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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:IGF1R-EFTUD1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: IGF1R-EFTUD1
FusionPDB ID: 38477
FusionGDB2.0 ID: 38477
HgeneTgene
Gene symbol

IGF1R

EFTUD1

Gene ID

3480

79631

Gene nameinsulin like growth factor 1 receptorelongation factor like GTPase 1
SynonymsCD221|IGFIR|IGFR|JTK13EFTUD1|FAM42A|HsT19294|RIA1|SDS2
Cytomap

15q26.3

15q25.2

Type of geneprotein-codingprotein-coding
Descriptioninsulin-like growth factor 1 receptorIGF-I receptorsoluble IGF1R variant 1soluble IGF1R variant 2elongation factor-like GTPase 1elongation factor Tu GTP binding domain containing 1elongation factor Tu GTP-binding domain-containing protein 1elongation factor-like 1ribosome assembly 1 homolog
Modification date2020032920200313
UniProtAcc

P08069

Main function of 5'-partner protein: FUNCTION: Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.; FUNCTION: When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.
.
Ensembl transtripts involved in fusion geneENST idsENST00000268035, ENST00000558762, 
ENST00000560432, 
ENST00000561331, 
ENST00000268206, ENST00000359445, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score24 X 15 X 6=21605 X 2 X 4=40
# samples 255
** MAII scorelog2(25/2160*10)=-3.11103131238874
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/40*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: IGF1R [Title/Abstract] AND EFTUD1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: IGF1R [Title/Abstract] AND EFTUD1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)IGF1R(99251336)-EFTUD1(82456325), # samples:1
Anticipated loss of major functional domain due to fusion event.IGF1R-EFTUD1 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.
IGF1R-EFTUD1 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
HgeneIGF1R

GO:0043066

negative regulation of apoptotic process

12556535

HgeneIGF1R

GO:0046328

regulation of JNK cascade

12556535

HgeneIGF1R

GO:0046777

protein autophosphorylation

1846292|7679099|11162456

HgeneIGF1R

GO:0048009

insulin-like growth factor receptor signaling pathway

7679099

HgeneIGF1R

GO:0048015

phosphatidylinositol-mediated signaling

7692086

HgeneIGF1R

GO:0051389

inactivation of MAPKK activity

12556535

TgeneEFTUD1

GO:0046039

GTP metabolic process

21536732



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/chr15:99251336/chr15:82456325)
- 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 IGF1R (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 EFTUD1 (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)
ENST00000268035IGF1Rchr1599251336+ENST00000268206EFTUD1chr1582456325-300712516112863750
ENST00000268035IGF1Rchr1599251336+ENST00000359445EFTUD1chr1582456325-300412516112863750
ENST00000558762IGF1Rchr1599251336+ENST00000268206EFTUD1chr1582456325-293411785382790750
ENST00000558762IGF1Rchr1599251336+ENST00000359445EFTUD1chr1582456325-293111785382790750

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
ENST00000268035ENST00000268206IGF1Rchr1599251336+EFTUD1chr1582456325-0.001693050.998307
ENST00000268035ENST00000359445IGF1Rchr1599251336+EFTUD1chr1582456325-0.001700450.99829954
ENST00000558762ENST00000268206IGF1Rchr1599251336+EFTUD1chr1582456325-0.0015192830.99848074
ENST00000558762ENST00000359445IGF1Rchr1599251336+EFTUD1chr1582456325-0.0015275930.9984724

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 IGF1R-EFTUD1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
IGF1Rchr1599251336EFTUD1chr15824563251178214NYRCWTTNRCQKRIGGLQDFVLKSAT
IGF1Rchr1599251336EFTUD1chr15824563251251214NYRCWTTNRCQKRIGGLQDFVLKSAT

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Potential FusionNeoAntigen Information of IGF1R-EFTUD1 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.
IGF1R-EFTUD1_99251336_82456325.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)
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:04KRIGGLQDF0.99960.64651120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:05KRIGGLQDF0.99960.5431120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:07KRIGGLQDF0.99760.50221120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B15:03KRIGGLQDF0.48570.73661120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B15:18KRIGGLQDF0.38490.67851120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:04QKRIGGLQDF0.99970.5641020
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:07KRIGGLQDFV0.9990.5461121
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:04KRIGGLQDFVL10.66541122
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:05KRIGGLQDFVL10.69751122
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:07KRIGGLQDFVL10.5861122
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:03KRIGGLQDF0.99140.55961120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C07:05KRIGGLQDF0.99090.78161120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C07:27KRIGGLQDF0.98130.82761120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C07:29KRIGGLQDF0.97520.8051120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C07:13KRIGGLQDF0.94490.77851120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C07:67KRIGGLQDF0.92250.8481120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C07:80KRIGGLQDF0.92250.8481120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C07:46KRIGGLQDF0.91790.72981120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C07:19KRIGGLQDF0.9170.51451120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C07:10KRIGGLQDF0.8160.85491120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C12:16KRIGGLQDF0.14140.93231120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:14KRIGGLQDFV0.99970.52741121
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:14KRIGGLQDFVL10.61141122
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:03KRIGGLQDFVL0.99950.71831122
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:10KRIGGLQDF0.99960.75771120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:06KRIGGLQDF0.99950.5661120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:09KRIGGLQDF0.99620.53171120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C07:17KRIGGLQDF0.960.89581120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C07:02KRIGGLQDF0.92250.8481120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C06:08KRIGGLQDF0.83270.97091120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C07:22KRIGGLQDF0.81940.57821120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C06:06KRIGGLQDF0.22350.9781120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B15:68KRIGGLQDF0.19180.52791120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B15:54KRIGGLQDF0.18720.82421120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C06:17KRIGGLQDF0.07650.98291120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C06:02KRIGGLQDF0.07650.98291120
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:09KRIGGLQDFV0.99920.54971121
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:08KRIGGLQDFVL10.55911122
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:09KRIGGLQDFVL10.64411122
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:06KRIGGLQDFVL10.67571122
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-B27:10KRIGGLQDFVL10.77141122
IGF1R-EFTUD1chr1599251336chr15824563251251HLA-C07:01KRIGGLQDFVL0.99990.56121122

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Potential FusionNeoAntigen Information of IGF1R-EFTUD1 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 IGF1R-EFTUD1

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
9526TNRCQKRIGGLQDFIGF1REFTUD1chr1599251336chr15824563251251

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of IGF1R-EFTUD1

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-B14:023BVN9526TNRCQKRIGGLQDF-7.15543-7.26883
HLA-B14:023BVN9526TNRCQKRIGGLQDF-4.77435-5.80965
HLA-B52:013W399526TNRCQKRIGGLQDF-6.80875-6.92215
HLA-B52:013W399526TNRCQKRIGGLQDF-4.20386-5.23916
HLA-A11:014UQ29526TNRCQKRIGGLQDF-7.5194-8.5547
HLA-A11:014UQ29526TNRCQKRIGGLQDF-6.9601-7.0735
HLA-A24:025HGA9526TNRCQKRIGGLQDF-7.52403-7.63743
HLA-A24:025HGA9526TNRCQKRIGGLQDF-5.82433-6.85963
HLA-B27:056PYJ9526TNRCQKRIGGLQDF-3.28285-4.31815
HLA-B44:053DX89526TNRCQKRIGGLQDF-5.91172-6.94702
HLA-B44:053DX89526TNRCQKRIGGLQDF-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of IGF1R-EFTUD1

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
IGF1R-EFTUD1chr1599251336chr15824563251020QKRIGGLQDFGCCAGAAAAGAATAGGAGGCCTTCAAGATT
IGF1R-EFTUD1chr1599251336chr15824563251120KRIGGLQDFAGAAAAGAATAGGAGGCCTTCAAGATT
IGF1R-EFTUD1chr1599251336chr15824563251121KRIGGLQDFVAGAAAAGAATAGGAGGCCTTCAAGATTTTG
IGF1R-EFTUD1chr1599251336chr15824563251122KRIGGLQDFVLAGAAAAGAATAGGAGGCCTTCAAGATTTTGTGC

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 IGF1R-EFTUD1

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
STADIGF1R-EFTUD1chr1599251336ENST00000268035chr1582456325ENST00000268206TCGA-CD-8528-01A

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Potential target of CAR-T therapy development for IGF1R-EFTUD1

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 IGF1R-EFTUD1

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 IGF1R-EFTUD1

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