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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:NEK3_CNOT1

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: NEK3_CNOT1
KinaseFusionDB ID: KFG4129
FusionGDB2.0 ID: KFG4129
HgeneTgene
Gene symbol

NEK3

CNOT1

Gene ID

4752

23019

Gene nameNIMA related kinase 3CCR4-NOT transcription complex subunit 1
SynonymsHSPK36AD-005|CDC39|HPE12|NOT1|NOT1H|VIBOS
Cytomap

13q14.3

16q21

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase Nek3HSPK 36NIMA (never in mitosis gene a)-related kinase 3glycogen synthase A kinasehydroxyalkyl-protein kinasenever in mitosis A-related kinase 3nimA-related protein kinase 3phosphorylase B kinase kinaseCCR4-NOT transcription complex subunit 1CCR4-associated factor 1NOT1 (negative regulator of transcription 1, yeast) homologadrenal gland protein AD-005negative regulator of transcription subunit 1 homolog
Modification date2024040320240407
UniProtAcc

P51956

Q9H9A5

Ensembl transtripts involved in fusion geneENST idsENST00000339406, ENST00000378101, 
ENST00000400357, ENST00000452082, 
ENST00000245138, ENST00000569732, 
ENST00000317147, ENST00000441024, 
ENST00000569240, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: NEK3 [Title/Abstract] AND CNOT1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NEK3(52730210)-CNOT1(58594266), # 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
TgeneCNOT1

GO:0000122

negative regulation of transcription by RNA polymerase II

16778766

TgeneCNOT1

GO:0010606

positive regulation of cytoplasmic mRNA processing body assembly

21976065

TgeneCNOT1

GO:0017148

negative regulation of translation

24736845

TgeneCNOT1

GO:0033147

negative regulation of intracellular estrogen receptor signaling pathway

16778766

TgeneCNOT1

GO:0035195

miRNA-mediated post-transcriptional gene silencing

23172285|24768540

TgeneCNOT1

GO:0048387

negative regulation of retinoic acid receptor signaling pathway

16778766

TgeneCNOT1

GO:0060213

positive regulation of nuclear-transcribed mRNA poly(A) tail shortening

23644599


check buttonKinase Fusion gene breakpoints across NEK3 (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 CNOT1 (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
ChimerDB4TCGA-BR-7851-11ANEK3chr13

52730210

CNOT1chr16

58594266



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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/:52730210/:58594266)
- 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
NEK3

P51956

CNOT1

Q9H9A5

FUNCTION: Protein kinase which influences neuronal morphogenesis and polarity through effects on microtubules. Regulates microtubule acetylation in neurons. Contributes to prolactin-mediated phosphorylation of PXN and VAV2. Implicated in prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells through mechanisms involving RAC1 activation and phosphorylation of PXN and VAV2. {ECO:0000269|PubMed:15618286, ECO:0000269|PubMed:17297458}.FUNCTION: Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Is not required for association of CNOT7 to the CCR4-NOT complex. {ECO:0000269|PubMed:23221646}.

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 NEK3_CNOT1


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
NEK3P51956humanNEK3P51956T165FACTYVGtPYYVPPEPkinase
NEK3P51956humanSNAP29O95721S105MDQDLkIsQkHINsIV-SNARE_C


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
NEK3IDDescription0.00e+00
NEK3GO:0016082synaptic vesicle priming1.98e-02
NEK3GO:0090043regulation of tubulin deacetylation1.98e-02
NEK3GO:0031629synaptic vesicle fusion to presynaptic active zone membrane1.98e-02
NEK3GO:0090042tubulin deacetylation1.98e-02
NEK3GO:0099500vesicle fusion to plasma membrane1.98e-02
NEK3GO:0048499synaptic vesicle membrane organization1.98e-02
NEK3GO:0090311regulation of protein deacetylation2.12e-02
NEK3GO:0006476protein deacetylation2.47e-02
NEK3GO:0097352autophagosome maturation2.47e-02
NEK3GO:0006903vesicle targeting2.47e-02
NEK3GO:0035601protein deacylation2.47e-02
NEK3GO:0098732macromolecule deacylation2.47e-02
NEK3GO:0140029exocytic process2.48e-02
NEK3GO:0140056organelle localization by membrane tethering2.48e-02
NEK3GO:0022406membrane docking2.54e-02
NEK3GO:0016079synaptic vesicle exocytosis2.54e-02
NEK3GO:0006906vesicle fusion2.84e-02
NEK3GO:0090174organelle membrane fusion2.84e-02
NEK3GO:0007269neurotransmitter secretion3.03e-02
NEK3GO:0099643signal release from synapse3.03e-02
NEK3GO:0030010establishment of cell polarity3.03e-02
NEK3GO:0048284organelle fusion3.03e-02
NEK3GO:0061025membrane fusion3.10e-02
NEK3GO:0001505regulation of neurotransmitter levels3.10e-02
NEK3GO:0051650establishment of vesicle localization3.10e-02
NEK3GO:0099504synaptic vesicle cycle3.10e-02
NEK3GO:0006836neurotransmitter transport3.10e-02
NEK3GO:0051648vesicle localization3.10e-02
NEK3GO:0099003vesicle-mediated transport in synapse3.10e-02
NEK3GO:0045055regulated exocytosis3.10e-02
NEK3GO:0007163establishment or maintenance of cell polarity3.10e-02
NEK3GO:0032984protein-containing complex disassembly3.22e-02
NEK3GO:0016236macroautophagy4.22e-02
NEK3GO:0006887exocytosis4.31e-02
NEK3GO:0016050vesicle organization4.39e-02
NEK3GO:0060271cilium assembly4.41e-02
NEK3GO:0044782cilium organization4.61e-02
NEK3GO:0051656establishment of organelle localization5.17e-02
NEK3GO:0023061signal release5.19e-02
NEK3GO:0022411cellular component disassembly5.20e-02

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Related Drugs to NEK3_CNOT1


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 NEK3-CNOT1 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 NEK3_CNOT1


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