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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:GRID1-CXCL12

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GRID1-CXCL12
FusionPDB ID: 34743
FusionGDB2.0 ID: 34743
HgeneTgene
Gene symbol

GRID1

CXCL12

Gene ID

2894

6387

Gene nameglutamate ionotropic receptor delta type subunit 1C-X-C motif chemokine ligand 12
SynonymsGluD1IRH|PBSF|SCYB12|SDF1|TLSF|TPAR1
Cytomap

10q23.1-q23.2

10q11.21

Type of geneprotein-codingprotein-coding
Descriptionglutamate receptor ionotropic, delta-1gluR delta-1 subunitglutamate receptor delta-1 subunitstromal cell-derived factor 1chemokine (C-X-C motif) ligand 12intercrine reduced in hepatomaspre-B cell growth-stimulating factor
Modification date2020031320200313
UniProtAcc

Q9ULK0

Main function of 5'-partner protein: FUNCTION: Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists.

P48061

Main function of 5'-partner protein: FUNCTION: Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Binds to the allosteric site (site 2) of integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner (PubMed:29301984). Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of ACKR3 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Stimulates the proliferation of bone marrow-derived B-cell progenitors in the presence of IL7 as well as growth of stromal cell-dependent pre-B-cells (By similarity). {ECO:0000250|UniProtKB:P40224, ECO:0000269|PubMed:11069075, ECO:0000269|PubMed:11859124, ECO:0000269|PubMed:16107333, ECO:0000269|PubMed:18802065, ECO:0000269|PubMed:19255243, ECO:0000269|PubMed:29301984, ECO:0000269|PubMed:8752281}.
Ensembl transtripts involved in fusion geneENST idsENST00000327946, ENST00000536331, 
ENST00000552278, 
ENST00000343575, 
ENST00000374426, ENST00000374429, 
ENST00000395793, ENST00000395794, 
ENST00000496375, ENST00000395795, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 8 X 6=4806 X 4 X 4=96
# samples 116
** MAII scorelog2(11/480*10)=-2.12553088208386
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/96*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: GRID1 [Title/Abstract] AND CXCL12 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GRID1 [Title/Abstract] AND CXCL12 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GRID1(87675943)-CXCL12(44793345), # samples:1
Anticipated loss of major functional domain due to fusion event.GRID1-CXCL12 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.
GRID1-CXCL12 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.
GRID1-CXCL12 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.
GRID1-CXCL12 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
TgeneCXCL12

GO:0033622

integrin activation

29301984

TgeneCXCL12

GO:0045785

positive regulation of cell adhesion

23620790

TgeneCXCL12

GO:0060326

cell chemotaxis

18308860

TgeneCXCL12

GO:0070098

chemokine-mediated signaling pathway

20388803

TgeneCXCL12

GO:0090026

positive regulation of monocyte chemotaxis

18802065

TgeneCXCL12

GO:1902230

negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage

20388803

TgeneCXCL12

GO:1903237

negative regulation of leukocyte tethering or rolling

18308860

TgeneCXCL12

GO:2000406

positive regulation of T cell migration

23620790

TgeneCXCL12

GO:2000669

negative regulation of dendritic cell apoptotic process

15059845



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/chr10:87675943/chr10:44793345)
- 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 GRID1 (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 CXCL12 (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)
ENST00000327946GRID1chr1087675943-ENST00000395795CXCL12chr1044793345-117486686991301

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
ENST00000327946ENST00000395795GRID1chr1087675943-CXCL12chr1044793345-0.0046711160.9953289

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 GRID1-CXCL12

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GRID1chr1087675943CXCL12chr1044793345866259NLASKDSHWVFVNELLEYGCTAMLRH

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Potential FusionNeoAntigen Information of GRID1-CXCL12 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.
GRID1-CXCL12_87675943_44793345.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)
GRID1-CXCL12chr1087675943chr1044793345866HLA-B15:02FVNELLEY0.99910.88651018
GRID1-CXCL12chr1087675943chr1044793345866HLA-B35:01FVNELLEY0.99620.82991018
GRID1-CXCL12chr1087675943chr1044793345866HLA-B39:01SHWVFVNEL0.99960.8926615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B39:06SHWVFVNEL0.99930.7881615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B38:02SHWVFVNEL0.99920.9718615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B38:01SHWVFVNEL0.99910.9671615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B39:13SHWVFVNEL0.9990.9105615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B14:02SHWVFVNEL0.99360.7309615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B14:01SHWVFVNEL0.99360.7309615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B15:10SHWVFVNEL0.99310.5855615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B15:37SHWVFVNEL0.94990.6521615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B15:18SHWVFVNEL0.75720.7659615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B39:01SHWVFVNELL0.9960.9055616
GRID1-CXCL12chr1087675943chr1044793345866HLA-B38:02SHWVFVNELL0.98930.9758616
GRID1-CXCL12chr1087675943chr1044793345866HLA-B38:01SHWVFVNELL0.98840.971616
GRID1-CXCL12chr1087675943chr1044793345866HLA-B15:31FVNELLEY0.99680.79261018
GRID1-CXCL12chr1087675943chr1044793345866HLA-C15:04FVNELLEY0.99480.90841018
GRID1-CXCL12chr1087675943chr1044793345866HLA-C03:14FVNELLEY0.96010.97881018
GRID1-CXCL12chr1087675943chr1044793345866HLA-B39:09SHWVFVNEL0.99960.5609615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B39:12SHWVFVNEL0.99940.9003615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B39:05SHWVFVNEL0.99920.87615
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:05SHWVFVNEL0.91860.9634615
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:27SHWVFVNEL0.90240.96615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B15:21VFVNELLEY0.89540.8807918
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:95SHWVFVNEL0.89060.7577615
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:29SHWVFVNEL0.85080.9416615
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:13SHWVFVNEL0.82870.9344615
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:10SHWVFVNEL0.75350.9608615
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:80SHWVFVNEL0.75040.9562615
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:67SHWVFVNEL0.75040.9562615
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:46SHWVFVNEL0.71010.9078615
GRID1-CXCL12chr1087675943chr1044793345866HLA-C12:16VFVNELLEY0.66620.9688918
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:19VFVNELLEY0.66610.6184918
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:67VFVNELLEY0.61870.9518918
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:80VFVNELLEY0.61870.9518918
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:10VFVNELLEY0.61540.9571918
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:46VFVNELLEY0.5490.8602918
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:27VFVNELLEY0.45680.9557918
GRID1-CXCL12chr1087675943chr1044793345866HLA-B14:03SHWVFVNEL0.33730.7901615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B73:01SHWVFVNEL0.12040.597615
GRID1-CXCL12chr1087675943chr1044793345866HLA-C12:16SHWVFVNEL0.07830.9753615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B39:05SHWVFVNELL0.99070.8817616
GRID1-CXCL12chr1087675943chr1044793345866HLA-B15:11FVNELLEY0.9990.81951018
GRID1-CXCL12chr1087675943chr1044793345866HLA-B35:11FVNELLEY0.9990.85771018
GRID1-CXCL12chr1087675943chr1044793345866HLA-B15:08FVNELLEY0.9990.81841018
GRID1-CXCL12chr1087675943chr1044793345866HLA-B35:43FVNELLEY0.99860.81621018
GRID1-CXCL12chr1087675943chr1044793345866HLA-C03:02FVNELLEY0.99810.97181018
GRID1-CXCL12chr1087675943chr1044793345866HLA-B35:23FVNELLEY0.99630.79691018
GRID1-CXCL12chr1087675943chr1044793345866HLA-B35:77FVNELLEY0.99620.82991018
GRID1-CXCL12chr1087675943chr1044793345866HLA-B35:20FVNELLEY0.99590.85751018
GRID1-CXCL12chr1087675943chr1044793345866HLA-C15:09FVNELLEY0.99480.90841018
GRID1-CXCL12chr1087675943chr1044793345866HLA-C12:02FVNELLEY0.99420.97791018
GRID1-CXCL12chr1087675943chr1044793345866HLA-B35:24FVNELLEY0.97870.87891018
GRID1-CXCL12chr1087675943chr1044793345866HLA-C02:02FVNELLEY0.91740.98381018
GRID1-CXCL12chr1087675943chr1044793345866HLA-C02:10FVNELLEY0.91740.98381018
GRID1-CXCL12chr1087675943chr1044793345866HLA-B39:31SHWVFVNEL0.99960.8954615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B39:02SHWVFVNEL0.99950.9106615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B38:05SHWVFVNEL0.99910.9671615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B15:09SHWVFVNEL0.99120.7112615
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:17SHWVFVNEL0.83070.9613615
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:02SHWVFVNEL0.75040.9562615
GRID1-CXCL12chr1087675943chr1044793345866HLA-B39:11SHWVFVNEL0.65030.7316615
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:02VFVNELLEY0.61870.9518918
GRID1-CXCL12chr1087675943chr1044793345866HLA-C07:17VFVNELLEY0.60780.9723918
GRID1-CXCL12chr1087675943chr1044793345866HLA-C14:03VFVNELLEY0.00390.959918
GRID1-CXCL12chr1087675943chr1044793345866HLA-C14:02VFVNELLEY0.00390.959918
GRID1-CXCL12chr1087675943chr1044793345866HLA-B38:05SHWVFVNELL0.98840.971616

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Potential FusionNeoAntigen Information of GRID1-CXCL12 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 GRID1-CXCL12

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
8634SHWVFVNELLEYGCGRID1CXCL12chr1087675943chr1044793345866

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GRID1-CXCL12

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-B14:023BVN8634SHWVFVNELLEYGC-5.6804-5.7938
HLA-B14:023BVN8634SHWVFVNELLEYGC-4.57262-5.60792
HLA-B52:013W398634SHWVFVNELLEYGC-6.21967-6.33307
HLA-B52:013W398634SHWVFVNELLEYGC-3.86069-4.89599
HLA-A11:014UQ28634SHWVFVNELLEYGC-6.23192-6.34532
HLA-A24:025HGA8634SHWVFVNELLEYGC-8.5237-8.6371
HLA-A24:025HGA8634SHWVFVNELLEYGC-7.27082-8.30612
HLA-B27:056PYJ8634SHWVFVNELLEYGC-4.67437-4.78777
HLA-B27:036PZ58634SHWVFVNELLEYGC-2.4762-2.5896
HLA-B44:053DX88634SHWVFVNELLEYGC-8.75385-8.86725
HLA-B44:053DX88634SHWVFVNELLEYGC-3.47269-4.50799
HLA-A02:016TDR8634SHWVFVNELLEYGC-5.16116-5.27456

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Vaccine Design for the FusionNeoAntigens of GRID1-CXCL12

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
GRID1-CXCL12chr1087675943chr10447933451018FVNELLEYGTGAATGAGTTGCTAGAATATGGC
GRID1-CXCL12chr1087675943chr1044793345615SHWVFVNELCACTGGGTCTTTGTGAATGAGTTGCTA
GRID1-CXCL12chr1087675943chr1044793345616SHWVFVNELLCACTGGGTCTTTGTGAATGAGTTGCTAGAA
GRID1-CXCL12chr1087675943chr1044793345918VFVNELLEYTTTGTGAATGAGTTGCTAGAATATGGC

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 GRID1-CXCL12

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
SKCMGRID1-CXCL12chr1087675943ENST00000327946chr1044793345ENST00000395795TCGA-ER-A19L-06A

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Potential target of CAR-T therapy development for GRID1-CXCL12

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 GRID1-CXCL12

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 GRID1-CXCL12

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