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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:DHX34-ARHGAP35

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DHX34-ARHGAP35
FusionPDB ID: 22665
FusionGDB2.0 ID: 22665
HgeneTgene
Gene symbol

DHX34

ARHGAP35

Gene ID

9704

2909

Gene nameDExH-box helicase 34Rho GTPase activating protein 35
SynonymsDDX34|HRH1GRF-1|GRLF1|P190-A|P190A|p190ARhoGAP|p190RhoGAP
Cytomap

19q13.32

19q13.32

Type of geneprotein-codingprotein-coding
Descriptionprobable ATP-dependent RNA helicase DHX34DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 34DEAH (Asp-Glu-Ala-His) box polypeptide 34DEAH box protein 34DEAH-box helicase 34probable ATP-dependent helicase DHX34rho GTPase-activating protein 35glucocorticoid receptor DNA-binding factor 1glucocorticoid receptor repression factor 1rho GAP p190A
Modification date2020032220200313
UniProtAcc

Q14147

Main function of 5'-partner protein: FUNCTION: Probable ATP-binding RNA helicase.

Q9NRY4

Main function of 5'-partner protein: FUNCTION: Rho GTPase-activating protein (GAP) (PubMed:19673492, PubMed:28894085). Binds several acidic phospholipids which inhibits the Rho GAP activity to promote the Rac GAP activity (PubMed:19673492). This binding is inhibited by phosphorylation by PRKCA (PubMed:19673492). Involved in cell differentiation as well as cell adhesion and migration, plays an important role in retinal tissue morphogenesis, neural tube fusion, midline fusion of the cerebral hemispheres and mammary gland branching morphogenesis (By similarity). Transduces signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP) (By similarity). Transduces SRC-dependent signals from cell-surface adhesion molecules, such as laminin, to promote neurite outgrowth. Regulates axon outgrowth, guidance and fasciculation (By similarity). Modulates Rho GTPase-dependent F-actin polymerization, organization and assembly, is involved in polarized cell migration and in the positive regulation of ciliogenesis and cilia elongation (By similarity). During mammary gland development, is required in both the epithelial and stromal compartments for ductal outgrowth (By similarity). Represses transcription of the glucocorticoid receptor by binding to the cis-acting regulatory sequence 5'-GAGAAAAGAAACTGGAGAAACTC-3'; this function is however unclear and would need additional experimental evidences (PubMed:1894621). {ECO:0000250|UniProtKB:P81128, ECO:0000250|UniProtKB:Q91YM2, ECO:0000269|PubMed:1894621, ECO:0000269|PubMed:19673492, ECO:0000269|PubMed:28894085}.
Ensembl transtripts involved in fusion geneENST idsENST00000471451, ENST00000328771, 
ENST00000404338, ENST00000598548, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 5 X 4=10014 X 8 X 8=896
# samples 514
** MAII scorelog2(5/100*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(14/896*10)=-2.67807190511264
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DHX34 [Title/Abstract] AND ARHGAP35 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DHX34 [Title/Abstract] AND ARHGAP35 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DHX34(47863327)-ARHGAP35(47491246), # samples:1
Anticipated loss of major functional domain due to fusion event.DHX34-ARHGAP35 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.
DHX34-ARHGAP35 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.
DHX34-ARHGAP35 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.
DHX34-ARHGAP35 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)

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


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/chr19:47863327/chr19:47491246)
- 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 DHX34 (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 ARHGAP35 (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)
ENST00000328771DHX34chr1947863327+ENST00000404338ARHGAP35chr1947491246+678717243222397691

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
ENST00000328771ENST00000404338DHX34chr1947863327+ARHGAP35chr1947491246+0.0019228410.99807715

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 DHX34-ARHGAP35

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DHX34chr1947863327ARHGAP35chr19474912461724466TSVTIDGIRFVVDSGLSTEGIYRVSG

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Potential FusionNeoAntigen Information of DHX34-ARHGAP35 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.
DHX34-ARHGAP35_47863327_47491246.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)
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-B27:04IRFVVDSGL0.99920.6821716
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-B27:05IRFVVDSGL0.99860.7777716
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-B27:04GIRFVVDSGL0.96870.6895616
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-B27:07GIRFVVDSGL0.930.5325616
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-B27:14IRFVVDSGL0.9990.7497716
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-B27:03IRFVVDSGL0.96270.8132716
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-B27:06IRFVVDSGL0.99930.6269716
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-B27:10IRFVVDSGL0.99910.8201716
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-B27:08IRFVVDSGL0.99880.602716
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-B27:09IRFVVDSGL0.99870.7229716
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-C06:08IRFVVDSGL0.88850.9822716
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-C06:17IRFVVDSGL0.08460.9898716
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-C06:02IRFVVDSGL0.08460.9898716
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-B27:08GIRFVVDSGL0.97120.5786616
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-B27:06GIRFVVDSGL0.93820.6262616
DHX34-ARHGAP35chr1947863327chr19474912461724HLA-B27:09GIRFVVDSGL0.92120.6438616

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Potential FusionNeoAntigen Information of DHX34-ARHGAP35 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.
DHX34-ARHGAP35_47863327_47491246.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)
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-0305DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-0305GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-0338DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-0338GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-0340DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-0340GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-0434DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-0434GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-0466DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-0466GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-0472DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-0472GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-1410IDGIRFVVDSGLSTE419
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-1410TIDGIRFVVDSGLST318
DHX34-ARHGAP35chr1947863327chr19474912461724DRB1-1615IDGIRFVVDSGLSTE419
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0101DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0101GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0101IDGIRFVVDSGLSTE419
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0104DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0104GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0104IDGIRFVVDSGLSTE419
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0105DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0105GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0105IDGIRFVVDSGLSTE419
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0108DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0108GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0108IDGIRFVVDSGLSTE419
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0109DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0109GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0109IDGIRFVVDSGLSTE419
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0111DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0111GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0111IDGIRFVVDSGLSTE419
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0112DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0112GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0112IDGIRFVVDSGLSTE419
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0113DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0113GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0113IDGIRFVVDSGLSTE419
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0114DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0114GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0114IDGIRFVVDSGLSTE419
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0205DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0205GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0209DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0212DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0213DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0213GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0219DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0219GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0221DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0222DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0222GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0303DGIRFVVDSGLSTEG520
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0303GIRFVVDSGLSTEGI621
DHX34-ARHGAP35chr1947863327chr19474912461724DRB3-0303IDGIRFVVDSGLSTE419

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Fusion breakpoint peptide structures of DHX34-ARHGAP35

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
2879GIRFVVDSGLSTEGDHX34ARHGAP35chr1947863327chr19474912461724

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DHX34-ARHGAP35

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-B14:023BVN2879GIRFVVDSGLSTEG-7.9962-8.1096
HLA-B14:023BVN2879GIRFVVDSGLSTEG-5.70842-6.74372
HLA-B52:013W392879GIRFVVDSGLSTEG-6.83737-6.95077
HLA-B52:013W392879GIRFVVDSGLSTEG-4.4836-5.5189
HLA-A11:014UQ22879GIRFVVDSGLSTEG-10.0067-10.1201
HLA-A11:014UQ22879GIRFVVDSGLSTEG-9.03915-10.0745
HLA-A24:025HGA2879GIRFVVDSGLSTEG-6.56204-6.67544
HLA-A24:025HGA2879GIRFVVDSGLSTEG-5.42271-6.45801
HLA-B44:053DX82879GIRFVVDSGLSTEG-7.85648-8.89178
HLA-B44:053DX82879GIRFVVDSGLSTEG-5.3978-5.5112
HLA-A02:016TDR2879GIRFVVDSGLSTEG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of DHX34-ARHGAP35

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
DHX34-ARHGAP35chr1947863327chr1947491246616GIRFVVDSGLTCCGCTTCGTAGTAGATTCCGGACTGAGCA
DHX34-ARHGAP35chr1947863327chr1947491246716IRFVVDSGLGCTTCGTAGTAGATTCCGGACTGAGCA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
DHX34-ARHGAP35chr1947863327chr1947491246318TIDGIRFVVDSGLSTTTGACGGGATCCGCTTCGTAGTAGATTCCGGACTGAGCACGGAAG
DHX34-ARHGAP35chr1947863327chr1947491246419IDGIRFVVDSGLSTEACGGGATCCGCTTCGTAGTAGATTCCGGACTGAGCACGGAAGGCA
DHX34-ARHGAP35chr1947863327chr1947491246520DGIRFVVDSGLSTEGGGATCCGCTTCGTAGTAGATTCCGGACTGAGCACGGAAGGCATCT
DHX34-ARHGAP35chr1947863327chr1947491246621GIRFVVDSGLSTEGITCCGCTTCGTAGTAGATTCCGGACTGAGCACGGAAGGCATCTACC

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Information of the samples that have these potential fusion neoantigens of DHX34-ARHGAP35

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
LUSCDHX34-ARHGAP35chr1947863327ENST00000328771chr1947491246ENST00000404338TCGA-39-5034-01A

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Potential target of CAR-T therapy development for DHX34-ARHGAP35

check button Predicted 3D structure. We used RoseTTAFold.

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

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

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Related Drugs to DHX34-ARHGAP35

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 DHX34-ARHGAP35

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