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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:TOM1L2-ULK2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TOM1L2-ULK2
FusionPDB ID: 93010
FusionGDB2.0 ID: 93010
HgeneTgene
Gene symbol

TOM1L2

ULK2

Gene ID

146691

9706

Gene nametarget of myb1 like 2 membrane trafficking proteinunc-51 like autophagy activating kinase 2
Synonyms-ATG1B|Unc51.2
Cytomap

17p11.2

17p11.2

Type of geneprotein-codingprotein-coding
DescriptionTOM1-like protein 2target of Myb-like protein 2target of myb1-like 2serine/threonine-protein kinase ULK2
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000318094, ENST00000379504, 
ENST00000395739, ENST00000535933, 
ENST00000540946, ENST00000542206, 
ENST00000581396, ENST00000478943, 
ENST00000577517, 
ENST00000580130, 
ENST00000361658, ENST00000395544, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score16 X 13 X 7=14569 X 7 X 6=378
# samples 1710
** MAII scorelog2(17/1456*10)=-3.098403704061
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/378*10)=-1.91838623444635
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TOM1L2 [Title/Abstract] AND ULK2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TOM1L2 [Title/Abstract] AND ULK2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TOM1L2(17782941)-ULK2(19769141), # samples:2
Anticipated loss of major functional domain due to fusion event.TOM1L2-ULK2 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.
TOM1L2-ULK2 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.
TOM1L2-ULK2 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.
TOM1L2-ULK2 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
HgeneTOM1L2

GO:0007165

signal transduction

16479011

HgeneTOM1L2

GO:0045839

negative regulation of mitotic nuclear division

16479011

TgeneULK2

GO:0006914

autophagy

18936157

TgeneULK2

GO:0046777

protein autophosphorylation

18936157



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/chr17:17782941/chr17:19769141)
- 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 TOM1L2 (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 ULK2 (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)
ENST00000581396TOM1L2chr1717782941-ENST00000361658ULK2chr1719769141-40237249737441215
ENST00000581396TOM1L2chr1717782941-ENST00000395544ULK2chr1719769141-61447249737441215
ENST00000379504TOM1L2chr1717782941-ENST00000361658ULK2chr1719769141-41608618438811265
ENST00000379504TOM1L2chr1717782941-ENST00000395544ULK2chr1719769141-62818618438811265
ENST00000318094TOM1L2chr1717782941-ENST00000361658ULK2chr1719769141-40257268437461220
ENST00000318094TOM1L2chr1717782941-ENST00000395544ULK2chr1719769141-61467268437461220
ENST00000395739TOM1L2chr1717782941-ENST00000361658ULK2chr1719769141-40327339137531220
ENST00000395739TOM1L2chr1717782941-ENST00000395544ULK2chr1719769141-61537339137531220
ENST00000535933TOM1L2chr1717782941-ENST00000361658ULK2chr1719769141-402472510737451212
ENST00000535933TOM1L2chr1717782941-ENST00000395544ULK2chr1719769141-614572510737451212
ENST00000540946TOM1L2chr1717782941-ENST00000361658ULK2chr1719769141-38665678435871167
ENST00000540946TOM1L2chr1717782941-ENST00000395544ULK2chr1719769141-59875678435871167
ENST00000542206TOM1L2chr1717782941-ENST00000361658ULK2chr1719769141-37194208734401117
ENST00000542206TOM1L2chr1717782941-ENST00000395544ULK2chr1719769141-58404208734401117

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
ENST00000581396ENST00000361658TOM1L2chr1717782941-ULK2chr1719769141-0.0010823490.9989177
ENST00000581396ENST00000395544TOM1L2chr1717782941-ULK2chr1719769141-0.0001564930.9998435
ENST00000379504ENST00000361658TOM1L2chr1717782941-ULK2chr1719769141-0.0009383940.99906164
ENST00000379504ENST00000395544TOM1L2chr1717782941-ULK2chr1719769141-0.0001563080.9998437
ENST00000318094ENST00000361658TOM1L2chr1717782941-ULK2chr1719769141-0.0009293810.9990707
ENST00000318094ENST00000395544TOM1L2chr1717782941-ULK2chr1719769141-0.0001523990.99984753
ENST00000395739ENST00000361658TOM1L2chr1717782941-ULK2chr1719769141-0.0009256010.99907434
ENST00000395739ENST00000395544TOM1L2chr1717782941-ULK2chr1719769141-0.000152340.99984765
ENST00000535933ENST00000361658TOM1L2chr1717782941-ULK2chr1719769141-0.0008597240.99914026
ENST00000535933ENST00000395544TOM1L2chr1717782941-ULK2chr1719769141-0.0001465910.9998534
ENST00000540946ENST00000361658TOM1L2chr1717782941-ULK2chr1719769141-0.000868770.99913126
ENST00000540946ENST00000395544TOM1L2chr1717782941-ULK2chr1719769141-0.0001424550.99985754
ENST00000542206ENST00000361658TOM1L2chr1717782941-ULK2chr1719769141-0.0010252890.9989747
ENST00000542206ENST00000395544TOM1L2chr1717782941-ULK2chr1719769141-0.0001459850.99985397

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 TOM1L2-ULK2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TOM1L2chr1717782941ULK2chr1719769141420110VPGQEDSSDLELLQKTDWEVAIKSIN
TOM1L2chr1717782941ULK2chr1719769141567160VPGQEDSSDLELLQKTDWEVAIKSIN
TOM1L2chr1717782941ULK2chr1719769141724208VPGQEDSSDLELLQKTDWEVAIKSIN
TOM1L2chr1717782941ULK2chr1719769141725205VPGQEDSSDLELLQKTDWEVAIKSIN
TOM1L2chr1717782941ULK2chr1719769141726213VPGQEDSSDLELLQKTDWEVAIKSIN
TOM1L2chr1717782941ULK2chr1719769141733213VPGQEDSSDLELLQKTDWEVAIKSIN
TOM1L2chr1717782941ULK2chr1719769141861258VPGQEDSSDLELLQKTDWEVAIKSIN

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Potential FusionNeoAntigen Information of TOM1L2-ULK2 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.
TOM1L2-ULK2_17782941_19769141.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)
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:03LELLQKTDW0.99850.9928918
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:02LELLQKTDW0.9980.688918
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:05LELLQKTDW0.99560.8307918
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:11LLQKTDWEV0.99540.7041120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:24LLQKTDWEV0.99530.67961120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:67LLQKTDWEV0.99530.67961120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:30LLQKTDWEV0.99530.67961120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:60LLQKTDWEV0.99510.69341120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:22LLQKTDWEV0.99460.67111120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:21LLQKTDWEV0.99370.77581120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:27LLQKTDWEV0.99080.63941120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:16LLQKTDWEV0.98950.66571120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:13LLQKTDWEV0.98550.70431120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:04LLQKTDWEV0.98310.92511120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:35LLQKTDWEV0.96580.68461120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:38LLQKTDWEV0.96470.63241120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:17LLQKTDWEV0.95270.89771120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:29LLQKTDWEV0.92530.68241120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:20LLQKTDWEV0.91070.68551120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:02DLELLQKTDW0.85390.562818
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:02SDLELLQKTDW0.99940.6173718
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:03SDLELLQKTDW0.9990.9868718
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:08LELLQKTDW0.99750.7309918
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:04LELLQKTDW0.9960.5606918
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:01LLQKTDWEV0.99530.67961120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:07LLQKTDWEV0.99470.71091120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:02LLQKTDWEV0.99460.57121120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:04SDLELLQKTDW0.99950.5937718
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:08SDLELLQKTDW0.99950.6557718
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:26LELLQKTDW0.99850.9928918
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:13LELLQKTDW0.99850.9928918
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:07LELLQKTDW0.99850.9928918
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:22LELLQKTDW0.9980.688918
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:14LLQKTDWEV0.99380.75411120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-A02:06LLQKTDWEV0.99370.77581120
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:21LELLQKTDW0.98610.6557918
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:22DLELLQKTDW0.85390.562818
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:22SDLELLQKTDW0.99940.6173718
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:26SDLELLQKTDW0.9990.9868718
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:13SDLELLQKTDW0.9990.9868718
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:07SDLELLQKTDW0.9990.9868718
TOM1L2-ULK2chr1717782941chr1719769141726HLA-B44:21SDLELLQKTDW0.99880.5793718

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Potential FusionNeoAntigen Information of TOM1L2-ULK2 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 TOM1L2-ULK2

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
8998SSDLELLQKTDWEVTOM1L2ULK2chr1717782941chr1719769141726

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TOM1L2-ULK2

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-B14:023BVN8998SSDLELLQKTDWEV-7.15543-7.26883
HLA-B14:023BVN8998SSDLELLQKTDWEV-4.77435-5.80965
HLA-B52:013W398998SSDLELLQKTDWEV-6.80875-6.92215
HLA-B52:013W398998SSDLELLQKTDWEV-4.20386-5.23916
HLA-A11:014UQ28998SSDLELLQKTDWEV-7.5194-8.5547
HLA-A11:014UQ28998SSDLELLQKTDWEV-6.9601-7.0735
HLA-A24:025HGA8998SSDLELLQKTDWEV-7.52403-7.63743
HLA-A24:025HGA8998SSDLELLQKTDWEV-5.82433-6.85963
HLA-B27:056PYJ8998SSDLELLQKTDWEV-3.28285-4.31815
HLA-B44:053DX88998SSDLELLQKTDWEV-5.91172-6.94702
HLA-B44:053DX88998SSDLELLQKTDWEV-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of TOM1L2-ULK2

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
TOM1L2-ULK2chr1717782941chr17197691411120LLQKTDWEVCTGCAGAAAACTGATTGGGAGGTAGCT
TOM1L2-ULK2chr1717782941chr1719769141718SDLELLQKTDWGATCTGGAGTTGCTGCAGAAAACTGATTGGGAG
TOM1L2-ULK2chr1717782941chr1719769141818DLELLQKTDWCTGGAGTTGCTGCAGAAAACTGATTGGGAG
TOM1L2-ULK2chr1717782941chr1719769141918LELLQKTDWGAGTTGCTGCAGAAAACTGATTGGGAG

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 TOM1L2-ULK2

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
BRCATOM1L2-ULK2chr1717782941ENST00000318094chr1719769141ENST00000361658TCGA-D8-A27G-01A

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Potential target of CAR-T therapy development for TOM1L2-ULK2

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 TOM1L2-ULK2

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 TOM1L2-ULK2

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