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Center for Computational Systems Medicine
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Kinase Fusion Gene Summary

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Kinase Fusion Gene Sample Information

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Kinase Fusion ORF Analysis

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Kinase Fusion Amino Acid Sequences

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Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

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Kinase Fusion Protein Structures

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Comparison of Fusion Protein Isoforms

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

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pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.

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Ramachandran Plot of Kinase Fusion Protein Structure

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Potential Active Site Information

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Virtual Screening Results

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Kinase-Substrate Information

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Related Drugs with This Kinase Fusion Protein

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Related Disease with This Kinase Fusion Protein

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Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:REXO2_EPHA3

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: REXO2_EPHA3
KinaseFusionDB ID: KFG5350
FusionGDB2.0 ID: KFG5350
HgeneTgene
Gene symbol

REXO2

EPHA3

Gene ID

25996

2042

Gene nameRNA exonuclease 2EPH receptor A3
SynonymsCGI-114|REX2|RFN|SFNEK4|ETK|ETK1|HEK|HEK4|TYRO4
Cytomap

11q23.2

3p11.1

Type of geneprotein-codingprotein-coding
Descriptionoligoribonuclease, mitochondrialREX2, RNA exonuclease 2 homologRNA exonuclease 2 homologsmall fragment nucleaseephrin type-A receptor 3EPH-like kinase 4TYRO4 protein tyrosine kinaseeph-like tyrosine kinase 1human embryo kinase 1testicular tissue protein Li 64tyrosine-protein kinase receptor ETK1
Modification date2024030520240411
UniProtAcc

Q9Y3B8

P29320

Ensembl transtripts involved in fusion geneENST idsENST00000265881, ENST00000539275, 
ENST00000538791, ENST00000539754, 
ENST00000544196, ENST00000544507, 
ENST00000336596, ENST00000452448, 
ENST00000494014, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: REXO2 [Title/Abstract] AND EPHA3 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)EPHA3(89401037)-REXO2(114321001), # samples:1
REXO2(114321001)-EPHA3(89401072), # samples:1
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneREXO2

GO:0006139

nucleobase-containing compound metabolic process

10851236

TgeneEPHA3

GO:0018108

peptidyl-tyrosine phosphorylation

-

TgeneEPHA3

GO:0032956

regulation of actin cytoskeleton organization

11870224

TgeneEPHA3

GO:0043087

regulation of GTPase activity

11870224

TgeneEPHA3

GO:0045806

negative regulation of endocytosis

-

TgeneEPHA3

GO:0048013

ephrin receptor signaling pathway

11870224

TgeneEPHA3

GO:0051893

regulation of focal adhesion assembly

11870224

TgeneEPHA3

GO:0070507

regulation of microtubule cytoskeleton organization

11870224

TgeneEPHA3

GO:1903078

positive regulation of protein localization to plasma membrane

-


check buttonKinase Fusion gene breakpoints across REXO2 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonKinase Fusion gene breakpoints across EPHA3 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.


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Kinase Fusion Gene Sample Information

check buttonKinase Fusion gene information.
check button Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
SourceSampleHgeneHchrHbpTgeneTchrTbp
ChiTaRS5.0BM014027REXO2chr11

114321001

EPHA3chr3

89401072



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Kinase Fusion ORF Analysis


check buttonKinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(amino acids)

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Kinase Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq

Multiple Sequence Alignment of All Fusion Protein Isoforms



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Kinase Fusion Protein Functional Features


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/:89401037/:114321001)
- 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 buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
REXO2

Q9Y3B8

EPHA3

P29320

FUNCTION: 3'-to-5'exoribonuclease that preferentially degrades DNA and RNA oligonucleotides composed of only two nucleotides (PubMed:31588022, PubMed:30926754, PubMed:32365187, PubMed:23741365). Binds and degrades longer oligonucleotides with a lower affinity (PubMed:31588022, PubMed:30926754, PubMed:32365187). Plays dual roles in mitochondria, scavenging nanoRNAs (small RNA oligonucleotides of <5 nucleotides) that are produced by the degradosome and clearing short RNAs that are generated by RNA processing (PubMed:31588022, PubMed:30926754, PubMed:32365187). Essential for correct initiation of mitochondrial transcription, degrading mitochondrial RNA dinucleotides to prevent RNA-primed transcription at non-canonical sites in the mitochondrial genome (PubMed:31588022). Essential for embryonic development (By similarity). {ECO:0000250|UniProtKB:Q9D8S4, ECO:0000269|PubMed:23741365, ECO:0000269|PubMed:30926754, ECO:0000269|PubMed:31588022, ECO:0000269|PubMed:32365187}.; FUNCTION: [Isoform 3]: 3'-to-5'exoribonuclease that preferentially degrades DNA and RNA oligonucleotides composed of only two nucleotides. {ECO:0000269|PubMed:10851236, ECO:0000269|PubMed:16682444}.FUNCTION: Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. {ECO:0000269|PubMed:11870224}.

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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.

check button - Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


check button - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


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Kinase-Substrate Information of REXO2_EPHA3


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain


check button Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

check button Enriched GO biological processes of the phosphorylation target genes of the kinase
KinaseGOIDGO termP.adjust

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Related Drugs to REXO2_EPHA3


check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

check button Distribution of the number of studies mentioning REXO2-EPHA3 and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1Fusion gene - drug pair 2PMIDPublication dateDOIStudy title

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Related Diseases to REXO2_EPHA3


check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)
MeSH IDMeSH term

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource


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Clinical Trials of the Found Drugs/Small Molecules


check button Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)

check button Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion GeneKinase InhibitorNCT IDStudy StatusPhasesDisease# EnrolmentDate