outgrowth (By similarity). Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (By similarity). {ECO:0000250|UniProtKB:P18265, ECO:0000250|UniProtKB:P49841, ECO:0000250|UniProtKB:Q2NL51, ECO:0000269|PubMed:10868943, ECO:0000269|PubMed:12761548, ECO:0000269|PubMed:17229088, ECO:0000269|PubMed:30704899, ECO:0000303|PubMed:11749387, ECO:0000303|PubMed:17478001, ECO:0000303|PubMed:19366350}. | FUNCTION: Might normally function as a transcriptional repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes. |
| 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 |
| Hgene | GSK3A | chr19:42744107 | chr19:12639510 | ENST00000222330 | - | 2 | 11 | 3_83 | 157.0 | 484.0 | Compositional bias | Note=Gly-rich |
| Hgene | GSK3A | chr19:42744107 | chr19:12639510 | ENST00000222330 | - | 2 | 11 | 125_133 | 157.0 | 484.0 | Nucleotide binding | ATP |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 4_83 | 1.0 | 554.0 | Domain | KRAB | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 103_125 | 1.0 | 554.0 | Zinc finger | C2H2-type 1 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 141_163 | 1.0 | 554.0 | Zinc finger | C2H2-type 2 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 169_191 | 1.0 | 554.0 | Zinc finger | C2H2-type 3 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 197_219 | 1.0 | 554.0 | Zinc finger | C2H2-type 4 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 225_247 | 1.0 | 554.0 | Zinc finger | C2H2-type 5 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 253_275 | 1.0 | 554.0 | Zinc finger | C2H2-type 6 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 281_303 | 1.0 | 554.0 | Zinc finger | C2H2-type 7 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 309_331 | 1.0 | 554.0 | Zinc finger | C2H2-type 8 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 337_359 | 1.0 | 554.0 | Zinc finger | C2H2-type 9 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 365_387 | 1.0 | 554.0 | Zinc finger | C2H2-type 10 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 393_415 | 1.0 | 554.0 | Zinc finger | C2H2-type 11 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 421_443 | 1.0 | 554.0 | Zinc finger | C2H2-type 12 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 449_471 | 1.0 | 554.0 | Zinc finger | C2H2-type 13 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 477_499 | 1.0 | 554.0 | Zinc finger | C2H2-type 14 | |
| Tgene | ZNF564 | chr19:42744107 | chr19:12639510 | ENST00000339282 | 0 | 4 | 505_527 | 1.0 | 554.0 | Zinc finger | C2H2-type 15 |
| - 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 |
| Hgene | GSK3A | chr19:42744107 | chr19:12639510 | ENST00000222330 | - | 2 | 11 | 119_403 | 157.0 | 484.0 | Domain | Protein kinase |
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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 |
| GSK3A | |
| ZNF564 |
| - 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 GSK3A-ZNF564 |
| 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 GSK3A-ZNF564 |
| 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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