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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:SLC35E4-HSCB

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SLC35E4-HSCB
FusionPDB ID: 82999
FusionGDB2.0 ID: 82999
HgeneTgene
Gene symbol

SLC35E4

HSCB

Gene ID

339665

150274

Gene namesolute carrier family 35 member E4HscB mitochondrial iron-sulfur cluster cochaperone
Synonyms-DNAJC20|HSC20|JAC1
Cytomap

22q12.2

22q12.1

Type of geneprotein-codingprotein-coding
Descriptionsolute carrier family 35 member E4iron-sulfur cluster co-chaperone protein HscBDnaJ (Hsp40) homolog, subfamily C, member 20HscB iron-sulfur cluster co-chaperone homologHscB mitochondrial iron-sulfur cluster co-chaperoneJ-type co-chaperone HSC20epididymis secretory sperm binding prote
Modification date2020031320200320
UniProtAcc.

Q8IWL3

Main function of 5'-partner protein: FUNCTION: Acts as a co-chaperone in iron-sulfur cluster assembly in both mitochondria and the cytoplasm (PubMed:20668094, PubMed:29309586). Required for incorporation of iron-sulfur clusters into SDHB, the iron-sulfur protein subunit of succinate dehydrogenase that is involved in complex II of the mitochondrial electron transport chain (PubMed:26749241). Recruited to SDHB by interaction with SDHAF1 which first binds SDHB and then recruits the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20 (PubMed:26749241). Also mediates complex formation between components of the cytosolic iron-sulfur biogenesis pathway and the CIA targeting complex composed of CIAO1, DIPK1B/FAM69B and MMS19 by binding directly to the scaffold protein ISCU and to CIAO1 (PubMed:29309586). This facilitates iron-sulfur cluster insertion into a number of cytoplasmic and nuclear proteins including POLD1, ELP3, DPYD and PPAT (PubMed:29309586). {ECO:0000269|PubMed:20668094, ECO:0000269|PubMed:26749241, ECO:0000269|PubMed:29309586}.
Ensembl transtripts involved in fusion geneENST idsENST00000300385, ENST00000343605, 
ENST00000406566, 
ENST00000495977, 
ENST00000216027, ENST00000398941, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 3 X 3=3612 X 9 X 8=864
# samples 418
** MAII scorelog2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(18/864*10)=-2.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: SLC35E4 [Title/Abstract] AND HSCB [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SLC35E4 [Title/Abstract] AND HSCB [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SLC35E4(31033056)-HSCB(29147229), # samples:1
Anticipated loss of major functional domain due to fusion event.SLC35E4-HSCB 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.
SLC35E4-HSCB 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.
SLC35E4-HSCB 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.
SLC35E4-HSCB 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


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/chr22:31033056/chr22:29147229)
- 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 SLC35E4 (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 HSCB (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)
ENST00000343605SLC35E4chr2231033056+ENST00000216027HSCBchr2229147229+189914187391557272
ENST00000343605SLC35E4chr2231033056+ENST00000398941HSCBchr2229147229+190414187391557272
ENST00000300385SLC35E4chr2231033056+ENST00000216027HSCBchr2229147229+174512645851403272
ENST00000300385SLC35E4chr2231033056+ENST00000398941HSCBchr2229147229+175012645851403272
ENST00000406566SLC35E4chr2231033056+ENST00000216027HSCBchr2229147229+122874768886272
ENST00000406566SLC35E4chr2231033056+ENST00000398941HSCBchr2229147229+123374768886272

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
ENST00000343605ENST00000216027SLC35E4chr2231033056+HSCBchr2229147229+0.403028880.5969711
ENST00000343605ENST00000398941SLC35E4chr2231033056+HSCBchr2229147229+0.407673060.59232694
ENST00000300385ENST00000216027SLC35E4chr2231033056+HSCBchr2229147229+0.38792440.6120756
ENST00000300385ENST00000398941SLC35E4chr2231033056+HSCBchr2229147229+0.393995340.6060046
ENST00000406566ENST00000216027SLC35E4chr2231033056+HSCBchr2229147229+0.332686540.66731346
ENST00000406566ENST00000398941SLC35E4chr2231033056+HSCBchr2229147229+0.336873650.66312635

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 SLC35E4-HSCB

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SLC35E4chr2231033056HSCBchr22291472291264227ATCLRGLKSVQQTKQKEFTDNVSSAF
SLC35E4chr2231033056HSCBchr22291472291418227ATCLRGLKSVQQTKQKEFTDNVSSAF
SLC35E4chr2231033056HSCBchr2229147229747227ATCLRGLKSVQQTKQKEFTDNVSSAF

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Potential FusionNeoAntigen Information of SLC35E4-HSCB 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.
SLC35E4-HSCB_31033056_29147229.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)
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:01VQQTKQKEF0.99870.7779918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-A30:08GLKSVQQTK0.97380.7144514
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:25VQQTKQKEF0.87040.8557918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:03VQQTKQKEF0.7590.72918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B13:01VQQTKQKEF0.24140.9238918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-A30:08RGLKSVQQTK0.97460.6407414
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B57:01KSVQQTKQKEF0.99980.89718
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B57:03KSVQQTKQKEF0.9990.9643718
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:07VQQTKQKEF0.97740.5871918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:05VQQTKQKEF0.52440.7946918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:34VQQTKQKEF0.99870.7779918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:125VQQTKQKEF0.99870.7779918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:135VQQTKQKEF0.99870.7798918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:33VQQTKQKEF0.99870.7779918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:27VQQTKQKEF0.99850.8113918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:24VQQTKQKEF0.99780.7804918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:50VQQTKQKEF0.99760.849918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-A30:01KSVQQTKQK0.97580.6284716
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:12VQQTKQKEF0.97290.8402918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:35VQQTKQKEF0.97170.7691918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-A30:01GLKSVQQTK0.97120.8401514
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:53VQQTKQKEF0.9280.7612918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:39VQQTKQKEF0.89340.7648918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:54VQQTKQKEF0.87590.7406918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:68VQQTKQKEF0.87310.5526918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:73VQQTKQKEF0.81610.9213918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:30VQQTKQKEF0.69360.9213918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B15:20VQQTKQKEF0.52640.838918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B35:28VQQTKQKEF0.50280.8474918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B48:02VQQTKQKEF0.4060.8139918
SLC35E4-HSCBchr2231033056chr22291472291264HLA-A30:01RGLKSVQQTK0.9710.7822414
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B57:10KSVQQTKQKEF0.99980.89718
SLC35E4-HSCBchr2231033056chr22291472291264HLA-B58:06KSVQQTKQKEF0.99970.909718

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Potential FusionNeoAntigen Information of SLC35E4-HSCB 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.
SLC35E4-HSCB_31033056_29147229.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)
SLC35E4-HSCBchr2231033056chr22291472291264DRB1-0415ATCLRGLKSVQQTKQ015
SLC35E4-HSCBchr2231033056chr22291472291264DRB1-0436ATCLRGLKSVQQTKQ015
SLC35E4-HSCBchr2231033056chr22291472291264DRB1-0453ATCLRGLKSVQQTKQ015
SLC35E4-HSCBchr2231033056chr22291472291264DRB1-0458ATCLRGLKSVQQTKQ015

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Fusion breakpoint peptide structures of SLC35E4-HSCB

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
5183LKSVQQTKQKEFTDSLC35E4HSCBchr2231033056chr22291472291264

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SLC35E4-HSCB

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-B14:023BVN5183LKSVQQTKQKEFTD-7.9962-8.1096
HLA-B14:023BVN5183LKSVQQTKQKEFTD-5.70842-6.74372
HLA-B52:013W395183LKSVQQTKQKEFTD-6.83737-6.95077
HLA-B52:013W395183LKSVQQTKQKEFTD-4.4836-5.5189
HLA-A11:014UQ25183LKSVQQTKQKEFTD-10.0067-10.1201
HLA-A11:014UQ25183LKSVQQTKQKEFTD-9.03915-10.0745
HLA-A24:025HGA5183LKSVQQTKQKEFTD-6.56204-6.67544
HLA-A24:025HGA5183LKSVQQTKQKEFTD-5.42271-6.45801
HLA-B44:053DX85183LKSVQQTKQKEFTD-7.85648-8.89178
HLA-B44:053DX85183LKSVQQTKQKEFTD-5.3978-5.5112
HLA-A02:016TDR5183LKSVQQTKQKEFTD-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of SLC35E4-HSCB

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
SLC35E4-HSCBchr2231033056chr2229147229414RGLKSVQQTKTCCGCGGACTCAAGTCGGTTCAGCAAACTA
SLC35E4-HSCBchr2231033056chr2229147229514GLKSVQQTKGCGGACTCAAGTCGGTTCAGCAAACTA
SLC35E4-HSCBchr2231033056chr2229147229716KSVQQTKQKTCAAGTCGGTTCAGCAAACTAAACAGA
SLC35E4-HSCBchr2231033056chr2229147229718KSVQQTKQKEFTCAAGTCGGTTCAGCAAACTAAACAGAAAGAAT
SLC35E4-HSCBchr2231033056chr2229147229918VQQTKQKEFCGGTTCAGCAAACTAAACAGAAAGAAT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
SLC35E4-HSCBchr2231033056chr2229147229015ATCLRGLKSVQQTKQCAGCCACCTGCCTCCGCGGACTCAAGTCGGTTCAGCAAACTAAAC

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Information of the samples that have these potential fusion neoantigens of SLC35E4-HSCB

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
BRCASLC35E4-HSCBchr2231033056ENST00000300385chr2229147229ENST00000216027TCGA-EW-A423-01A

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Potential target of CAR-T therapy development for SLC35E4-HSCB

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
HgeneSLC35E4chr22:31033056chr22:29147229ENST00000300385+12110_132206235.0TransmembraneHelical
HgeneSLC35E4chr22:31033056chr22:29147229ENST00000300385+12135_155206235.0TransmembraneHelical
HgeneSLC35E4chr22:31033056chr22:29147229ENST00000300385+1251_71206235.0TransmembraneHelical
HgeneSLC35E4chr22:31033056chr22:29147229ENST00000300385+1273_93206235.0TransmembraneHelical
HgeneSLC35E4chr22:31033056chr22:29147229ENST00000343605+12110_132206351.0TransmembraneHelical
HgeneSLC35E4chr22:31033056chr22:29147229ENST00000343605+12135_155206351.0TransmembraneHelical
HgeneSLC35E4chr22:31033056chr22:29147229ENST00000343605+1251_71206351.0TransmembraneHelical
HgeneSLC35E4chr22:31033056chr22:29147229ENST00000343605+1273_93206351.0TransmembraneHelical
HgeneSLC35E4chr22:31033056chr22:29147229ENST00000406566+13110_132206399.3333333333333TransmembraneHelical
HgeneSLC35E4chr22:31033056chr22:29147229ENST00000406566+13135_155206399.3333333333333TransmembraneHelical
HgeneSLC35E4chr22:31033056chr22:29147229ENST00000406566+1351_71206399.3333333333333TransmembraneHelical
HgeneSLC35E4chr22:31033056chr22:29147229ENST00000406566+1373_93206399.3333333333333TransmembraneHelical

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 SLC35E4-HSCB

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 SLC35E4-HSCB

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