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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:ERCC6L2-TRPM6

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ERCC6L2-TRPM6
FusionPDB ID: 27324
FusionGDB2.0 ID: 27324
HgeneTgene
Gene symbol

ERCC6L2

TRPM6

Gene ID

375748

140803

Gene nameERCC excision repair 6 like 2transient receptor potential cation channel subfamily M member 6
SynonymsBMFS2|C9orf102|HEBO|RAD26L|SR278CHAK2|HMGX|HOMG|HOMG1|HSH
Cytomap

9q22.32

9q21.13

Type of geneprotein-codingprotein-coding
DescriptionDNA excision repair protein ERCC-6-like 2DNA repair and recombination protein RAD26-likeexcision repair cross-complementation group 6 like 2excision repair cross-complementing rodent repair deficiency, complementation group 6-like 2putative repair andtransient receptor potential cation channel subfamily M member 6channel kinase 2melastatin-related TRP cation channel 6
Modification date2020031320200313
UniProtAcc

Q5T890

Main function of 5'-partner protein: FUNCTION: May be involved in early DNA damage response. {ECO:0000269|PubMed:24507776}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000466840, ENST00000288985, 
ENST00000407474, ENST00000437817, 
ENST00000359047, ENST00000360774, 
ENST00000361255, ENST00000376864, 
ENST00000376871, ENST00000376872, 
ENST00000449912, ENST00000451710, 
ENST00000483186, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 8 X 6=3844 X 3 X 3=36
# samples 84
** MAII scorelog2(8/384*10)=-2.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: ERCC6L2 [Title/Abstract] AND TRPM6 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ERCC6L2 [Title/Abstract] AND TRPM6 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ERCC6L2(98660253)-TRPM6(77473664), # samples:1
Anticipated loss of major functional domain due to fusion event.ERCC6L2-TRPM6 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.
ERCC6L2-TRPM6 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.
ERCC6L2-TRPM6 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.
ERCC6L2-TRPM6 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
TgeneTRPM6

GO:0009636

response to toxic substance

17575980



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/chr9:98660253/chr9:77473664)
- 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 ERCC6L2 (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 TRPM6 (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)
ENST00000288985ERCC6L2chr998660253+ENST00000361255TRPM6chr977473664-908693214369672274
ENST00000288985ERCC6L2chr998660253+ENST00000449912TRPM6chr977473664-908693214369672274
ENST00000288985ERCC6L2chr998660253+ENST00000451710TRPM6chr977473664-909893214369792278
ENST00000288985ERCC6L2chr998660253+ENST00000376872TRPM6chr977473664-595193214338321229
ENST00000288985ERCC6L2chr998660253+ENST00000360774TRPM6chr977473664-908693214369672274
ENST00000288985ERCC6L2chr998660253+ENST00000376871TRPM6chr977473664-559793214334781111
ENST00000288985ERCC6L2chr998660253+ENST00000376864TRPM6chr977473664-674393214367422200
ENST00000288985ERCC6L2chr998660253+ENST00000359047TRPM6chr977473664-22299321431810555

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
ENST00000288985ENST00000361255ERCC6L2chr998660253+TRPM6chr977473664-0.0006197610.99938023
ENST00000288985ENST00000449912ERCC6L2chr998660253+TRPM6chr977473664-0.0006197610.99938023
ENST00000288985ENST00000451710ERCC6L2chr998660253+TRPM6chr977473664-0.0008457760.9991542
ENST00000288985ENST00000376872ERCC6L2chr998660253+TRPM6chr977473664-0.000383890.999616
ENST00000288985ENST00000360774ERCC6L2chr998660253+TRPM6chr977473664-0.0006197610.99938023
ENST00000288985ENST00000376871ERCC6L2chr998660253+TRPM6chr977473664-0.0003054740.9996946
ENST00000288985ENST00000376864ERCC6L2chr998660253+TRPM6chr977473664-0.0005415680.9994585
ENST00000288985ENST00000359047ERCC6L2chr998660253+TRPM6chr977473664-0.0021718140.9978282

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 ERCC6L2-TRPM6

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ERCC6L2chr998660253TRPM6chr977473664932263SMKKEPLSSTAKKSQKSWIKGVFDKR

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Potential FusionNeoAntigen Information of ERCC6L2-TRPM6 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.
ERCC6L2-TRPM6_98660253_77473664.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)
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:01TAKKSQKSW0.99860.9691918
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B58:02TAKKSQKSW0.99260.8818918
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B58:01TAKKSQKSW0.98940.9173918
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B15:16TAKKSQKSW0.97680.7303918
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B15:17TAKKSQKSW0.96680.848918
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:03TAKKSQKSW0.95280.9765918
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:01STAKKSQKSW0.99950.9356818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B58:02STAKKSQKSW0.99780.8273818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B58:01STAKKSQKSW0.9960.8507818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B15:17STAKKSQKSW0.98660.8133818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:03STAKKSQKSW0.97460.9718818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B15:16STAKKSQKSW0.95390.6387818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-A32:13STAKKSQKSW0.74940.9214818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:01SSTAKKSQKSW0.99990.9201718
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B58:02SSTAKKSQKSW0.99950.8411718
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B58:01SSTAKKSQKSW0.9970.8339718
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:03SSTAKKSQKSW0.99560.9686718
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:10TAKKSQKSW0.99860.9691918
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:04TAKKSQKSW0.99670.7327918
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B58:06TAKKSQKSW0.99350.8114918
ERCC6L2-TRPM6chr998660253chr977473664932HLA-A30:01SSTAKKSQK0.97830.6874716
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B15:13TAKKSQKSW0.89930.6506918
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:02TAKKSQKSW0.86190.8841918
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B15:24TAKKSQKSW0.72770.8921918
ERCC6L2-TRPM6chr998660253chr977473664932HLA-A25:01TAKKSQKSW0.0480.7562918
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:10STAKKSQKSW0.99950.9356818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:04STAKKSQKSW0.99890.7105818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B58:06STAKKSQKSW0.99610.7662818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:02STAKKSQKSW0.97450.8739818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-A32:01STAKKSQKSW0.90010.8801818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B15:24STAKKSQKSW0.89960.8224818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-A25:01STAKKSQKSW0.37480.6802818
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:10SSTAKKSQKSW0.99990.9201718
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:04SSTAKKSQKSW0.99970.7248718
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B58:06SSTAKKSQKSW0.99930.7806718
ERCC6L2-TRPM6chr998660253chr977473664932HLA-B57:02SSTAKKSQKSW0.99350.9718

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Potential FusionNeoAntigen Information of ERCC6L2-TRPM6 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 ERCC6L2-TRPM6

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
5668LSSTAKKSQKSWIKERCC6L2TRPM6chr998660253chr977473664932

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ERCC6L2-TRPM6

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-B14:023BVN5668LSSTAKKSQKSWIK-7.9962-8.1096
HLA-B14:023BVN5668LSSTAKKSQKSWIK-5.70842-6.74372
HLA-B52:013W395668LSSTAKKSQKSWIK-6.83737-6.95077
HLA-B52:013W395668LSSTAKKSQKSWIK-4.4836-5.5189
HLA-A11:014UQ25668LSSTAKKSQKSWIK-10.0067-10.1201
HLA-A11:014UQ25668LSSTAKKSQKSWIK-9.03915-10.0745
HLA-A24:025HGA5668LSSTAKKSQKSWIK-6.56204-6.67544
HLA-A24:025HGA5668LSSTAKKSQKSWIK-5.42271-6.45801
HLA-B44:053DX85668LSSTAKKSQKSWIK-7.85648-8.89178
HLA-B44:053DX85668LSSTAKKSQKSWIK-5.3978-5.5112
HLA-A02:016TDR5668LSSTAKKSQKSWIK-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ERCC6L2-TRPM6

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
ERCC6L2-TRPM6chr998660253chr977473664716SSTAKKSQKTCTTCTACAGCAAAAAAGTCCCAGAAA
ERCC6L2-TRPM6chr998660253chr977473664718SSTAKKSQKSWTCTTCTACAGCAAAAAAGTCCCAGAAATCCTGG
ERCC6L2-TRPM6chr998660253chr977473664818STAKKSQKSWTCTACAGCAAAAAAGTCCCAGAAATCCTGG
ERCC6L2-TRPM6chr998660253chr977473664918TAKKSQKSWACAGCAAAAAAGTCCCAGAAATCCTGG

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 ERCC6L2-TRPM6

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
BRCAERCC6L2-TRPM6chr998660253ENST00000288985chr977473664ENST00000359047TCGA-D8-A1XD-01A

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Potential target of CAR-T therapy development for ERCC6L2-TRPM6

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
TgeneTRPM6chr9:98660253chr9:77473664ENST000003607740391013_103302023.0IntramembranePore-forming
TgeneTRPM6chr9:98660253chr9:77473664ENST000003612550391013_103302018.0IntramembranePore-forming
TgeneTRPM6chr9:98660253chr9:77473664ENST000004499120391013_103302018.0IntramembranePore-forming
TgeneTRPM6chr9:98660253chr9:77473664ENST000003607740391048_106802023.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000360774039742_76202023.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000360774039842_86202023.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000360774039906_92602023.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000360774039940_96002023.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000360774039973_99302023.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST000003612550391048_106802018.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000361255039742_76202018.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000361255039842_86202018.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000361255039906_92602018.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000361255039940_96002018.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000361255039973_99302018.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST000004499120391048_106802018.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000449912039742_76202018.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000449912039842_86202018.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000449912039906_92602018.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000449912039940_96002018.0TransmembraneHelical
TgeneTRPM6chr9:98660253chr9:77473664ENST00000449912039973_99302018.0TransmembraneHelical

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 ERCC6L2-TRPM6

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 ERCC6L2-TRPM6

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