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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:CENPF-EGLN1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CENPF-EGLN1
FusionPDB ID: 15696
FusionGDB2.0 ID: 15696
HgeneTgene
Gene symbol

CENPF

EGLN1

Gene ID

1063

54583

Gene namecentromere protein Fegl-9 family hypoxia inducible factor 1
SynonymsCENF|CILD31|PRO1779|STROMS|hcp-1C1orf12|ECYT3|HALAH|HIF-PH2|HIFPH2|HPH-2|HPH2|PHD2|SM20|ZMYND6
Cytomap

1q41

1q42.2

Type of geneprotein-codingprotein-coding
Descriptioncentromere protein FAH antigenCENP-F kinetochore proteincell-cycle-dependent 350K nuclear proteincentromere protein F, 350/400kDakinetochore protein CENPFmitosinegl nine homolog 1HIF-prolyl hydroxylase 2egl nine-like protein 1hypoxia-inducible factor prolyl hydroxylase 2prolyl hydroxylase domain-containing protein 2zinc finger MYND domain-containing protein 6
Modification date2020031320200313
UniProtAcc

P49454

Main function of 5'-partner protein: FUNCTION: Required for kinetochore function and chromosome segregation in mitosis. Required for kinetochore localization of dynein, LIS1, NDE1 and NDEL1. Regulates recycling of the plasma membrane by acting as a link between recycling vesicles and the microtubule network though its association with STX4 and SNAP25. Acts as a potential inhibitor of pocket protein-mediated cellular processes during development by regulating the activity of RB proteins during cell division and proliferation. May play a regulatory or permissive role in the normal embryonic cardiomyocyte cell cycle and in promoting continued mitosis in transformed, abnormally dividing neonatal cardiomyocytes. Interaction with RB directs embryonic stem cells toward a cardiac lineage. Involved in the regulation of DNA synthesis and hence cell cycle progression, via its C-terminus. Has a potential role regulating skeletal myogenesis and in cell differentiation in embryogenesis. Involved in dendritic cell regulation of T-cell immunity against chlamydia. {ECO:0000269|PubMed:12974617, ECO:0000269|PubMed:17600710, ECO:0000269|PubMed:7542657, ECO:0000269|PubMed:7651420}.

Q9GZT9

Main function of 5'-partner protein: FUNCTION: Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif. {ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12181324, ECO:0000269|PubMed:12351678, ECO:0000269|PubMed:15897452, ECO:0000269|PubMed:19339211, ECO:0000269|PubMed:21792862, ECO:0000269|PubMed:25129147}.
Ensembl transtripts involved in fusion geneENST idsENST00000366955, ENST00000467765, 
ENST00000476717, ENST00000366641, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 5 X 3=907 X 4 X 5=140
# samples 57
** MAII scorelog2(5/90*10)=-0.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/140*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CENPF [Title/Abstract] AND EGLN1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CENPF [Title/Abstract] AND EGLN1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CENPF(214795624)-EGLN1(231509845), # samples:1
Anticipated loss of major functional domain due to fusion event.CENPF-EGLN1 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.
CENPF-EGLN1 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
HgeneCENPF

GO:0015031

protein transport

12974617

HgeneCENPF

GO:0045892

negative regulation of transcription, DNA-templated

15677469

HgeneCENPF

GO:0051310

metaphase plate congression

15870278

TgeneEGLN1

GO:0001666

response to hypoxia

16956324

TgeneEGLN1

GO:0018401

peptidyl-proline hydroxylation to 4-hydroxy-L-proline

11598268

TgeneEGLN1

GO:0032364

oxygen homeostasis

16956324

TgeneEGLN1

GO:0043433

negative regulation of DNA-binding transcription factor activity

16956324

TgeneEGLN1

GO:0071731

response to nitric oxide

21601578



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/chr1:214795624/chr1:231509845)
- 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 CENPF (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 EGLN1 (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)
ENST00000366955CENPFchr1214795624+ENST00000366641EGLN1chr1231509845-428612361681625485

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
ENST00000366955ENST00000366641CENPFchr1214795624+EGLN1chr1231509845-0.0001073480.9998926

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 CENPF-EGLN1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CENPFchr1214795624EGLN1chr12315098451236356VRTTAQYDQASTKAMVACYPGNGTGY

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Potential FusionNeoAntigen Information of CENPF-EGLN1 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.
CENPF-EGLN1_214795624_231509845.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)
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:37DQASTKAM0.99150.513715
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:01STKAMVACY0.99580.86181019
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:25STKAMVACY0.99420.86951019
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:02STKAMVACY0.98020.88841019
CENPF-EGLN1chr1214795624chr12315098451236HLA-B08:09QASTKAMVA0.97950.693817
CENPF-EGLN1chr1214795624chr12315098451236HLA-B50:01AQYDQASTKA0.8040.7898414
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:01AQYDQASTKAM10.8623415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B48:01AQYDQASTKAM0.99940.843415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:25AQYDQASTKAM0.99810.8969415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:03AQYDQASTKAM0.99370.7635415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B13:01AQYDQASTKAM0.99230.9767415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B39:13AQYDQASTKAM0.96240.9441415
CENPF-EGLN1chr1214795624chr12315098451236HLA-C04:10QYDQASTKA0.99710.9123514
CENPF-EGLN1chr1214795624chr12315098451236HLA-C04:07QYDQASTKA0.99670.9149514
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:07STKAMVACY0.94790.61931019
CENPF-EGLN1chr1214795624chr12315098451236HLA-B51:07DQASTKAMV0.84940.9128716
CENPF-EGLN1chr1214795624chr12315098451236HLA-C04:14QYDQASTKA0.51480.9061514
CENPF-EGLN1chr1214795624chr12315098451236HLA-C04:10QYDQASTKAM0.99890.9367515
CENPF-EGLN1chr1214795624chr12315098451236HLA-C04:07QYDQASTKAM0.99880.9385515
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:04AQYDQASTKA0.99090.8884414
CENPF-EGLN1chr1214795624chr12315098451236HLA-C04:14QYDQASTKAM0.89830.9136515
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:04AQYDQASTKAM0.99990.9132415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:07AQYDQASTKAM0.99990.7592415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:05AQYDQASTKAM0.99590.8726415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B48:03AQYDQASTKAM0.98940.6153415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B18:04DQASTKAM0.98090.8663715
CENPF-EGLN1chr1214795624chr12315098451236HLA-C04:01QYDQASTKA0.99670.9149514
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:27STKAMVACY0.99610.85651019
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:33STKAMVACY0.99580.86181019
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:125STKAMVACY0.99580.86181019
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:34STKAMVACY0.99580.86181019
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:135STKAMVACY0.99540.89181019
CENPF-EGLN1chr1214795624chr12315098451236HLA-C18:01QYDQASTKA0.9950.9295514
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:50STKAMVACY0.99320.80471019
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:11STKAMVACY0.99210.80051019
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:08STKAMVACY0.99070.78791019
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:12STKAMVACY0.96330.86411019
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:35STKAMVACY0.94490.84151019
CENPF-EGLN1chr1214795624chr12315098451236HLA-A25:01STKAMVACY0.85990.69441019
CENPF-EGLN1chr1214795624chr12315098451236HLA-C04:01QYDQASTKAM0.99880.9385515
CENPF-EGLN1chr1214795624chr12315098451236HLA-C18:01QYDQASTKAM0.99850.9446515
CENPF-EGLN1chr1214795624chr12315098451236HLA-C14:02QYDQASTKAM0.97770.9677515
CENPF-EGLN1chr1214795624chr12315098451236HLA-C14:03QYDQASTKAM0.97770.9677515
CENPF-EGLN1chr1214795624chr12315098451236HLA-B50:05AQYDQASTKA0.8040.7898414
CENPF-EGLN1chr1214795624chr12315098451236HLA-B50:04AQYDQASTKA0.8040.7898414
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:34AQYDQASTKAM10.8623415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:135AQYDQASTKAM10.875415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:24AQYDQASTKAM10.9246415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:125AQYDQASTKAM10.8623415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:50AQYDQASTKAM10.8972415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:27AQYDQASTKAM10.8817415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:33AQYDQASTKAM10.8623415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:35AQYDQASTKAM0.99990.8876415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:53AQYDQASTKAM0.99980.8528415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:54AQYDQASTKAM0.99960.8219415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:68AQYDQASTKAM0.99960.6934415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:73AQYDQASTKAM0.99950.9397415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:30AQYDQASTKAM0.99930.9138415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:12AQYDQASTKAM0.9990.8702415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:39AQYDQASTKAM0.99790.8231415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B15:20AQYDQASTKAM0.99590.9221415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B35:28AQYDQASTKAM0.99560.9376415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B48:02AQYDQASTKAM0.99310.919415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B40:21AQYDQASTKAM0.9930.7191415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B39:02AQYDQASTKAM0.990.9386415
CENPF-EGLN1chr1214795624chr12315098451236HLA-B40:12AQYDQASTKAM0.98940.6153415

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Potential FusionNeoAntigen Information of CENPF-EGLN1 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.

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)

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Fusion breakpoint peptide structures of CENPF-EGLN1

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
10601YDQASTKAMVACYPCENPFEGLN1chr1214795624chr12315098451236

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CENPF-EGLN1

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-B14:023BVN10601YDQASTKAMVACYP-7.15543-7.26883
HLA-B14:023BVN10601YDQASTKAMVACYP-4.77435-5.80965
HLA-B52:013W3910601YDQASTKAMVACYP-6.80875-6.92215
HLA-B52:013W3910601YDQASTKAMVACYP-4.20386-5.23916
HLA-A11:014UQ210601YDQASTKAMVACYP-7.5194-8.5547
HLA-A11:014UQ210601YDQASTKAMVACYP-6.9601-7.0735
HLA-A24:025HGA10601YDQASTKAMVACYP-7.52403-7.63743
HLA-A24:025HGA10601YDQASTKAMVACYP-5.82433-6.85963
HLA-B27:056PYJ10601YDQASTKAMVACYP-3.28285-4.31815
HLA-B44:053DX810601YDQASTKAMVACYP-5.91172-6.94702
HLA-B44:053DX810601YDQASTKAMVACYP-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of CENPF-EGLN1

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
CENPF-EGLN1chr1214795624chr12315098451019STKAMVACYTCAACCAAGGCCATGGTTGCTTGTTAT
CENPF-EGLN1chr1214795624chr1231509845414AQYDQASTKAGCACAATACGACCAGGCGTCAACCAAGGCC
CENPF-EGLN1chr1214795624chr1231509845415AQYDQASTKAMGCACAATACGACCAGGCGTCAACCAAGGCCATG
CENPF-EGLN1chr1214795624chr1231509845514QYDQASTKACAATACGACCAGGCGTCAACCAAGGCC
CENPF-EGLN1chr1214795624chr1231509845515QYDQASTKAMCAATACGACCAGGCGTCAACCAAGGCCATG
CENPF-EGLN1chr1214795624chr1231509845715DQASTKAMGACCAGGCGTCAACCAAGGCCATG
CENPF-EGLN1chr1214795624chr1231509845716DQASTKAMVGACCAGGCGTCAACCAAGGCCATGGTT
CENPF-EGLN1chr1214795624chr1231509845817QASTKAMVACAGGCGTCAACCAAGGCCATGGTTGCT

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

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Information of the samples that have these potential fusion neoantigens of CENPF-EGLN1

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
LUSCCENPF-EGLN1chr1214795624ENST00000366955chr1231509845ENST00000366641TCGA-56-7582-01A

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Potential target of CAR-T therapy development for CENPF-EGLN1

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 CENPF-EGLN1

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 CENPF-EGLN1

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