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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:GSK3A_PWP1

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: GSK3A_PWP1
KinaseFusionDB ID: KFG2587
FusionGDB2.0 ID: KFG2587
HgeneTgene
Gene symbol

GSK3A

PWP1

Gene ID

2931

11137

Gene nameglycogen synthase kinase 3 alphaPWP1 homolog, endonuclein
Synonyms-IEF-SSP-9502|NCLB
Cytomap

19q13.2

12q23.3

Type of geneprotein-codingprotein-coding
Descriptionglycogen synthase kinase-3 alphaGSK-3 alphaserine/threonine-protein kinase GSK3Aperiodic tryptophan protein 1 homologendonucleinkeratinocyte protein IEF SSP 9502nuclear phosphoprotein similar to S. cerevisiae PWP1
Modification date2024041120240305
UniProtAcc

P49840

Q13610

Ensembl transtripts involved in fusion geneENST idsENST00000222330, ENST00000398249, 
ENST00000412830, ENST00000541166, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: GSK3A [Title/Abstract] AND PWP1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GSK3A(42734626)-PWP1(108082549), # 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
HgeneGSK3A

GO:0006468

protein phosphorylation

11035810

HgeneGSK3A

GO:0018107

peptidyl-threonine phosphorylation

25897075

TgenePWP1

GO:1901838

positive regulation of transcription of nucleolar large rRNA by RNA polymerase I

29065309


check buttonKinase Fusion gene breakpoints across GSK3A (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 PWP1 (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
ChiTaRS5.0AA885364GSK3Achr19

42734626

PWP1chr12

108082549



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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/:42734626/:108082549)
- 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
GSK3A

P49840

PWP1

Q13610

FUNCTION: Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1 (PubMed:11749387, PubMed:17478001, PubMed:19366350). Requires primed phosphorylation of the majority of its substrates (PubMed:11749387, PubMed:17478001, PubMed:19366350). Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:11749387, PubMed:17478001, PubMed:19366350). Regulates glycogen metabolism in liver, but not in muscle (By similarity). May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:10868943, PubMed:17478001). In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin (PubMed:17229088). Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease (PubMed:12761548). May be involved in the regulation of replication in pancreatic beta-cells (By similarity). Is necessary for the establishment of neuronal polarity and axon outgrowth (By similarity). Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions which activates KAT5/TIP60 acetyltransferase activity and promotes acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (By similarity). Phosphorylates mTORC2 complex component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR (PubMed:25897075). {ECO:0000250|UniProtKB:P18265, ECO:0000250|UniProtKB:P49841, ECO:0000250|UniProtKB:Q2NL51, ECO:0000269|PubMed:10868943, ECO:0000269|PubMed:12761548, ECO:0000269|PubMed:17229088, ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:30704899, ECO:0000303|PubMed:11749387, ECO:0000303|PubMed:17478001, ECO:0000303|PubMed:19366350}.FUNCTION: Chromatin-associated factor that regulates transcription (PubMed:29065309). Regulates Pol I-mediated rRNA biogenesis and, probably, Pol III-mediated transcription (PubMed:29065309). Regulates the epigenetic status of rDNA (PubMed:29065309). {ECO:0000269|PubMed:29065309}.

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 GSK3A_PWP1


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
GSK3AP49840humanPPARAQ07869S280FHCCQCTsVETVTELHormone_recep
GSK3AP49840humanMAPTP10636-8T231KKVAVVRtPPKsPss
GSK3AP49840humanGRB14Q14449S362QGRsGCSsQSIsPMR
GSK3AP49840humanMAPTP10636-8S199GDRsGyssPGsPGtP
GSK3AP49840humanLRP6O75581S1544CDSDyAPsRRMtSVA
GSK3AP49840humanIRF3Q14653T180sPsLDNPtPFPNLGP
GSK3AP49840humanMAFAQ8NHW3S61PLStPCSsVPSsPSF
GSK3AP49840humanNBR1Q14596T586HNtPVDVtPCMsPLP
GSK3AP49840humanFBXL20Q96IG2T417HAYFAPVtPPPsVGG
GSK3AP49840humanGSK3AP49840Y279RGEPNVsyICsRyyRPkinase
GSK3AP49840humanSTAT2P52630S393LtPEKGQsQGLIWDFSTAT_bind
GSK3AP49840humanDESP17661S32PLGsPLssPVFPrAGFilament_head
GSK3AP49840humanCTNNB1P35222S37yLDsGIHsGATtTAP
GSK3AP49840humanFBXL20Q96IG2S251RGCHKLQsLCAsGCS
GSK3AP49840humanMAPTP10636-8S396GAEIVyKsPVVsGDt
GSK3AP49840humanFBXL20Q96IG2S255KLQsLCAsGCSNITD
GSK3AP49840humanNDRG1Q92597S362HtsEGtRsRsHtsEG
GSK3AP49840humanMAPTP10636-8S404PVVsGDtsPRHLsNV
GSK3AP49840humanMITFO75030-9S298QARAHGLsLIPSTGLDUF3371
GSK3AP49840humanMAFAQ8NHW3T57LSStPLStPCSsVPS
GSK3AP49840humanMAPTP10636-8S262NVKskIGstENLkHQTubulin-binding
GSK3AP49840humanLRP6O75581S1490AILNPPPsPAtERsH
GSK3AP49840humanMAFAQ8NHW3S49CHRLPPGsLSStPLS
GSK3AP49840humanRICTORQ6R327T1695EAEAVLAtPPKQPIV
GSK3AP49840humanFBXL20Q96IG2S139DATCTSLskFCsKLR
GSK3AP49840humanMYCP01106T73kkFELLPtPPLsPsRMyc_N
GSK3AP49840humanNIFKQ9BYG3S230tPEKtVDsQGPtPVChNIFK_binding
GSK3AP49840humanSTAT3P40763S727NtIDLPMsPrTLDSL
GSK3AP49840humanDESP17661S28APGFPLGsPLssPVFFilament_head
GSK3AP49840humanCD274Q9NZQ7S279CGIQDTNsKkQsDtH
GSK3AP49840humanFBXL20Q96IG2S425PPPsVGGsRQRFCRC
GSK3AP49840humanBCL2L1Q07817S62PSWHLADsPAVNGAT
GSK3AP49840humanOSBP2Q969R2S762ECSKVMHssPssPsSOxysterol_BP
GSK3AP49840humanUNGP13051S64EPGtPPssPLsAEQL
GSK3AP49840humanGPSM3Q9Y4H4S35STTRPWRsAPPsPPP
GSK3AP49840humanSTMN3Q9NZ72S60sFEVILksPSDLsPEStathmin
GSK3AP49840humanOSBP2Q969R2S766VMHssPssPsSDGKQOxysterol_BP
GSK3AP49840humanUNGP13051T60AGQEEPGtPPssPLs
GSK3AP49840humanFBXL20Q96IG2S143TSLskFCsKLRHLDLLRR_6
GSK3AP49840humanSTAT3P40763T714ktKFICVtPTtCsNt
GSK3AP49840humanSTAT2P52630T385ILTsNQktLtPEKGQSTAT_bind
GSK3AP49840humanDPYSL2Q16555S518ktVtPAssAktsPAk
GSK3AP49840humanIRF3Q14653S123DFSQPDTsPDTNGGG
GSK3AP49840humanMAFAQ8NHW3T53PPGsLSStPLStPCS
GSK3AP49840humanPRKAA1Q13131T490EAksGtAtPQRsGsVAdenylateSensor
GSK3AP49840humanCD274Q9NZQ7S283DTNsKkQsDtHLEEt
GSK3AP49840humanSTAT2P52630S381RkFNILTsNQktLtPSTAT_bind
GSK3AP49840humanGRB14Q14449S358MHPYQGRsGCSsQSI
GSK3AP49840humanBCL3P20749S402LSASPSSsPSQsPPR
GSK3AP49840humanGRB14Q14449S423THGsPtAsSQSSATN
GSK3AP49840humanIL17RAQ96F46T780MVLTDPHtPYEEEQR
GSK3AP49840humanNCOA3Q9Y6Q9S509GVHsPMAsSGNTGNHNCOA_u2
GSK3AP49840humanIKZF3Q9UKT9S378VPSERGLsPNNSGHD
GSK3AP49840humanNDRG1Q92597S342tsLDGtRsRsHtsEG
GSK3AP49840humanBCL3P20749S406PSSsPSQsPPRDPPG
GSK3AP49840humanGRB14Q14449S419LRLGTHGsPtAsSQS
GSK3AP49840humanCCNE1P24864T395PLPSGLLtPPQsGKK
GSK3AP49840humanOSBP2Q969R2S768HssPssPsSDGKQKTOxysterol_BP
GSK3AP49840humanLRP6O75581S1607HLYPPPPsPCTDss_
GSK3AP49840humanCTNNB1P35222S33QQQsyLDsGIHsGAT
GSK3AP49840humanLRP6O75581T1572EPVPPPPtPRsQyLs
GSK3AP49840humanOSBP2Q969R2S763CSKVMHssPssPsSDOxysterol_BP
GSK3AP49840humanCTNNB1P35222T41GIHsGATtTAPsLsG
GSK3AP49840humanNDRG1Q92597S352HtsEGtRsRsHtsEG
GSK3AP49840humanPKD2Q13563S76AGAAAsPsPPLsSCS
GSK3AP49840humanANKRD28O15084S1007INRyTNTskTVsFEA
GSK3AP49840humanNIFKQ9BYG3T234tVDsQGPtPVCtPtFhNIFK_binding
GSK3AP49840humanFBXL20Q96IG2S421APVtPPPsVGGsRQR
GSK3AP49840humanGRB14Q14449S366GCSsQSIsPMRsIsE
GSK3AP49840humanMAPTP10636-8S235VVRtPPKsPssAKsR
GSK3AP49840humanIRF3Q14653S173PCPQPLRsPsLDNPt
GSK3AP49840humanCDKN1AP38936T57NFDFVtEtPLEGDFACDI
GSK3AP49840humanAKT1P31749T312tMKtFCGtPEyLAPEPkinase
GSK3AP49840humanNCOA3Q9Y6Q9S505SPVAGVHsPMAsSGNNCOA_u2


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
GSK3AIDDescription0.00e+00
GSK3AGO:0097305response to alcohol6.04e-04
GSK3AGO:0043434response to peptide hormone7.63e-04
GSK3AGO:0010332response to gamma radiation1.24e-03
GSK3AGO:0071887leukocyte apoptotic process1.24e-03
GSK3AGO:0043467regulation of generation of precursor metabolites and energy1.42e-03
GSK3AGO:0043470regulation of carbohydrate catabolic process1.42e-03
GSK3AGO:0035821modulation of process of another organism1.42e-03
GSK3AGO:0097284hepatocyte apoptotic process1.42e-03
GSK3AGO:0009411response to UV1.42e-03
GSK3AGO:0010821regulation of mitochondrion organization1.42e-03
GSK3AGO:0051347positive regulation of transferase activity1.42e-03
GSK3AGO:0002534cytokine production involved in inflammatory response1.74e-03
GSK3AGO:1900015regulation of cytokine production involved in inflammatory response1.74e-03
GSK3AGO:0000079regulation of cyclin-dependent protein serine/threonine kinase activity1.74e-03
GSK3AGO:0072331signal transduction by p53 class mediator1.74e-03
GSK3AGO:0016055Wnt signaling pathway1.74e-03
GSK3AGO:0072594establishment of protein localization to organelle1.74e-03
GSK3AGO:0198738cell-cell signaling by wnt1.74e-03
GSK3AGO:1904029regulation of cyclin-dependent protein kinase activity1.75e-03
GSK3AGO:0050673epithelial cell proliferation1.93e-03
GSK3AGO:0097193intrinsic apoptotic signaling pathway1.93e-03
GSK3AGO:0006109regulation of carbohydrate metabolic process1.93e-03
GSK3AGO:1900017positive regulation of cytokine production involved in inflammatory response2.03e-03
GSK3AGO:0048638regulation of developmental growth2.03e-03
GSK3AGO:0016049cell growth2.03e-03
GSK3AGO:0070482response to oxygen levels2.41e-03
GSK3AGO:0097306cellular response to alcohol2.63e-03
GSK3AGO:0002532production of molecular mediator involved in inflammatory response2.79e-03
GSK3AGO:0010038response to metal ion2.79e-03
GSK3AGO:0050679positive regulation of epithelial cell proliferation2.88e-03
GSK3AGO:0051348negative regulation of transferase activity3.24e-03
GSK3AGO:0062014negative regulation of small molecule metabolic process3.42e-03
GSK3AGO:0046627negative regulation of insulin receptor signaling pathway3.42e-03
GSK3AGO:0032733positive regulation of interleukin-10 production3.47e-03
GSK3AGO:1900077negative regulation of cellular response to insulin stimulus3.47e-03
GSK3AGO:0032944regulation of mononuclear cell proliferation3.84e-03
GSK3AGO:0002065columnar/cuboidal epithelial cell differentiation3.84e-03
GSK3AGO:0072655establishment of protein localization to mitochondrion3.86e-03
GSK3AGO:0008286insulin receptor signaling pathway3.88e-03
GSK3AGO:0051090regulation of DNA-binding transcription factor activity4.01e-03
GSK3AGO:0000082G1/S transition of mitotic cell cycle4.09e-03
GSK3AGO:0010001glial cell differentiation4.09e-03
GSK3AGO:0070585protein localization to mitochondrion4.22e-03
GSK3AGO:0001558regulation of cell growth4.22e-03
GSK3AGO:0050727regulation of inflammatory response4.25e-03
GSK3AGO:0098781ncRNA transcription4.25e-03
GSK3AGO:0009314response to radiation4.25e-03
GSK3AGO:1903747regulation of establishment of protein localization to mitochondrion4.25e-03
GSK3AGO:0010212response to ionizing radiation4.25e-03

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Related Drugs to GSK3A_PWP1


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 GSK3A-PWP1 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 GSK3A_PWP1


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