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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:GRB10-GPBP1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GRB10-GPBP1
FusionPDB ID: 34621
FusionGDB2.0 ID: 34621
HgeneTgene
Gene symbol

GRB10

GPBP1

Gene ID

2887

65056

Gene namegrowth factor receptor bound protein 10GC-rich promoter binding protein 1
SynonymsGRB-IR|Grb-10|IRBP|MEG1|RSSGPBP|SSH6|VASCULIN
Cytomap

7p12.1

5q11.2

Type of geneprotein-codingprotein-coding
Descriptiongrowth factor receptor-bound protein 10GRB10 adapter proteinGRB10 adaptor proteininsulin receptor-binding protein Grb-IRmaternally expressed gene 1vasculinvascular wall-linked protein
Modification date2020032720200327
UniProtAcc

Q13322

Main function of 5'-partner protein: FUNCTION: Adapter protein which modulates coupling of a number of cell surface receptor kinases with specific signaling pathways. Binds to, and suppress signals from, activated receptors tyrosine kinases, including the insulin (INSR) and insulin-like growth factor (IGF1R) receptors. The inhibitory effect can be achieved by 2 mechanisms: interference with the signaling pathway and increased receptor degradation. Delays and reduces AKT1 phosphorylation in response to insulin stimulation. Blocks association between INSR and IRS1 and IRS2 and prevents insulin-stimulated IRS1 and IRS2 tyrosine phosphorylation. Recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased internalization and degradation by both the proteasomal and lysosomal pathways. May play a role in mediating insulin-stimulated ubiquitination of INSR, leading to proteasomal degradation. Negatively regulates Wnt signaling by interacting with LRP6 intracellular portion and interfering with the binding of AXIN1 to LRP6. Positive regulator of the KDR/VEGFR-2 signaling pathway. May inhibit NEDD4-mediated degradation of KDR/VEGFR-2. {ECO:0000269|PubMed:12493740, ECO:0000269|PubMed:15060076, ECO:0000269|PubMed:16434550, ECO:0000269|PubMed:17376403}.

Q9HC44

Main function of 5'-partner protein: FUNCTION: Possible transcription factor. {ECO:0000305}.
Ensembl transtripts involved in fusion geneENST idsENST00000335866, ENST00000357271, 
ENST00000398810, ENST00000398812, 
ENST00000401949, ENST00000402497, 
ENST00000402578, ENST00000403097, 
ENST00000406641, ENST00000407526, 
ENST00000439599, ENST00000483819, 
ENST00000264779, ENST00000454432, 
ENST00000506184, ENST00000511209, 
ENST00000514387, ENST00000538707, 
ENST00000424459, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 10 X 8=104017 X 16 X 9=2448
# samples 1617
** MAII scorelog2(16/1040*10)=-2.70043971814109
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(17/2448*10)=-3.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: GRB10 [Title/Abstract] AND GPBP1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GRB10 [Title/Abstract] AND GPBP1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GRB10(50685768)-GPBP1(56526673), # samples:1
Anticipated loss of major functional domain due to fusion event.GRB10-GPBP1 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.
GRB10-GPBP1 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.
GRB10-GPBP1 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.
GRB10-GPBP1 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.
GRB10-GPBP1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
GRB10-GPBP1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
GRB10-GPBP1 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted 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
HgeneGRB10

GO:0030178

negative regulation of Wnt signaling pathway

17376403

HgeneGRB10

GO:0030949

positive regulation of vascular endothelial growth factor receptor signaling pathway

15060076



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/chr7:50685768/chr5:56526673)
- 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 GRB10 (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 GPBP1 (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)
ENST00000398810GRB10chr750685768-ENST00000424459GPBP1chr556526673+43039571322375747
ENST00000439599GRB10chr750685768-ENST00000424459GPBP1chr556526673+417482802246748
ENST00000398812GRB10chr750685768-ENST00000424459GPBP1chr556526673+4223877312295754
ENST00000402578GRB10chr750685768-ENST00000424459GPBP1chr556526673+42839372442355703
ENST00000357271GRB10chr750685768-ENST00000424459GPBP1chr556526673+4223877312295754

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
ENST00000398810ENST00000424459GRB10chr750685768-GPBP1chr556526673+0.0006660770.9993339
ENST00000439599ENST00000424459GRB10chr750685768-GPBP1chr556526673+0.0003166530.9996834
ENST00000398812ENST00000424459GRB10chr750685768-GPBP1chr556526673+0.0001659570.99983406
ENST00000402578ENST00000424459GRB10chr750685768-GPBP1chr556526673+0.0006309140.9993691
ENST00000357271ENST00000424459GRB10chr750685768-GPBP1chr556526673+0.0001659570.99983406

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 GRB10-GPBP1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GRB10chr750685768GPBP1chr556526673828229CLEDHELVVQVESTMASESKFLFRKN
GRB10chr750685768GPBP1chr556526673877235CLEDHELVVQVESTMASESKFLFRKN
GRB10chr750685768GPBP1chr556526673937184CLEDHELVVQVESTMASESKFLFRKN
GRB10chr750685768GPBP1chr556526673957228CLEDHELVVQVESTMASESKFLFRKN

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Potential FusionNeoAntigen Information of GRB10-GPBP1 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.
GRB10-GPBP1_50685768_56526673.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)
GRB10-GPBP1chr750685768chr556526673877HLA-B15:17STMASESKF0.9910.88711221
GRB10-GPBP1chr750685768chr556526673877HLA-B15:16STMASESKF0.98370.65061221
GRB10-GPBP1chr750685768chr556526673877HLA-B58:01STMASESKF0.97560.82061221
GRB10-GPBP1chr750685768chr556526673877HLA-B58:02STMASESKF0.97080.87331221
GRB10-GPBP1chr750685768chr556526673877HLA-B57:03STMASESKF0.95160.97311221
GRB10-GPBP1chr750685768chr556526673877HLA-B35:03LVVQVESTM0.80570.8737615
GRB10-GPBP1chr750685768chr556526673877HLA-A32:13STMASESKF0.68470.89141221
GRB10-GPBP1chr750685768chr556526673877HLA-B35:02LVVQVESTM0.45950.9643615
GRB10-GPBP1chr750685768chr556526673877HLA-B35:04LVVQVESTM0.45950.9643615
GRB10-GPBP1chr750685768chr556526673877HLA-B58:02STMASESKFLF0.99990.92611223
GRB10-GPBP1chr750685768chr556526673877HLA-B57:01STMASESKFLF0.99990.96671223
GRB10-GPBP1chr750685768chr556526673877HLA-B57:03STMASESKFLF0.99980.9851223
GRB10-GPBP1chr750685768chr556526673877HLA-B15:16STMASESKFLF0.99960.73521223
GRB10-GPBP1chr750685768chr556526673877HLA-B15:17STMASESKFLF0.99950.92751223
GRB10-GPBP1chr750685768chr556526673877HLA-A32:13STMASESKFLF0.99590.93881223
GRB10-GPBP1chr750685768chr556526673877HLA-C15:04STMASESKF0.95770.88171221
GRB10-GPBP1chr750685768chr556526673877HLA-B15:05STMASESKF0.95490.89551221
GRB10-GPBP1chr750685768chr556526673877HLA-B35:12LVVQVESTM0.45950.9643615
GRB10-GPBP1chr750685768chr556526673877HLA-C03:03LVVQVESTM0.99680.9862615
GRB10-GPBP1chr750685768chr556526673877HLA-C03:04LVVQVESTM0.99680.9862615
GRB10-GPBP1chr750685768chr556526673877HLA-B57:04STMASESKF0.99570.64951221
GRB10-GPBP1chr750685768chr556526673877HLA-C03:02LVVQVESTM0.99540.9718615
GRB10-GPBP1chr750685768chr556526673877HLA-B57:02STMASESKF0.98850.83171221
GRB10-GPBP1chr750685768chr556526673877HLA-B58:06STMASESKF0.97740.74761221
GRB10-GPBP1chr750685768chr556526673877HLA-B15:08LVVQVESTM0.97730.8354615
GRB10-GPBP1chr750685768chr556526673877HLA-B35:43LVVQVESTM0.9730.8406615
GRB10-GPBP1chr750685768chr556526673877HLA-B15:24STMASESKF0.96020.91431221
GRB10-GPBP1chr750685768chr556526673877HLA-C15:09STMASESKF0.95770.88171221
GRB10-GPBP1chr750685768chr556526673877HLA-C03:02STMASESKF0.9570.96951221
GRB10-GPBP1chr750685768chr556526673877HLA-A25:01STMASESKF0.93880.7891221
GRB10-GPBP1chr750685768chr556526673877HLA-A32:01STMASESKF0.9360.8751221
GRB10-GPBP1chr750685768chr556526673877HLA-B35:13LVVQVESTM0.78210.8772615
GRB10-GPBP1chr750685768chr556526673877HLA-B15:30LVVQVESTM0.67220.9179615
GRB10-GPBP1chr750685768chr556526673877HLA-B35:09LVVQVESTM0.45950.9643615
GRB10-GPBP1chr750685768chr556526673877HLA-C16:02STMASESKF0.45440.98471221
GRB10-GPBP1chr750685768chr556526673877HLA-C02:10STMASESKF0.15180.9731221
GRB10-GPBP1chr750685768chr556526673877HLA-C02:02STMASESKF0.15180.9731221
GRB10-GPBP1chr750685768chr556526673877HLA-A25:01ESTMASESKF0.92050.83981121
GRB10-GPBP1chr750685768chr556526673877HLA-A25:01ELVVQVESTM0.88530.8275515
GRB10-GPBP1chr750685768chr556526673877HLA-B57:10STMASESKFLF0.99990.96671223
GRB10-GPBP1chr750685768chr556526673877HLA-B57:04STMASESKFLF0.99990.70671223
GRB10-GPBP1chr750685768chr556526673877HLA-B57:02STMASESKFLF0.99980.88971223

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Potential FusionNeoAntigen Information of GRB10-GPBP1 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.
GRB10-GPBP1_50685768_56526673.msa

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)
GRB10-GPBP1chr750685768chr556526673877DRB1-0413ELVVQVESTMASESK520
GRB10-GPBP1chr750685768chr556526673877DRB1-0422ELVVQVESTMASESK520
GRB10-GPBP1chr750685768chr556526673877DRB1-0440ELVVQVESTMASESK520
GRB10-GPBP1chr750685768chr556526673877DRB1-0444ELVVQVESTMASESK520
GRB10-GPBP1chr750685768chr556526673877DRB1-0444HELVVQVESTMASES419
GRB10-GPBP1chr750685768chr556526673877DRB1-0455ELVVQVESTMASESK520
GRB10-GPBP1chr750685768chr556526673877DRB1-0468ELVVQVESTMASESK520
GRB10-GPBP1chr750685768chr556526673877DRB1-0470ELVVQVESTMASESK520
GRB10-GPBP1chr750685768chr556526673877DRB1-0479ELVVQVESTMASESK520
GRB10-GPBP1chr750685768chr556526673877DRB1-0479HELVVQVESTMASES419

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Fusion breakpoint peptide structures of GRB10-GPBP1

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
5806LVVQVESTMASESKGRB10GPBP1chr750685768chr556526673877

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GRB10-GPBP1

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-B14:023BVN5806LVVQVESTMASESK-7.15543-7.26883
HLA-B14:023BVN5806LVVQVESTMASESK-4.77435-5.80965
HLA-B52:013W395806LVVQVESTMASESK-6.80875-6.92215
HLA-B52:013W395806LVVQVESTMASESK-4.20386-5.23916
HLA-A11:014UQ25806LVVQVESTMASESK-7.5194-8.5547
HLA-A11:014UQ25806LVVQVESTMASESK-6.9601-7.0735
HLA-A24:025HGA5806LVVQVESTMASESK-7.52403-7.63743
HLA-A24:025HGA5806LVVQVESTMASESK-5.82433-6.85963
HLA-B27:056PYJ5806LVVQVESTMASESK-3.28285-4.31815
HLA-B44:053DX85806LVVQVESTMASESK-5.91172-6.94702
HLA-B44:053DX85806LVVQVESTMASESK-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of GRB10-GPBP1

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
GRB10-GPBP1chr750685768chr5565266731121ESTMASESKFTTGCAGTCGTCATTGAATTTTGAGAAGCAT
GRB10-GPBP1chr750685768chr5565266731221STMASESKFCAGTCGTCATTGAATTTTGAGAAGCAT
GRB10-GPBP1chr750685768chr5565266731223STMASESKFLFCAGTCGTCATTGAATTTTGAGAAGCATTCTGAA
GRB10-GPBP1chr750685768chr556526673515ELVVQVESTMGGCAGTCAAACCCAGCTTTTGCAGTCGTCA
GRB10-GPBP1chr750685768chr556526673615LVVQVESTMAGTCAAACCCAGCTTTTGCAGTCGTCA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
GRB10-GPBP1chr750685768chr556526673419HELVVQVESTMASESAATGGCAGTCAAACCCAGCTTTTGCAGTCGTCATTGAATTTTGAG
GRB10-GPBP1chr750685768chr556526673520ELVVQVESTMASESKGGCAGTCAAACCCAGCTTTTGCAGTCGTCATTGAATTTTGAGAAG

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Information of the samples that have these potential fusion neoantigens of GRB10-GPBP1

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
STADGRB10-GPBP1chr750685768ENST00000357271chr556526673ENST00000424459TCGA-HU-8238-01A

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Potential target of CAR-T therapy development for GRB10-GPBP1

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 GRB10-GPBP1

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 GRB10-GPBP1

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