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	Kinase Fusion Gene Summary
	Kinase Fusion Gene Sample Information
	Kinase Fusion ORF Analysis
	Kinase Fusion Amino Acid Sequences
	Multiple Sequence Alignment of All Fusion Protein Isoforms
	Kinase Fusion Protein Functional Features
	Kinase Fusion Protein Structures
	Comparison of Fusion Protein Isoforms
	Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB
	pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.
	Ramachandran Plot of Kinase Fusion Protein Structure
	Potential Active Site Information
	Virtual Screening Results
	Kinase-Substrate Information
	Related Drugs with This Kinase Fusion Protein
	Related Disease with This Kinase Fusion Protein
	Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:TBCK_USP10

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: TBCK_USP10
	KinaseFusionDB ID: KFG6440
	FusionGDB2.0 ID: KFG6440
		Hgene	Tgene
	Gene symbol	TBCK	USP10
	Gene ID	93627	84669
	Gene name	TBC1 domain containing kinase	ubiquitin specific peptidase 32
	Synonyms	FERRY1\|Fy-1\|HSPC302\|IHPRF3\|TBCKL	NY-REN-60\|USP10
	Cytomap	4q24	17q23.1-q23.2
	Type of gene	protein-coding	protein-coding
	Description	TBC domain-containing protein kinase-like protein	ubiquitin carboxyl-terminal hydrolase 32deubiquitinating enzyme 32renal carcinoma antigen NY-REN-60ubiquitin specific protease 32ubiquitin thioesterase 32ubiquitin thiolesterase 32ubiquitin-specific-processing protease 32
	Modification date	20240305	20240407
	UniProtAcc	Q8TEA7	Q8NFA0
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000273980, ENST00000361687, ENST00000394706, ENST00000394708, ENST00000432496, ENST00000514689,	ENST00000562743, ENST00000219473, ENST00000570191,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: TBCK [Title/Abstract] AND USP10 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	TBCK(107016639)-USP10(84806147), # samples:1

Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner

Gene

GO ID

GO term

PubMed ID

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

Kinase Fusion gene breakpoints across USP10 (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

Kinase Fusion gene information.

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.

Source	Sample	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp
ChimerDB4	TCGA-B6-A0RS-01A	TBCK	chr4	107016639	USP10	chr16	84806147

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Kinase Fusion ORF Analysis

Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.

Henst	Tenst	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	Seq length (transcript)	Seq length (amino acids)
ENST00000273980	ENST00000219473	TBCK	chr4	107016639	USP10	chr16	84806147	3917	989

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Kinase Fusion Amino Acid Sequences

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

>ENST00000273980_ENST00000219473_TBCK_chr4_107016639_USP10_chr16_84806147_length(amino acids)=989
MFPLKDAEMGAFTFFASALPHDVCGSNGLPLTPNSIKILGRFQILKTITHPRLCQYVDISRGKHERLVVVAEHCERSLEDLLRERKPVSC
STVLCIAFEVLQGLQYMNKHGIVHRALSPHNILLDRKGHIKLAKFGLYHMTAHGDDVDFPIGYPSYLAPEVIAQGIFKTTDHMPSKKPLP
SGPKSDVWSLGIILFELCVGRKLFQSLDISERLKFLLTLDCVDDTLIVLAEEHGCLDIIKELPETVIDLLNKCLTFHPSKRPTPDQLMKD
KVFSEVSPLYTPFTKPASLFSSSLRCADLTLPEDISQLCKDINNDYLAERSIEEVYYLWCLAGGDLEKELVNKEIIRSKPPICTLPNFLF
EDGESFGQGRDRSSLLDDTTVTLSLCQLRNRLKDVGGEAFYPLLEDDQSNLPHSNSNNELSAAATLPLIIREKDTEYQLNRIILFDRLLK
AYPYKKNQIWKEARVDIPPLMRGLTWAALLGVEGAIHAKYDAIDKDTPIPTDRQIEVDIPRCHQYDELLSSPEGHAKFRRVLKAWVVSHP
DLVYWQGLDSLCAPFLYLNFNNEALAYACMSAFIPKYLYNFFLKDNSHVIQEYLTVFSQMIAFHDPELSNHLNEIGFIPDLYAIPWFLTM
FTHVFPLHKIFHLWDTLLLGNSSFPFCIGVAILQQLRDRLLANGFNECILLFSDLPEIDIERCVRESINLFCWTPKSATYRQHAQPPKPS
SDSSGGRSSAPYFSAECPDPPKTDLSRESIPLNDLKSEVSPRISAEDLIDLCELTVTGHFKTPSKKTKSSKPKLLVVDIRNSEDFIRGHI
SGSINIPFSAAFTAEGELTQGPYTAMLQNFKGKVIVIVGHVAKHTAEVEISRRVTLEKLPPVLVLHLKRFVYEKTGGCQKLIKNIEYPVD

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Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr4:107016639/chr16:84806147)
- 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.

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
TBCK Q8TEA7	USP10 Q8NFA0
FUNCTION: Involved in the modulation of mTOR signaling and expression of mTOR complex components (PubMed:27040691, PubMed:23977024). Involved in the regulation of cell proliferation and growth (PubMed:23977024, PubMed:24576458). Involved in the control of actin-cytoskeleton organization (PubMed:23977024). {ECO:0000269\|PubMed:23977024, ECO:0000269\|PubMed:24576458, ECO:0000269\|PubMed:27040691}.	FUNCTION: Deubiquitinase that can remove conjugated ubiquitin from target proteins, such as RAB7A and LAMTOR1 (PubMed:36476874). Acts as a positive regulator of the mTORC1 signaling by mediating deubiquitination of LAMTOR1, thereby promoting the association between LAMTOR1 and the lysosomal V-ATPase complex and subsequent activation of the mTORC1 complex (PubMed:36476874). {ECO:0000269\|PubMed:36476874}.

Retention 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.

- Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt).

794818857857794818857857

Partner	Hgeneene	Hbp	Tgeneene	Tbp	ENST	BPexon	TotalExon	Protein feature loci	BPloci	TotalLen	Feature	Note
Hgene	TBCK	107016639	USP10	84806147	ENST00000273980	23	24	1_273	1	831	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	TBCK	107016639	USP10	84806147	ENST00000273980	25	26	1_273	1	855	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	TBCK	107016639	USP10	84806147	ENST00000273980	25	26	1_273	1	894	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	TBCK	107016639	USP10	84806147	ENST00000273980	26	27	1_273	1	894	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	TBCK	107016639	USP10	84806147	ENST00000273980	23	24	466_651	1	831	Domain	Note=Rab-GAP TBC;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00163
Hgene	TBCK	107016639	USP10	84806147	ENST00000273980	25	26	466_651	1	855	Domain	Note=Rab-GAP TBC;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00163
Hgene	TBCK	107016639	USP10	84806147	ENST00000273980	25	26	466_651	1	894	Domain	Note=Rab-GAP TBC;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00163
Hgene	TBCK	107016639	USP10	84806147	ENST00000273980	26	27	466_651	1	894	Domain	Note=Rab-GAP TBC;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00163

- Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).

Partner

Hgeneene

Hbp

Tgeneene

Tbp

ENST

BPexon

TotalExon

Protein feature loci

BPloci

TotalLen

Feature

Note

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Kinase Fusion Protein Structures

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)	Henst	Tenst	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	AA seq	Len(AA seq)
PDB file >>>278_TBCK_USP10	ENST00000273980	ENST00000219473	TBCK	chr4	107016639	USP10	chr16	84806147	MFPLKDAEMGAFTFFASALPHDVCGSNGLPLTPNSIKILGRFQILKTITHPRLCQYVDISRGKHERLVVVAEHCERSLEDLLRERKPVSC STVLCIAFEVLQGLQYMNKHGIVHRALSPHNILLDRKGHIKLAKFGLYHMTAHGDDVDFPIGYPSYLAPEVIAQGIFKTTDHMPSKKPLP SGPKSDVWSLGIILFELCVGRKLFQSLDISERLKFLLTLDCVDDTLIVLAEEHGCLDIIKELPETVIDLLNKCLTFHPSKRPTPDQLMKD KVFSEVSPLYTPFTKPASLFSSSLRCADLTLPEDISQLCKDINNDYLAERSIEEVYYLWCLAGGDLEKELVNKEIIRSKPPICTLPNFLF EDGESFGQGRDRSSLLDDTTVTLSLCQLRNRLKDVGGEAFYPLLEDDQSNLPHSNSNNELSAAATLPLIIREKDTEYQLNRIILFDRLLK AYPYKKNQIWKEARVDIPPLMRGLTWAALLGVEGAIHAKYDAIDKDTPIPTDRQIEVDIPRCHQYDELLSSPEGHAKFRRVLKAWVVSHP DLVYWQGLDSLCAPFLYLNFNNEALAYACMSAFIPKYLYNFFLKDNSHVIQEYLTVFSQMIAFHDPELSNHLNEIGFIPDLYAIPWFLTM FTHVFPLHKIFHLWDTLLLGNSSFPFCIGVAILQQLRDRLLANGFNECILLFSDLPEIDIERCVRESINLFCWTPKSATYRQHAQPPKPS SDSSGGRSSAPYFSAECPDPPKTDLSRESIPLNDLKSEVSPRISAEDLIDLCELTVTGHFKTPSKKTKSSKPKLLVVDIRNSEDFIRGHI SGSINIPFSAAFTAEGELTQGPYTAMLQNFKGKVIVIVGHVAKHTAEVEISRRVTLEKLPPVLVLHLKRFVYEKTGGCQKLIKNIEYPVD	989
3D view using mol* of 278_TBCK_USP10

PDB file >>>HKFP_404_TBCK_USP10	ENST00000273980	ENST00000219473	TBCK	chr4	107016639	USP10	chr16	84806147	MFPLKDAEMGAFTFFASALPHDVCGSNGLPLTPNSIKILGRFQILKTITHPRLCQYVDISRGKHERLVVVAEHCERSLEDLLRERKPVSC STVLCIAFEVLQGLQYMNKHGIVHRALSPHNILLDRKGHIKLAKFGLYHMTAHGDDVDFPIGYPSYLAPEVIAQGIFKTTDHMPSKKPLP SGPKSDVWSLGIILFELCVGRKLFQSLDISERLKFLLTLDCVDDTLIVLAEEHGCLDIIKELPETVIDLLNKCLTFHPSKRPTPDQLMKD KVFSEVSPLYTPFTKPASLFSSSLRCADLTLPEDISQLCKDINNDYLAERSIEEVYYLWCLAGGDLEKELVNKEIIRSKPPICTLPNFLF EDGESFGQGRDRSSLLDDTTVTLSLCQLRNRLKDVGGEAFYPLLEDDQSNLPHSNSNNELSAAATLPLIIREKDTEYQLNRIILFDRLLK AYPYKKNQIWKEARVDIPPLMRGLTWAALLGVEGAIHAKYDAIDKDTPIPTDRQIEVDIPRCHQYDELLSSPEGHAKFRRVLKAWVVSHP DLVYWQGLDSLCAPFLYLNFNNEALAYACMSAFIPKYLYNFFLKDNSHVIQEYLTVFSQMIAFHDPELSNHLNEIGFIPDLYAIPWFLTM FTHVFPLHKIFHLWDTLLLGNSSFPFCIGVAILQQLRDRLLANGFNECILLFSDLPEIDIERCVRESINLFCWTPKSATYRQHAQPPKPS SDSSGGRSSAPYFSAECPDPPKTDLSRESIPLNDLKSEVSPRISAEDLIDLCELTVTGHFKTPSKKTKSSKPKLLVVDIRNSEDFIRGHI SGSINIPFSAAFTAEGELTQGPYTAMLQNFKGKVIVIVGHVAKHTAEVEISRRVTLEKLPPVLVLHLKRFVYEKTGGCQKLIKNIEYPVD	989_TBCK_USP10

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Comparison of Fusion Protein Isoforms

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

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

TBCK_USP10 does not have any known PDB structures.

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pLDDT score distribution

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

The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.

Kinase Fusion AA seq ID in KinaseFusionDB

Site score

Size

Dscore

Volume

Exposure

Enclosure

Contact

Phobic

Philic

Balance

Don/Acc

Residues

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Ramachandran Plot of Kinase Fusion Protein Structure

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

278_TBCK_USP10_ramachandran.png

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Virtual Screening Results

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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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 info	Drug	Docking score	Glide g score	Glide energy
278_TBCK_USP10-DOCK_HTVS_1-001	Pazopanib	-6.49746	-6.50436	-48.3285
278_TBCK_USP10-DOCK_HTVS_1-001	Pazopanib	-6.49746	-6.50436	-48.3285
278_TBCK_USP10-DOCK_HTVS_1-001	Tofacitinib	-6.45529	-6.4667900000000005	-35.5204
278_TBCK_USP10-DOCK_HTVS_1-001	Tofacitinib	-6.45529	-6.4667900000000005	-35.5204
278_TBCK_USP10-DOCK_HTVS_1-001	Asciminib	-6.41445	-6.77755	-58.1714
278_TBCK_USP10-DOCK_HTVS_1-001	Asciminib	-6.222659999999999	-6.5857600000000005	-57.8002
278_TBCK_USP10-DOCK_HTVS_1-001	Vandetanib	-6.03538	-6.03538	-50.5062
278_TBCK_USP10-DOCK_HTVS_1-001	Ruxolitinib	-6.004580000000001	-6.004580000000001	-38.372
278_TBCK_USP10-DOCK_HTVS_1-001	Axitinib	-5.88172	-5.88492	-44.6275
278_TBCK_USP10-DOCK_HTVS_1-001	Tepotinib	-5.80236	-5.80346	-46.3114
278_TBCK_USP10-DOCK_HTVS_1-001	Cobimetinib	-5.767	-5.7698	-42.6148
278_TBCK_USP10-DOCK_HTVS_1-001	Lapatinib	-5.76145	-5.85025	-58.0751
278_TBCK_USP10-DOCK_HTVS_1-001	Futibatinib	-5.7188099999999995	-5.7188099999999995	-43.6366
278_TBCK_USP10-DOCK_HTVS_1-001	Afatinib	-5.713509999999999	-5.89581	-43.33
278_TBCK_USP10-DOCK_HTVS_1-001	Afatinib	-5.713509999999999	-5.89581	-43.33
278_TBCK_USP10-DOCK_HTVS_1-001	Afatinib	-5.71211	-5.89581	-43.33
278_TBCK_USP10-DOCK_HTVS_1-001	Ruxolitinib	-5.63797	-5.63797	-38.5516
278_TBCK_USP10-DOCK_HTVS_1-001	Larotrectinib	-5.573230000000001	-5.573230000000001	-28.9072
278_TBCK_USP10-DOCK_HTVS_1-001	Asciminib	-5.572769999999999	-6.03777	-55.3971
278_TBCK_USP10-DOCK_HTVS_1-001	Vandetanib	-5.56084	-5.56084	-45.5208

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Kinase-Substrate Information of TBCK_USP10

Phosphorylation target of the kinase
(phosphosite, 03-17-2024)

Kinase

Kinase UniProt Acc

Kinase species

Substrate

Substrate UniProt Acc

Substrate phosphorylated residues

Substrate phosphorylated sites (+/-7AA)

Domain

Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

Enriched GO biological processes of the phosphorylation target genes of the kinase

Kinase

GOID

GO term

P.adjust

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Related Drugs to TBCK_USP10

Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Drug

Source

PMID

Distribution of the number of studies mentioning TBCK-USP10 and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1

Fusion gene - drug pair 2

PMID

Publication date

DOI

Study title

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Related Diseases to TBCK_USP10

Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Disease

Source

PMID

Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)

MeSH ID

MeSH term

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source

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Clinical Trials of the Found Drugs/Small Molecules

Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)

Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion Gene

Kinase Inhibitor

NCT ID

Study Status

Phases

Disease

# Enrolment

Date