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Fusion Protein:RASGRF1-HCN4 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: RASGRF1-HCN4 | FusionPDB ID: 72452 | FusionGDB2.0 ID: 72452 | Hgene | Tgene | Gene symbol | RASGRF1 | HCN4 | Gene ID | 5923 | 10021 |
| Gene name | Ras protein specific guanine nucleotide releasing factor 1 | hyperpolarization activated cyclic nucleotide gated potassium channel 4 | |
| Synonyms | CDC25|CDC25L|GNRP|GRF1|GRF55|H-GRF55|PP13187|ras-GRF1 | SSS2 | |
| Cytomap | 15q25.1 | 15q24.1 | |
| Type of gene | protein-coding | protein-coding | |
| Description | ras-specific guanine nucleotide-releasing factor 1Ras-specific guanine nucleotide-releasing factor, CDC25 homologRas-specific nucleotide exchange factor CDC25guanine nucleotide exchange factorguanine nucleotide-releasing factor 1guanine nucleotide-re | potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4hyperpolarization activated cyclic nucleotide-gated cation channel 4 | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | . | . | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000419573, ENST00000558480, ENST00000394745, ENST00000560334, | ENST00000261917, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 15 X 9 X 3=405 | 1 X 1 X 1=1 |
| # samples | 15 | 1 | |
| ** MAII score | log2(15/405*10)=-1.43295940727611 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(1/1*10)=3.32192809488736 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: RASGRF1 [Title/Abstract] AND HCN4 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | RASGRF1(79264208)-HCN4(73636149), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | RASGRF1-HCN4 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. RASGRF1-HCN4 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. RASGRF1-HCN4 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. RASGRF1-HCN4 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. RASGRF1-HCN4 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. RASGRF1-HCN4 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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 | HCN4 | GO:0003254 | regulation of membrane depolarization | 12750403 |
| Tgene | HCN4 | GO:0006812 | cation transport | 12750403 |
| Tgene | HCN4 | GO:0071320 | cellular response to cAMP | 12750403|16407510|22748890 |
| Tgene | HCN4 | GO:0071321 | cellular response to cGMP | 22748890 |
| Tgene | HCN4 | GO:0071805 | potassium ion transmembrane transport | 16407510 |
| Tgene | HCN4 | GO:0098719 | sodium ion import across plasma membrane | 10228147 |
| Tgene | HCN4 | GO:1990573 | potassium ion import across plasma membrane | 10228147 |
| Fusion gene breakpoints across RASGRF1 (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 HCN4 (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 | SARC | TCGA-FX-A3TO-01A | RASGRF1 | chr15 | 79264208 | - | HCN4 | chr15 | 73636149 | - |
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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) |
| ENST00000394745 | RASGRF1 | chr15 | 79264208 | - | ENST00000261917 | HCN4 | chr15 | 73636149 | - | 8004 | 2555 | 2568 | 5381 | 937 |
| 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 |
| ENST00000394745 | ENST00000261917 | RASGRF1 | chr15 | 79264208 | - | HCN4 | chr15 | 73636149 | - | 0.028073339 | 0.9719267 |
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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 >72452_72452_1_RASGRF1-HCN4_RASGRF1_chr15_79264208_ENST00000394745_HCN4_chr15_73636149_ENST00000261917_length(amino acids)=937AA_BP= MTMLLLMVGNLIIIPVGITFFKDENTTPWIVFNVVSDTFFLIDLVLNFRTGIVVEDNTEIILDPQRIKMKYLKSWFMVDFISSIPVDYIF LIVETRIDSEVYKTARALRIVRFTKILSLLRLLRLSRLIRYIHQWEEIFHMTYDLASAVVRIVNLIGMMLLLCHWDGCLQFLVPMLQDFP DDCWVSINNMVNNSWGKQYSYALFKAMSHMLCIGYGRQAPVGMSDVWLTMLSMIVGATCYAMFIGHATALIQSLDSSRRQYQEKYKQVEQ YMSFHKLPPDTRQRIHDYYEHRYQGKMFDEESILGELSEPLREEIINFNCRKLVASMPLFANADPNFVTSMLTKLRFEVFQPGDYIIREG TIGKKMYFIQHGVVSVLTKGNKETKLADGSYFGEICLLTRGRRTASVRADTYCRLYSLSVDNFNEVLEEYPMMRRAFETVALDRLDRIGK KNSILLHKVQHDLNSGVFNYQENEIIQQIVQHDREMAHCAHRVQAAASATPTPTPVIWTPLIQAPLQAAAATTSVAIALTHHPRLPAAIF RPPPGSGLGNLGAGQTPRHLKRLQSLIPSALGSASPASSPSQVDTPSSSSFHIQQLAGFSAPAGLSPLLPSSSSSPPPGACGSPSAPTPS AGVAATTIAGFGHFHKALGGSLSSSDSPLLTPLQPGARSPQAAQPSPAPPGARGGLGLPEHFLPPPPSSRSPSSSPGQLGQPPGELSLGL ATGPLSTPETPPRQPEPPSLVAGASGGASPVGFTPRGGLSPPGHSPGPPRTFPSAPPRASGSHGSLLLPPASSPPPPQVPQRRGTPPLTP GRLTQDLKLISASQPALPQDGAQTLRRASPHSSGESMAAFPLFPRAGGGSGGSGSSGGLGPPGRPYGAIPGQHVTLPRKTSSGSLPPPLS -------------------------------------------------------------- |
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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/chr15:79264208/chr15:73636149) - 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 |
| . | . |
| 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. | 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 | RASGRF1 | chr15:79264208 | chr15:73636149 | ENST00000394745 | - | 13 | 14 | 204_229 | 459.0 | 490.0 | Domain | IQ |
| Hgene | RASGRF1 | chr15:79264208 | chr15:73636149 | ENST00000394745 | - | 13 | 14 | 22_129 | 459.0 | 490.0 | Domain | PH 1 |
| Hgene | RASGRF1 | chr15:79264208 | chr15:73636149 | ENST00000394745 | - | 13 | 14 | 240_426 | 459.0 | 490.0 | Domain | DH |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 924_1076 | 261.6666666666667 | 1204.0 | Compositional bias | Note=Pro-rich | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 465_486 | 261.6666666666667 | 1204.0 | Intramembrane | Pore-forming%3B Name%3DSegment H5 | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 659_662 | 261.6666666666667 | 1204.0 | Nucleotide binding | cAMP | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 669_670 | 261.6666666666667 | 1204.0 | Nucleotide binding | cAMP | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 710_713 | 261.6666666666667 | 1204.0 | Nucleotide binding | cAMP | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 288_293 | 261.6666666666667 | 1204.0 | Topological domain | Extracellular | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 315_340 | 261.6666666666667 | 1204.0 | Topological domain | Cytoplasmic | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 362_368 | 261.6666666666667 | 1204.0 | Topological domain | Extracellular | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 390_420 | 261.6666666666667 | 1204.0 | Topological domain | Cytoplasmic | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 442_464 | 261.6666666666667 | 1204.0 | Topological domain | Extracellular | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 487_496 | 261.6666666666667 | 1204.0 | Topological domain | Extracellular | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 518_1203 | 261.6666666666667 | 1204.0 | Topological domain | Cytoplasmic | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 267_287 | 261.6666666666667 | 1204.0 | Transmembrane | Helical%3B Name%3DSegment S1 | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 294_314 | 261.6666666666667 | 1204.0 | Transmembrane | Helical%3B Name%3DSegment S2 | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 341_361 | 261.6666666666667 | 1204.0 | Transmembrane | Helical%3B Name%3DSegment S3 | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 369_389 | 261.6666666666667 | 1204.0 | Transmembrane | Helical%3B Voltage-sensor%3B Name%3DSegment S4 | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 421_441 | 261.6666666666667 | 1204.0 | Transmembrane | Helical%3B Name%3DSegment S5 | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 497_517 | 261.6666666666667 | 1204.0 | Transmembrane | Helical%3B Name%3DSegment S6 |
| - 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 | RASGRF1 | chr15:79264208 | chr15:73636149 | ENST00000394745 | - | 13 | 14 | 1038_1270 | 459.0 | 490.0 | Domain | Ras-GEF |
| Hgene | RASGRF1 | chr15:79264208 | chr15:73636149 | ENST00000394745 | - | 13 | 14 | 467_584 | 459.0 | 490.0 | Domain | PH 2 |
| Hgene | RASGRF1 | chr15:79264208 | chr15:73636149 | ENST00000394745 | - | 13 | 14 | 644_761 | 459.0 | 490.0 | Domain | N-terminal Ras-GEF |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 209_260 | 261.6666666666667 | 1204.0 | Region | Involved in subunit assembly | |
| Tgene | HCN4 | chr15:79264208 | chr15:73636149 | ENST00000261917 | 0 | 8 | 1_266 | 261.6666666666667 | 1204.0 | Topological domain | Cytoplasmic |
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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 |
| RASGRF1 | |
| HCN4 |
| - 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 RASGRF1-HCN4 |
| 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 RASGRF1-HCN4 |
| 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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