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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:HECW2_PRKCE

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: HECW2_PRKCE
KinaseFusionDB ID: KFG2665
FusionGDB2.0 ID: KFG2665
HgeneTgene
Gene symbol

HECW2

PRKCE

Gene ID

57520

5581

Gene nameHECT, C2 and WW domain containing E3 ubiquitin protein ligase 2protein kinase C epsilon
SynonymsNDHSAL|NEDL2PKCE|nPKC-epsilon
Cytomap

2q32.3

2p21

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase HECW2HECT-type E3 ubiquitin transferase HECW2NEDD4-like E3 ubiquitin-protein ligase 2NEDD4-related E3 ubiquitin ligase NEDL2protein kinase C epsilon type
Modification date2024041120240403
UniProtAcc

Q9P2P5

Q02156

Ensembl transtripts involved in fusion geneENST idsENST00000260983, ENST00000409111, 
ENST00000306156, ENST00000467135, 
ENST00000394874, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: HECW2 [Title/Abstract] AND PRKCE [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)HECW2(197458232)-PRKCE(46070139), # 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
TgenePRKCE

GO:0006468

protein phosphorylation

18556656|34593629

TgenePRKCE

GO:0018105

peptidyl-serine phosphorylation

15695813


check buttonKinase Fusion gene breakpoints across HECW2 (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 PRKCE (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-RW-A688-01AHECW2chr2

197458232

PRKCEchr2

46070139



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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/:197458232/:46070139)
- 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
HECW2

Q9P2P5

PRKCE

Q02156

FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of TP73. Acts to stabilize TP73 and enhance activation of transcription by TP73 (PubMed:12890487). Involved in the regulation of mitotic metaphase/anaphase transition (PubMed:24163370). {ECO:0000269|PubMed:12890487, ECO:0000269|PubMed:24163370}.FUNCTION: Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (PubMed:19542546). {ECO:0000269|PubMed:11884385, ECO:0000269|PubMed:1374067, ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:16757566, ECO:0000269|PubMed:17603037, ECO:0000269|PubMed:17875639, ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:19542546}.

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 HECW2_PRKCE


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
PRKCEQ02156humanUGT1A7Q9HAW7S432KAVINDKsYkENIMRUDPGT
PRKCEQ02156humanMAPTP10636-8S352DFKDrVQskIGsLDNTubulin-binding
PRKCEQ02156humanADAP1O75689T276GFRkRWFtMDDRRLMPH
PRKCEQ02156humanKEAP1Q14145S602TRMTsGRsGVGVAVT
PRKCEQ02156humanADAM17P78536T735kPFPAPQtPGRLQPA
PRKCEQ02156humanPKMP14618Y105FAsDPILyRPVAVALPK
PRKCEQ02156humanGNAI2P04899S144VQACFGRsREyQLNDG-alpha
PRKCEQ02156humanNANOGQ9H9S0T200LPMWSNQtWNNSTWS
PRKCEQ02156humanNANOGQ9H9S0S135LSNILNLsYKQVKTWHomeodomain
PRKCEQ02156humanPRKCEQ02156S316tPDKITNsGQRRkKL
PRKCEQ02156humanNANOGQ9H9S0S79PKGKQPtsAEKSVAK
PRKCEQ02156humanGNAI2P04899S302NkYDEAAsyIQSkFEG-alpha
PRKCEQ02156humanPPP1R14AQ96A00T38QkRHARVtVkYDRREPP1_inhibitor
PRKCEQ02156humanMCUQ8NE86S92VISVRLPsRRERCQF
PRKCEQ02156humanEGFRP00533T678RHIVRKRtLRRLLQE
PRKCEQ02156humanSLC6A2P23975S259LWKGVKtsGKVVWITSNF
PRKCEQ02156humanMIIPQ5JXC2S303YHIHRRKsFDASDTLMIIP
PRKCEQ02156humanKEAP1Q14145S599SEVTRMTsGRsGVGV
PRKCEQ02156humanADAP1O75689S87AARARFEsKVPSFYYArfGap
PRKCEQ02156humanMAPTP10636-8S324kVTskCGsLGNIHHkTubulin-binding
PRKCEQ02156humanAURKBQ96GD4S227GWSVHAPsLRRktMCPkinase
PRKCEQ02156humanPRKCEQ02156S234EtPDQVGsQRFSVNM
PRKCEQ02156humanCHATP28329-3S440VPTYESAsIRRFQEGCarn_acyltransf
PRKCEQ02156humanITGB1P05556T789IyksAVttVVNPkyEIntegrin_b_cyt
PRKCEQ02156humanSTAT3P40763S727NtIDLPMsPrTLDSL
PRKCEQ02156humanTNNI3P19429S44KKskIsAsRKLQLKt
PRKCEQ02156humanNREPQ16612S59LGSSELRsPRISYLHAlveol-reg_P311
PRKCEQ02156humanPRKCEQ02156K534GVIYRDLkLDNILLDPkinase
PRKCEQ02156humanMAPTP10636-8S293NVQskCGsKDNIkHVTubulin-binding
PRKCEQ02156humanBADQ92934S99PFrGrsRsAPPNLWABcl-2_BAD
PRKCEQ02156humanALDH2P05091T429MQILkFKtIEEVVGRAldedh
PRKCEQ02156humanPRKD2Q9BZL6S706ARIIGEksFRRsVVGPkinase
PRKCEQ02156humanPRKD2Q9BZL6S710GEksFRRsVVGtPAyPkinase
PRKCEQ02156humanOCLNQ16625T404HyEtDyttGGEsCDE
PRKCEQ02156humanKCNK3O14649T383TGLHSLStFRGLMKR
PRKCEQ02156humanFGFR1P11362S779PLDQysPsFPDTRSS
PRKCEQ02156humanTRPV1Q8NER1S801VPLLREAsARDRQsA
PRKCEQ02156humanTICAM2Q86XR7S16NSCPLsLsWGKRHsV
PRKCEQ02156humanNANOGQ9H9S0T78sPKGKQPtsAEKSVA
PRKCEQ02156humanBADQ92934S75EIRsRHssyPAGtEDBcl-2_BAD
PRKCEQ02156humanMAPTP10636-8S258PDLkNVKskIGstENTubulin-binding
PRKCEQ02156humanCREB1P16220S119EILsRRPsyRkILNDpKID
PRKCEQ02156humanKIR3DL1P43629S415QRKITRPsQRPKtPP
PRKCEQ02156humanXIAPP98170S87VGRHRKVsPNCRFINBIR
PRKCEQ02156humanRPS6KB2Q9UBS0S473PPSGTKKsKRGRGRP
PRKCEQ02156humanKRT18P05783S53IsVsrstsFrGGMGs
PRKCEQ02156humanGNAI2P04899S44LLLGAGEsGkSTIVkG-alpha
PRKCEQ02156humanPRKCEQ02156S729QEEFKGFsYFGEDLMPkinase_C
PRKCEQ02156humanBADQ92934S118GRELRRMsDEFVDsFBcl-2_BAD
PRKCEQ02156humanGLSO94925-3S314RYVGKEPsGLRFNKLGlutaminase
PRKCEQ02156humanIQGAP1P46940S1443DKMKKsksVkEDsNL
PRKCEQ02156humanALDH2P05091T202KLGPALAtGNVVVMKAldedh
PRKCEQ02156humanPRKD1Q15139S738ARIIGEksFRRsVVGPkinase
PRKCEQ02156humanCORO1BQ9BR76S2______MsFRKVVRQ
PRKCEQ02156humanRAB11AP62491S177TEIYRIVsQkQMSDR
PRKCEQ02156humanRAB5AP20339T7_MAsrGAtRPNGPNT
PRKCEQ02156humanNANOGQ9H9S0T280GLNVIQQtTRYFStP
PRKCEQ02156humanITGB1P05556T788PIyksAVttVVNPkyIntegrin_b_cyt
PRKCEQ02156humanCHATP28329-3S476HKAAVPAsEKLLLLKCarn_acyltransf
PRKCEQ02156humanGJA1P17302S368QRPssRAssRAssRP
PRKCEQ02156humanPRKD2Q9BZL6S876QGLAERIsVL_____
PRKCEQ02156humanIKBKBO14920S177AkELDQGsLCtsFVGPkinase
PRKCEQ02156humanALDH2P05091S296KSPNIIMsDADMDWAAldedh
PRKCEQ02156humanOCLNQ16625T403DHyEtDyttGGEsCD
PRKCEQ02156humanPRKCEQ02156S368NNIRKALsFDNRGEE
PRKCEQ02156humanATF2P15336T52HkHKHEMtLKFGPAR
PRKCEQ02156humanPRKD1Q15139S742GEksFRRsVVGtPAyPkinase
PRKCEQ02156humanCTNND1O60716S268PQVRVGGssVDLHRF
PRKCEQ02156humanMETP08581S985PHLDRLVsARsVsPt


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
PRKCEIDDescription0.00e+00
PRKCEGO:0035767endothelial cell chemotaxis1.33e-05
PRKCEGO:0001667ameboidal-type cell migration1.33e-05
PRKCEGO:2001028positive regulation of endothelial cell chemotaxis2.30e-05
PRKCEGO:0010634positive regulation of epithelial cell migration5.39e-05
PRKCEGO:0010631epithelial cell migration5.39e-05
PRKCEGO:0090132epithelium migration5.39e-05
PRKCEGO:0090130tissue migration5.39e-05
PRKCEGO:2001026regulation of endothelial cell chemotaxis6.60e-05
PRKCEGO:0051347positive regulation of transferase activity8.62e-05
PRKCEGO:0050679positive regulation of epithelial cell proliferation1.33e-04
PRKCEGO:0033674positive regulation of kinase activity1.59e-04
PRKCEGO:0050920regulation of chemotaxis1.59e-04
PRKCEGO:0050921positive regulation of chemotaxis1.59e-04
PRKCEGO:0043542endothelial cell migration5.52e-04
PRKCEGO:0010632regulation of epithelial cell migration6.62e-04
PRKCEGO:0001938positive regulation of endothelial cell proliferation6.96e-04
PRKCEGO:0043123positive regulation of canonical NF-kappaB signal transduction6.96e-04
PRKCEGO:0002756MyD88-independent toll-like receptor signaling pathway7.21e-04
PRKCEGO:0062197cellular response to chemical stress8.37e-04
PRKCEGO:0060326cell chemotaxis9.35e-04
PRKCEGO:0010595positive regulation of endothelial cell migration1.20e-03
PRKCEGO:0042886amide transport1.48e-03
PRKCEGO:0046887positive regulation of hormone secretion1.62e-03
PRKCEGO:0051091positive regulation of DNA-binding transcription factor activity1.71e-03
PRKCEGO:0046883regulation of hormone secretion1.93e-03
PRKCEGO:0051092positive regulation of NF-kappaB transcription factor activity1.93e-03
PRKCEGO:0034599cellular response to oxidative stress1.95e-03
PRKCEGO:0043536positive regulation of blood vessel endothelial cell migration2.09e-03
PRKCEGO:0043122regulation of canonical NF-kappaB signal transduction2.22e-03
PRKCEGO:1905564positive regulation of vascular endothelial cell proliferation2.22e-03
PRKCEGO:0051090regulation of DNA-binding transcription factor activity2.48e-03
PRKCEGO:0050678regulation of epithelial cell proliferation2.48e-03
PRKCEGO:1903532positive regulation of secretion by cell3.08e-03
PRKCEGO:1902905positive regulation of supramolecular fiber organization3.08e-03
PRKCEGO:0072659protein localization to plasma membrane3.08e-03
PRKCEGO:0031116positive regulation of microtubule polymerization3.08e-03
PRKCEGO:0032273positive regulation of protein polymerization3.08e-03
PRKCEGO:0018105peptidyl-serine phosphorylation3.08e-03
PRKCEGO:0001936regulation of endothelial cell proliferation3.08e-03
PRKCEGO:0043534blood vessel endothelial cell migration3.08e-03
PRKCEGO:0007249canonical NF-kappaB signal transduction3.11e-03
PRKCEGO:0051495positive regulation of cytoskeleton organization3.11e-03
PRKCEGO:0045766positive regulation of angiogenesis3.11e-03
PRKCEGO:1904018positive regulation of vasculature development3.11e-03
PRKCEGO:0018209peptidyl-serine modification3.26e-03
PRKCEGO:0046879hormone secretion3.26e-03
PRKCEGO:0019932second-messenger-mediated signaling3.26e-03
PRKCEGO:0051047positive regulation of secretion3.26e-03
PRKCEGO:0031112positive regulation of microtubule polymerization or depolymerization3.27e-03

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Related Drugs to HECW2_PRKCE


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 HECW2-PRKCE 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 HECW2_PRKCE


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
TgenePRKCEC0020429Hyperalgesia3CTD_human
TgenePRKCEC0458247Allodynia3CTD_human
TgenePRKCEC0751211Hyperalgesia, Primary3CTD_human
TgenePRKCEC0751212Hyperalgesia, Secondary3CTD_human
TgenePRKCEC0751213Tactile Allodynia3CTD_human
TgenePRKCEC0751214Hyperalgesia, Thermal3CTD_human
TgenePRKCEC2936719Mechanical Allodynia3CTD_human


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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