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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:CLPTM1-CBLC

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CLPTM1-CBLC
FusionPDB ID: 17302
FusionGDB2.0 ID: 17302
HgeneTgene
Gene symbol

CLPTM1

CBLC

Gene ID

1209

23624

Gene nameCLPTM1 regulator of GABA type A receptor forward traffickingCbl proto-oncogene C
Synonyms-CBL-3|CBL-SL|RNF57
Cytomap

19q13.32

19q13.32

Type of geneprotein-codingprotein-coding
Descriptioncleft lip and palate transmembrane protein 1CLPTM1, transmembrane proteincleft lip and palate associated transmembrane protein 1E3 ubiquitin-protein ligase CBL-CCas-Br-M (murine) ecotropic retroviral transforming sequence cCas-Br-M (murine) ectropic retroviral transforming sequence cCbl proto-oncogene C, E3 ubiquitin protein ligaseCbl proto-oncogene, E3 ubiquitin protein ligas
Modification date2020031320200313
UniProtAcc

Q96KA5

Main function of 5'-partner protein: FUNCTION: Enhances cisplatin-mediated apoptosis, when overexpressed. {ECO:0000269|PubMed:11162647}.

Q9ULV8

Main function of 5'-partner protein: FUNCTION: Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Functionally coupled with the E2 ubiquitin-protein ligases UB2D1, UB2D2 and UB2D3. Regulator of EGFR mediated signal transduction; upon EGF activation, ubiquitinates EGFR. Isoform 1, but not isoform 2, inhibits EGF stimulated MAPK1 activation. Promotes ubiquitination of SRC phosphorylated at 'Tyr-419'. In collaboration with CD2AP may act as regulatory checkpoint for Ret signaling by modulating the rate of RET degradation after ligand activation; CD2AP converts it from an inhibitor to a promoter of RET degradation; the function limits the potency of GDNF on neuronal survival. {ECO:0000269|PubMed:10362357, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:18753381, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:23145173}.
Ensembl transtripts involved in fusion geneENST idsENST00000546079, ENST00000337392, 
ENST00000541297, ENST00000589158, 
ENST00000270279, ENST00000341505, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score16 X 12 X 8=15364 X 7 X 2=56
# samples 207
** MAII scorelog2(20/1536*10)=-2.94110631094643
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/56*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: CLPTM1 [Title/Abstract] AND CBLC [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CLPTM1 [Title/Abstract] AND CBLC [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CLPTM1(45465332)-CBLC(45293261), # samples:2
Anticipated loss of major functional domain due to fusion event.CLPTM1-CBLC 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.
CLPTM1-CBLC 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.
CLPTM1-CBLC 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.
CLPTM1-CBLC 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
TgeneCBLC

GO:0006511

ubiquitin-dependent protein catabolic process

14661060

TgeneCBLC

GO:0007175

negative regulation of epidermal growth factor-activated receptor activity

10362357

TgeneCBLC

GO:0016567

protein ubiquitination

14661060

TgeneCBLC

GO:0042059

negative regulation of epidermal growth factor receptor signaling pathway

10362357

TgeneCBLC

GO:0043407

negative regulation of MAP kinase activity

10362357



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/chr19:45465332/chr19:45293261)
- 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 CLPTM1 (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 CBLC (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)
ENST00000541297CLPTM1chr1945465332+ENST00000341505CBLCchr1945293260+12076084651115216
ENST00000541297CLPTM1chr1945465332+ENST00000270279CBLCchr1945293260+12076084651115216
ENST00000337392CLPTM1chr1945465332+ENST00000341505CBLCchr1945293260+93433587842251
ENST00000337392CLPTM1chr1945465332+ENST00000270279CBLCchr1945293260+93433587842251
ENST00000541297CLPTM1chr1945465332+ENST00000341505CBLCchr1945293261+12076084651115216
ENST00000541297CLPTM1chr1945465332+ENST00000270279CBLCchr1945293261+12076084651115216
ENST00000337392CLPTM1chr1945465332+ENST00000341505CBLCchr1945293261+93433587842251
ENST00000337392CLPTM1chr1945465332+ENST00000270279CBLCchr1945293261+93433587842251

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
ENST00000541297ENST00000341505CLPTM1chr1945465332+CBLCchr1945293260+0.042664940.95733505
ENST00000541297ENST00000270279CLPTM1chr1945465332+CBLCchr1945293260+0.042664940.95733505
ENST00000337392ENST00000341505CLPTM1chr1945465332+CBLCchr1945293260+0.0310868470.9689132
ENST00000337392ENST00000270279CLPTM1chr1945465332+CBLCchr1945293260+0.0310868470.9689132
ENST00000541297ENST00000341505CLPTM1chr1945465332+CBLCchr1945293261+0.042664940.95733505
ENST00000541297ENST00000270279CLPTM1chr1945465332+CBLCchr1945293261+0.042664940.95733505
ENST00000337392ENST00000341505CLPTM1chr1945465332+CBLCchr1945293261+0.0310868470.9689132
ENST00000337392ENST00000270279CLPTM1chr1945465332+CBLCchr1945293261+0.0310868470.9689132

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 CLPTM1-CBLC

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CLPTM1chr1945465332CBLCchr194529326033582APNAWQVIKGVLFSYLYPDGKTHNPD
CLPTM1chr1945465332CBLCchr194529326060847APNAWQVIKGVLFSYLYPDGKTHNPD
CLPTM1chr1945465332CBLCchr194529326133582APNAWQVIKGVLFSYLYPDGKTHNPD
CLPTM1chr1945465332CBLCchr194529326160847APNAWQVIKGVLFSYLYPDGKTHNPD

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Potential FusionNeoAntigen Information of CLPTM1-CBLC 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.
CLPTM1-CBLC_45465332_45293260.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)
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:01VIKGVLFSY0.99970.8042615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:25VIKGVLFSY0.99850.8112615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:02VIKGVLFSY0.99630.819615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-A32:13VIKGVLFSY0.63160.7214615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:01QVIKGVLFSY0.99970.8453515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:25QVIKGVLFSY0.99860.8799515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:02QVIKGVLFSY0.99660.8946515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:21VIKGVLFSY0.99470.7864615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:05VIKGVLFSY0.96150.7442615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:04VIKGVLFSY0.94310.7881615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:31VIKGVLFSY0.91420.7641615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-C15:04VIKGVLFSY0.73290.8866615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:07QVIKGVLFSY0.99930.5912515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:05QVIKGVLFSY0.99030.8807515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:31QVIKGVLFSY0.98020.8908515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:07WQVIKGVLFSY0.9980.6782415
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:125VIKGVLFSY0.99970.8042615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:27VIKGVLFSY0.99970.8187615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:33VIKGVLFSY0.99970.8042615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:34VIKGVLFSY0.99970.8042615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:135VIKGVLFSY0.99960.7982615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:50VIKGVLFSY0.99960.8712615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:35VIKGVLFSY0.99940.6824615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:11VIKGVLFSY0.99930.7518615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:08VIKGVLFSY0.99910.7461615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B35:43VIKGVLFSY0.99890.7332615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:24VIKGVLFSY0.99850.6779615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:39VIKGVLFSY0.99840.6363615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:12VIKGVLFSY0.99010.7422615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:20VIKGVLFSY0.96610.8366615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B35:28VIKGVLFSY0.93460.8325615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B35:30VIKGVLFSY0.91930.5514615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B35:17VIKGVLFSY0.91930.5514615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B35:20VIKGVLFSY0.91470.8418615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-C12:02VIKGVLFSY0.88730.936615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-A32:01VIKGVLFSY0.8660.6942615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-C15:09VIKGVLFSY0.73290.8866615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-A25:01VIKGVLFSY0.46910.6329615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-C02:10VIKGVLFSY0.08720.9551615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-C02:02VIKGVLFSY0.08720.9551615
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:50QVIKGVLFSY0.99970.905515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:135QVIKGVLFSY0.99970.8447515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:33QVIKGVLFSY0.99970.8453515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:34QVIKGVLFSY0.99970.8453515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:125QVIKGVLFSY0.99970.8453515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:27QVIKGVLFSY0.99970.8603515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:35QVIKGVLFSY0.99930.7923515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:08QVIKGVLFSY0.99930.7851515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:11QVIKGVLFSY0.99930.7895515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:12QVIKGVLFSY0.99880.8458515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:39QVIKGVLFSY0.99830.7532515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:20QVIKGVLFSY0.99170.925515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-A25:01QVIKGVLFSY0.94880.7068515
CLPTM1-CBLCchr1945465332chr1945293260335HLA-B15:35WQVIKGVLFSY0.99810.8772415

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Potential FusionNeoAntigen Information of CLPTM1-CBLC 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.
CLPTM1-CBLC_45465332_45293260.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)
CLPTM1-CBLCchr1945465332chr1945293260335DRB1-1222APNAWQVIKGVLFSY015
CLPTM1-CBLCchr1945465332chr1945293260335DRB1-1222PNAWQVIKGVLFSYL116

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Fusion breakpoint peptide structures of CLPTM1-CBLC

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
10015VIKGVLFSYLYPDGCLPTM1CBLCchr1945465332chr1945293260335

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CLPTM1-CBLC

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-B14:023BVN10015VIKGVLFSYLYPDG-7.9962-8.1096
HLA-B14:023BVN10015VIKGVLFSYLYPDG-5.70842-6.74372
HLA-B52:013W3910015VIKGVLFSYLYPDG-6.83737-6.95077
HLA-B52:013W3910015VIKGVLFSYLYPDG-4.4836-5.5189
HLA-A11:014UQ210015VIKGVLFSYLYPDG-10.0067-10.1201
HLA-A11:014UQ210015VIKGVLFSYLYPDG-9.03915-10.0745
HLA-A24:025HGA10015VIKGVLFSYLYPDG-6.56204-6.67544
HLA-A24:025HGA10015VIKGVLFSYLYPDG-5.42271-6.45801
HLA-B44:053DX810015VIKGVLFSYLYPDG-7.85648-8.89178
HLA-B44:053DX810015VIKGVLFSYLYPDG-5.3978-5.5112
HLA-B35:011A1N10015VIKGVLFSYLYPDG-6.27422-6.38762
HLA-B35:011A1N10015VIKGVLFSYLYPDG-5.27424-6.30954
HLA-A02:016TDR10015VIKGVLFSYLYPDG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of CLPTM1-CBLC

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
CLPTM1-CBLCchr1945465332chr1945293260415WQVIKGVLFSYGCAGGTCATCAAAGGTGTGCTGTTTAGCTACCT
CLPTM1-CBLCchr1945465332chr1945293260515QVIKGVLFSYGGTCATCAAAGGTGTGCTGTTTAGCTACCT
CLPTM1-CBLCchr1945465332chr1945293260615VIKGVLFSYCATCAAAGGTGTGCTGTTTAGCTACCT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CLPTM1-CBLCchr1945465332chr1945293260015APNAWQVIKGVLFSYACCCAATGCCTGGCAGGTCATCAAAGGTGTGCTGTTTAGCTACCT
CLPTM1-CBLCchr1945465332chr1945293260116PNAWQVIKGVLFSYLCAATGCCTGGCAGGTCATCAAAGGTGTGCTGTTTAGCTACCTCTA

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Information of the samples that have these potential fusion neoantigens of CLPTM1-CBLC

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
STADCLPTM1-CBLCchr1945465332ENST00000337392chr1945293260ENST00000270279TCGA-VQ-A8P3

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Potential target of CAR-T therapy development for CLPTM1-CBLC

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 CLPTM1-CBLC

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 CLPTM1-CBLC

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