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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:ROCK1-LRIG3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ROCK1-LRIG3
FusionPDB ID: 75311
FusionGDB2.0 ID: 75311
HgeneTgene
Gene symbol

ROCK1

LRIG3

Gene ID

6093

121227

Gene nameRho associated coiled-coil containing protein kinase 1leucine rich repeats and immunoglobulin like domains 3
SynonymsP160ROCK|ROCK-ILIG3
Cytomap

18q11.1

12q14.1

Type of geneprotein-codingprotein-coding
Descriptionrho-associated protein kinase 1p160 ROCK-1renal carcinoma antigen NY-REN-35leucine-rich repeats and immunoglobulin-like domains protein 3LIG-3
Modification date2020032220200313
UniProtAcc.

Q6UXM1

Main function of 5'-partner protein: FUNCTION: May play a role in craniofacial and inner ear morphogenesis during embryonic development. May act within the otic vesicle epithelium to control formation of the lateral semicircular canal in the inner ear, possibly by restricting the expression of NTN1 (By similarity). {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000399799, ENST00000320743, 
ENST00000379141, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score24 X 16 X 12=46086 X 3 X 5=90
# samples 317
** MAII scorelog2(31/4608*10)=-3.89380059616807
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/90*10)=-0.362570079384708
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ROCK1 [Title/Abstract] AND LRIG3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ROCK1 [Title/Abstract] AND LRIG3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ROCK1(18625253)-LRIG3(59308117), # samples:3
Anticipated loss of major functional domain due to fusion event.ROCK1-LRIG3 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.
ROCK1-LRIG3 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.
ROCK1-LRIG3 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.
ROCK1-LRIG3 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
HgeneROCK1

GO:0006468

protein phosphorylation

23093407

HgeneROCK1

GO:0007159

leukocyte cell-cell adhesion

12082081

HgeneROCK1

GO:0018105

peptidyl-serine phosphorylation

18573880

HgeneROCK1

GO:0022614

membrane to membrane docking

12082081

HgeneROCK1

GO:0030334

regulation of cell migration

23093407

HgeneROCK1

GO:0032091

negative regulation of protein binding

18573880

HgeneROCK1

GO:0032956

regulation of actin cytoskeleton organization

25911094

HgeneROCK1

GO:0050900

leukocyte migration

12082081

HgeneROCK1

GO:0050901

leukocyte tethering or rolling

12082081

HgeneROCK1

GO:0070507

regulation of microtubule cytoskeleton organization

23093407



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/chr18:18625253/chr12:59308117)
- 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 ROCK1 (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 LRIG3 (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)
ENST00000399799ROCK1chr1818625253-ENST00000379141LRIG3chr1259308117-5078153189946541251
ENST00000399799ROCK1chr1818625253-ENST00000320743LRIG3chr1259308117-5078153189946541251

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
ENST00000399799ENST00000379141ROCK1chr1818625253-LRIG3chr1259308117-0.0008451320.9991549
ENST00000399799ENST00000320743ROCK1chr1818625253-LRIG3chr1259308117-0.0008451320.9991549

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 ROCK1-LRIG3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ROCK1chr1818625253LRIG3chr12593081171531210LALDAIHSMGFIHRDLSHNRLSFIKA

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Potential FusionNeoAntigen Information of ROCK1-LRIG3 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.
ROCK1-LRIG3_18625253_59308117.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)
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B39:01HRDLSHNRL0.99640.53971221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B38:01HRDLSHNRL0.99260.62381221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B38:02HRDLSHNRL0.99150.63931221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B39:13HRDLSHNRL0.98910.59591221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B27:04HRDLSHNRL0.98640.77261221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B15:18HRDLSHNRL0.42530.5691221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-A74:09AIHSMGFIHR0.98660.5162414
ROCK1-LRIG3chr1818625253chr12593081171531HLA-A74:03AIHSMGFIHR0.98660.5162414
ROCK1-LRIG3chr1818625253chr12593081171531HLA-A74:11AIHSMGFIHR0.98660.5162414
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B39:01IHRDLSHNRL0.89920.721121
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B38:01IHRDLSHNRL0.73650.80831121
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B38:02IHRDLSHNRL0.73420.82341121
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B27:02HRDLSHNRLSF0.99980.51461223
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B38:02HRDLSHNRLSF0.99190.74691223
ROCK1-LRIG3chr1818625253chr12593081171531HLA-A31:02GFIHRDLSHNR0.9870.547920
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B07:10HRDLSHNRLSF0.96760.5241223
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B39:12HRDLSHNRL0.99540.54441221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:95HRDLSHNRL0.9930.54531221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:27HRDLSHNRL0.99160.83511221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B39:05HRDLSHNRL0.99020.52821221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:05HRDLSHNRL0.98910.80431221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:13HRDLSHNRL0.98020.85591221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:29HRDLSHNRL0.97450.8541221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C04:10HRDLSHNRL0.8960.74761221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C04:07HRDLSHNRL0.86720.75411221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:46HRDLSHNRL0.83710.71691221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:67HRDLSHNRL0.8180.86921221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:80HRDLSHNRL0.8180.86921221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:10HRDLSHNRL0.81390.88321221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B39:08HRDLSHNRL0.56450.62561221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B14:03HRDLSHNRL0.46030.55151221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C04:14HRDLSHNRL0.39270.7691221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C12:16HRDLSHNRL0.00770.95461221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B39:05IHRDLSHNRL0.73280.69951121
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:46HRDLSHNRLSF0.99950.77131223
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B39:12HRDLSHNRLSF0.99490.61761223
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B39:31HRDLSHNRL0.99630.54271221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B39:02HRDLSHNRL0.99580.5971221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:01HRDLSHNRL0.99370.51121221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B38:05HRDLSHNRL0.99260.62381221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B27:09HRDLSHNRL0.98820.88231221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B27:06HRDLSHNRL0.98720.73551221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B27:10HRDLSHNRL0.98330.8761221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B27:08HRDLSHNRL0.9830.84271221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C18:01HRDLSHNRL0.92010.75811221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:17HRDLSHNRL0.90490.95971221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C04:01HRDLSHNRL0.86720.75411221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:02HRDLSHNRL0.8180.86921221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:04HRDLSHNRL0.78130.87761221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C07:22HRDLSHNRL0.71480.56451221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B39:11HRDLSHNRL0.70580.50861221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C06:08HRDLSHNRL0.55240.98321221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C06:06HRDLSHNRL0.54580.98431221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C04:04HRDLSHNRL0.51490.66481221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C03:67HRDLSHNRL0.37260.93091221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C06:02HRDLSHNRL0.01040.98431221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C06:17HRDLSHNRL0.01040.98431221
ROCK1-LRIG3chr1818625253chr12593081171531HLA-A74:01AIHSMGFIHR0.98660.5162414
ROCK1-LRIG3chr1818625253chr12593081171531HLA-C18:01IHRDLSHNRL0.88820.73891121
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B38:05IHRDLSHNRL0.73650.80831121
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B39:11IHRDLSHNRL0.49340.69971121
ROCK1-LRIG3chr1818625253chr12593081171531HLA-B27:06HRDLSHNRLSF0.99980.59921223

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Potential FusionNeoAntigen Information of ROCK1-LRIG3 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.

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)

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Fusion breakpoint peptide structures of ROCK1-LRIG3

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
3505HSMGFIHRDLSHNRROCK1LRIG3chr1818625253chr12593081171531

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ROCK1-LRIG3

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-B14:023BVN3505HSMGFIHRDLSHNR-4.42471-4.53811
HLA-B14:023BVN3505HSMGFIHRDLSHNR-4.03277-5.06807
HLA-B52:013W393505HSMGFIHRDLSHNR-6.10891-6.22231
HLA-B52:013W393505HSMGFIHRDLSHNR-4.66918-5.70448
HLA-A11:014UQ23505HSMGFIHRDLSHNR-7.66591-7.77931
HLA-A24:025HGA3505HSMGFIHRDLSHNR-8.15837-8.27177
HLA-A24:025HGA3505HSMGFIHRDLSHNR-6.25992-7.29522
HLA-B44:053DX83505HSMGFIHRDLSHNR-7.54511-7.65851
HLA-B44:053DX83505HSMGFIHRDLSHNR-6.31075-7.34605
HLA-A02:016TDR3505HSMGFIHRDLSHNR-2.23538-3.27068

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Vaccine Design for the FusionNeoAntigens of ROCK1-LRIG3

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
ROCK1-LRIG3chr1818625253chr12593081171121IHRDLSHNRLTCACAGGGACTTAAGTCACAACAGATTATC
ROCK1-LRIG3chr1818625253chr12593081171221HRDLSHNRLCAGGGACTTAAGTCACAACAGATTATC
ROCK1-LRIG3chr1818625253chr12593081171223HRDLSHNRLSFCAGGGACTTAAGTCACAACAGATTATCTTTCAT
ROCK1-LRIG3chr1818625253chr1259308117414AIHSMGFIHRAATCCATTCCATGGGTTTTATTCACAGGGA
ROCK1-LRIG3chr1818625253chr1259308117920GFIHRDLSHNRTTTTATTCACAGGGACTTAAGTCACAACAGATT

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

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Information of the samples that have these potential fusion neoantigens of ROCK1-LRIG3

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
BRCAROCK1-LRIG3chr1818625253ENST00000399799chr1259308117ENST00000320743TCGA-A8-A091-01A

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Potential target of CAR-T therapy development for ROCK1-LRIG3

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
TgeneLRIG3chr18:18625253chr12:59308117ENST00000320743019810_83001120.0TransmembraneHelical
TgeneLRIG3chr18:18625253chr12:59308117ENST00000379141019810_83001060.0TransmembraneHelical

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 ROCK1-LRIG3

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 ROCK1-LRIG3

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