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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:KMT2E-ORC5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: KMT2E-ORC5
FusionPDB ID: 43291
FusionGDB2.0 ID: 43291
HgeneTgene
Gene symbol

KMT2E

ORC5

Gene ID

55904

5001

Gene namelysine methyltransferase 2E (inactive)origin recognition complex subunit 5
SynonymsHDCMC04P|MLL5|NKp44L|ODLUROORC5L|ORC5P|ORC5T|PPP1R117
Cytomap

7q22.3

7q22.1-q22.2

Type of geneprotein-codingprotein-coding
Descriptioninactive histone-lysine N-methyltransferase 2Ehistone-lysine N-methyltransferase 2Ehistone-lysine N-methyltransferase MLL5inactive lysine N-methyltransferase 2Elysine (K)-specific methyltransferase 2Emyeloid/lymphoid or mixed-lineage leukemia 5 (tritorigin recognition complex subunit 5protein phosphatase 1, regulatory subunit 117
Modification date2020031420200313
UniProtAcc

Q8IZD2

Main function of 5'-partner protein: FUNCTION: Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription (PubMed:23629655, PubMed:24130829, PubMed:23798402). Chromatin interaction is mediated via the binding to tri-methylated histone H3 at 'Lys-4' (H3K4me3) (PubMed:24130829, PubMed:23798402). Key regulator of hematopoiesis involved in terminal myeloid differentiation and in the regulation of hematopoietic stem cell (HSCs) self-renewal by a mechanism that involves DNA methylation (By similarity). Also acts as an important cell cycle regulator, participating in cell cycle regulatory network machinery at multiple cell cycle stages including G1/S transition, S phase progression and mitotic entry (PubMed:14718661, PubMed:18573682, PubMed:19264965, PubMed:23629655). Recruited to E2F1 responsive promoters by HCFC1 where it stimulates tri-methylation of histone H3 at 'Lys-4' and transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). During myoblast differentiation, required to suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells (By similarity). {ECO:0000250|UniProtKB:Q3UG20, ECO:0000269|PubMed:14718661, ECO:0000269|PubMed:18573682, ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829}.; FUNCTION: [Isoform NKp44L]: Cellular ligand for NCR2/NKp44, may play a role as a danger signal in cytotoxicity and NK-cell-mediated innate immunity. {ECO:0000269|PubMed:23958951}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000257745, ENST00000311117, 
ENST00000334877, ENST00000334914, 
ENST00000476671, ENST00000480368, 
ENST00000447452, ENST00000485726, 
ENST00000297431, ENST00000545943, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score18 X 21 X 9=34027 X 6 X 7=294
# samples 2811
** MAII scorelog2(28/3402*10)=-3.60288440871842
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(11/294*10)=-1.4183126313117
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: KMT2E [Title/Abstract] AND ORC5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: KMT2E [Title/Abstract] AND ORC5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)KMT2E(104742641)-ORC5(103777340), # samples:1
Anticipated loss of major functional domain due to fusion event.KMT2E-ORC5 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.
KMT2E-ORC5 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.
KMT2E-ORC5 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.
KMT2E-ORC5 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
TgeneORC5

GO:0006275

regulation of DNA replication

31160578



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/chr7:104742641/chr7:103777340)
- 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 KMT2E (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 ORC5 (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)
ENST00000311117KMT2Echr7104742641+ENST00000297431ORC5chr7103777340-340727415452899784
ENST00000311117KMT2Echr7104742641+ENST00000545943ORC5chr7103777340-340527415452899784
ENST00000257745KMT2Echr7104742641+ENST00000297431ORC5chr7103777340-324825823862740784
ENST00000257745KMT2Echr7104742641+ENST00000545943ORC5chr7103777340-324625823862740784
ENST00000334877KMT2Echr7104742641+ENST00000297431ORC5chr7103777340-339627305342888784
ENST00000334877KMT2Echr7104742641+ENST00000545943ORC5chr7103777340-339427305342888784

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
ENST00000311117ENST00000297431KMT2Echr7104742641+ORC5chr7103777340-0.0009772110.99902284
ENST00000311117ENST00000545943KMT2Echr7104742641+ORC5chr7103777340-0.0009712630.9990288
ENST00000257745ENST00000297431KMT2Echr7104742641+ORC5chr7103777340-0.0010547210.9989453
ENST00000257745ENST00000545943KMT2Echr7104742641+ORC5chr7103777340-0.0010488140.9989512
ENST00000334877ENST00000297431KMT2Echr7104742641+ORC5chr7103777340-0.0009488520.99905115
ENST00000334877ENST00000545943KMT2Echr7104742641+ORC5chr7103777340-0.0009424650.9990576

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 KMT2E-ORC5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
KMT2Echr7104742641ORC5chr71037773402582732LNKCPTKYPKTKKITSLVTLQLLTLV
KMT2Echr7104742641ORC5chr71037773402730732LNKCPTKYPKTKKITSLVTLQLLTLV
KMT2Echr7104742641ORC5chr71037773402741732LNKCPTKYPKTKKITSLVTLQLLTLV

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Potential FusionNeoAntigen Information of KMT2E-ORC5 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.
KMT2E-ORC5_104742641_103777340.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)
KMT2E-ORC5chr7104742641chr71037773402582HLA-A30:08KTKKITSL0.99230.5668917
KMT2E-ORC5chr7104742641chr71037773402582HLA-B39:01KKITSLVTL0.98870.83421120
KMT2E-ORC5chr7104742641chr71037773402582HLA-B39:13KKITSLVTL0.9180.86511120
KMT2E-ORC5chr7104742641chr71037773402582HLA-B14:02TKYPKTKKI0.660.6175514
KMT2E-ORC5chr7104742641chr71037773402582HLA-B14:01TKYPKTKKI0.660.6175514
KMT2E-ORC5chr7104742641chr71037773402582HLA-B15:10KKITSLVTL0.48470.51031120
KMT2E-ORC5chr7104742641chr71037773402582HLA-B15:03KKITSLVTL0.44480.64881120
KMT2E-ORC5chr7104742641chr71037773402582HLA-B52:01TKYPKTKKI0.00140.9118514
KMT2E-ORC5chr7104742641chr71037773402582HLA-B35:03YPKTKKITSL0.73650.6852717
KMT2E-ORC5chr7104742641chr71037773402582HLA-B35:02YPKTKKITSL0.60240.7539717
KMT2E-ORC5chr7104742641chr71037773402582HLA-B35:04YPKTKKITSL0.60240.7539717
KMT2E-ORC5chr7104742641chr71037773402582HLA-A30:08KTKKITSLVTL0.99790.5995920
KMT2E-ORC5chr7104742641chr71037773402582HLA-B57:03KTKKITSLVTL0.99560.944920
KMT2E-ORC5chr7104742641chr71037773402582HLA-C15:04KTKKITSLV0.99680.7501918
KMT2E-ORC5chr7104742641chr71037773402582HLA-C15:06KTKKITSLV0.99210.7629918
KMT2E-ORC5chr7104742641chr71037773402582HLA-C07:13KKITSLVTL0.97290.81171120
KMT2E-ORC5chr7104742641chr71037773402582HLA-C07:29KKITSLVTL0.96860.92241120
KMT2E-ORC5chr7104742641chr71037773402582HLA-C06:03KTKKITSLV0.9450.962918
KMT2E-ORC5chr7104742641chr71037773402582HLA-C12:04KTKKITSLV0.93530.9548918
KMT2E-ORC5chr7104742641chr71037773402582HLA-B39:05KKITSLVTL0.87120.8081120
KMT2E-ORC5chr7104742641chr71037773402582HLA-C07:95TKYPKTKKI0.57770.6309514
KMT2E-ORC5chr7104742641chr71037773402582HLA-C07:05TKYPKTKKI0.56360.9234514
KMT2E-ORC5chr7104742641chr71037773402582HLA-C12:16KKITSLVTL0.11450.93031120
KMT2E-ORC5chr7104742641chr71037773402582HLA-C06:03TKYPKTKKI0.00260.9873514
KMT2E-ORC5chr7104742641chr71037773402582HLA-C12:16TKYPKTKKI0.00090.9354514
KMT2E-ORC5chr7104742641chr71037773402582HLA-B39:10YPKTKKITSL0.78670.7378717
KMT2E-ORC5chr7104742641chr71037773402582HLA-B35:12YPKTKKITSL0.60240.7539717
KMT2E-ORC5chr7104742641chr71037773402582HLA-C15:02KTKKITSL0.99960.8064917
KMT2E-ORC5chr7104742641chr71037773402582HLA-A30:01KTKKITSL0.99270.778917
KMT2E-ORC5chr7104742641chr71037773402582HLA-B27:06KKITSLVTL0.99910.74991120
KMT2E-ORC5chr7104742641chr71037773402582HLA-A30:01KTKKITSLV0.99820.6804918
KMT2E-ORC5chr7104742641chr71037773402582HLA-C15:09KTKKITSLV0.99680.7501918
KMT2E-ORC5chr7104742641chr71037773402582HLA-B27:09KKITSLVTL0.99650.86671120
KMT2E-ORC5chr7104742641chr71037773402582HLA-C15:02KTKKITSLV0.99540.7007918
KMT2E-ORC5chr7104742641chr71037773402582HLA-C15:05KTKKITSLV0.99350.7199918
KMT2E-ORC5chr7104742641chr71037773402582HLA-B39:02KKITSLVTL0.99030.87051120
KMT2E-ORC5chr7104742641chr71037773402582HLA-A32:01KTKKITSLV0.9280.7661918
KMT2E-ORC5chr7104742641chr71037773402582HLA-C06:08KKITSLVTL0.75190.9781120
KMT2E-ORC5chr7104742641chr71037773402582HLA-C07:01TKYPKTKKI0.59310.6378514
KMT2E-ORC5chr7104742641chr71037773402582HLA-C07:22TKYPKTKKI0.46630.6078514
KMT2E-ORC5chr7104742641chr71037773402582HLA-B48:02KKITSLVTL0.37920.90431120
KMT2E-ORC5chr7104742641chr71037773402582HLA-C07:04TKYPKTKKI0.16110.8669514
KMT2E-ORC5chr7104742641chr71037773402582HLA-C06:08TKYPKTKKI0.10410.9743514
KMT2E-ORC5chr7104742641chr71037773402582HLA-B15:54KKITSLVTL0.08960.76891120
KMT2E-ORC5chr7104742641chr71037773402582HLA-C06:06TKYPKTKKI0.04610.9594514
KMT2E-ORC5chr7104742641chr71037773402582HLA-C06:02TKYPKTKKI0.00230.9883514
KMT2E-ORC5chr7104742641chr71037773402582HLA-C06:17TKYPKTKKI0.00230.9883514
KMT2E-ORC5chr7104742641chr71037773402582HLA-B67:01YPKTKKITSL0.73760.507717
KMT2E-ORC5chr7104742641chr71037773402582HLA-B35:09YPKTKKITSL0.60240.7539717
KMT2E-ORC5chr7104742641chr71037773402582HLA-A30:01KTKKITSLVTL0.99820.7834920

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Potential FusionNeoAntigen Information of KMT2E-ORC5 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 KMT2E-ORC5

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
4717KYPKTKKITSLVTLKMT2EORC5chr7104742641chr71037773402582

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of KMT2E-ORC5

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-B14:023BVN4717KYPKTKKITSLVTL-7.9962-8.1096
HLA-B14:023BVN4717KYPKTKKITSLVTL-5.70842-6.74372
HLA-B52:013W394717KYPKTKKITSLVTL-6.83737-6.95077
HLA-B52:013W394717KYPKTKKITSLVTL-4.4836-5.5189
HLA-A11:014UQ24717KYPKTKKITSLVTL-10.0067-10.1201
HLA-A11:014UQ24717KYPKTKKITSLVTL-9.03915-10.0745
HLA-A24:025HGA4717KYPKTKKITSLVTL-6.56204-6.67544
HLA-A24:025HGA4717KYPKTKKITSLVTL-5.42271-6.45801
HLA-B44:053DX84717KYPKTKKITSLVTL-7.85648-8.89178
HLA-B44:053DX84717KYPKTKKITSLVTL-5.3978-5.5112
HLA-A02:016TDR4717KYPKTKKITSLVTL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of KMT2E-ORC5

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
KMT2E-ORC5chr7104742641chr71037773401120KKITSLVTLAAGAAGATTACCTCTCTAGTGACCCTT
KMT2E-ORC5chr7104742641chr7103777340514TKYPKTKKIACCAAGTACCCCAAAACAAAGAAGATT
KMT2E-ORC5chr7104742641chr7103777340717YPKTKKITSLTACCCCAAAACAAAGAAGATTACCTCTCTA
KMT2E-ORC5chr7104742641chr7103777340917KTKKITSLAAAACAAAGAAGATTACCTCTCTA
KMT2E-ORC5chr7104742641chr7103777340918KTKKITSLVAAAACAAAGAAGATTACCTCTCTAGTG
KMT2E-ORC5chr7104742641chr7103777340920KTKKITSLVTLAAAACAAAGAAGATTACCTCTCTAGTGACCCTT

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 KMT2E-ORC5

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
STADKMT2E-ORC5chr7104742641ENST00000257745chr7103777340ENST00000297431TCGA-BR-A4J5-01A

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Potential target of CAR-T therapy development for KMT2E-ORC5

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 KMT2E-ORC5

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 KMT2E-ORC5

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