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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:PRKCI_PLK3

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: PRKCI_PLK3
KinaseFusionDB ID: KFG4974
FusionGDB2.0 ID: KFG4974
HgeneTgene
Gene symbol

PRKCI

PLK3

Gene ID

5584

1263

Gene nameprotein kinase C iotapolo like kinase 3
SynonymsDXS1179E|PKCI|nPKC-iotaCNK|FNK|PLK-3|PRK
Cytomap

3q26.2

1p34.1

Type of geneprotein-codingprotein-coding
Descriptionprotein kinase C iota typePRKC-lambda/iotaaPKC-lambda/iotaatypical protein kinase C-lambda/iotaserine/threonine-protein kinase PLK3FGF-inducible kinasecytokine-inducible serine/threonine-protein kinaseproliferation-related kinase
Modification date2024040320240305
UniProtAcc

P41743

Q9H4B4

Ensembl transtripts involved in fusion geneENST idsENST00000295797, ENST00000372201, 
ENST00000465443, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: PRKCI [Title/Abstract] AND PLK3 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PRKCI(170021535)-PLK3(45270539), # 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
HgenePRKCI

GO:0006468

protein phosphorylation

8226978

HgenePRKCI

GO:0010976

positive regulation of neuron projection development

36250347

HgenePRKCI

GO:0043524

negative regulation of neuron apoptotic process

10467349

HgenePRKCI

GO:0045197

establishment or maintenance of epithelial cell apical/basal polarity

11257119

HgenePRKCI

GO:0051092

positive regulation of NF-kappaB transcription factor activity

10467349

TgenePLK3

GO:0000122

negative regulation of transcription by RNA polymerase II

19490146

TgenePLK3

GO:0000302

response to reactive oxygen species

11447225

TgenePLK3

GO:0006970

response to osmotic stress

21098032

TgenePLK3

GO:0006974

DNA damage response

19490146

TgenePLK3

GO:0009314

response to radiation

21376736

TgenePLK3

GO:0043066

negative regulation of apoptotic process

19490146

TgenePLK3

GO:0051302

regulation of cell division

20951827

TgenePLK3

GO:0090166

Golgi disassembly

14980500|19103756

TgenePLK3

GO:1904716

positive regulation of chaperone-mediated autophagy

27344333

TgenePLK3

GO:2000777

positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia

20889502


check buttonKinase Fusion gene breakpoints across PRKCI (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 PLK3 (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
ChiTaRS5.0BE930931PRKCIchr3

170021535

PLK3chr1

45270539



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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/:170021535/:45270539)
- 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
PRKCI

P41743

PLK3

Q9H4B4

FUNCTION: Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity). {ECO:0000250|UniProtKB:F1M7Y5, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10467349, ECO:0000269|PubMed:10906326, ECO:0000269|PubMed:11042363, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:12871960, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15994303, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19327373, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21419810, ECO:0000269|PubMed:8226978, ECO:0000269|PubMed:9346882}.FUNCTION: Serine/threonine-protein kinase involved in cell cycle regulation, response to stress and Golgi disassembly. Polo-like kinases act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates ATF2, BCL2L1, CDC25A, CDC25C, CHEK2, HIF1A, JUN, p53/TP53, p73/TP73, PTEN, TOP2A and VRK1. Involved in cell cycle regulation: required for entry into S phase and cytokinesis. Phosphorylates BCL2L1, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Plays a key role in response to stress: rapidly activated upon stress stimulation, such as ionizing radiation, reactive oxygen species (ROS), hyperosmotic stress, UV irradiation and hypoxia. Involved in DNA damage response and G1/S transition checkpoint by phosphorylating CDC25A, p53/TP53 and p73/TP73. Phosphorylates p53/TP53 in response to reactive oxygen species (ROS), thereby promoting p53/TP53-mediated apoptosis. Phosphorylates CHEK2 in response to DNA damage, promoting the G2/M transition checkpoint. Phosphorylates the transcription factor p73/TP73 in response to DNA damage, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates HIF1A and JUN is response to hypoxia. Phosphorylates ATF2 following hyperosmotic stress in corneal epithelium. Also involved in Golgi disassembly during the cell cycle: part of a MEK1/MAP2K1-dependent pathway that induces Golgi fragmentation during mitosis by mediating phosphorylation of VRK1. May participate in endomitotic cell cycle, a form of mitosis in which both karyokinesis and cytokinesis are interrupted and is a hallmark of megakaryocyte differentiation, via its interaction with CIB1. {ECO:0000269|PubMed:10557092, ECO:0000269|PubMed:11156373, ECO:0000269|PubMed:11447225, ECO:0000269|PubMed:11551930, ECO:0000269|PubMed:11971976, ECO:0000269|PubMed:12242661, ECO:0000269|PubMed:14968113, ECO:0000269|PubMed:14980500, ECO:0000269|PubMed:15021912, ECO:0000269|PubMed:16478733, ECO:0000269|PubMed:16481012, ECO:0000269|PubMed:17264206, ECO:0000269|PubMed:17804415, ECO:0000269|PubMed:18062778, ECO:0000269|PubMed:18650425, ECO:0000269|PubMed:19103756, ECO:0000269|PubMed:19490146, ECO:0000269|PubMed:20889502, ECO:0000269|PubMed:20940307, ECO:0000269|PubMed:20951827, ECO:0000269|PubMed:21098032, ECO:0000269|PubMed:21264284, ECO:0000269|PubMed:21376736, ECO:0000269|PubMed:21840391, ECO:0000269|PubMed:9353331}.

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 PRKCI_PLK3


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
PLK3Q9H4B4humanATF2P15336T69sVIVADQtPtPtRFL
PLK3Q9H4B4humanYWHAEP62258T208DAIAELDtLsEEsyk14-3-3
PLK3Q9H4B4humanATF2P15336T71IVADQtPtPtRFLkN
PLK3Q9H4B4humanTOP2AP11388T1343FsDFDEKtDDEDFVP
PLK3Q9H4B4humanCALUO43852S44kVHNDAQsFDyDHDA
PLK3Q9H4B4humanCHEK2O96017S62sSSGTLSsLEtVstQ
PLK3Q9H4B4humanHSP90AB1P08238S718LEGDEDAsRMEEVD_
PLK3Q9H4B4humanCALUO43852T254GkMDKEEtkDWILPs
PLK3Q9H4B4humanCALUO43852T60LGAEEAktFDQLtPE
PLK3Q9H4B4humanPTENP60484S370TSVtPDVsDNEPDHy
PLK3Q9H4B4humanCDC25CP30307S191EDQAEEIsDELMEFsM-inducer_phosp
PLK3Q9H4B4humanSNCBQ16143S118LMEPEGEsYEDPPQESynuclein
PLK3Q9H4B4humanBCL2L1Q07817S49ESEMEtPsAINGNPS
PLK3Q9H4B4humanSNCAP37840S129NEAyEMPsEEGyQDySynuclein
PLK3Q9H4B4humanHIF1AQ16665S657EttsATssPYRDTQS
PLK3Q9H4B4humanCHEK2O96017S73VstQELYsIPEDQEP
PLK3Q9H4B4humanPTENP60484T366ASSsTSVtPDVsDNE
PLK3Q9H4B4humanCALUO43852T196KDIVVQEtMEDIDKNEF-hand_5
PLK3Q9H4B4humanNPM1P06748S4____MEDsMDMDMsP
PLK3Q9H4B4humanCDC25CP30307S198sDELMEFsLKDQEAKM-inducer_phosp
PLK3Q9H4B4humanJUNP05412S73VGLLkLAsPELERLIJun
PLK3Q9H4B4humanTP53P04637S20PLsQEtFsDLWkLLPP53_TAD
PLK3Q9H4B4humanCCNB1P14635S133sPsPMETsGCAPAEE
PLK3Q9H4B4humanJUNP05412S63kNsDLLtsPDVGLLkJun
PLK3Q9H4B4humanCASP8Q14790T273DAGALTTtFEELHFEPeptidase_C14
PLK3Q9H4B4humanVRK1Q99986S342DDGkLDLsVVENGGL
PLK3Q9H4B4humanCDC25AP30304T80RMGssEstDsGFCLD
PLK3Q9H4B4humanOCLNQ16625S471LDDyREEsEEyMAAAOccludin_ELL
PLK3Q9H4B4humanHIF1AQ16665S576DDDFQLRsFDQLSPLHIF-1
PLK3Q9H4B4humanCALUO43852T177IATkEEFtAFLHPEE
PRKCIP41743humanMARK2Q7KZI7T596rGVssRstFHAGQLR
PRKCIP41743humanAMOTQ4VCS5T750DMEGRIKtLHAQIIEAngiomotin_C
PRKCIP41743humanMAPTP10636-8S352DFKDrVQskIGsLDNTubulin-binding
PRKCIP41743humanROCK1Q13464T1334AsPRtLstRstANQs
PRKCIP41743humanEZRP15311T567QGRDkyKtLRQIRQGERM_C
PRKCIP41743humanSP1P08047S59GGQEsQPsPLALLAA
PRKCIP41743humanROCK1Q13464S1333RAsPRtLstRstANQ
PRKCIP41743humanNUMBP49757S295sPFKRQLsLRINELPNumbF
PRKCIP41743humanMARK3P27448T564RGTASRStFHGQPRE
PRKCIP41743humanCDK7P50613T170GsPNRAytHQVVtRWPkinase
PRKCIP41743humanGLI1P08151S243DCRWDGCsQEFDSQE
PRKCIP41743humanROCK1Q13464T1337RtLstRstANQsFRK
PRKCIP41743humanNUMBP49757S7_MNKLRQsFRRKkDV
PRKCIP41743humanNUMBP49757S276EQLARQGsFrGFPALNumbF
PRKCIP41743humanMAPTP10636-8S324kVTskCGsLGNIHHkTubulin-binding
PRKCIP41743humanPPP1R14CQ8TAE6T73RHQQGKVtVkYDRKEPP1_inhibitor
PRKCIP41743humanFBXW7Q969H0S10QELLSVGsKRRRTGG
PRKCIP41743humanDOC2BQ14184S34IRPIKQIsDYFPRFP
PRKCIP41743humanFBXW7Q969H0S18KRRRTGGsLRGNPSs
PRKCIP41743humanROCK1Q13464T1024IDRKKANtQDLRKKE
PRKCIP41743humanMAPTP10636-8S293NVQskCGsKDNIkHVTubulin-binding
PRKCIP41743humanBADQ92934S99PFrGrsRsAPPNLWABcl-2_BAD
PRKCIP41743humanUBTFP17480S412EkPKRPVsAMFIFSEHMG_box
PRKCIP41743humanELF3P78545S68GEQPQFWsKTQVLDWSAM_PNT
PRKCIP41743humanPARD6AQ9NPB6S345RGDGSGFsL______
PRKCIP41743humanECT2Q9H8V3T359YLYEKANtPELKksV
PRKCIP41743humanAMOTQ4VCS5T536GSEDTRKtIsQLFAK
PRKCIP41743humanGLI1P08151T304GEKPHKCtFEGCRKSzf-C2H2
PRKCIP41743humanBADQ92934S75EIRsRHssyPAGtEDBcl-2_BAD
PRKCIP41743humanVIMP08670S34srsyVttstrtysLGFilament_head
PRKCIP41743humanKLF10Q13118S384GkTYFKssHLkAHTR
PRKCIP41743humanMAPTP10636-8S258PDLkNVKskIGstENTubulin-binding
PRKCIP41743humanEZH2Q15910T487APAEDVDtPPRKKKR
PRKCIP41743humanEZH2Q15910S690KIRFANHsVNPNCyASET
PRKCIP41743humanCTTNQ14247S261EKLQLHEsQkDyktGHS1_rep
PRKCIP41743humanRPS6KB2Q9UBS0S473PPSGTKKsKRGRGRP
PRKCIP41743humanBADQ92934S118GRELRRMsDEFVDsFBcl-2_BAD
PRKCIP41743humanYKT6O15498S174LDDLVsksEVLGtQSSynaptobrevin
PRKCIP41743humanVIMP08670S39ttstrtysLGsALrPFilament_head
PRKCIP41743humanROCK1Q13464S1341tRstANQsFRKVVKN
PRKCIP41743humanAMOTQ4VCS5S538EDTRKtIsQLFAKNk
PRKCIP41743humanEP300Q09472S89SELLRSGsSPNLNMG
PRKCIP41743humanPARD3Q8TEW0S827REGFGRQsMSEKRtK
PRKCIP41743humanKLF10Q13118T445FMRSDHLtkHARRHLzf-C2H2
PRKCIP41743humanEZH2Q15910T345LtAERIKtPPkRPGG
PRKCIP41743humanNFE2L2Q16236S40SREVFDFsQRRkEYE
PRKCIP41743humanVIMP08670S56srsLyAssPGGVyAtFilament_head


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
PLK3IDDescription0.00e+00
PLK3GO:0051402neuron apoptotic process5.63e-06
PLK3GO:0044839cell cycle G2/M phase transition5.63e-06
PLK3GO:1901987regulation of cell cycle phase transition5.63e-06
PLK3GO:1904029regulation of cyclin-dependent protein kinase activity7.35e-06
PLK3GO:1902751positive regulation of cell cycle G2/M phase transition7.35e-06
PLK3GO:0071214cellular response to abiotic stimulus7.35e-06
PLK3GO:0104004cellular response to environmental stimulus7.35e-06
PLK3GO:0043523regulation of neuron apoptotic process2.04e-05
PLK3GO:1902749regulation of cell cycle G2/M phase transition2.04e-05
PLK3GO:1901522positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus1.04e-04
PLK3GO:0010948negative regulation of cell cycle process1.04e-04
PLK3GO:0031647regulation of protein stability1.04e-04
PLK3GO:0071478cellular response to radiation1.29e-04
PLK3GO:0070242thymocyte apoptotic process1.30e-04
PLK3GO:1901990regulation of mitotic cell cycle phase transition1.39e-04
PLK3GO:0010639negative regulation of organelle organization1.42e-04
PLK3GO:0000079regulation of cyclin-dependent protein serine/threonine kinase activity1.42e-04
PLK3GO:0045936negative regulation of phosphate metabolic process1.56e-04
PLK3GO:0010563negative regulation of phosphorus metabolic process1.56e-04
PLK3GO:0097194execution phase of apoptosis1.67e-04
PLK3GO:0001701in utero embryonic development1.77e-04
PLK3GO:0050821protein stabilization1.86e-04
PLK3GO:0045786negative regulation of cell cycle1.93e-04
PLK3GO:0071480cellular response to gamma radiation1.93e-04
PLK3GO:0010971positive regulation of G2/M transition of mitotic cell cycle2.31e-04
PLK3GO:0009314response to radiation2.37e-04
PLK3GO:0045930negative regulation of mitotic cell cycle2.91e-04
PLK3GO:0043618regulation of transcription from RNA polymerase II promoter in response to stress3.08e-04
PLK3GO:0034599cellular response to oxidative stress3.10e-04
PLK3GO:0044772mitotic cell cycle phase transition3.35e-04
PLK3GO:1901989positive regulation of cell cycle phase transition3.35e-04
PLK3GO:0007006mitochondrial membrane organization3.35e-04
PLK3GO:1903829positive regulation of protein localization3.35e-04
PLK3GO:0071887leukocyte apoptotic process3.35e-04
PLK3GO:1901988negative regulation of cell cycle phase transition3.85e-04
PLK3GO:0043620regulation of DNA-templated transcription in response to stress3.99e-04
PLK3GO:0071900regulation of protein serine/threonine kinase activity4.18e-04
PLK3GO:0071634regulation of transforming growth factor beta production4.74e-04
PLK3GO:0043467regulation of generation of precursor metabolites and energy5.06e-04
PLK3GO:0000086G2/M transition of mitotic cell cycle5.07e-04
PLK3GO:0007093mitotic cell cycle checkpoint signaling5.23e-04
PLK3GO:0071604transforming growth factor beta production5.29e-04
PLK3GO:0062197cellular response to chemical stress6.01e-04
PLK3GO:0097193intrinsic apoptotic signaling pathway6.05e-04
PLK3GO:0010332response to gamma radiation7.22e-04
PLK3GO:1902895positive regulation of miRNA transcription7.49e-04
PLK3GO:0043524negative regulation of neuron apoptotic process7.86e-04
PLK3GO:0070231T cell apoptotic process9.98e-04
PLK3GO:0046902regulation of mitochondrial membrane permeability1.14e-03

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Related Drugs to PRKCI_PLK3


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 PRKCI-PLK3 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 PRKCI_PLK3


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