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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:RYK-RABL3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RYK-RABL3
FusionPDB ID: 78790
FusionGDB2.0 ID: 78790
HgeneTgene
Gene symbol

RYK

RABL3

Gene ID

6259

285282

Gene namereceptor like tyrosine kinaseRAB, member of RAS oncogene family like 3
SynonymsD3S3195|JTK5|JTK5A|RYK1PNCA5
Cytomap

3q22.2

3q13.33

Type of geneprotein-codingprotein-coding
Descriptiontyrosine-protein kinase RYKJTK5A protein tyrosine kinasehydroxyaryl-protein kinaserab-like protein 3
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000296084, ENST00000427044, 
ENST00000484106, 
ENST00000483733, 
ENST00000491398, ENST00000273375, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 10 X 6=5403 X 3 X 3=27
# samples 124
** MAII scorelog2(12/540*10)=-2.16992500144231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/27*10)=0.567040592723894
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: RYK [Title/Abstract] AND RABL3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RYK [Title/Abstract] AND RABL3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RYK(133913926)-RABL3(120417420), # samples:2
RYK(133921574)-RABL3(120417420), # samples:2
Anticipated loss of major functional domain due to fusion event.RYK-RABL3 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.
RYK-RABL3 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.
RYK-RABL3 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.
RYK-RABL3 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.
RYK-RABL3 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
RYK-RABL3 seems lost the major protein functional domain in Hgene partner, which is a kinase 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
HgeneRYK

GO:0006468

protein phosphorylation

10454588

HgeneRYK

GO:0043410

positive regulation of MAPK cascade

10454588



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/chr3:133913926/chr3:120417420)
- 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 RYK (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 RABL3 (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)
ENST00000296084RYKchr3133921573-ENST00000273375RABL3chr3120417420-4252782151109364
ENST00000427044RYKchr3133921573-ENST00000273375RABL3chr3120417420-4293823741150358
ENST00000296084RYKchr3133921574-ENST00000273375RABL3chr3120417420-4252782151109364
ENST00000427044RYKchr3133921574-ENST00000273375RABL3chr3120417420-4293823741150358

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
ENST00000296084ENST00000273375RYKchr3133921573-RABL3chr3120417420-0.0015951970.9984048
ENST00000427044ENST00000273375RYKchr3133921573-RABL3chr3120417420-0.0015754720.99842453
ENST00000296084ENST00000273375RYKchr3133921574-RABL3chr3120417420-0.0015951970.9984048
ENST00000427044ENST00000273375RYKchr3133921574-RABL3chr3120417420-0.0015754720.99842453

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 RYK-RABL3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RYKchr3133921573RABL3chr3120417420823249LHLHSMKRIELDDRDYDQEQFADNQI
RYKchr3133921574RABL3chr3120417420823249LHLHSMKRIELDDRDYDQEQFADNQI

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Potential FusionNeoAntigen Information of RYK-RABL3 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.
RYK-RABL3_133921573_120417420.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)
RYK-RABL3chr3133921573chr3120417420823HLA-B39:01DRDYDQEQF0.9030.92121221
RYK-RABL3chr3133921573chr3120417420823HLA-B38:01DRDYDQEQF0.87320.96371221
RYK-RABL3chr3133921573chr3120417420823HLA-B38:02DRDYDQEQF0.86850.95611221
RYK-RABL3chr3133921573chr3120417420823HLA-B15:37DRDYDQEQF0.73730.67821221
RYK-RABL3chr3133921573chr3120417420823HLA-B15:18DRDYDQEQF0.44140.80661221
RYK-RABL3chr3133921573chr3120417420823HLA-B27:05KRIELDDRDY0.99920.7102616
RYK-RABL3chr3133921573chr3120417420823HLA-B39:09DRDYDQEQF0.91780.82311221
RYK-RABL3chr3133921573chr3120417420823HLA-B39:12DRDYDQEQF0.89240.92131221
RYK-RABL3chr3133921573chr3120417420823HLA-B39:05DRDYDQEQF0.83280.90581221
RYK-RABL3chr3133921573chr3120417420823HLA-B27:03KRIELDDRDY0.99360.7394616
RYK-RABL3chr3133921573chr3120417420823HLA-B73:01DRDYDQEQFA0.92240.94121222
RYK-RABL3chr3133921573chr3120417420823HLA-B39:31DRDYDQEQF0.91630.92081221
RYK-RABL3chr3133921573chr3120417420823HLA-B38:05DRDYDQEQF0.87320.96371221
RYK-RABL3chr3133921573chr3120417420823HLA-B39:11DRDYDQEQF0.45890.87571221
RYK-RABL3chr3133921573chr3120417420823HLA-B27:08KRIELDDRDY0.9990.5682616

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Potential FusionNeoAntigen Information of RYK-RABL3 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.
RYK-RABL3_133921573_120417420.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)
RYK-RABL3chr3133921573chr3120417420823DRB1-0301MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0301SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0307MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0310MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0310SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0310KRIELDDRDYDQEQF621
RYK-RABL3chr3133921573chr3120417420823DRB1-0310HSMKRIELDDRDYDQ318
RYK-RABL3chr3133921573chr3120417420823DRB1-0313MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0313SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0315MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0315SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0315KRIELDDRDYDQEQF621
RYK-RABL3chr3133921573chr3120417420823DRB1-0315HSMKRIELDDRDYDQ318
RYK-RABL3chr3133921573chr3120417420823DRB1-0318MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0318SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0320MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0320SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0322MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0322SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0324MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0326MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0326SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0326KRIELDDRDYDQEQF621
RYK-RABL3chr3133921573chr3120417420823DRB1-0328MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0328SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0330MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0330SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0332MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0332SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0334MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0334SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0336MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0336SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0342MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0344MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0344SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0346MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0346SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0348MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0348SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0350MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0350SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0352MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0352SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-0354MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-0354SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-1107MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-1192LHLHSMKRIELDDRD015
RYK-RABL3chr3133921573chr3120417420823DRB1-1303MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-13101MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-1310MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-1333MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-1333SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-1333KRIELDDRDYDQEQF621
RYK-RABL3chr3133921573chr3120417420823DRB1-1381MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-1381SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-1388MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-1389MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-1389SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-1390MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-1394MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-1394SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-1394KRIELDDRDYDQEQF621
RYK-RABL3chr3133921573chr3120417420823DRB1-1394HSMKRIELDDRDYDQ318
RYK-RABL3chr3133921573chr3120417420823DRB1-1395MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-1476MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-1476SMKRIELDDRDYDQE419
RYK-RABL3chr3133921573chr3120417420823DRB1-1479MKRIELDDRDYDQEQ520
RYK-RABL3chr3133921573chr3120417420823DRB1-1479SMKRIELDDRDYDQE419

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Fusion breakpoint peptide structures of RYK-RABL3

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
4557KRIELDDRDYDQEQRYKRABL3chr3133921573chr3120417420823

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RYK-RABL3

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-B14:023BVN4557KRIELDDRDYDQEQ-7.9962-8.1096
HLA-B14:023BVN4557KRIELDDRDYDQEQ-5.70842-6.74372
HLA-B52:013W394557KRIELDDRDYDQEQ-6.83737-6.95077
HLA-B52:013W394557KRIELDDRDYDQEQ-4.4836-5.5189
HLA-A11:014UQ24557KRIELDDRDYDQEQ-10.0067-10.1201
HLA-A11:014UQ24557KRIELDDRDYDQEQ-9.03915-10.0745
HLA-A24:025HGA4557KRIELDDRDYDQEQ-6.56204-6.67544
HLA-A24:025HGA4557KRIELDDRDYDQEQ-5.42271-6.45801
HLA-B44:053DX84557KRIELDDRDYDQEQ-7.85648-8.89178
HLA-B44:053DX84557KRIELDDRDYDQEQ-5.3978-5.5112
HLA-A02:016TDR4557KRIELDDRDYDQEQ-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of RYK-RABL3

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
RYK-RABL3chr3133921573chr31204174201221DRDYDQEQFCAGGGATTATGATCAAGAACAGTTTGC
RYK-RABL3chr3133921573chr31204174201222DRDYDQEQFACAGGGATTATGATCAAGAACAGTTTGCTGA
RYK-RABL3chr3133921573chr3120417420616KRIELDDRDYAAGGATTGAACTGGATGACAGGGATTATGA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
RYK-RABL3chr3133921573chr3120417420015LHLHSMKRIELDDRDGCACCTTCATAGTATGAAAAGGATTGAACTGGATGACAGGGATTA
RYK-RABL3chr3133921573chr3120417420318HSMKRIELDDRDYDQTAGTATGAAAAGGATTGAACTGGATGACAGGGATTATGATCAAGA
RYK-RABL3chr3133921573chr3120417420419SMKRIELDDRDYDQETATGAAAAGGATTGAACTGGATGACAGGGATTATGATCAAGAACA
RYK-RABL3chr3133921573chr3120417420520MKRIELDDRDYDQEQGAAAAGGATTGAACTGGATGACAGGGATTATGATCAAGAACAGTT
RYK-RABL3chr3133921573chr3120417420621KRIELDDRDYDQEQFAAGGATTGAACTGGATGACAGGGATTATGATCAAGAACAGTTTGC

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Information of the samples that have these potential fusion neoantigens of RYK-RABL3

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
BRCARYK-RABL3chr3133921573ENST00000427044chr3120417420ENST00000273375TCGA-BH-A0DL

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Potential target of CAR-T therapy development for RYK-RABL3

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
HgeneRYKchr3:133921573chr3:120417420ENST00000296084-716228_248260609.0TransmembraneHelical
HgeneRYKchr3:133921574chr3:120417420ENST00000296084-716228_248260609.0TransmembraneHelical

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 RYK-RABL3

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 RYK-RABL3

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