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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:ARHGAP15-MBNL1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ARHGAP15-MBNL1
FusionPDB ID: 5951
FusionGDB2.0 ID: 5951
HgeneTgene
Gene symbol

ARHGAP15

MBNL1

Gene ID

55843

4154

Gene nameRho GTPase activating protein 15muscleblind like splicing regulator 1
SynonymsBM046EXP|MBNL
Cytomap

2q22.2-q22.3

3q25.1-q25.2

Type of geneprotein-codingprotein-coding
Descriptionrho GTPase-activating protein 15rho-type GTPase-activating protein 15muscleblind-like protein 1muscleblind-liketriplet-expansion RNA-binding protein
Modification date2020031320200327
UniProtAcc

Q53QZ3

Main function of 5'-partner protein: FUNCTION: GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has activity toward RAC1. Overexpression results in an increase in actin stress fibers and cell contraction. {ECO:0000269|PubMed:12650940}.

Q9NR56

Main function of 5'-partner protein: FUNCTION: Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. Regulates the TNNT2 exon 5 skipping through competition with U2AF2. Inhibits the formation of the spliceosome A complex on intron 4 of TNNT2 pre-mRNA. Binds to the stem-loop structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Binds to the 5'-YGCU(U/G)Y-3'consensus sequence. Binds to the IR RNA. Binds to expanded CUG repeat RNA, which folds into a hairpin structure containing GC base pairs and bulged, unpaired U residues. {ECO:0000269|PubMed:10970838, ECO:0000269|PubMed:15257297, ECO:0000269|PubMed:16946708, ECO:0000269|PubMed:18335541, ECO:0000269|PubMed:19470458}.
Ensembl transtripts involved in fusion geneENST idsENST00000295095, ENST00000409869, 
ENST00000473426, 
ENST00000461436, 
ENST00000282486, ENST00000282488, 
ENST00000324196, ENST00000324210, 
ENST00000355460, ENST00000357472, 
ENST00000463374, ENST00000485509, 
ENST00000485910, ENST00000492948, 
ENST00000493459, ENST00000498502, 
ENST00000545754, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 13 X 5=97528 X 14 X 6=2352
# samples 1628
** MAII scorelog2(16/975*10)=-2.60733031374961
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(28/2352*10)=-3.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ARHGAP15 [Title/Abstract] AND MBNL1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ARHGAP15 [Title/Abstract] AND MBNL1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ARHGAP15(144008170)-MBNL1(152132728), # samples:1
Anticipated loss of major functional domain due to fusion event.ARHGAP15-MBNL1 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.
ARHGAP15-MBNL1 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.
ARHGAP15-MBNL1 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.
ARHGAP15-MBNL1 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
HgeneARHGAP15

GO:0008360

regulation of cell shape

12650940

TgeneMBNL1

GO:0008380

RNA splicing

18335541

TgeneMBNL1

GO:0043484

regulation of RNA splicing

15257297|16946708



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/chr2:144008170/chr3:152132728)
- 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 ARHGAP15 (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 MBNL1 (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)
ENST00000295095ARHGAP15chr2144008170+ENST00000282488MBNL1chr3152132728+47896411671375402
ENST00000295095ARHGAP15chr2144008170+ENST00000282486MBNL1chr3152132728+50476411671633488
ENST00000295095ARHGAP15chr2144008170+ENST00000355460MBNL1chr3152132728+49946411671579470
ENST00000295095ARHGAP15chr2144008170+ENST00000493459MBNL1chr3152132728+45226411671669500
ENST00000295095ARHGAP15chr2144008170+ENST00000324210MBNL1chr3152132728+50136411671615482
ENST00000295095ARHGAP15chr2144008170+ENST00000498502MBNL1chr3152132728+49366411671513448
ENST00000295095ARHGAP15chr2144008170+ENST00000545754MBNL1chr3152132728+48256411671411414
ENST00000295095ARHGAP15chr2144008170+ENST00000357472MBNL1chr3152132728+49346411671495442
ENST00000295095ARHGAP15chr2144008170+ENST00000324196MBNL1chr3152132728+49036411671489440
ENST00000295095ARHGAP15chr2144008170+ENST00000485910MBNL1chr3152132728+42136411671375402
ENST00000295095ARHGAP15chr2144008170+ENST00000463374MBNL1chr3152132728+50486411671633488
ENST00000295095ARHGAP15chr2144008170+ENST00000492948MBNL1chr3152132728+15216411671495442
ENST00000295095ARHGAP15chr2144008170+ENST00000485509MBNL1chr3152132728+14906411671489441

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
ENST00000295095ENST00000282488ARHGAP15chr2144008170+MBNL1chr3152132728+0.0011131320.9988869
ENST00000295095ENST00000282486ARHGAP15chr2144008170+MBNL1chr3152132728+0.00053480.99946517
ENST00000295095ENST00000355460ARHGAP15chr2144008170+MBNL1chr3152132728+0.0006393410.9993606
ENST00000295095ENST00000493459ARHGAP15chr2144008170+MBNL1chr3152132728+0.0007363890.9992636
ENST00000295095ENST00000324210ARHGAP15chr2144008170+MBNL1chr3152132728+0.0007429580.999257
ENST00000295095ENST00000498502ARHGAP15chr2144008170+MBNL1chr3152132728+0.0005987890.9994012
ENST00000295095ENST00000545754ARHGAP15chr2144008170+MBNL1chr3152132728+0.0013712610.99862874
ENST00000295095ENST00000357472ARHGAP15chr2144008170+MBNL1chr3152132728+0.0007399780.99926
ENST00000295095ENST00000324196ARHGAP15chr2144008170+MBNL1chr3152132728+0.0012165330.9987835
ENST00000295095ENST00000485910ARHGAP15chr2144008170+MBNL1chr3152132728+0.0012618520.9987381
ENST00000295095ENST00000463374ARHGAP15chr2144008170+MBNL1chr3152132728+0.0005352560.9994648
ENST00000295095ENST00000492948ARHGAP15chr2144008170+MBNL1chr3152132728+0.0033118180.9966882
ENST00000295095ENST00000485509ARHGAP15chr2144008170+MBNL1chr3152132728+0.0050340140.994966

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 ARHGAP15-MBNL1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ARHGAP15chr2144008170MBNL1chr3152132728641158WAKEKSSRKNVFQGRCSRENCKYLHP
ARHGAP15chr2144008170MBNL1chr3152132728641281AAAAAQKLMRTDRLEVCREYQRGNCN

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Potential FusionNeoAntigen Information of ARHGAP15-MBNL1 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.
ARHGAP15-MBNL1_144008170_152132728.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)
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-B39:06MRTDRLEVC0.97920.8041817
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-B14:02QKLMRTDRL0.96450.5456514
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-B14:01QKLMRTDRL0.96450.5456514
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-B15:18DRLEVCREY0.2480.56131120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-A02:13KLMRTDRLEV0.99240.656616
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-C07:27DRLEVCREY0.91650.89461120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-C07:95DRLEVCREY0.90630.56741120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-C07:05DRLEVCREY0.78170.90131120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-C07:19DRLEVCREY0.72450.56921120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-C07:46DRLEVCREY0.72280.78241120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-C07:80DRLEVCREY0.71240.87251120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-C07:67DRLEVCREY0.71240.87251120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-C07:10DRLEVCREY0.70860.91141120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-B14:03QKLMRTDRL0.26030.6782514
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-C12:16DRLEVCREY0.02240.87421120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-B27:03RTDRLEVCREY0.74540.6915920
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-C07:01DRLEVCREY0.9340.52021120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-C07:02DRLEVCREY0.71240.87251120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-C07:17DRLEVCREY0.69650.89771120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-C07:22DRLEVCREY0.65670.59921120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-B18:07DRLEVCREY0.63380.67961120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-B18:06DRLEVCREY0.62350.73591120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-B18:03DRLEVCREY0.60420.73841120
ARHGAP15-MBNL1chr2144008170chr3152132728641HLA-B57:04RTDRLEVCREY0.9980.6563920

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Potential FusionNeoAntigen Information of ARHGAP15-MBNL1 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.
ARHGAP15-MBNL1_144008170_152132728.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)
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1401AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1418AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1426AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1435AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1438AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1443AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1445AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1454AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1458AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1460AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1462AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1462AAQKLMRTDRLEVCR318
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1475AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1482AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1486AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1487AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1488AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1490AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1497AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1499AQKLMRTDRLEVCRE419
ARHGAP15-MBNL1chr2144008170chr3152132728641DRB1-1499AAQKLMRTDRLEVCR318

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Fusion breakpoint peptide structures of ARHGAP15-MBNL1

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
4396KLMRTDRLEVCREYARHGAP15MBNL1chr2144008170chr3152132728641

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ARHGAP15-MBNL1

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-B14:023BVN4396KLMRTDRLEVCREY-7.9962-8.1096
HLA-B14:023BVN4396KLMRTDRLEVCREY-5.70842-6.74372
HLA-B52:013W394396KLMRTDRLEVCREY-6.83737-6.95077
HLA-B52:013W394396KLMRTDRLEVCREY-4.4836-5.5189
HLA-A11:014UQ24396KLMRTDRLEVCREY-10.0067-10.1201
HLA-A11:014UQ24396KLMRTDRLEVCREY-9.03915-10.0745
HLA-A24:025HGA4396KLMRTDRLEVCREY-6.56204-6.67544
HLA-A24:025HGA4396KLMRTDRLEVCREY-5.42271-6.45801
HLA-B44:053DX84396KLMRTDRLEVCREY-7.85648-8.89178
HLA-B44:053DX84396KLMRTDRLEVCREY-5.3978-5.5112
HLA-A02:016TDR4396KLMRTDRLEVCREY-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ARHGAP15-MBNL1

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
ARHGAP15-MBNL1chr2144008170chr31521327281120DRLEVCREYTTTCAGGGCCGTTGCTCCAGGGAGAAC
ARHGAP15-MBNL1chr2144008170chr3152132728514QKLMRTDRLTCGAGCAGAAAGAATGTCTTTCAGGGC
ARHGAP15-MBNL1chr2144008170chr3152132728616KLMRTDRLEVAGCAGAAAGAATGTCTTTCAGGGCCGTTGC
ARHGAP15-MBNL1chr2144008170chr3152132728817MRTDRLEVCAAGAATGTCTTTCAGGGCCGTTGCTCC
ARHGAP15-MBNL1chr2144008170chr3152132728920RTDRLEVCREYAATGTCTTTCAGGGCCGTTGCTCCAGGGAGAAC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ARHGAP15-MBNL1chr2144008170chr3152132728318AAQKLMRTDRLEVCRGAAAAATCGAGCAGAAAGAATGTCTTTCAGGGCCGTTGCTCCAGG
ARHGAP15-MBNL1chr2144008170chr3152132728419AQKLMRTDRLEVCREAAATCGAGCAGAAAGAATGTCTTTCAGGGCCGTTGCTCCAGGGAG

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Information of the samples that have these potential fusion neoantigens of ARHGAP15-MBNL1

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
N/AARHGAP15-MBNL1chr2144008170ENST00000295095chr3152132728ENST00000282486AL832395

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Potential target of CAR-T therapy development for ARHGAP15-MBNL1

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 ARHGAP15-MBNL1

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 ARHGAP15-MBNL1

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