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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:CCNY_BRAF

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: CCNY_BRAF
KinaseFusionDB ID: KFG972
FusionGDB2.0 ID: KFG972
HgeneTgene
Gene symbol

CCNY

BRAF

Gene ID

219771

673

Gene namecyclin YB-Raf proto-oncogene, serine/threonine kinase
SynonymsC10orf9|CBCP1|CCNX|CFP1B-RAF1|B-raf|BRAF-1|BRAF1|NS7|RAFB1
Cytomap

10p11.21

7q34

Type of geneprotein-codingprotein-coding
Descriptioncyclin-Ycyc-Ycyclin box protein 1cyclin fold protein 1cyclin-Xcyclin-box carrying protein 1serine/threonine-protein kinase B-raf94 kDa B-raf proteinB-Raf proto-oncogene serine/threonine-protein kinase (p94)B-Raf serine/threonine-proteinmurine sarcoma viral (v-raf) oncogene homolog B1proto-oncogene B-Rafv-raf murine sarcoma viral oncogene
Modification date2024030520240416
UniProtAcc

Q8ND76

P15056

Ensembl transtripts involved in fusion geneENST idsENST00000492478, ENST00000265375, 
ENST00000339497, ENST00000374704, 
ENST00000374706, 		ENST00000288602, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: CCNY [Title/Abstract] AND BRAF [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CCNY(35626135)-BRAF(140482957), # 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
HgeneCCNY

GO:0000086

G2/M transition of mitotic cell cycle

20059949

HgeneCCNY

GO:0010508

positive regulation of autophagy

32098961

HgeneCCNY

GO:0045737

positive regulation of cyclin-dependent protein serine/threonine kinase activity

19524571|20059949

HgeneCCNY

GO:0060828

regulation of canonical Wnt signaling pathway

20059949

TgeneBRAF

GO:0000165

MAPK cascade

18567582|29433126

TgeneBRAF

GO:0006468

protein phosphorylation

17563371

TgeneBRAF

GO:0007173

epidermal growth factor receptor signaling pathway

18567582

TgeneBRAF

GO:0010828

positive regulation of glucose transmembrane transport

23010278

TgeneBRAF

GO:0033138

positive regulation of peptidyl-serine phosphorylation

19667065

TgeneBRAF

GO:0043066

negative regulation of apoptotic process

19667065

TgeneBRAF

GO:0070374

positive regulation of ERK1 and ERK2 cascade

22065586

TgeneBRAF

GO:0071277

cellular response to calcium ion

18567582

TgeneBRAF

GO:0090150

establishment of protein localization to membrane

23010278


check buttonKinase Fusion gene breakpoints across CCNY (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonKinase Fusion gene breakpoints across BRAF (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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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-EM-A3AQ-01ACCNYchr10

35626135

BRAFchr7

140482957



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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)
ENST00000339497ENST00000288602CCNYchr1035626135BRAFchr71404829571576425

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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

>ENST00000339497_ENST00000288602_CCNY_chr10_35626135_BRAF_chr7_140482957_length(amino acids)=425
MGNTTSCCVSSSPKLRRNAHSRLESYRPDTDLSREDTGCNLQHISDRENIDGSTTGLSATPPASLPGSLTNVKALQKSPGPQRERKSSSS
SEDRNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYST
KPQLAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSGSHQFE
QLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKR

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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/chr10:35626135/chr7:140482957)
- 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
CCNY

Q8ND76

BRAF

P15056

FUNCTION: Positive regulatory subunit of the cyclin-dependent kinases CDK14/PFTK1 and CDK16. Acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase by recruiting CDK14/PFTK1 to the plasma membrane and promoting phosphorylation of LRP6, leading to the activation of the Wnt signaling pathway. Recruits CDK16 to the plasma membrane. Isoform 3 might play a role in the activation of MYC-mediated transcription. {ECO:0000269|PubMed:18060517, ECO:0000269|PubMed:19524571, ECO:0000269|PubMed:20059949, ECO:0000269|PubMed:22184064}.FUNCTION: Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000269|PubMed:36402789, ECO:0000305}.

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
TgeneCCNY35626135BRAF140482957ENST00000339497818457_717392767DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159


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Kinase Fusion Protein Structures

check button CIF files of the predicted kinase fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB)HenstTenstHgeneHchrHbpTgeneTchrTbpAA seqLen(AA seq)
PDB file >>>89_CCNY_BRAFENST00000339497ENST00000288602CCNYchr1035626135BRAFchr7140482957
MGNTTSCCVSSSPKLRRNAHSRLESYRPDTDLSREDTGCNLQHISDRENIDGSTTGLSATPPASLPGSLTNVKALQKSPGPQRERKSSSS
SEDRNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYST
KPQLAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSGSHQFE
QLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKR
425
3D view using mol* of 89_CCNY_BRAF
PDB file >>>TKFP_152_CCNY_BRAFENST00000339497ENST00000288602CCNYchr1035626135BRAFchr7140482957
MGNTTSCCVSSSPKLRRNAHSRLESYRPDTDLSREDTGCNLQHISDRENIDGSTTGLSATPPASLPGSLTNVKALQKSPGPQRERKSSSS
SEDRNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYST
KPQLAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSGSHQFE
QLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKR
425_CCNY_BRAF


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Comparison of Fusion Protein Isoforms

check button Superimpose the 3D Structures Among All Fusion Protein Isoforms
* Download the pdb file and open it from the molstar online viewer.

check button Comparison of the Secondary Structures of Fusion Protein Isoforms

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

CCNY_BRAF does not have any known PDB structures.

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pLDDT score distribution

check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
* The blue color at the bottom marks the best active site residues.


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Potential Active Site Information


check button The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.
Kinase Fusion AA seq ID in KinaseFusionDBSite scoreSizeDscoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues

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Ramachandran Plot of Kinase Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.


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Virtual Screening Results


check button Distribution of the average docking score across all approved kinase inhibitors.
Distribution of the number of occurrence across all approved kinase inhibitors.
5'-kinase fusion protein case
3'-kinase fusion protein case

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check button Drug information from DrugBank of the top 20 interacting small molecules.
* The detailed information of individual kinase inhibitors are available in the download page.
Fusion gene name infoDrugDocking scoreGlide g scoreGlide energy

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Kinase-Substrate Information of CCNY_BRAF


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
BRAFP15056humanSLC9A1P19634T653LRsYNRHtLVADPyENEXCaM_BD
BRAFP15056humanEEF1A1P68104T88EtSkyyVtIIDAPGHGTP_EFTU
BRAFP15056humanBRAFP15056S465tVGQRIGsGsFGtVYPK_Tyr_Ser-Thr
BRAFP15056humanMAP2K1Q02750S222LIDsMANsFVGtRSYPkinase
BRAFP15056humanEEF1A2Q05639S21GHVDSGkstttGHLIGTP_EFTU
BRAFP15056humanMAP2K1Q02750S218VsGQLIDsMANsFVGPkinase
BRAFP15056humanTTKP33981S281VPVNLLNsPDCDVkt
BRAFP15056humanBADQ92934S99PFrGrsRsAPPNLWABcl-2_BAD
BRAFP15056humanMAP2K2P36507S222VsGQLIDsMANsFVGPkinase
BRAFP15056humanBADQ92934S75EIRsRHssyPAGtEDBcl-2_BAD
BRAFP15056humanNANOGQ9H9S0S68LIQDsPDsStsPKGK
BRAFP15056humanEEF1A1P68104S21GHVDSGkstttGHLIGTP_EFTU
BRAFP15056humanBRAFP15056S614SHQFEQLsGSILWMAPK_Tyr_Ser-Thr
BRAFP15056humanBADQ92934S118GRELRRMsDEFVDsFBcl-2_BAD
BRAFP15056humanBRAFP15056S467GQRIGsGsFGtVYkGPK_Tyr_Ser-Thr
BRAFP15056humanBRAFP15056T373APNVHINtIEPVNID
BRAFP15056humanMAP2K2P36507S226LIDsMANsFVGtRSYPkinase
BRAFP15056humanTTKP33981S436VFSVskQsPPIsTSk
BRAFP15056humanBADQ92934S134KGLPRPKsAGtAtQMBcl-2_BAD


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
BRAFIDDescription0.00e+00
BRAFGO:0048679regulation of axon regeneration5.62e-05
BRAFGO:0030878thyroid gland development5.62e-05
BRAFGO:0035270endocrine system development5.62e-05
BRAFGO:0070570regulation of neuron projection regeneration5.62e-05
BRAFGO:0048538thymus development1.42e-04
BRAFGO:0031103axon regeneration1.42e-04
BRAFGO:0060324face development1.42e-04
BRAFGO:0031102neuron projection regeneration1.74e-04
BRAFGO:0050772positive regulation of axonogenesis3.79e-04
BRAFGO:0048678response to axon injury4.26e-04
BRAFGO:0060502epithelial cell proliferation involved in lung morphogenesis5.02e-04
BRAFGO:0060439trachea morphogenesis5.09e-04
BRAFGO:0048534hematopoietic or lymphoid organ development5.09e-04
BRAFGO:0033674positive regulation of kinase activity5.09e-04
BRAFGO:0048308organelle inheritance7.57e-04
BRAFGO:0048313Golgi inheritance7.57e-04
BRAFGO:0061684chaperone-mediated autophagy7.57e-04
BRAFGO:1903358regulation of Golgi organization8.17e-04
BRAFGO:0051347positive regulation of transferase activity8.44e-04
BRAFGO:0060438trachea development9.59e-04
BRAFGO:2000641regulation of early endosome to late endosome transport9.59e-04
BRAFGO:0010720positive regulation of cell development9.59e-04
BRAFGO:0050770regulation of axonogenesis1.21e-03
BRAFGO:1903034regulation of response to wounding1.55e-03
BRAFGO:0044342type B pancreatic cell proliferation1.85e-03
BRAFGO:0031099regeneration1.92e-03
BRAFGO:0002520immune system development2.09e-03
BRAFGO:1903649regulation of cytoplasmic transport2.16e-03
BRAFGO:0043550regulation of lipid kinase activity3.11e-03
BRAFGO:0050769positive regulation of neurogenesis3.35e-03
BRAFGO:0045022early endosome to late endosome transport3.60e-03
BRAFGO:0060428lung epithelium development3.60e-03
BRAFGO:0035987endodermal cell differentiation4.20e-03
BRAFGO:0098927vesicle-mediated transport between endosomal compartments4.20e-03
BRAFGO:0048009insulin-like growth factor receptor signaling pathway4.60e-03
BRAFGO:0051962positive regulation of nervous system development4.69e-03
BRAFGO:0060425lung morphogenesis4.69e-03
BRAFGO:0018105peptidyl-serine phosphorylation4.74e-03
BRAFGO:0001706endoderm formation5.11e-03
BRAFGO:0018209peptidyl-serine modification5.11e-03
BRAFGO:0046902regulation of mitochondrial membrane permeability5.41e-03
BRAFGO:0070371ERK1 and ERK2 cascade6.22e-03
BRAFGO:0048645animal organ formation6.22e-03
BRAFGO:0035019somatic stem cell population maintenance6.45e-03
BRAFGO:0006414translational elongation6.46e-03
BRAFGO:0071260cellular response to mechanical stimulus6.46e-03
BRAFGO:0010506regulation of autophagy6.46e-03
BRAFGO:0031346positive regulation of cell projection organization6.46e-03
BRAFGO:0090559regulation of membrane permeability6.84e-03

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Related Drugs to CCNY_BRAF


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 CCNY-BRAF 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 CCNY_BRAF


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
TgeneBRAFC0025202melanoma24CGI;CTD_human;UNIPROT
TgeneBRAFC1275081Cardio-facio-cutaneous syndrome14CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
TgeneBRAFC0009402Colorectal Carcinoma8CTD_human;UNIPROT
TgeneBRAFC0028326Noonan Syndrome8CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET
TgeneBRAFC0238463Papillary thyroid carcinoma8CTD_human;ORPHANET
TgeneBRAFC0040136Thyroid Neoplasm6CGI;CTD_human
TgeneBRAFC0151468Thyroid Gland Follicular Adenoma6CTD_human
TgeneBRAFC0175704LEOPARD Syndrome6CLINGEN;GENOMICS_ENGLAND
TgeneBRAFC0549473Thyroid carcinoma6CGI;CTD_human
TgeneBRAFC3150970NOONAN SYNDROME 75CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneBRAFC0009404Colorectal Neoplasms4CTD_human
TgeneBRAFC3150971LEOPARD SYNDROME 34CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneBRAFC1519086Pilomyxoid astrocytoma3ORPHANET
TgeneBRAFC0004565Melanoma, B162CTD_human
TgeneBRAFC0009075Melanoma, Cloudman S912CTD_human
TgeneBRAFC0018598Melanoma, Harding-Passey2CTD_human
TgeneBRAFC0023443Hairy Cell Leukemia2CGI;ORPHANET
TgeneBRAFC0025205Melanoma, Experimental2CTD_human
TgeneBRAFC0033578Prostatic Neoplasms2CTD_human
TgeneBRAFC0152013Adenocarcinoma of lung (disorder)2CGI;CTD_human
TgeneBRAFC0376358Malignant neoplasm of prostate2CTD_human
TgeneBRAFC0587248Costello syndrome (disorder)2CLINGEN;CTD_human
TgeneBRAFC3501843Nonmedullary Thyroid Carcinoma2CTD_human
TgeneBRAFC3501844Familial Nonmedullary Thyroid Cancer2CTD_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