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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:NEK7_SYK

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: NEK7_SYK
KinaseFusionDB ID: KFG4162
FusionGDB2.0 ID: KFG4162
HgeneTgene
Gene symbol

NEK7

SYK

Gene ID

140609

6850

Gene nameNIMA related kinase 7spleen associated tyrosine kinase
Synonyms-IMD82|p72-Syk
Cytomap

1q31.3

9q22.2

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase Nek7NIMA (never in mitosis gene a)-related kinase 7never in mitosis A-related kinase 7nimA-related protein kinase 7tyrosine-protein kinase SYKspleen tyrosine kinase
Modification date2024040720240411
UniProtAcc

Q8TDX7

P43405

Ensembl transtripts involved in fusion geneENST idsENST00000367385, ENST00000538004, 
ENST00000367383, ENST00000417895, 
ENST00000375751, ENST00000375754, 
ENST00000375747, ENST00000476708, 
ENST00000375746, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: NEK7 [Title/Abstract] AND SYK [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneNEK7

GO:0006468

protein phosphorylation

12840024|31409757

HgeneNEK7

GO:0007346

regulation of mitotic cell cycle

19941817

HgeneNEK7

GO:1900227

positive regulation of NLRP3 inflammasome complex assembly

31189953|36442502

TgeneSYK

GO:0006468

protein phosphorylation

17681949

TgeneSYK

GO:0007159

leukocyte cell-cell adhesion

12885943

TgeneSYK

GO:0018108

peptidyl-tyrosine phosphorylation

11606584

TgeneSYK

GO:0030593

neutrophil chemotaxis

12885943

TgeneSYK

GO:0035556

intracellular signal transduction

11606584|15509800

TgeneSYK

GO:1904263

positive regulation of TORC1 signaling

34634301


check buttonKinase Fusion gene breakpoints across NEK7 (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 SYK (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
CCLEHCC-95NEK7chr1

198126406

SYKchr9

93607716



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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/:/:)
- 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
NEK7

Q8TDX7

SYK

P43405

FUNCTION: Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:17101132, PubMed:31409757, PubMed:19941817). Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis (PubMed:17586473, PubMed:19414596, PubMed:31409757, PubMed:19941817, PubMed:26522158). Phosphorylates EML4 at 'Ser-146', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757). Phosphorylates RPS6KB1 (By similarity). Acts as an essential activator of the NLRP3 inflammasome assembly independently of its kinase activity (PubMed:26642356, PubMed:36442502). Acts by unlocking NLRP3 following NLRP3 tranlocation into the microtubule organizing center (MTOC), relieving NLRP3 autoinhibition and promoting formation of the NLRP3:PYCARD complex, and activation of CASP1 (PubMed:26642356, PubMed:31189953, PubMed:36442502). Serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division: interaction with NEK9 prevents interaction with NLRP3 and activation of the inflammasome during mitosis (PubMed:26642356, PubMed:31189953). {ECO:0000250|UniProtKB:D3ZBE5, ECO:0000269|PubMed:17101132, ECO:0000269|PubMed:17586473, ECO:0000269|PubMed:19414596, ECO:0000269|PubMed:19941817, ECO:0000269|PubMed:26522158, ECO:0000269|PubMed:26642356, ECO:0000269|PubMed:31189953, ECO:0000269|PubMed:31409757, ECO:0000269|PubMed:36442502}.FUNCTION: Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development (PubMed:12387735, PubMed:33782605). Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include DEPTOR, VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK (PubMed:12456653, PubMed:15388330, PubMed:8657103, PubMed:34634301). Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition (PubMed:12456653). Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR also plays a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade (By similarity). Required for the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). Also functions downstream of receptors mediating cell adhesion (PubMed:12387735). Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Also plays a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity). {ECO:0000250|UniProtKB:P48025, ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:12456653, ECO:0000269|PubMed:15123770, ECO:0000269|PubMed:15388330, ECO:0000269|PubMed:19909739, ECO:0000269|PubMed:33782605, ECO:0000269|PubMed:34634301, ECO:0000269|PubMed:8657103, ECO:0000269|PubMed:9535867}.

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 NEK7_SYK


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
NEK7Q8TDX7humanKIF14Q15058S1220NLHSsHssGLMDkSS
NEK7Q8TDX7humanKIF14Q15058S607NLIDLAGsERCSTAHKinesin
NEK7Q8TDX7humanKIF11P52732S1033GINtLERskVEETTEMicrotub_bind
NEK7Q8TDX7humanKIF14Q15058S1219KNLHSsHssGLMDkS
NEK7Q8TDX7humanKIF14Q15058S56NDDPLLRsAGKVRDI
NEK7Q8TDX7humanTERF1P54274S114AIIHGLSsLTACQLRTRF
NEK7Q8TDX7humanKIF14Q15058S1217PIKNLHSsHssGLMD
SYKP43405humanSLC4A1P02730Y904EEEGRDEyDEVAMPV
SYKP43405humanGCSAMQ8N6F7Y106sGNsAEEyyENVPCkHGAL
SYKP43405humanSHC1P29353-2Y317ELFDDPSyVNVQNLD
SYKP43405humanFCGR2CP31995Y310tDDDKNIyLTLPPND
SYKP43405humanPRDX2P32119Y193NVDDskEyFskHN__1-cysPrx_C
SYKP43405humanSLC4A1P02730Y21ENLEQEEyEDPDIPE
SYKP43405humanLAX1Q8IWV1Y268SSQISNDyVNMTGLDLAX
SYKP43405humanSLC4A1P02730Y8MEELQDDyEDMMEEN
SYKP43405humanPLCG1P19174Y771IGtAEPdyGALyEGR
SYKP43405humanBLNKQ8WV28Y96EENADDSyEPPPVEQ
SYKP43405humanPLCG2P16885Y759LyDVsRMyVDPsEIN
SYKP43405humanHCLS1P14317Y378EPEPENDyEDVEEMD
SYKP43405humanSHC1P29353-2Y239EEPPDHQyyNDFPGK
SYKP43405humanFCGR2AP12318Y304tDDDKNIyLTLPPND
SYKP43405humanIKZF1Q13422S361LAEGtPRsNHsAQDs
SYKP43405humanCFTRP13569Y512NIIFGVsyDEyRYRSABC_tran
SYKP43405humanLAT2Q9GZY6Y233EEDGEPDyVNGEVAALAT2
SYKP43405humanIKZF1Q13422S364GtPRsNHsAQDsAVE
SYKP43405humanDEPTORQ8TB45Y289ssCGssGyFsssPtL
SYKP43405humanCTTNQ14247Y421rLPssPVyEDAAsFK
SYKP43405humanARHGDIBP52566Y24ELdskLNykPPPQksRho_GDI
SYKP43405humanBLNKQ8WV28Y84EHSDSEMyVMPAEEN
SYKP43405humanPLCG1P19174Y783EGRNPGFyVEANPMP
SYKP43405humanSTAT5AP42229Y694LAkAVDGyVkPQIkQ
SYKP43405humanLAT2Q9GZY6Y193EDEEsEDyQNsAsIHLAT2
SYKP43405humanCBLP22681Y700EGEEDtEyMtPssRP
SYKP43405humanFCGR2CP31995Y287PEETNNDyETADGGy
SYKP43405humanGCSAMQ8N6F7Y86tysEELCytLINHRVHGAL
SYKP43405humanSLC4A1P02730Y359AKPDssFyKGLDLNG
SYKP43405humanSNCAP37840Y133EMPsEEGyQDyEPEA
SYKP43405humanSHC1P29353-2Y240EPPDHQyyNDFPGKE
SYKP43405humanLAT2Q9GZY6Y136EDDDANsyENVLICKLAT2
SYKP43405humanSNCAP37840Y136sEEGyQDyEPEA___
SYKP43405humanDUSP3P51452Y138SPTLVIAyLMMRQKMDSPc
SYKP43405humanSYKP43405Y352tEVyEsPyADPEEIR
SYKP43405humanSNCAP37840Y125VDPDNEAyEMPsEEGSynuclein
SYKP43405humanDOCK2Q92608Y224SsPTHsLyVFVRNFVDOCK_N
SYKP43405humanBLNKQ8WV28Y178LLEDEADyVVPVEDN
SYKP43405humanFCGR2AP12318Y281LEEtNNDyEtADGGy
SYKP43405humanDOCK2Q92608Y122LQVQSMMyDLMEWRSDOCK_N
SYKP43405humanDOCK2Q92608Y985DLIGKNVyPGDWMAM
SYKP43405humanBTKQ06187Y551RYVLDDEytsSVGSkPK_Tyr_Ser-Thr
SYKP43405humanLAX1Q8IWV1Y294AFQCCRDyENVPAADLAX
SYKP43405humanGCSAMQ8N6F7Y128LGGTEtEySLLHMPSHGAL
SYKP43405humanSYKP43405Y348LPMDtEVyEsPyADP
SYKP43405humanCBLP22681Y774sENEDDGyDVPKPPV
SYKP43405humanDUSP3P51452Y38NEVTPRIyVGNASVADSPc
SYKP43405humanGCSAMQ8N6F7Y107GNsAEEyyENVPCkAHGAL
SYKP43405humanCBLP22681Y731QQIDSCTyEAMyNIQ
SYKP43405humanBLNKQ8WV28Y72SDDFDSDyENPDEHS
SYKP43405humanLAX1Q8IWV1Y373SNEDSSDyENVLTAKLAX
SYKP43405humanMAPTP10636Y18MEDHAGTyGLGDRKD
SYKP43405humanGCSAMQ8N6F7Y80QDNVDQtysEELCytHGAL
SYKP43405humanSYKP43405Y525ALRADENyykAQtHGPK_Tyr_Ser-Thr
SYKP43405humanPTPN11Q06124Y542sKRkGHEytNIKysL
SYKP43405humanRHBGQ9H310Y429SPPDSQHyEDQVHWQ
SYKP43405humanLCP2Q13094Y113ssFEEDDyESPNDDQ
SYKP43405humanSYKP43405Y526LRADENyykAQtHGKPK_Tyr_Ser-Thr
SYKP43405humanBLNKQ8WV28Y189VEDNDENyIHPtESS
SYKP43405humanHCLS1P14317Y397EDEPEGDyEEVLEPE
SYKP43405humanDOCK2Q92608Y1405VkNAPGQyIQCFTVQDHR-2_Lobe_B
SYKP43405humanSTAT1P42224Y701DGPkGtGyIktELIs
SYKP43405humanPIP5K1BO14986Y105FGIKPDDyLYSICSE
SYKP43405humanLCP2Q13094Y128DGEDDGDyEsPNEEE
SYKP43405humanSTING1Q86WV6Y240AGIKDRVysNSIyELTMEM173
SYKP43405humanLAX1Q8IWV1Y193SSEDSHDyVNVPTAELAX


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
NEK7IDDescription0.00e+00
NEK7GO:0098813nuclear chromosome segregation6.72e-04
NEK7GO:0007059chromosome segregation6.72e-04
NEK7GO:0000280nuclear division6.72e-04
NEK7GO:0048285organelle fission6.83e-04
NEK7GO:0051303establishment of chromosome localization2.97e-03
NEK7GO:0050000chromosome localization2.97e-03
NEK7GO:0000070mitotic sister chromatid segregation6.40e-03
NEK7GO:0000819sister chromatid segregation8.37e-03
NEK7GO:0140014mitotic nuclear division1.10e-02
NEK7GO:0043254regulation of protein-containing complex assembly1.40e-02
NEK7GO:0007018microtubule-based movement1.40e-02
NEK7GO:0045141meiotic telomere clustering1.40e-02
NEK7GO:0070203regulation of establishment of protein localization to telomere1.40e-02
NEK7GO:0090220chromosome localization to nuclear envelope involved in homologous chromosome segregation1.40e-02
NEK7GO:0090657telomeric loop disassembly1.40e-02
NEK7GO:0051656establishment of organelle localization1.40e-02
NEK7GO:0034397telomere localization1.40e-02
NEK7GO:0070202regulation of establishment of protein localization to chromosome1.40e-02
NEK7GO:0021681cerebellar granular layer development1.40e-02
NEK7GO:0007100mitotic centrosome separation1.40e-02
NEK7GO:0032486Rap protein signal transduction1.40e-02
NEK7GO:0051231spindle elongation1.40e-02
NEK7GO:1904814regulation of protein localization to chromosom2.22e-03
NEK7GO:0051299centrosome separation1.40e-02
NEK7GO:0090656t-circle formation1.40e-02
NEK7GO:0090737telomere maintenance via telomere trimming1.40e-02
NEK7GO:0048532anatomical structure arrangement1.44e-02
NEK7GO:0033623regulation of integrin activation1.48e-02
NEK7GO:0070200establishment of protein localization to telomere1.52e-02
NEK7GO:0021692cerebellar Purkinje cell layer morphogenesis1.55e-02
NEK7GO:0032211negative regulation of telomere maintenance via telomerase1.58e-02
NEK7GO:1903429regulation of cell maturation1.61e-02
NEK7GO:0032069regulation of nuclease activity1.63e-02
NEK7GO:0008156negative regulation of DNA replication1.77e-02
NEK7GO:0033622integrin activation1.77e-02
NEK7GO:0021846cell proliferation in forebrain1.77e-02
NEK7GO:1904357negative regulation of telomere maintenance via telomere lengthening1.77e-02
NEK7GO:0021680cerebellar Purkinje cell layer development1.77e-02
NEK7GO:0070199establishment of protein localization to chromosome1.77e-02
NEK7GO:0070198protein localization to chromosom4.92e-03
NEK7GO:0032205negative regulation of telomere maintenance2.03e-02
NEK7GO:0021696cerebellar cortex morphogenesis2.03e-02
NEK7GO:0021988olfactory lobe development2.03e-02
NEK7GO:2000279negative regulation of DNA biosynthetic process2.03e-02
NEK7GO:0016233telomere capping2.09e-02
NEK7GO:0033260nuclear DNA replication2.10e-02
NEK7GO:0021587cerebellum morphogenesis2.15e-02
NEK7GO:0044786cell cycle DNA replication2.15e-02
NEK7GO:0031641regulation of myelination2.15e-02

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Related Drugs to NEK7_SYK


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 NEK7-SYK 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 NEK7_SYK


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