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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:SHFM1-EZH2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SHFM1-EZH2
FusionPDB ID: 81673
FusionGDB2.0 ID: 81673
HgeneTgene
Gene symbol

SHFM1

EZH2

Gene ID

7979

2146

Gene nameSEM1 26S proteasome complex subunitenhancer of zeste 2 polycomb repressive complex 2 subunit
SynonymsC7orf76|DSS1|ECD|SHFD1|SHFM1|SHSF1|Shfdg1ENX-1|ENX1|EZH2b|KMT6|KMT6A|WVS|WVS2
Cytomap

7q21.3

7q36.1

Type of geneprotein-codingprotein-coding
Description26S proteasome complex subunit SEM126S proteasome complex subunit DSS1deleted in split hand/split foot protein 1deleted in split-hand/split-foot 1split hand/foot deleted protein 1split hand/foot malformation (ectrodactyly) type 1split hand/foot malfhistone-lysine N-methyltransferase EZH2enhancer of zeste homolog 2lysine N-methyltransferase 6
Modification date2020032220200329
UniProtAcc.

Q15910

Main function of 5'-partner protein: FUNCTION: Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2 (PubMed:22323599, PubMed:30923826). Compared to EZH1-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA. Regulates the circadian clock via histone methylation at the promoter of the circadian genes. Essential for the CRY1/2-mediated repression of the transcriptional activation of PER1/2 by the CLOCK-ARNTL/BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-27' of histone H3 on PER1/2 promoters which is necessary for the CRY1/2 proteins to inhibit transcription. {ECO:0000269|PubMed:14532106, ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:16179254, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:16618801, ECO:0000269|PubMed:16717091, ECO:0000269|PubMed:16936726, ECO:0000269|PubMed:17210787, ECO:0000269|PubMed:17344414, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:19026781, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:22323599, ECO:0000269|PubMed:23063525, ECO:0000269|PubMed:24474760, ECO:0000269|PubMed:30923826}.
Ensembl transtripts involved in fusion geneENST idsENST00000248566, ENST00000413065, 
ENST00000417009, ENST00000444799, 
ENST00000493858, 
ENST00000536783, 
ENST00000320356, ENST00000350995, 
ENST00000460911, ENST00000476773, 
ENST00000478654, ENST00000483967, 
ENST00000541220, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score17 X 9 X 5=76510 X 7 X 5=350
# samples 189
** MAII scorelog2(18/765*10)=-2.08746284125034
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/350*10)=-1.95935801550265
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SHFM1 [Title/Abstract] AND EZH2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SHFM1 [Title/Abstract] AND EZH2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SHFM1(96324109)-EZH2(148512638), # samples:1
Anticipated loss of major functional domain due to fusion event.SHFM1-EZH2 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.
SHFM1-EZH2 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.
SHFM1-EZH2 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.
SHFM1-EZH2 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
TgeneEZH2

GO:0000122

negative regulation of transcription by RNA polymerase II

20154697

TgeneEZH2

GO:0010718

positive regulation of epithelial to mesenchymal transition

20154697

TgeneEZH2

GO:0043406

positive regulation of MAP kinase activity

20154697

TgeneEZH2

GO:0043547

positive regulation of GTPase activity

20154697

TgeneEZH2

GO:0045814

negative regulation of gene expression, epigenetic

20154697

TgeneEZH2

GO:0070734

histone H3-K27 methylation

24474760

TgeneEZH2

GO:0071902

positive regulation of protein serine/threonine kinase activity

20154697



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/chr7:96324109/chr7:148512638)
- 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 SHFM1 (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 EZH2 (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)
ENST00000417009SHFM1chr796324109-ENST00000478654EZH2chr7148512638-115526898892264
ENST00000417009SHFM1chr796324109-ENST00000460911EZH2chr7148512638-1280268981018306
ENST00000417009SHFM1chr796324109-ENST00000350995EZH2chr7148512638-1280268981018306
ENST00000417009SHFM1chr796324109-ENST00000320356EZH2chr7148512638-1280268981018306
ENST00000417009SHFM1chr796324109-ENST00000541220EZH2chr7148512638-115426898892264
ENST00000417009SHFM1chr796324109-ENST00000476773EZH2chr7148512638-105726898892264
ENST00000417009SHFM1chr796324109-ENST00000483967EZH2chr7148512638-1140268981018306
ENST00000444799SHFM1chr796324109-ENST00000478654EZH2chr7148512638-115226595889264
ENST00000444799SHFM1chr796324109-ENST00000460911EZH2chr7148512638-1277265951015306
ENST00000444799SHFM1chr796324109-ENST00000350995EZH2chr7148512638-1277265951015306
ENST00000444799SHFM1chr796324109-ENST00000320356EZH2chr7148512638-1277265951015306
ENST00000444799SHFM1chr796324109-ENST00000541220EZH2chr7148512638-115126595889264
ENST00000444799SHFM1chr796324109-ENST00000476773EZH2chr7148512638-105426595889264
ENST00000444799SHFM1chr796324109-ENST00000483967EZH2chr7148512638-1137265951015306
ENST00000413065SHFM1chr796324109-ENST00000478654EZH2chr7148512638-114525888882264
ENST00000413065SHFM1chr796324109-ENST00000460911EZH2chr7148512638-1270258881008306
ENST00000413065SHFM1chr796324109-ENST00000350995EZH2chr7148512638-1270258881008306
ENST00000413065SHFM1chr796324109-ENST00000320356EZH2chr7148512638-1270258881008306
ENST00000413065SHFM1chr796324109-ENST00000541220EZH2chr7148512638-114425888882264
ENST00000413065SHFM1chr796324109-ENST00000476773EZH2chr7148512638-104725888882264
ENST00000413065SHFM1chr796324109-ENST00000483967EZH2chr7148512638-1130258881008306
ENST00000248566SHFM1chr796324109-ENST00000478654EZH2chr7148512638-1185298128922264
ENST00000248566SHFM1chr796324109-ENST00000460911EZH2chr7148512638-13102981281048306
ENST00000248566SHFM1chr796324109-ENST00000350995EZH2chr7148512638-13102981281048306
ENST00000248566SHFM1chr796324109-ENST00000320356EZH2chr7148512638-13102981281048306
ENST00000248566SHFM1chr796324109-ENST00000541220EZH2chr7148512638-1184298128922264
ENST00000248566SHFM1chr796324109-ENST00000476773EZH2chr7148512638-1087298128922264
ENST00000248566SHFM1chr796324109-ENST00000483967EZH2chr7148512638-11702981281048306

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
ENST00000417009ENST00000478654SHFM1chr796324109-EZH2chr7148512638-0.0005191070.9994809
ENST00000417009ENST00000460911SHFM1chr796324109-EZH2chr7148512638-0.0003041790.9996959
ENST00000417009ENST00000350995SHFM1chr796324109-EZH2chr7148512638-0.0003041790.9996959
ENST00000417009ENST00000320356SHFM1chr796324109-EZH2chr7148512638-0.0003041790.9996959
ENST00000417009ENST00000541220SHFM1chr796324109-EZH2chr7148512638-0.0005228790.9994771
ENST00000417009ENST00000476773SHFM1chr796324109-EZH2chr7148512638-0.0005307890.9994692
ENST00000417009ENST00000483967SHFM1chr796324109-EZH2chr7148512638-0.0003742380.9996257
ENST00000444799ENST00000478654SHFM1chr796324109-EZH2chr7148512638-0.0005053040.9994947
ENST00000444799ENST00000460911SHFM1chr796324109-EZH2chr7148512638-0.0002921460.9997079
ENST00000444799ENST00000350995SHFM1chr796324109-EZH2chr7148512638-0.0002921460.9997079
ENST00000444799ENST00000320356SHFM1chr796324109-EZH2chr7148512638-0.0002921460.9997079
ENST00000444799ENST00000541220SHFM1chr796324109-EZH2chr7148512638-0.000509490.9994905
ENST00000444799ENST00000476773SHFM1chr796324109-EZH2chr7148512638-0.0005095140.9994905
ENST00000444799ENST00000483967SHFM1chr796324109-EZH2chr7148512638-0.0003573560.9996426
ENST00000413065ENST00000478654SHFM1chr796324109-EZH2chr7148512638-0.0004829020.9995171
ENST00000413065ENST00000460911SHFM1chr796324109-EZH2chr7148512638-0.0002887640.9997112
ENST00000413065ENST00000350995SHFM1chr796324109-EZH2chr7148512638-0.0002887640.9997112
ENST00000413065ENST00000320356SHFM1chr796324109-EZH2chr7148512638-0.0002887640.9997112
ENST00000413065ENST00000541220SHFM1chr796324109-EZH2chr7148512638-0.0004860280.999514
ENST00000413065ENST00000476773SHFM1chr796324109-EZH2chr7148512638-0.0004876820.9995123
ENST00000413065ENST00000483967SHFM1chr796324109-EZH2chr7148512638-0.0003518350.9996482
ENST00000248566ENST00000478654SHFM1chr796324109-EZH2chr7148512638-0.0005260070.999474
ENST00000248566ENST00000460911SHFM1chr796324109-EZH2chr7148512638-0.0003123070.9996877
ENST00000248566ENST00000350995SHFM1chr796324109-EZH2chr7148512638-0.0003123070.9996877
ENST00000248566ENST00000320356SHFM1chr796324109-EZH2chr7148512638-0.0003123070.9996877
ENST00000248566ENST00000541220SHFM1chr796324109-EZH2chr7148512638-0.0005307050.99946934
ENST00000248566ENST00000476773SHFM1chr796324109-EZH2chr7148512638-0.0005357590.9994642
ENST00000248566ENST00000483967SHFM1chr796324109-EZH2chr7148512638-0.0003684830.9996315

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 SHFM1-EZH2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SHFM1chr796324109EZH2chr714851263825856DDDNVEDDFSNQLRLWAAHCRKIQLK
SHFM1chr796324109EZH2chr714851263826556DDDNVEDDFSNQLRLWAAHCRKIQLK
SHFM1chr796324109EZH2chr714851263826856DDDNVEDDFSNQLRLWAAHCRKIQLK
SHFM1chr796324109EZH2chr714851263829856DDDNVEDDFSNQLRLWAAHCRKIQLK

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Potential FusionNeoAntigen Information of SHFM1-EZH2 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.
SHFM1-EZH2_96324109_148512638.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)
SHFM1-EZH2chr796324109chr7148512638298HLA-B57:01FSNQLRLW0.99990.9142816
SHFM1-EZH2chr796324109chr7148512638298HLA-B58:02FSNQLRLW0.99950.8175816
SHFM1-EZH2chr796324109chr7148512638298HLA-B58:01FSNQLRLW0.99920.7767816
SHFM1-EZH2chr796324109chr7148512638298HLA-B08:09SNQLRLWAA0.9870.6843918
SHFM1-EZH2chr796324109chr7148512638298HLA-B57:10FSNQLRLW0.99990.9142816
SHFM1-EZH2chr796324109chr7148512638298HLA-B57:04FSNQLRLW0.99950.6384816
SHFM1-EZH2chr796324109chr7148512638298HLA-B58:06FSNQLRLW0.99880.7027816

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Potential FusionNeoAntigen Information of SHFM1-EZH2 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.
SHFM1-EZH2_96324109_148512638.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)
SHFM1-EZH2chr796324109chr7148512638298DRB5-0106SNQLRLWAAHCRKIQ924
SHFM1-EZH2chr796324109chr7148512638298DRB5-0202SNQLRLWAAHCRKIQ924
SHFM1-EZH2chr796324109chr7148512638298DRB5-0202FSNQLRLWAAHCRKI823
SHFM1-EZH2chr796324109chr7148512638298DRB5-0204SNQLRLWAAHCRKIQ924

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Fusion breakpoint peptide structures of SHFM1-EZH2

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
1026DDFSNQLRLWAAHCSHFM1EZH2chr796324109chr7148512638298

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SHFM1-EZH2

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-B14:023BVN1026DDFSNQLRLWAAHC-7.9962-8.1096
HLA-B14:023BVN1026DDFSNQLRLWAAHC-5.70842-6.74372
HLA-B52:013W391026DDFSNQLRLWAAHC-6.83737-6.95077
HLA-B52:013W391026DDFSNQLRLWAAHC-4.4836-5.5189
HLA-A11:014UQ21026DDFSNQLRLWAAHC-10.0067-10.1201
HLA-A11:014UQ21026DDFSNQLRLWAAHC-9.03915-10.0745
HLA-A24:025HGA1026DDFSNQLRLWAAHC-6.56204-6.67544
HLA-A24:025HGA1026DDFSNQLRLWAAHC-5.42271-6.45801
HLA-B44:053DX81026DDFSNQLRLWAAHC-7.85648-8.89178
HLA-B44:053DX81026DDFSNQLRLWAAHC-5.3978-5.5112
HLA-B35:011A1N1026DDFSNQLRLWAAHC-6.27422-6.38762
HLA-B35:011A1N1026DDFSNQLRLWAAHC-5.27424-6.30954
HLA-A02:016TDR1026DDFSNQLRLWAAHC-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of SHFM1-EZH2

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
SHFM1-EZH2chr796324109chr7148512638816FSNQLRLWCTCTAATCAGTTACGGTTGTGGGC
SHFM1-EZH2chr796324109chr7148512638918SNQLRLWAATAATCAGTTACGGTTGTGGGCTGCACA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
SHFM1-EZH2chr796324109chr7148512638823FSNQLRLWAAHCRKICTCTAATCAGTTACGGTTGTGGGCTGCACACTGCAGAAAGATACA
SHFM1-EZH2chr796324109chr7148512638924SNQLRLWAAHCRKIQTAATCAGTTACGGTTGTGGGCTGCACACTGCAGAAAGATACAGCT

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Information of the samples that have these potential fusion neoantigens of SHFM1-EZH2

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
STADSHFM1-EZH2chr796324109ENST00000248566chr7148512638ENST00000320356TCGA-CD-8527

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Potential target of CAR-T therapy development for SHFM1-EZH2

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 SHFM1-EZH2

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 SHFM1-EZH2

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