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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:BCAS3_TLK2

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: BCAS3_TLK2
KinaseFusionDB ID: KFG575
FusionGDB2.0 ID: KFG575
HgeneTgene
Gene symbol

BCAS3

TLK2

Gene ID

54828

11011

Gene nameBCAS3 microtubule associated cell migration factortousled like kinase 2
SynonymsGAOB1|HEMARS|MAAB|PHAF2HsHPK|MRD57|PKU-ALPHA
Cytomap

17q23.2

17q23.2

Type of geneprotein-codingprotein-coding
DescriptionBCAS3 microtubule associated cell migration factorBCAS4/BCAS3 fusionRudhirabreast carcinoma amplified sequence 4/3 fusion proteinbreast carcinoma-amplified sequence 3metastasis associated antigen of breast cancerphagophore assembly factor 2protein serine/threonine-protein kinase tousled-like 2
Modification date2024030520240403
UniProtAcc

Q9H6U6

Q86UE8

Ensembl transtripts involved in fusion geneENST idsENST00000390652, ENST00000407086, 
ENST00000408905, ENST00000585744, 
ENST00000588462, ENST00000588874, 
ENST00000589222, ENST00000585812, 
ENST00000326270, ENST00000343388, 
ENST00000346027, ENST00000542523, 
ENST00000577616, ENST00000582809, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: BCAS3 [Title/Abstract] AND TLK2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TLK2(60558567)-BCAS3(58945937), # samples:2
BCAS3(59155890)-TLK2(60673946), # samples:1
BCAS3(59161925)-TLK2(60673946), # 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
HgeneBCAS3

GO:0043085

positive regulation of catalytic activity

17505058

HgeneBCAS3

GO:0043627

response to estrogen

16617102

HgeneBCAS3

GO:0045944

positive regulation of transcription by RNA polymerase II

17505058

HgeneBCAS3

GO:0071391

cellular response to estrogen stimulus

17505058

TgeneTLK2

GO:0006468

protein phosphorylation

12660173

TgeneTLK2

GO:0006974

DNA damage response

12660173

TgeneTLK2

GO:0018105

peptidyl-serine phosphorylation

20016786

TgeneTLK2

GO:0035556

intracellular signal transduction

12660173

TgeneTLK2

GO:0071480

cellular response to gamma radiation

12660173

TgeneTLK2

GO:1902275

regulation of chromatin organization

12660173


check buttonKinase Fusion gene breakpoints across BCAS3 (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 TLK2 (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-DQ-7589-01ABCAS3chr17

59155890

TLK2chr17

60673946

ChimerDB4TCGA-DQ-7589BCAS3chr17

59161925

TLK2chr17

60673946



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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)
ENST00000589222ENST00000582809BCAS3chr1759155890TLK2chr176067394642871039

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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

>ENST00000589222_ENST00000582809_BCAS3_chr17_59155890_TLK2_chr17_60673946_length(amino acids)=1039
MNEAMATDSPRRPSRCTGGVVVRPQAVTEQSYMESVVTFLQDVVPQAYSGTPLTEEKEKIVWVRFENADLNDTSRNLEFHEIHSTGNEPP
LLIMIGYSDGMQVWSIPISGEAQELFSVRHGPIRAARILPAPQFGAQKCDNFAEKRPLLGVCKSIGSSGTSPPYCCVDLYSLRTGEMVKS
IQFKTPIYDLHCNKRILVVVLQEKIAAFDSCTFTKKFFVTSCYPCPGPNMNPIALGSRWLAYAENKLIRCHQSRGGACGDNIQSYTATVI
SAAKTLKSGLTMVGKVVTQLTGTLPSGVTEDDVAIHSNSRRSPLVPGIITVIDTETVGEGQVLVSEDSDSDGIVAHFPAHEKPVCCMAFN
TSGMLLVTTDTLGHDFHVFQILTHPWSSSQCAVHHLYTLHRGETEAKVQDICFSHDCRWVVVSTLRGTSHVFPINPYGGQPCVRTHMSPR
VVNRMSRFQKSAGLEEIEQELTSKQGGRCSPVPGLSSSPSGSPLHGKLNSQDSYNNFTNNNPGNPRLSPLPSLMVVMPLAQIKQPMTLGT
ITKRTGKVKPPPQISPSKSMGGEFCVAAIFGTSRSWFANNAGLKREKDQSKQVVVESLYIISCYGTLVEHMMEPRPLSTAPKISDDTPLE
MMTSPRASWTLVRTPQWNELQPPFNANHPLLLAADAVQYYQFLLAGLVPPGSPGPITRHGSYDSLASDHSGQEDEEWLSQVEIVTHTGPH
RRLWMGPQFQFKTIHPSGQTTVISSSSSVLQSHGPSDTPQPLLDFDTDDLDLNSLRHACREYRIHKELDHPRIVKLYDYFSLDTDSFCTV
LEYCEGNDLDFYLKQHKLMSEKEARSIIMQIVNALKYLNEIKPPIIHYDLKPGNILLVNGTACGEIKITDFGLSKIMDDDSYNSVDGMEL
TSQGAGTYWYLPPECFVVGKEPPKISNKVDVWSVGVIFYQCLYGRKPFGHNQSQQDILQENTILKATEVQFPPKPVVTPEAKAFIRRCLA

--------------------------------------------------------------

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/chr17:60558567/chr17:58945937)
- 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
BCAS3

Q9H6U6

TLK2

Q86UE8

FUNCTION: Plays a role in angiogenesis. Participates in the regulation of cell polarity and directional endothelial cell migration by mediating both the activation and recruitment of CDC42 and the reorganization of the actin cytoskeleton at the cell leading edge. Promotes filipodia formation (By similarity). Functions synergistically with PELP1 as a transcriptional coactivator of estrogen receptor-responsive genes. Stimulates histone acetyltransferase activity. Binds to chromatin. Plays a regulatory role in autophagic activity. In complex with PHAF1, associates with the preautophagosomal structure during both non-selective and selective autophagy (PubMed:33499712). Probably binds phosphatidylinositol 3-phosphate (PtdIns3P) which would mediate the recruitment preautophagosomal structures (PubMed:33499712). {ECO:0000250|UniProtKB:Q8CCN5, ECO:0000269|PubMed:17505058, ECO:0000269|PubMed:33499712}.FUNCTION: Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (PubMed:9427565, PubMed:10523312, PubMed:11470414, PubMed:12660173, PubMed:12955071, PubMed:29955062, PubMed:33323470). Phosphorylates the chromatin assembly factors ASF1A and ASF1B (PubMed:11470414, PubMed:20016786, PubMed:29955062, PubMed:35136069). Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (PubMed:20016786). Negative regulator of amino acid starvation-induced autophagy (PubMed:22354037). {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:20016786, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:29955062, ECO:0000269|PubMed:33323470, ECO:0000269|PubMed:35136069, ECO:0000269|PubMed:9427565}.

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
TgeneBCAS359155890TLK260673946ENST000005892221421462_741454719DomainNote=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 >>>54_BCAS3_TLK2ENST00000589222ENST00000582809BCAS3chr1759155890TLK2chr1760673946
MNEAMATDSPRRPSRCTGGVVVRPQAVTEQSYMESVVTFLQDVVPQAYSGTPLTEEKEKIVWVRFENADLNDTSRNLEFHEIHSTGNEPP
LLIMIGYSDGMQVWSIPISGEAQELFSVRHGPIRAARILPAPQFGAQKCDNFAEKRPLLGVCKSIGSSGTSPPYCCVDLYSLRTGEMVKS
IQFKTPIYDLHCNKRILVVVLQEKIAAFDSCTFTKKFFVTSCYPCPGPNMNPIALGSRWLAYAENKLIRCHQSRGGACGDNIQSYTATVI
SAAKTLKSGLTMVGKVVTQLTGTLPSGVTEDDVAIHSNSRRSPLVPGIITVIDTETVGEGQVLVSEDSDSDGIVAHFPAHEKPVCCMAFN
TSGMLLVTTDTLGHDFHVFQILTHPWSSSQCAVHHLYTLHRGETEAKVQDICFSHDCRWVVVSTLRGTSHVFPINPYGGQPCVRTHMSPR
VVNRMSRFQKSAGLEEIEQELTSKQGGRCSPVPGLSSSPSGSPLHGKLNSQDSYNNFTNNNPGNPRLSPLPSLMVVMPLAQIKQPMTLGT
ITKRTGKVKPPPQISPSKSMGGEFCVAAIFGTSRSWFANNAGLKREKDQSKQVVVESLYIISCYGTLVEHMMEPRPLSTAPKISDDTPLE
MMTSPRASWTLVRTPQWNELQPPFNANHPLLLAADAVQYYQFLLAGLVPPGSPGPITRHGSYDSLASDHSGQEDEEWLSQVEIVTHTGPH
RRLWMGPQFQFKTIHPSGQTTVISSSSSVLQSHGPSDTPQPLLDFDTDDLDLNSLRHACREYRIHKELDHPRIVKLYDYFSLDTDSFCTV
LEYCEGNDLDFYLKQHKLMSEKEARSIIMQIVNALKYLNEIKPPIIHYDLKPGNILLVNGTACGEIKITDFGLSKIMDDDSYNSVDGMEL
TSQGAGTYWYLPPECFVVGKEPPKISNKVDVWSVGVIFYQCLYGRKPFGHNQSQQDILQENTILKATEVQFPPKPVVTPEAKAFIRRCLA
1039
3D view using mol* of 54_BCAS3_TLK2
PDB file >>>TKFP_78_BCAS3_TLK2ENST00000589222ENST00000582809BCAS3chr1759155890TLK2chr1760673946
MNEAMATDSPRRPSRCTGGVVVRPQAVTEQSYMESVVTFLQDVVPQAYSGTPLTEEKEKIVWVRFENADLNDTSRNLEFHEIHSTGNEPP
LLIMIGYSDGMQVWSIPISGEAQELFSVRHGPIRAARILPAPQFGAQKCDNFAEKRPLLGVCKSIGSSGTSPPYCCVDLYSLRTGEMVKS
IQFKTPIYDLHCNKRILVVVLQEKIAAFDSCTFTKKFFVTSCYPCPGPNMNPIALGSRWLAYAENKLIRCHQSRGGACGDNIQSYTATVI
SAAKTLKSGLTMVGKVVTQLTGTLPSGVTEDDVAIHSNSRRSPLVPGIITVIDTETVGEGQVLVSEDSDSDGIVAHFPAHEKPVCCMAFN
TSGMLLVTTDTLGHDFHVFQILTHPWSSSQCAVHHLYTLHRGETEAKVQDICFSHDCRWVVVSTLRGTSHVFPINPYGGQPCVRTHMSPR
VVNRMSRFQKSAGLEEIEQELTSKQGGRCSPVPGLSSSPSGSPLHGKLNSQDSYNNFTNNNPGNPRLSPLPSLMVVMPLAQIKQPMTLGT
ITKRTGKVKPPPQISPSKSMGGEFCVAAIFGTSRSWFANNAGLKREKDQSKQVVVESLYIISCYGTLVEHMMEPRPLSTAPKISDDTPLE
MMTSPRASWTLVRTPQWNELQPPFNANHPLLLAADAVQYYQFLLAGLVPPGSPGPITRHGSYDSLASDHSGQEDEEWLSQVEIVTHTGPH
RRLWMGPQFQFKTIHPSGQTTVISSSSSVLQSHGPSDTPQPLLDFDTDDLDLNSLRHACREYRIHKELDHPRIVKLYDYFSLDTDSFCTV
LEYCEGNDLDFYLKQHKLMSEKEARSIIMQIVNALKYLNEIKPPIIHYDLKPGNILLVNGTACGEIKITDFGLSKIMDDDSYNSVDGMEL
TSQGAGTYWYLPPECFVVGKEPPKISNKVDVWSVGVIFYQCLYGRKPFGHNQSQQDILQENTILKATEVQFPPKPVVTPEAKAFIRRCLA
1039_BCAS3_TLK2


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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

BCAS3_TLK2 does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/54_BCAS3_TLK2.png
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.
54_BCAS3_TLK2.png
all structure sitemap plddt3 54_BCAS3_TLK2.png
54_BCAS3_TLK2.png
all structure sitemap plddt4 54_BCAS3_TLK2.png


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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.

54_BCAS3_TLK2_ramachandran.png
all structure BCAS3-TLK2

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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
all structure BCAS3-TLK2

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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
54_BCAS3_TLK2-DOCK_HTVS_1-001Lapatinib-7.98535-8.07415-76.7907
54_BCAS3_TLK2-DOCK_HTVS_1-001Lapatinib-7.69195-7.78075-76.5132
54_BCAS3_TLK2-DOCK_HTVS_1-001Ponatinib-7.368580000000001-7.5751800000000005-66.8629
54_BCAS3_TLK2-DOCK_HTVS_1-001Ponatinib-7.368580000000001-7.5751800000000005-66.8629
54_BCAS3_TLK2-DOCK_HTVS_1-001Ponatinib-7.368580000000001-7.5751800000000005-66.8629
54_BCAS3_TLK2-DOCK_HTVS_1-001Selpercatinib-7.198169999999999-7.22867-62.4927
54_BCAS3_TLK2-DOCK_HTVS_1-001Nilotinib-7.129980000000001-8.054780000000001-66.2889
54_BCAS3_TLK2-DOCK_HTVS_1-001Nilotinib-7.129980000000001-8.054780000000001-66.2889
54_BCAS3_TLK2-DOCK_HTVS_1-001Pacritinib-7.12639-7.131489999999999-54.6117
54_BCAS3_TLK2-DOCK_HTVS_1-001Tepotinib-7.03573-7.03683-69.5063
54_BCAS3_TLK2-DOCK_HTVS_1-001Palbociclib-7.034680000000001-7.44158-63.1737
54_BCAS3_TLK2-DOCK_HTVS_1-001Selpercatinib-7.01285-7.04335-65.6106
54_BCAS3_TLK2-DOCK_HTVS_1-001Selpercatinib-7.01285-7.04335-65.6106
54_BCAS3_TLK2-DOCK_HTVS_1-001Pralsetinib-6.914969999999999-7.006469999999999-68.8814
54_BCAS3_TLK2-DOCK_HTVS_1-001Trilaciclib-6.9095699999999995-7.04437-56.5274
54_BCAS3_TLK2-DOCK_HTVS_1-001Trilaciclib-6.9095699999999995-7.04437-56.5274
54_BCAS3_TLK2-DOCK_HTVS_1-001Trilaciclib-6.9095699999999995-7.04437-56.5274
54_BCAS3_TLK2-DOCK_HTVS_1-001Trilaciclib-6.9095699999999995-7.04437-56.5274
54_BCAS3_TLK2-DOCK_HTVS_1-001Dacomitinib-6.88593-6.99423-53.5389
54_BCAS3_TLK2-DOCK_HTVS_1-001Dacomitinib-6.88593-6.99423-53.5389

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Kinase-Substrate Information of BCAS3_TLK2


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
TLK2Q86UE8humanASF1BQ9NVP2S198PGLLPENsMDCI___
TLK2Q86UE8humanASF1AQ9Y294S192GWSTSENsLNVMLES


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
TLK2IDDescription0.00e+00
TLK2GO:0006334nucleosome assembly4.25e-04
TLK2GO:0034728nucleosome organization4.25e-04
TLK2GO:0065004protein-DNA complex assembly8.59e-04
TLK2GO:0140861DNA repair-dependent chromatin remodeling6.29e-03
TLK2GO:0001835blastocyst hatching6.29e-03
TLK2GO:0035188hatching6.29e-03
TLK2GO:0071684organism emergence from protective structure6.29e-03
TLK2GO:0031297replication fork processing1.04e-02
TLK2GO:0045005DNA-templated DNA replication maintenance of fidelity1.05e-02
TLK2GO:0001824blastocyst development1.96e-02
TLK2GO:0006261DNA-templated DNA replication2.47e-02
TLK2GO:0001649osteoblast differentiation3.60e-02
TLK2GO:0006260DNA replication3.60e-02
TLK2GO:0001701in utero embryonic development4.65e-02
TLK2GO:0042692muscle cell differentiation4.65e-02
TLK2GO:0001503ossification4.65e-02

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Related Drugs to BCAS3_TLK2


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 BCAS3-TLK2 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 BCAS3_TLK2


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