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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:CLIP1_TNIK

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: CLIP1_TNIK
	KinaseFusionDB ID: KFG1322
	FusionGDB2.0 ID: KFG1322
		Hgene	Tgene
	Gene symbol	CLIP1	TNIK
	Gene ID	6249	23043
	Gene name	CAP-Gly domain containing linker protein 1	TRAF2 and NCK interacting kinase
	Synonyms	CLIP\|CLIP-170\|CLIP170\|CYLN1\|RSN	MRT54
	Cytomap	12q24.31	3q26.2-q26.31
	Type of gene	protein-coding	protein-coding
	Description	CAP-Gly domain-containing linker protein 1cytoplasmic linker protein 1cytoplasmic linker protein 170 alpha-2cytoplasmic linker protein CLIP-170restin (Reed-Steinberg cell-expressed intermediate filament-associated protein)	TRAF2 and NCK-interacting protein kinase
	Modification date	20240407	20240407
	UniProtAcc	P30622	Q9UKE5
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000302528, ENST00000358808, ENST00000361654, ENST00000537178, ENST00000540338, ENST00000536634, ENST00000540539, ENST00000545889,	ENST00000464785, ENST00000465393, ENST00000284483, ENST00000341852, ENST00000357327, ENST00000369326, ENST00000436636, ENST00000460047, ENST00000470834, ENST00000475336, ENST00000488470, ENST00000538048,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: CLIP1 [Title/Abstract] AND TNIK [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	CLIP1(122861936)-TNIK(170908576), # samples:2

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
Tgene	TNIK	GO:0006468	protein phosphorylation	10521462\|15342639\|22797597
Tgene	TNIK	GO:0030036	actin cytoskeleton organization	15342639
Tgene	TNIK	GO:0035556	intracellular signal transduction	10521462
Tgene	TNIK	GO:0046330	positive regulation of JNK cascade	15342639
Tgene	TNIK	GO:0046777	protein autophosphorylation	10521462\|15342639
Tgene	TNIK	GO:0048814	regulation of dendrite morphogenesis	20159449

Kinase Fusion gene breakpoints across CLIP1 (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 TNIK (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-BR-4369-01A	CLIP1	chr12	122861936	TNIK	chr3	170908576
ChimerDB4	TCGA-BR-4369	CLIP1	chr12	122861935	TNIK	chr3	170908576

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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)
ENST00000302528	ENST00000436636	CLIP1	chr12	122861935	TNIK	chr3	170908576	6973	1440
ENST00000302528	ENST00000436636	CLIP1	chr12	122861936	TNIK	chr3	170908576	6973	1440

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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

>ENST00000302528_ENST00000436636_CLIP1_chr12_122861935_TNIK_chr3_170908576_length(amino acids)=1440
MSMLKPSGLKAPTKILKPGSTALKTPTAVVAPVEKTISSEKASSTPSSETQEEFVDDFRVGERVWVNGNKPGFIQFLGETQFAPGQWAGI
VLDEPIGKNDGSVAGVRYFQCEPLKGIFTRPSKLTRKVQAEDEANGLQTTPASRATSPLCTSTASMVSSSPSTPSNIPQKPSQPAAKEPS
ATPPISNLTKTASESISNLSEAGSIKKGERELKIGDRVLGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDRTVGRRNTFIG
TPYWMAPEVIACDENPDATYDFKSDLWSLGITAIEMAEGAPPLCDMHPMRALFLIPRNPAPRLKSKKWSKKFQSFIESCLVKNHSQRPAT
EQLMKHPFIRDQPNERQVRIQLKDHIDRTKKKRGEKDETEYEYSGSEEEEEENDSGEPSSILNLPGESTLRRDFLRLQLANKERSEALRR
QQLEQQQRENEEHKRQLLAERQKRIEEQKEQRRRLEEQQRREKELRKQQEREQRRHYEEQMRREEERRRAEHEQEYIRRQLEEEQRQLEI
LQQQLLHEQALLLEYKRKQLEEQRQAERLQRQLKQERDYLVSLQHQRQEQRPVEKKPLYHYKEGMSPSEKPAWAKEVEERSRLNRQSSPA
MPHKVANRISDPNLPPRSESFSISGVQPARTPPMLRPVDPQIPHLVAVKSQGPALTASQSVHEQPTKGLSGFQEALNVTSHRVEMPRQNS
DPTSENPPLPTRIEKFDRSSWLRQEEDIPPKVPQRTTSISPALARKNSPGNGSALGPRLGSQPIRASNPDLRRTEPILESPLQRTSSGSS
SSSSTPSSQPSSQGGSQPGSQAGSSERTRVRANSKSEGSPVLPHEPAKVKPEESRDITRPSRPASYKKAIDEDLTALAKELRELRIEETN
RPMKKVTDYSSSSEESESSEEEEEDGESETHDGTVAVSDIPRLIPTGAPGSNEQYNVGMVGTHGLETSHADSFSGSISREGTLMIRETSG
EKKRSGHSDSNGFAGHINLPDLVQQSHSPAGTPTEGLGRVSTHSQEMDSGTEYGMGSSTKASFTPFVDPRVYQTSPTDEDEEDEESSAAA
LFTSELLRQEQAKLNEARKISVVNVNPTNIRPHSDTPEIRKYKKRFNSEILCAALWGVNLLVGTENGLMLLDRSGQGKVYNLINRRRFQQ
MDVLEGLNVLVTISGKKNKLRVYYLSWLRNRILHNDPEVEKKQGWITVGDLEGCIHYKVVKYERIKFLVIALKNAVEIYAWAPKPYHKFM
AFKSFADLQHKPLLVDLTVEEGQRLKVIFGSHTGFHVIDVDSGNSYDIYIPSHIQGNITPHAIVILPKTDGMEMLVCYEDEGVYVNTYGR
ITKDVVLQWGEMPTSVAYIHSNQIMGWGEKAIEIRSVETGHLDGVFMHKRAQRLKFLCERNDKVFFASVRSGGSSQVFFMTLNRNSMMNW

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

>ENST00000302528_ENST00000436636_CLIP1_chr12_122861936_TNIK_chr3_170908576_length(amino acids)=1440
MSMLKPSGLKAPTKILKPGSTALKTPTAVVAPVEKTISSEKASSTPSSETQEEFVDDFRVGERVWVNGNKPGFIQFLGETQFAPGQWAGI
VLDEPIGKNDGSVAGVRYFQCEPLKGIFTRPSKLTRKVQAEDEANGLQTTPASRATSPLCTSTASMVSSSPSTPSNIPQKPSQPAAKEPS
ATPPISNLTKTASESISNLSEAGSIKKGERELKIGDRVLGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDRTVGRRNTFIG
TPYWMAPEVIACDENPDATYDFKSDLWSLGITAIEMAEGAPPLCDMHPMRALFLIPRNPAPRLKSKKWSKKFQSFIESCLVKNHSQRPAT
EQLMKHPFIRDQPNERQVRIQLKDHIDRTKKKRGEKDETEYEYSGSEEEEEENDSGEPSSILNLPGESTLRRDFLRLQLANKERSEALRR
QQLEQQQRENEEHKRQLLAERQKRIEEQKEQRRRLEEQQRREKELRKQQEREQRRHYEEQMRREEERRRAEHEQEYIRRQLEEEQRQLEI
LQQQLLHEQALLLEYKRKQLEEQRQAERLQRQLKQERDYLVSLQHQRQEQRPVEKKPLYHYKEGMSPSEKPAWAKEVEERSRLNRQSSPA
MPHKVANRISDPNLPPRSESFSISGVQPARTPPMLRPVDPQIPHLVAVKSQGPALTASQSVHEQPTKGLSGFQEALNVTSHRVEMPRQNS
DPTSENPPLPTRIEKFDRSSWLRQEEDIPPKVPQRTTSISPALARKNSPGNGSALGPRLGSQPIRASNPDLRRTEPILESPLQRTSSGSS
SSSSTPSSQPSSQGGSQPGSQAGSSERTRVRANSKSEGSPVLPHEPAKVKPEESRDITRPSRPASYKKAIDEDLTALAKELRELRIEETN
RPMKKVTDYSSSSEESESSEEEEEDGESETHDGTVAVSDIPRLIPTGAPGSNEQYNVGMVGTHGLETSHADSFSGSISREGTLMIRETSG
EKKRSGHSDSNGFAGHINLPDLVQQSHSPAGTPTEGLGRVSTHSQEMDSGTEYGMGSSTKASFTPFVDPRVYQTSPTDEDEEDEESSAAA
LFTSELLRQEQAKLNEARKISVVNVNPTNIRPHSDTPEIRKYKKRFNSEILCAALWGVNLLVGTENGLMLLDRSGQGKVYNLINRRRFQQ
MDVLEGLNVLVTISGKKNKLRVYYLSWLRNRILHNDPEVEKKQGWITVGDLEGCIHYKVVKYERIKFLVIALKNAVEIYAWAPKPYHKFM
AFKSFADLQHKPLLVDLTVEEGQRLKVIFGSHTGFHVIDVDSGNSYDIYIPSHIQGNITPHAIVILPKTDGMEMLVCYEDEGVYVNTYGR
ITKDVVLQWGEMPTSVAYIHSNQIMGWGEKAIEIRSVETGHLDGVFMHKRAQRLKFLCERNDKVFFASVRSGGSSQVFFMTLNRNSMMNW

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

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/chr12:122861936/chr3:170908576)
- 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
CLIP1 P30622	TNIK Q9UKE5
FUNCTION: Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking. {ECO:0000269\|PubMed:12433698, ECO:0000269\|PubMed:17563362, ECO:0000269\|PubMed:17889670}.	FUNCTION: Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322. {ECO:0000269\|PubMed:10521462, ECO:0000269\|PubMed:15342639, ECO:0000269\|PubMed:19061864, ECO:0000269\|PubMed:19816403, ECO:0000269\|PubMed:20159449, ECO:0000269\|PubMed:21690388}.

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).

Partner

Hgeneene

Hbp

Tgeneene

Tbp

ENST

BPexon

TotalExon

Protein feature loci

BPloci

TotalLen

Feature

Note

- 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
Tgene	CLIP1	122861935	TNIK	170908576	ENST00000302528	4	30	1047_1334	139	1269	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861935	TNIK	170908576	ENST00000302528	4	31	1047_1334	139	1277	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861935	TNIK	170908576	ENST00000302528	4	31	1047_1334	139	1298	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861935	TNIK	170908576	ENST00000302528	4	31	1047_1334	139	1324	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861935	TNIK	170908576	ENST00000302528	4	32	1047_1334	139	1306	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861935	TNIK	170908576	ENST00000302528	4	32	1047_1334	139	1332	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861935	TNIK	170908576	ENST00000302528	4	32	1047_1334	139	1353	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861935	TNIK	170908576	ENST00000302528	4	33	1047_1334	139	1361	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861936	TNIK	170908576	ENST00000302528	4	30	1047_1334	139	1269	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861936	TNIK	170908576	ENST00000302528	4	31	1047_1334	139	1277	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861936	TNIK	170908576	ENST00000302528	4	31	1047_1334	139	1298	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861936	TNIK	170908576	ENST00000302528	4	31	1047_1334	139	1324	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861936	TNIK	170908576	ENST00000302528	4	32	1047_1334	139	1306	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861936	TNIK	170908576	ENST00000302528	4	32	1047_1334	139	1332	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861936	TNIK	170908576	ENST00000302528	4	32	1047_1334	139	1353	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795
Tgene	CLIP1	122861936	TNIK	170908576	ENST00000302528	4	33	1047_1334	139	1361	Domain	Note=CNH;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00795

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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 >>>107_CLIP1_TNIK	ENST00000302528	ENST00000436636	CLIP1	chr12	122861936	TNIK	chr3	170908576	MSMLKPSGLKAPTKILKPGSTALKTPTAVVAPVEKTISSEKASSTPSSETQEEFVDDFRVGERVWVNGNKPGFIQFLGETQFAPGQWAGI VLDEPIGKNDGSVAGVRYFQCEPLKGIFTRPSKLTRKVQAEDEANGLQTTPASRATSPLCTSTASMVSSSPSTPSNIPQKPSQPAAKEPS ATPPISNLTKTASESISNLSEAGSIKKGERELKIGDRVLGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDRTVGRRNTFIG TPYWMAPEVIACDENPDATYDFKSDLWSLGITAIEMAEGAPPLCDMHPMRALFLIPRNPAPRLKSKKWSKKFQSFIESCLVKNHSQRPAT EQLMKHPFIRDQPNERQVRIQLKDHIDRTKKKRGEKDETEYEYSGSEEEEEENDSGEPSSILNLPGESTLRRDFLRLQLANKERSEALRR QQLEQQQRENEEHKRQLLAERQKRIEEQKEQRRRLEEQQRREKELRKQQEREQRRHYEEQMRREEERRRAEHEQEYIRRQLEEEQRQLEI LQQQLLHEQALLLEYKRKQLEEQRQAERLQRQLKQERDYLVSLQHQRQEQRPVEKKPLYHYKEGMSPSEKPAWAKEVEERSRLNRQSSPA MPHKVANRISDPNLPPRSESFSISGVQPARTPPMLRPVDPQIPHLVAVKSQGPALTASQSVHEQPTKGLSGFQEALNVTSHRVEMPRQNS DPTSENPPLPTRIEKFDRSSWLRQEEDIPPKVPQRTTSISPALARKNSPGNGSALGPRLGSQPIRASNPDLRRTEPILESPLQRTSSGSS SSSSTPSSQPSSQGGSQPGSQAGSSERTRVRANSKSEGSPVLPHEPAKVKPEESRDITRPSRPASYKKAIDEDLTALAKELRELRIEETN RPMKKVTDYSSSSEESESSEEEEEDGESETHDGTVAVSDIPRLIPTGAPGSNEQYNVGMVGTHGLETSHADSFSGSISREGTLMIRETSG EKKRSGHSDSNGFAGHINLPDLVQQSHSPAGTPTEGLGRVSTHSQEMDSGTEYGMGSSTKASFTPFVDPRVYQTSPTDEDEEDEESSAAA LFTSELLRQEQAKLNEARKISVVNVNPTNIRPHSDTPEIRKYKKRFNSEILCAALWGVNLLVGTENGLMLLDRSGQGKVYNLINRRRFQQ MDVLEGLNVLVTISGKKNKLRVYYLSWLRNRILHNDPEVEKKQGWITVGDLEGCIHYKVVKYERIKFLVIALKNAVEIYAWAPKPYHKFM AFKSFADLQHKPLLVDLTVEEGQRLKVIFGSHTGFHVIDVDSGNSYDIYIPSHIQGNITPHAIVILPKTDGMEMLVCYEDEGVYVNTYGR ITKDVVLQWGEMPTSVAYIHSNQIMGWGEKAIEIRSVETGHLDGVFMHKRAQRLKFLCERNDKVFFASVRSGGSSQVFFMTLNRNSMMNW	1440
3D view using mol* of 107_CLIP1_TNIK

PDB file >>>TKFP_181_CLIP1_TNIK	ENST00000302528	ENST00000436636	CLIP1	chr12	122861935	TNIK	chr3	170908576	MSMLKPSGLKAPTKILKPGSTALKTPTAVVAPVEKTISSEKASSTPSSETQEEFVDDFRVGERVWVNGNKPGFIQFLGETQFAPGQWAGI VLDEPIGKNDGSVAGVRYFQCEPLKGIFTRPSKLTRKVQAEDEANGLQTTPASRATSPLCTSTASMVSSSPSTPSNIPQKPSQPAAKEPS ATPPISNLTKTASESISNLSEAGSIKKGERELKIGDRVLGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDRTVGRRNTFIG TPYWMAPEVIACDENPDATYDFKSDLWSLGITAIEMAEGAPPLCDMHPMRALFLIPRNPAPRLKSKKWSKKFQSFIESCLVKNHSQRPAT EQLMKHPFIRDQPNERQVRIQLKDHIDRTKKKRGEKDETEYEYSGSEEEEEENDSGEPSSILNLPGESTLRRDFLRLQLANKERSEALRR QQLEQQQRENEEHKRQLLAERQKRIEEQKEQRRRLEEQQRREKELRKQQEREQRRHYEEQMRREEERRRAEHEQEYIRRQLEEEQRQLEI LQQQLLHEQALLLEYKRKQLEEQRQAERLQRQLKQERDYLVSLQHQRQEQRPVEKKPLYHYKEGMSPSEKPAWAKEVEERSRLNRQSSPA MPHKVANRISDPNLPPRSESFSISGVQPARTPPMLRPVDPQIPHLVAVKSQGPALTASQSVHEQPTKGLSGFQEALNVTSHRVEMPRQNS DPTSENPPLPTRIEKFDRSSWLRQEEDIPPKVPQRTTSISPALARKNSPGNGSALGPRLGSQPIRASNPDLRRTEPILESPLQRTSSGSS SSSSTPSSQPSSQGGSQPGSQAGSSERTRVRANSKSEGSPVLPHEPAKVKPEESRDITRPSRPASYKKAIDEDLTALAKELRELRIEETN RPMKKVTDYSSSSEESESSEEEEEDGESETHDGTVAVSDIPRLIPTGAPGSNEQYNVGMVGTHGLETSHADSFSGSISREGTLMIRETSG EKKRSGHSDSNGFAGHINLPDLVQQSHSPAGTPTEGLGRVSTHSQEMDSGTEYGMGSSTKASFTPFVDPRVYQTSPTDEDEEDEESSAAA LFTSELLRQEQAKLNEARKISVVNVNPTNIRPHSDTPEIRKYKKRFNSEILCAALWGVNLLVGTENGLMLLDRSGQGKVYNLINRRRFQQ MDVLEGLNVLVTISGKKNKLRVYYLSWLRNRILHNDPEVEKKQGWITVGDLEGCIHYKVVKYERIKFLVIALKNAVEIYAWAPKPYHKFM AFKSFADLQHKPLLVDLTVEEGQRLKVIFGSHTGFHVIDVDSGNSYDIYIPSHIQGNITPHAIVILPKTDGMEMLVCYEDEGVYVNTYGR ITKDVVLQWGEMPTSVAYIHSNQIMGWGEKAIEIRSVETGHLDGVFMHKRAQRLKFLCERNDKVFFASVRSGGSSQVFFMTLNRNSMMNW	1440_CLIP1_TNIK
PDB file >>>TKFP_182_CLIP1_TNIK	ENST00000302528	ENST00000436636	CLIP1	chr12	122861936	TNIK	chr3	170908576	MSMLKPSGLKAPTKILKPGSTALKTPTAVVAPVEKTISSEKASSTPSSETQEEFVDDFRVGERVWVNGNKPGFIQFLGETQFAPGQWAGI VLDEPIGKNDGSVAGVRYFQCEPLKGIFTRPSKLTRKVQAEDEANGLQTTPASRATSPLCTSTASMVSSSPSTPSNIPQKPSQPAAKEPS ATPPISNLTKTASESISNLSEAGSIKKGERELKIGDRVLGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDRTVGRRNTFIG TPYWMAPEVIACDENPDATYDFKSDLWSLGITAIEMAEGAPPLCDMHPMRALFLIPRNPAPRLKSKKWSKKFQSFIESCLVKNHSQRPAT EQLMKHPFIRDQPNERQVRIQLKDHIDRTKKKRGEKDETEYEYSGSEEEEEENDSGEPSSILNLPGESTLRRDFLRLQLANKERSEALRR QQLEQQQRENEEHKRQLLAERQKRIEEQKEQRRRLEEQQRREKELRKQQEREQRRHYEEQMRREEERRRAEHEQEYIRRQLEEEQRQLEI LQQQLLHEQALLLEYKRKQLEEQRQAERLQRQLKQERDYLVSLQHQRQEQRPVEKKPLYHYKEGMSPSEKPAWAKEVEERSRLNRQSSPA MPHKVANRISDPNLPPRSESFSISGVQPARTPPMLRPVDPQIPHLVAVKSQGPALTASQSVHEQPTKGLSGFQEALNVTSHRVEMPRQNS DPTSENPPLPTRIEKFDRSSWLRQEEDIPPKVPQRTTSISPALARKNSPGNGSALGPRLGSQPIRASNPDLRRTEPILESPLQRTSSGSS SSSSTPSSQPSSQGGSQPGSQAGSSERTRVRANSKSEGSPVLPHEPAKVKPEESRDITRPSRPASYKKAIDEDLTALAKELRELRIEETN RPMKKVTDYSSSSEESESSEEEEEDGESETHDGTVAVSDIPRLIPTGAPGSNEQYNVGMVGTHGLETSHADSFSGSISREGTLMIRETSG EKKRSGHSDSNGFAGHINLPDLVQQSHSPAGTPTEGLGRVSTHSQEMDSGTEYGMGSSTKASFTPFVDPRVYQTSPTDEDEEDEESSAAA LFTSELLRQEQAKLNEARKISVVNVNPTNIRPHSDTPEIRKYKKRFNSEILCAALWGVNLLVGTENGLMLLDRSGQGKVYNLINRRRFQQ MDVLEGLNVLVTISGKKNKLRVYYLSWLRNRILHNDPEVEKKQGWITVGDLEGCIHYKVVKYERIKFLVIALKNAVEIYAWAPKPYHKFM AFKSFADLQHKPLLVDLTVEEGQRLKVIFGSHTGFHVIDVDSGNSYDIYIPSHIQGNITPHAIVILPKTDGMEMLVCYEDEGVYVNTYGR ITKDVVLQWGEMPTSVAYIHSNQIMGWGEKAIEIRSVETGHLDGVFMHKRAQRLKFLCERNDKVFFASVRSGGSSQVFFMTLNRNSMMNW	1440_CLIP1_TNIK

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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

CLIP1_TNIK does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/107_CLIP1_TNIK.png

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.

107_CLIP1_TNIK.png

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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.

107_CLIP1_TNIK_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
107_CLIP1_TNIK-DOCK_HTVS_1-001	Zanubrutinib	-5.653630000000001	-5.653630000000001	-27.1576
107_CLIP1_TNIK-DOCK_HTVS_1-001	Capmatinib	-5.43015	-5.43575	-34.1567
107_CLIP1_TNIK-DOCK_HTVS_1-001	Vemurafenib	-5.0155199999999995	-5.3947199999999995	-49.5796
107_CLIP1_TNIK-DOCK_HTVS_1-001	Vemurafenib	-5.0155199999999995	-5.3947199999999995	-49.5796
107_CLIP1_TNIK-DOCK_HTVS_1-001	Netarsudil	-4.9522	-4.9633	-31.6202
107_CLIP1_TNIK-DOCK_HTVS_1-001	Netarsudil	-4.9522	-4.9633	-31.6202
107_CLIP1_TNIK-DOCK_HTVS_1-001	Tofacitinib	-4.8920900000000005	-4.90359	-11.9015
107_CLIP1_TNIK-DOCK_HTVS_1-001	Tofacitinib	-4.8920900000000005	-4.90359	-11.9015
107_CLIP1_TNIK-DOCK_HTVS_1-001	Sorafenib	-4.857069999999999	-4.8691699999999996	-29.0723
107_CLIP1_TNIK-DOCK_HTVS_1-001	Sorafenib	-4.857069999999999	-4.8691699999999996	-29.0723
107_CLIP1_TNIK-DOCK_HTVS_1-001	Selumetinib	-4.8417	-4.8504	-26.3833
107_CLIP1_TNIK-DOCK_HTVS_1-001	Selumetinib	-4.8417	-4.8504	-26.3833
107_CLIP1_TNIK-DOCK_HTVS_1-001	Lapatinib	-4.82716	-4.91596	-51.6668
107_CLIP1_TNIK-DOCK_HTVS_1-001	Asciminib	-4.824669999999999	-5.28967	-39.3536
107_CLIP1_TNIK-DOCK_HTVS_1-001	Ruxolitinib	-4.75424	-4.75424	-28.2384
107_CLIP1_TNIK-DOCK_HTVS_1-001	Palbociclib	-4.74411	-5.21361	-43.7072
107_CLIP1_TNIK-DOCK_HTVS_1-001	Palbociclib	-4.74411	-5.21361	-43.7072
107_CLIP1_TNIK-DOCK_HTVS_1-001	Palbociclib	-4.74411	-5.21361	-43.7072
107_CLIP1_TNIK-DOCK_HTVS_1-001	Larotrectinib	-4.7041900000000005	-4.7041900000000005	-13.5966
107_CLIP1_TNIK-DOCK_HTVS_1-001	Ribociclib	-4.678999999999999	-6.0806	-42.3308

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Kinase-Substrate Information of CLIP1_TNIK

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
TNIK	Q9UKE5	human	SMAD1	Q15797	T322	sNVNRNStIENTRRH	MH2
TNIK	Q9UKE5	human	TCF7L2	Q9NQB0	S177	QALkDARsPsPAHIV	CTNNB1_binding
TNIK	Q9UKE5	human	HTT	P42858	S13	kLMkAFEsLksFQQQ
TNIK	Q9UKE5	human	HTT	P42858	T3	_____MAtLEkLMkA

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
TNIK	ID	Description	0.00e+00
TNIK	GO:2001237	negative regulation of extrinsic apoptotic signaling pathway	2.23e-02
TNIK	GO:2001236	regulation of extrinsic apoptotic signaling pathway	2.78e-02
TNIK	GO:0097191	extrinsic apoptotic signaling pathway	2.78e-02
TNIK	GO:2001234	negative regulation of apoptotic signaling pathway	2.78e-02
TNIK	GO:0033002	muscle cell proliferation	2.78e-02
TNIK	GO:0045165	cell fate commitment	3.10e-02
TNIK	GO:2001233	regulation of apoptotic signaling pathway	4.35e-02
TNIK	GO:0097050	type B pancreatic cell apoptotic process	4.35e-02
TNIK	GO:0098598	learned vocalization behavior or vocal learning	4.35e-02
TNIK	GO:0099004	calmodulin dependent kinase signaling pathway	4.35e-02
TNIK	GO:0031223	auditory behavior	4.35e-02
TNIK	GO:0007638	mechanosensory behavior	4.35e-02
TNIK	GO:0042762	regulation of sulfur metabolic process	4.35e-02
TNIK	GO:1903599	positive regulation of autophagy of mitochondrion	4.35e-02
TNIK	GO:2000479	regulation of cAMP-dependent protein kinase activity	4.35e-02
TNIK	GO:0001710	mesodermal cell fate commitment	4.35e-02
TNIK	GO:1901522	positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus	4.35e-02
TNIK	GO:0045721	negative regulation of gluconeogenesis	4.38e-02
TNIK	GO:0031053	primary miRNA processing	4.38e-02
TNIK	GO:0010560	positive regulation of glycoprotein biosynthetic process	4.38e-02
TNIK	GO:1903020	positive regulation of glycoprotein metabolic process	4.38e-02
TNIK	GO:0045724	positive regulation of cilium assembly	4.38e-02
TNIK	GO:1903672	positive regulation of sprouting angiogenesis	4.38e-02
TNIK	GO:1901021	positive regulation of calcium ion transmembrane transporter activity	4.38e-02
TNIK	GO:0010996	response to auditory stimulus	4.38e-02
TNIK	GO:0060795	cell fate commitment involved in formation of primary germ layer	4.38e-02
TNIK	GO:0061036	positive regulation of cartilage development	4.38e-02
TNIK	GO:0015012	heparan sulfate proteoglycan biosynthetic process	4.38e-02
TNIK	GO:0048333	mesodermal cell differentiation	4.38e-02
TNIK	GO:0000132	establishment of mitotic spindle orientation	4.38e-02
TNIK	GO:0003161	cardiac conduction system development	4.38e-02
TNIK	GO:0032350	regulation of hormone metabolic process	4.38e-02
TNIK	GO:0040001	establishment of mitotic spindle localization	4.38e-02
TNIK	GO:1903146	regulation of autophagy of mitochondrion	4.38e-02
TNIK	GO:0051281	positive regulation of release of sequestered calcium ion into cytosol	4.38e-02
TNIK	GO:0051294	establishment of spindle orientation	4.38e-02
TNIK	GO:0047496	vesicle transport along microtubule	4.38e-02
TNIK	GO:0035196	miRNA processing	4.38e-02
TNIK	GO:0043666	regulation of phosphoprotein phosphatase activity	4.38e-02
TNIK	GO:0031648	protein destabilization	4.38e-02
TNIK	GO:2001259	positive regulation of cation channel activity	4.38e-02
TNIK	GO:0006890	retrograde vesicle-mediated transpor	8.24e-03
TNIK	GO:0006111	regulation of gluconeogenesis	4.38e-02
TNIK	GO:0010559	regulation of glycoprotein biosynthetic process	4.38e-02
TNIK	GO:0045912	negative regulation of carbohydrate metabolic process	4.38e-02
TNIK	GO:0051293	establishment of spindle localization	4.38e-02
TNIK	GO:0010718	positive regulation of epithelial to mesenchymal transition	4.38e-02
TNIK	GO:0060038	cardiac muscle cell proliferation	4.38e-02
TNIK	GO:0010921	regulation of phosphatase activity	4.38e-02

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Related Drugs to CLIP1_TNIK

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 CLIP1-TNIK 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 CLIP1_TNIK

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