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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:SKIV2L2-F2R

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SKIV2L2-F2R
FusionPDB ID: 82108
FusionGDB2.0 ID: 82108
HgeneTgene
Gene symbol

SKIV2L2

F2R

Gene ID

23517

2149

Gene nameMtr4 exosome RNA helicasecoagulation factor II thrombin receptor
SynonymsDob1|KIAA0052|Mtr4|SKIV2L2|fSAP118CF2R|HTR|PAR-1|PAR1|TR
Cytomap

5q11.2

5q13.3

Type of geneprotein-codingprotein-coding
Descriptionexosome RNA helicase MTR4ATP-dependent RNA helicase DOB1ATP-dependent RNA helicase SKIV2L2ATP-dependent helicase SKIV2L2Ski2 like RNA helicase 2TRAMP-like complex helicasefunctional spliceosome-associated protein 118superkiller viralicidic activityproteinase-activated receptor 1protease-activated receptor 1
Modification date2020031320200313
UniProtAcc.

P55085

Main function of 5'-partner protein: FUNCTION: Receptor for trypsin and trypsin-like enzymes coupled to G proteins (PubMed:28445455). Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho (PubMed:28445455). Can also be transactivated by cleaved F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can signal synergistically with TLR4 and probably TLR2 in inflammatory responses and modulates TLR3 signaling. Has a protective role in establishing the endothelial barrier; the activity involves coagulation factor X. Regulates endothelial cell barrier integrity during neutrophil extravasation, probably following proteolytic cleavage by PRTN3 (PubMed:23202369). Proposed to have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by interrupting E-cadherin adhesion (PubMed:10086357). Involved in the regulation of vascular tone; activation results in hypotension presumably mediated by vasodilation. Associates with a subset of G proteins alpha subunits such as GNAQ, GNA11, GNA14, GNA12 and GNA13, but probably not with G(o) alpha, G(i) subunit alpha-1 and G(i) subunit alpha-2. However, according to PubMed:21627585 can signal through G(i) subunit alpha. Believed to be a class B receptor which internalizes as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptor, for extended periods of time. Mediates inhibition of TNF-alpha stimulated JNK phosphorylation via coupling to GNAQ and GNA11; the function involves dissociation of RIPK1 and TRADD from TNFR1. Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at 'Ser-536'; the function involves IKBKB and is predominantly independent of G proteins. Involved in cellular migration. Involved in cytoskeletal rearrangement and chemotaxis through beta-arrestin-promoted scaffolds; the function is independent of GNAQ and GNA11 and involves promotion of cofilin dephosphorylation and actin filament severing. Induces redistribution of COPS5 from the plasma membrane to the cytosol and activation of the JNK cascade is mediated by COPS5. Involved in the recruitment of leukocytes to the sites of inflammation and is the major PAR receptor capable of modulating eosinophil function such as proinflammatory cytokine secretion, superoxide production and degranulation. During inflammation promotes dendritic cell maturation, trafficking to the lymph nodes and subsequent T-cell activation. Involved in antimicrobial response of innate immune cells; activation enhances phagocytosis of Gram-positive and killing of Gram-negative bacteria. Acts synergistically with interferon-gamma in enhancing antiviral responses. Implicated in a number of acute and chronic inflammatory diseases such as of the joints, lungs, brain, gastrointestinal tract, periodontium, skin, and vascular systems, and in autoimmune disorders. {ECO:0000269|PubMed:10086357, ECO:0000269|PubMed:10725339, ECO:0000269|PubMed:11413129, ECO:0000269|PubMed:11441110, ECO:0000269|PubMed:11447194, ECO:0000269|PubMed:11714832, ECO:0000269|PubMed:12832443, ECO:0000269|PubMed:15155775, ECO:0000269|PubMed:16359518, ECO:0000269|PubMed:16410250, ECO:0000269|PubMed:16478888, ECO:0000269|PubMed:16714334, ECO:0000269|PubMed:17404307, ECO:0000269|PubMed:17500066, ECO:0000269|PubMed:18424071, ECO:0000269|PubMed:18453611, ECO:0000269|PubMed:18474671, ECO:0000269|PubMed:18622013, ECO:0000269|PubMed:19494303, ECO:0000269|PubMed:19781631, ECO:0000269|PubMed:19864598, ECO:0000269|PubMed:19865078, ECO:0000269|PubMed:20826780, ECO:0000269|PubMed:21501162, ECO:0000269|PubMed:23202369, ECO:0000269|PubMed:28445455}.
Ensembl transtripts involved in fusion geneENST idsENST00000504388, ENST00000230640, 
ENST00000545714, 
ENST00000319211, 
ENST00000505600, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score34 X 12 X 8=32643 X 3 X 2=18
# samples 153
** MAII scorelog2(15/3264*10)=-4.44360665147561
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: SKIV2L2 [Title/Abstract] AND F2R [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SKIV2L2 [Title/Abstract] AND F2R [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SKIV2L2(54603975)-F2R(76028139), # samples:1
Anticipated loss of major functional domain due to fusion event.SKIV2L2-F2R 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.
SKIV2L2-F2R 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.
SKIV2L2-F2R 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.
SKIV2L2-F2R 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.
SKIV2L2-F2R seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
SKIV2L2-F2R 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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneSKIV2L2

GO:0006401

RNA catabolic process

29906447

TgeneF2R

GO:0002248

connective tissue replacement involved in inflammatory response wound healing

9639571

TgeneF2R

GO:0006919

activation of cysteine-type endopeptidase activity involved in apoptotic process

10692450

TgeneF2R

GO:0007200

phospholipase C-activating G protein-coupled receptor signaling pathway

20164183

TgeneF2R

GO:0008285

negative regulation of cell proliferation

10692450

TgeneF2R

GO:0009611

response to wounding

9639571

TgeneF2R

GO:0030168

platelet activation

9038223

TgeneF2R

GO:0030193

regulation of blood coagulation

17848177

TgeneF2R

GO:0030194

positive regulation of blood coagulation

9038223

TgeneF2R

GO:0032967

positive regulation of collagen biosynthetic process

9639571

TgeneF2R

GO:0043280

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

10692450

TgeneF2R

GO:0043410

positive regulation of MAPK cascade

17848177

TgeneF2R

GO:0045893

positive regulation of transcription, DNA-templated

17848177

TgeneF2R

GO:0051281

positive regulation of release of sequestered calcium ion into cytosol

1672265

TgeneF2R

GO:2000484

positive regulation of interleukin-8 secretion

17404307

TgeneF2R

GO:2000778

positive regulation of interleukin-6 secretion

11447194



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/chr5:54603975/chr5:76028139)
- 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 buttonRetention 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.

check buttonFusion gene breakpoints across SKIV2L2 (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 F2R (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000230640SKIV2L2chr554603975-ENST00000319211F2Rchr576028139+38563882731577434

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
ENST00000230640ENST00000319211SKIV2L2chr554603975-F2Rchr576028139+0.001668970.998331

check button 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 SKIV2L2-F2R

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SKIV2L2chr554603975F2Rchr57602813938838GNGRGLQGLQTRQESKATNATLDPRS

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Potential FusionNeoAntigen Information of SKIV2L2-F2R in HLA I

check button 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.
SKIV2L2-F2R_54603975_76028139.msa
SKIV2L2-IGF2R_54603975_160412216.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
SKIV2L2-F2Rchr554603975chr576028139388HLA-B45:01QESKATNA0.99860.91551220
SKIV2L2-F2Rchr554603975chr576028139388HLA-B45:01QESKATNAT0.89170.95171221
SKIV2L2-F2Rchr554603975chr576028139388HLA-B50:02QESKATNAT0.83980.79131221
SKIV2L2-F2Rchr554603975chr576028139388HLA-B41:01QESKATNAT0.3060.90511221
SKIV2L2-F2Rchr554603975chr576028139388HLA-B50:01QESKATNAT0.16380.87611221
SKIV2L2-F2Rchr554603975chr576028139388HLA-B39:13QESKATNATL0.89710.96731222
SKIV2L2-F2Rchr554603975chr576028139388HLA-B48:01RQESKATNATL0.99870.58951122
SKIV2L2-F2Rchr554603975chr576028139388HLA-B44:09QESKATNATL0.97630.54241222
SKIV2L2-F2Rchr554603975chr576028139388HLA-B44:10QESKATNATL0.96650.59351222
SKIV2L2-F2Rchr554603975chr576028139388HLA-B73:01TRQESKATNA0.96470.74191020
SKIV2L2-F2Rchr554603975chr576028139388HLA-B39:08QESKATNATL0.95060.89691222
SKIV2L2-F2Rchr554603975chr576028139388HLA-B48:03RQESKATNATL0.98730.51891122
SKIV2L2-F2Rchr554603975chr576028139388HLA-B39:08RQESKATNATL0.96880.7611122
SKIV2L2-F2Rchr554603975chr576028139388HLA-B50:05QESKATNAT0.16380.87611221
SKIV2L2-F2Rchr554603975chr576028139388HLA-B50:04QESKATNAT0.16380.87611221
SKIV2L2-F2Rchr554603975chr576028139388HLA-B40:04QESKATNATL0.9930.78871222
SKIV2L2-F2Rchr554603975chr576028139388HLA-B40:36QESKATNATL0.99030.51411222
SKIV2L2-F2Rchr554603975chr576028139388HLA-B40:49QESKATNATL0.98220.52121222
SKIV2L2-F2Rchr554603975chr576028139388HLA-B41:03QESKATNATL0.81690.63021222
SKIV2L2-F2Rchr554603975chr576028139388HLA-B15:73RQESKATNATL0.99280.89441122
SKIV2L2-F2Rchr554603975chr576028139388HLA-B15:30RQESKATNATL0.99010.86491122
SKIV2L2-F2Rchr554603975chr576028139388HLA-B40:12RQESKATNATL0.98730.51891122
SKIV2L2-F2Rchr554603975chr576028139388HLA-B40:21RQESKATNATL0.94530.6541122

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Potential FusionNeoAntigen Information of SKIV2L2-F2R in HLA II

check button 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.
SKIV2L2-F2R_54603975_76028139.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)
SKIV2L2-F2Rchr554603975chr576028139388DRB1-0411GRGLQGLQTRQESKA217
SKIV2L2-F2Rchr554603975chr576028139388DRB1-0415GRGLQGLQTRQESKA217
SKIV2L2-F2Rchr554603975chr576028139388DRB1-0436GRGLQGLQTRQESKA217
SKIV2L2-F2Rchr554603975chr576028139388DRB1-0437GRGLQGLQTRQESKA217
SKIV2L2-F2Rchr554603975chr576028139388DRB1-0453GRGLQGLQTRQESKA217
SKIV2L2-F2Rchr554603975chr576028139388DRB1-0458GRGLQGLQTRQESKA217
SKIV2L2-F2Rchr554603975chr576028139388DRB1-0467GRGLQGLQTRQESKA217
SKIV2L2-F2Rchr554603975chr576028139388DRB1-0491GRGLQGLQTRQESKA217
SKIV2L2-F2Rchr554603975chr576028139388DRB1-1457GRGLQGLQTRQESKA217
SKIV2L2-F2Rchr554603975chr576028139388DRB1-1457NGRGLQGLQTRQESK116

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Fusion breakpoint peptide structures of SKIV2L2-F2R

check button3D 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 nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
7280QGLQTRQESKATNASKIV2L2F2Rchr554603975chr576028139388

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SKIV2L2-F2R

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN7280QGLQTRQESKATNA-7.9962-8.1096
HLA-B14:023BVN7280QGLQTRQESKATNA-5.70842-6.74372
HLA-B52:013W397280QGLQTRQESKATNA-6.83737-6.95077
HLA-B52:013W397280QGLQTRQESKATNA-4.4836-5.5189
HLA-A11:014UQ27280QGLQTRQESKATNA-10.0067-10.1201
HLA-A11:014UQ27280QGLQTRQESKATNA-9.03915-10.0745
HLA-A24:025HGA7280QGLQTRQESKATNA-6.56204-6.67544
HLA-A24:025HGA7280QGLQTRQESKATNA-5.42271-6.45801
HLA-B44:053DX87280QGLQTRQESKATNA-7.85648-8.89178
HLA-B44:053DX87280QGLQTRQESKATNA-5.3978-5.5112
HLA-A02:016TDR7280QGLQTRQESKATNA-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of SKIV2L2-F2R

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
SKIV2L2-F2Rchr554603975chr5760281391020TRQESKATNACAAGGCAGGAATCAAAAGCAACAAATGCCA
SKIV2L2-F2Rchr554603975chr5760281391122RQESKATNATLGGCAGGAATCAAAAGCAACAAATGCCACCTTAG
SKIV2L2-F2Rchr554603975chr5760281391220QESKATNAAGGAATCAAAAGCAACAAATGCCA
SKIV2L2-F2Rchr554603975chr5760281391221QESKATNATAGGAATCAAAAGCAACAAATGCCACCT
SKIV2L2-F2Rchr554603975chr5760281391222QESKATNATLAGGAATCAAAAGCAACAAATGCCACCTTAG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
SKIV2L2-F2Rchr554603975chr576028139116NGRGLQGLQTRQESKATGGAAGGGGCCTCCAGGGTCTGCAGACAAGGCAGGAATCAAAAG
SKIV2L2-F2Rchr554603975chr576028139217GRGLQGLQTRQESKAGAAGGGGCCTCCAGGGTCTGCAGACAAGGCAGGAATCAAAAGCAA

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Information of the samples that have these potential fusion neoantigens of SKIV2L2-F2R

check button 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 typeFusion geneHchrHbpHenstTchrTbpTenstSample
PRADSKIV2L2-F2Rchr554603975ENST00000230640chr576028139ENST00000319211TCGA-J4-A83I-01A

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Potential target of CAR-T therapy development for SKIV2L2-F2R

check button Predicted 3D structure. We used RoseTTAFold.
413_SKIV2L2-F2R_1198b_pred.pdb


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, 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'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
TgeneF2Rchr5:54603975chr5:76028139ENST0000031921102103_1280426.0TransmembraneHelical%3B Name%3D1
TgeneF2Rchr5:54603975chr5:76028139ENST0000031921102138_1570426.0TransmembraneHelical%3B Name%3D2
TgeneF2Rchr5:54603975chr5:76028139ENST0000031921102177_1980426.0TransmembraneHelical%3B Name%3D3
TgeneF2Rchr5:54603975chr5:76028139ENST0000031921102219_2390426.0TransmembraneHelical%3B Name%3D4
TgeneF2Rchr5:54603975chr5:76028139ENST0000031921102269_2880426.0TransmembraneHelical%3B Name%3D5
TgeneF2Rchr5:54603975chr5:76028139ENST0000031921102312_3340426.0TransmembraneHelical%3B Name%3D6
TgeneF2Rchr5:54603975chr5:76028139ENST0000031921102351_3740426.0TransmembraneHelical%3B Name%3D7

check button 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.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result
SKIV2L2chr554603975ENST00000230640F2Rchr576028139ENST00000319211

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Related Drugs to SKIV2L2-F2R

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to SKIV2L2-F2R

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

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