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Fusion Protein:HSP90AA1-ZC3H8 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: HSP90AA1-ZC3H8 | FusionPDB ID: 37781 | FusionGDB2.0 ID: 37781 | Hgene | Tgene | Gene symbol | HSP90AA1 | ZC3H8 | Gene ID | 3320 | 84524 |
| Gene name | heat shock protein 90 alpha family class A member 1 | zinc finger CCCH-type containing 8 | |
| Synonyms | EL52|HEL-S-65p|HSP86|HSP89A|HSP90A|HSP90N|HSPC1|HSPCA|HSPCAL1|HSPCAL4|HSPN|Hsp103|Hsp89|Hsp90|LAP-2|LAP2 | Fliz1|ZC3HDC8 | |
| Cytomap | 14q32.31 | 2q14.1 | |
| Type of gene | protein-coding | protein-coding | |
| Description | heat shock protein HSP 90-alphaHSP 86LPS-associated protein 2epididymis luminal secretory protein 52epididymis secretory sperm binding protein Li 65pheat shock 86 kDaheat shock 90kD protein 1, alphaheat shock 90kD protein 1, alpha-like 4heat shock | zinc finger CCCH domain-containing protein 8zinc finger CCCH-type domain containing 8 | |
| Modification date | 20200327 | 20200313 | |
| UniProtAcc | P07900 Main function of 5'-partner protein: FUNCTION: Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155, PubMed:12526792). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:27295069, PubMed:26991466). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues(PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochodria outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}. | . | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000216281, ENST00000334701, ENST00000441629, ENST00000558600, | ENST00000476902, ENST00000272570, ENST00000409573, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 38 X 40 X 8=12160 | 2 X 2 X 2=8 |
| # samples | 43 | 2 | |
| ** MAII score | log2(43/12160*10)=-4.82166275874149 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(2/8*10)=1.32192809488736 | |
| Fusion gene context | PubMed: HSP90AA1 [Title/Abstract] AND ZC3H8 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: HSP90AA1 [Title/Abstract] AND ZC3H8 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | HSP90AA1(102549371)-ZC3H8(112990948), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | HSP90AA1-ZC3H8 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. HSP90AA1-ZC3H8 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. HSP90AA1-ZC3H8 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. HSP90AA1-ZC3H8 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. HSP90AA1-ZC3H8 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF. HSP90AA1-ZC3H8 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. HSP90AA1-ZC3H8 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. HSP90AA1-ZC3H8 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF. HSP90AA1-ZC3H8 seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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 |
| Hgene | HSP90AA1 | GO:0001934 | positive regulation of protein phosphorylation | 19363271 |
| Hgene | HSP90AA1 | GO:0007004 | telomere maintenance via telomerase | 10197982 |
| Hgene | HSP90AA1 | GO:0031396 | regulation of protein ubiquitination | 16809764 |
| Hgene | HSP90AA1 | GO:0032273 | positive regulation of protein polymerization | 19363271 |
| Hgene | HSP90AA1 | GO:0045040 | protein import into mitochondrial outer membrane | 15644312 |
| Hgene | HSP90AA1 | GO:0051131 | chaperone-mediated protein complex assembly | 15644312 |
| Hgene | HSP90AA1 | GO:0051973 | positive regulation of telomerase activity | 10197982 |
| Hgene | HSP90AA1 | GO:1902949 | positive regulation of tau-protein kinase activity | 19363271 |
| Hgene | HSP90AA1 | GO:1905323 | telomerase holoenzyme complex assembly | 10197982 |
| Tgene | ZC3H8 | GO:0045892 | negative regulation of transcription, DNA-templated | 12077251 |
| Tgene | ZC3H8 | GO:0046677 | response to antibiotic | 12153508 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr14:102549371/chr2:112990948) - 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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| Retention 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. |
| Fusion gene breakpoints across HSP90AA1 (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 ZC3H8 (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 Amino Acid Sequences |
| 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) |
| ENST00000334701 | HSP90AA1 | chr14 | 102549371 | - | ENST00000409573 | ZC3H8 | chr2 | 112990948 | - | 7617 | 2403 | 282 | 2657 | 791 |
| ENST00000334701 | HSP90AA1 | chr14 | 102549371 | - | ENST00000272570 | ZC3H8 | chr2 | 112990948 | - | 3277 | 2403 | 282 | 2657 | 791 |
| 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 |
| ENST00000334701 | ENST00000409573 | HSP90AA1 | chr14 | 102549371 | - | ZC3H8 | chr2 | 112990948 | - | 0.000425738 | 0.99957424 |
| ENST00000334701 | ENST00000272570 | HSP90AA1 | chr14 | 102549371 | - | ZC3H8 | chr2 | 112990948 | - | 0.00083122 | 0.99916875 |
| 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 HSP90AA1-ZC3H8 |
| +/-13 AA sequence from the breakpoints of the fusion protein sequences. |
| Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Length(fusion protein) | BP in fusion protein | Peptide |
| HSP90AA1 | chr14 | 102549371 | ZC3H8 | chr2 | 112990948 | 2403 | 707 | KIMKDILEKKVEKGDQCKFDHDAEIE |
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Potential FusionNeoAntigen Information of HSP90AA1-ZC3H8 in HLA I |
| 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. |
| HSP90AA1-ZC3H8_102549371_112990948.msa |
| Potential FusionNeoAntigen Information * We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5) |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA I | FusionNeoAntigen peptide | Binding score | Immunogenic score | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | HLA-B44:03 | VEKGDQCKF | 0.9719 | 0.8228 | 10 | 19 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | HLA-B18:01 | VEKGDQCKF | 0.8712 | 0.8347 | 10 | 19 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | HLA-B44:13 | VEKGDQCKF | 0.9719 | 0.8228 | 10 | 19 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | HLA-B44:26 | VEKGDQCKF | 0.9719 | 0.8228 | 10 | 19 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | HLA-B44:07 | VEKGDQCKF | 0.9719 | 0.8228 | 10 | 19 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | HLA-B18:05 | VEKGDQCKF | 0.8712 | 0.8347 | 10 | 19 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | HLA-B18:03 | VEKGDQCKF | 0.7989 | 0.8248 | 10 | 19 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | HLA-B18:11 | VEKGDQCKF | 0.6755 | 0.7854 | 10 | 19 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | HLA-B15:53 | VEKGDQCKF | 0.322 | 0.7443 | 10 | 19 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | HLA-B15:54 | VEKGDQCKF | 0.148 | 0.7076 | 10 | 19 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | HLA-B48:02 | VEKGDQCKF | 0.0528 | 0.851 | 10 | 19 |
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Potential FusionNeoAntigen Information of HSP90AA1-ZC3H8 in HLA II |
| 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. |
| HSP90AA1-ZC3H8_102549371_112990948.msa |
| Potential FusionNeoAntigen Information * We used NetMHCIIpan v4.1 (%rank<0.5). |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA II | FusionNeoAntigen peptide | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | DRB1-0437 | IMKDILEKKVEKGDQ | 1 | 16 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | DRB1-0804 | IMKDILEKKVEKGDQ | 1 | 16 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | DRB1-0804 | MKDILEKKVEKGDQC | 2 | 17 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | DRB1-0820 | IMKDILEKKVEKGDQ | 1 | 16 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | DRB1-0828 | IMKDILEKKVEKGDQ | 1 | 16 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | DRB1-1167 | IMKDILEKKVEKGDQ | 1 | 16 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | DRB1-1412 | IMKDILEKKVEKGDQ | 1 | 16 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | DRB1-1415 | IMKDILEKKVEKGDQ | 1 | 16 |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 | DRB1-1415 | MKDILEKKVEKGDQC | 2 | 17 |
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Fusion breakpoint peptide structures of HSP90AA1-ZC3H8 |
| 3D 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. |
| File name | BPseq | Hgene | Tgene | Hchr | Hbp | Tchr | Tbp | AAlen |
| 4898 | LEKKVEKGDQCKFD | HSP90AA1 | ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2403 |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of HSP90AA1-ZC3H8 |
| Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens * We used Glide to predict the interaction between HLAs and neoantigens. |
| HLA allele | PDB ID | File name | BPseq | Docking score | Glide score |
| HLA-B14:02 | 3BVN | 4898 | LEKKVEKGDQCKFD | -7.15543 | -7.26883 |
| HLA-B14:02 | 3BVN | 4898 | LEKKVEKGDQCKFD | -4.77435 | -5.80965 |
| HLA-B52:01 | 3W39 | 4898 | LEKKVEKGDQCKFD | -6.80875 | -6.92215 |
| HLA-B52:01 | 3W39 | 4898 | LEKKVEKGDQCKFD | -4.20386 | -5.23916 |
| HLA-A11:01 | 4UQ2 | 4898 | LEKKVEKGDQCKFD | -7.5194 | -8.5547 |
| HLA-A11:01 | 4UQ2 | 4898 | LEKKVEKGDQCKFD | -6.9601 | -7.0735 |
| HLA-A24:02 | 5HGA | 4898 | LEKKVEKGDQCKFD | -7.52403 | -7.63743 |
| HLA-A24:02 | 5HGA | 4898 | LEKKVEKGDQCKFD | -5.82433 | -6.85963 |
| HLA-B27:05 | 6PYJ | 4898 | LEKKVEKGDQCKFD | -3.28285 | -4.31815 |
| HLA-B44:05 | 3DX8 | 4898 | LEKKVEKGDQCKFD | -5.91172 | -6.94702 |
| HLA-B44:05 | 3DX8 | 4898 | LEKKVEKGDQCKFD | -4.24346 | -4.35686 |
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Vaccine Design for the FusionNeoAntigens of HSP90AA1-ZC3H8 |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide sequence | FusionNeoAntigen RNA sequence |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 10 | 19 | VEKGDQCKF | GTTGAAAAGGGAGACCAGTGTAAATTT |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide | FusionNEoAntigen RNA sequence |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 1 | 16 | IMKDILEKKVEKGDQ | ATCATGAAAGACATATTGGAGAAAAAAGTTGAAAAGGGAGACCAG |
| HSP90AA1-ZC3H8 | chr14 | 102549371 | chr2 | 112990948 | 2 | 17 | MKDILEKKVEKGDQC | ATGAAAGACATATTGGAGAAAAAAGTTGAAAAGGGAGACCAGTGT |
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Information of the samples that have these potential fusion neoantigens of HSP90AA1-ZC3H8 |
| 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 type | Fusion gene | Hchr | Hbp | Henst | Tchr | Tbp | Tenst | Sample |
| BRCA | HSP90AA1-ZC3H8 | chr14 | 102549371 | ENST00000334701 | chr2 | 112990948 | ENST00000272570 | TCGA-AQ-A04L-01B |
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Potential target of CAR-T therapy development for HSP90AA1-ZC3H8 |
| Predicted 3D structure. We used RoseTTAFold. |
| 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, 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'. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| 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. |
| Hgene | Hchr | Hbp | Henst | Tgene | Tchr | Tbp | Tenst | DeepLoc result |
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Related Drugs to HSP90AA1-ZC3H8 |
| 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 HSP90AA1-ZC3H8 |
| 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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