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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:SCYL1_FRMD8

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: SCYL1_FRMD8
	KinaseFusionDB ID: KFG5698
	FusionGDB2.0 ID: KFG5698
		Hgene	Tgene
	Gene symbol	SCYL1	FRMD8
	Gene ID	57410	83786
	Gene name	SCY1 like pseudokinase 1	FERM domain containing 8
	Synonyms	GKLP\|HT019\|NKTL\|NTKL\|P105\|SCAR21\|TAPK\|TEIF\|TRAP	FKSG44\|iTAP
	Cytomap	11q13.1	11q13.1
	Type of gene	protein-coding	protein-coding
	Description	N-terminal kinase-like proteinSCY1-like protein 1SCY1-like, kinase-like 1coated vesicle-associated kinase of 90 kDalikely ortholog of mouse N-terminal kinase-like proteintelomerase regulation-associated proteintelomerase transcriptional elements-int	FERM domain-containing protein 8band4.1 inhibitor LRP interactorbiliiRhom Tail-Associated Protein
	Modification date	20240407	20240403
	UniProtAcc	Q96KG9	Q9BZ67
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000270176, ENST00000279270, ENST00000420247, ENST00000524944, ENST00000525364, ENST00000527009, ENST00000533862, ENST00000534462,	ENST00000355991, ENST00000416776, ENST00000531296, ENST00000317568,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: SCYL1 [Title/Abstract] AND FRMD8 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	SCYL1(65294588)-FRMD8(65172335), # samples:3 SCYL1(65300276)-FRMD8(65172335), # samples:3

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
Hgene	SCYL1	GO:0006890	retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	18556652
Tgene	FRMD8	GO:0032760	positive regulation of tumor necrosis factor production	29897333

Kinase Fusion gene breakpoints across SCYL1 (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 FRMD8 (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-24-1431	SCYL1	chr11	65300276	FRMD8	chr11	65172334
ChimerDB4	TCGA-44-4112-01A	SCYL1	chr11	65300276	FRMD8	chr11	65172335
ChimerDB4	TCGA-55-8510-01A	SCYL1	chr11	65300276	FRMD8	chr11	65178713
ChimerDB4	TCGA-BH-A0B7-01A	SCYL1	chr11	65294588	FRMD8	chr11	65172335
ChimerDB4	TCGA-BH-A0B7	SCYL1	chr11	65294588	FRMD8	chr11	65172334
ChimerDB4	TCGA-BK-A139-02A	SCYL1	chr11	65300276	FRMD8	chr11	65156832
CCLE	HT-1376	SCYL1	chr11	65303805	FRMD8	chr11	65161044
CCLE	HT-1376	SCYL1	chr11	65300276	FRMD8	chr11	65161730

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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)
ENST00000525364	ENST00000317568	SCYL1	chr11	65303805	FRMD8	chr11	65161044	5035	930
ENST00000525364	ENST00000317568	SCYL1	chr11	65300276	FRMD8	chr11	65161730	4453	736
ENST00000525364	ENST00000317568	SCYL1	chr11	65300276	FRMD8	chr11	65172335	3796	517
ENST00000525364	ENST00000317568	SCYL1	chr11	65300276	FRMD8	chr11	65172334	3796	517

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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

>ENST00000525364_ENST00000317568_SCYL1_chr11_65303805_FRMD8_chr11_65161044_length(amino acids)=930
MWFFARDPVRDFPFELIPEPPEGGLPGPWALHRGRKKATGSPVSIFVYDVKPGAEEQTQVAKAAFKRFKTLRHPNILAYIDGLETEKCLH
VVTEAVTPLGIYLKARVEAGGLKELEISWGLHQIVKALSFLVNDCSLIHNNVCMAAVFVDRAGEWKLGGLDYMYSAQGNGGGPPRKGIPE
LEQYDPPELADSSGRVVREKWSADMWRLGCLIWEVFNGPLPRAAALRNPGKIPKTLVPHYCELVGANPKVRPNPARFLQNCRAPGGFMSN
RFVETNLFLEEIQIKEPAEKQKFFQELSKSLDAFPEDFCRHKVLPQLLTAFEFGNAGAVVLTPLFKVGKFLSAEEYQQKIIPVVVKMFSS
TDRAMRIRLLQQMEQFIQYLDEPTVNTQIFPHVVHGFLDTNPAIREQTVKSMLLLAPKLNEANLNVELMKHFARLQAKDEQGPIRCNTTV
CLGKIGSYLSASTRHRVLTSAFSRATRDPFAPSRVAGVLGFAATHNLYSMNDCAQKILPVLCGLTVDPEKSVRDQAFKAIRSFLSKLESV
SEDPTQLEEVEVQLKPKHQPYKLGRQWPELLLRFTSAPDDDVAMDEPFLQFRRNVFFPKRRELQIHDEEVLRLLYEEAKGNVLAARYPCD
VEDCEALGALVCRVQLGPYQPGRPAACDLREKLDSFLPAHLCKRGQSLFAALRGRGARAGPGEQGLLNAYRQVQEVSSDGGCEAALGTHY
RAYLLKCHELPFYGCAFFHGEVDKPAQGFLHRGGRKPVSVAISLEGVHVIDSREKHVLLGLRFQELSWDHTSPEEEEPILWLEFDGDSEG
TPVNKLLKIYSKQAELMSSLIEYCIELSQAAEPAGPQDSATGSPSDPSSSLAPVQRPKLRRQGSVVSSRIQHLSTIDYVEDGKGIRRVKP

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

>ENST00000525364_ENST00000317568_SCYL1_chr11_65300276_FRMD8_chr11_65161730_length(amino acids)=736
MWFFARDPVRDFPFELIPEPPEGGLPGPWALHRGRKKATGSPVSIFVYDVKPGAEEQTQVAKAAFKRFKTLRHPNILAYIDGLETEKCLH
VVTEAVTPLGIYLKARVEAGGLKELEISWGLHQIVKALSFLVNDCSLIHNNVCMAAVFVDRAGEWKLGGLDYMYSAQGNGGGPPRKGIPE
LEQYDPPELADSSGRVVREKWSADMWRLGCLIWEVFNGPLPRAAALRNPGKIPKTLVPHYCELVGANPKVRPNPARFLQNCRAPGGFMSN
RFVETNLFLEEIQIKEPAEKQKFFQELSKSLDAFPEDFCRHKVLPQLLTAFEFGNAGAVVLTPLFKVGKFLSAEEYQQKIIPVVVKMFSS
TDRAMRIRLLQQMEQFIQYLDEPTVNTQIFPHVVHGFLDTNPAIREQTVKIHDEEVLRLLYEEAKGNVLAARYPCDVEDCEALGALVCRV
QLGPYQPGRPAACDLREKLDSFLPAHLCKRGQSLFAALRGRGARAGPGEQGLLNAYRQVQEVSSDGGCEAALGTHYRAYLLKCHELPFYG
CAFFHGEVDKPAQGFLHRGGRKPVSVAISLEGVHVIDSREKHVLLGLRFQELSWDHTSPEEEEPILWLEFDGDSEGTPVNKLLKIYSKQA
ELMSSLIEYCIELSQAAEPAGPQDSATGSPSDPSSSLAPVQRPKLRRQGSVVSSRIQHLSTIDYVEDGKGIRRVKPKRTTSFFSRQLSLG

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

>ENST00000525364_ENST00000317568_SCYL1_chr11_65300276_FRMD8_chr11_65172335_length(amino acids)=517
MWFFARDPVRDFPFELIPEPPEGGLPGPWALHRGRKKATGSPVSIFVYDVKPGAEEQTQVAKAAFKRFKTLRHPNILAYIDGLETEKCLH
VVTEAVTPLGIYLKARVEAGGLKELEISWGLHQIVKALSFLVNDCSLIHNNVCMAAVFVDRAGEWKLGGLDYMYSAQGNGGGPPRKGIPE
LEQYDPPELADSSGRVVREKWSADMWRLGCLIWEVFNGPLPRAAALRNPGKIPKTLVPHYCELVGANPKVRPNPARFLQNCRAPGGFMSN
RFVETNLFLEEIQIKEPAEKQKFFQELSKSLDAFPEDFCRHKVLPQLLTAFEFGNAGAVVLTPLFKVGKFLSAEEYQQKIIPVVVKMFSS
TDRAMRIRLLQQMEQFIQYLDEPTVNTQIFPHVVHGFLDTNPAIREQTVKAELMSSLIEYCIELSQAAEPAGPQDSATGSPSDPSSSLAP

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

>ENST00000525364_ENST00000317568_SCYL1_chr11_65300276_FRMD8_chr11_65172334_length(amino acids)=517
MWFFARDPVRDFPFELIPEPPEGGLPGPWALHRGRKKATGSPVSIFVYDVKPGAEEQTQVAKAAFKRFKTLRHPNILAYIDGLETEKCLH
VVTEAVTPLGIYLKARVEAGGLKELEISWGLHQIVKALSFLVNDCSLIHNNVCMAAVFVDRAGEWKLGGLDYMYSAQGNGGGPPRKGIPE
LEQYDPPELADSSGRVVREKWSADMWRLGCLIWEVFNGPLPRAAALRNPGKIPKTLVPHYCELVGANPKVRPNPARFLQNCRAPGGFMSN
RFVETNLFLEEIQIKEPAEKQKFFQELSKSLDAFPEDFCRHKVLPQLLTAFEFGNAGAVVLTPLFKVGKFLSAEEYQQKIIPVVVKMFSS
TDRAMRIRLLQQMEQFIQYLDEPTVNTQIFPHVVHGFLDTNPAIREQTVKAELMSSLIEYCIELSQAAEPAGPQDSATGSPSDPSSSLAP

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

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/chr11:65294588/chr11:65172335)
- 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
SCYL1 Q96KG9	FRMD8 Q9BZ67
FUNCTION: Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morphology (PubMed:26581903). Has no detectable kinase activity in vitro (PubMed:18556652). {ECO:0000269\|PubMed:18556652, ECO:0000269\|PubMed:26581903}.; FUNCTION: Isoform 6 acts as a transcriptional activator. It binds to three different types of GC-rich DNA binding sites (box-A, -B and -C) in the beta-polymerase promoter region. It also binds to the TERT promoter region. {ECO:0000269\|PubMed:18556652}.	FUNCTION: Promotes the cell surface stability of iRhom1/RHBDF1 and iRhom2/RHBDF2 and prevents their degradation via the endolysosomal pathway. By acting on iRhoms, involved in ADAM17-mediated shedding of TNF, amphiregulin/AREG, HBEGF and TGFA from the cell surface (PubMed:29897333, PubMed:29897336). Negatively regulates Wnt signaling, possibly by antagonizing the recruitment of AXIN1 to LRP6 (PubMed:19572019). {ECO:0000269\|PubMed:19572019, ECO:0000269\|PubMed:29897333, ECO:0000269\|PubMed:29897336}.

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).

410410410410410410410410410410410410550550550550

Partner	Hgeneene	Hbp	Tgeneene	Tbp	ENST	BPexon	TotalExon	Protein feature loci	BPloci	TotalLen	Feature	Note
Hgene	SCYL1	65300276	FRMD8	65161730	ENST00000525364	9	17	14_314	1	782	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65300276	FRMD8	65161730	ENST00000525364	9	18	14_314	1	788	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65300276	FRMD8	65161730	ENST00000525364	9	18	14_314	1	792	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65300276	FRMD8	65161730	ENST00000525364	9	18	14_314	1	809	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65300276	FRMD8	65172334	ENST00000525364	9	17	14_314	1	782	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65300276	FRMD8	65172334	ENST00000525364	9	18	14_314	1	788	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65300276	FRMD8	65172334	ENST00000525364	9	18	14_314	1	792	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65300276	FRMD8	65172334	ENST00000525364	9	18	14_314	1	809	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65300276	FRMD8	65172335	ENST00000525364	9	17	14_314	1	782	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65300276	FRMD8	65172335	ENST00000525364	9	18	14_314	1	788	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65300276	FRMD8	65172335	ENST00000525364	9	18	14_314	1	792	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65300276	FRMD8	65172335	ENST00000525364	9	18	14_314	1	809	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65303805	FRMD8	65161044	ENST00000525364	12	17	14_314	1	782	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65303805	FRMD8	65161044	ENST00000525364	12	18	14_314	1	788	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65303805	FRMD8	65161044	ENST00000525364	12	18	14_314	1	792	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Hgene	SCYL1	65303805	FRMD8	65161044	ENST00000525364	12	18	14_314	1	809	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159

- 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 >>>HKFP_368_SCYL1_FRMD8	ENST00000525364	ENST00000317568	SCYL1	chr11	65303805	FRMD8	chr11	65161044	MWFFARDPVRDFPFELIPEPPEGGLPGPWALHRGRKKATGSPVSIFVYDVKPGAEEQTQVAKAAFKRFKTLRHPNILAYIDGLETEKCLH VVTEAVTPLGIYLKARVEAGGLKELEISWGLHQIVKALSFLVNDCSLIHNNVCMAAVFVDRAGEWKLGGLDYMYSAQGNGGGPPRKGIPE LEQYDPPELADSSGRVVREKWSADMWRLGCLIWEVFNGPLPRAAALRNPGKIPKTLVPHYCELVGANPKVRPNPARFLQNCRAPGGFMSN RFVETNLFLEEIQIKEPAEKQKFFQELSKSLDAFPEDFCRHKVLPQLLTAFEFGNAGAVVLTPLFKVGKFLSAEEYQQKIIPVVVKMFSS TDRAMRIRLLQQMEQFIQYLDEPTVNTQIFPHVVHGFLDTNPAIREQTVKSMLLLAPKLNEANLNVELMKHFARLQAKDEQGPIRCNTTV CLGKIGSYLSASTRHRVLTSAFSRATRDPFAPSRVAGVLGFAATHNLYSMNDCAQKILPVLCGLTVDPEKSVRDQAFKAIRSFLSKLESV SEDPTQLEEVEVQLKPKHQPYKLGRQWPELLLRFTSAPDDDVAMDEPFLQFRRNVFFPKRRELQIHDEEVLRLLYEEAKGNVLAARYPCD VEDCEALGALVCRVQLGPYQPGRPAACDLREKLDSFLPAHLCKRGQSLFAALRGRGARAGPGEQGLLNAYRQVQEVSSDGGCEAALGTHY RAYLLKCHELPFYGCAFFHGEVDKPAQGFLHRGGRKPVSVAISLEGVHVIDSREKHVLLGLRFQELSWDHTSPEEEEPILWLEFDGDSEG TPVNKLLKIYSKQAELMSSLIEYCIELSQAAEPAGPQDSATGSPSDPSSSLAPVQRPKLRRQGSVVSSRIQHLSTIDYVEDGKGIRRVKP	930_SCYL1_FRMD8
3D view using mol* of HKFP_368_SCYL1_FRMD8

PDB file >>>HKFP_369_SCYL1_FRMD8	ENST00000525364	ENST00000317568	SCYL1	chr11	65300276	FRMD8	chr11	65161730	MWFFARDPVRDFPFELIPEPPEGGLPGPWALHRGRKKATGSPVSIFVYDVKPGAEEQTQVAKAAFKRFKTLRHPNILAYIDGLETEKCLH VVTEAVTPLGIYLKARVEAGGLKELEISWGLHQIVKALSFLVNDCSLIHNNVCMAAVFVDRAGEWKLGGLDYMYSAQGNGGGPPRKGIPE LEQYDPPELADSSGRVVREKWSADMWRLGCLIWEVFNGPLPRAAALRNPGKIPKTLVPHYCELVGANPKVRPNPARFLQNCRAPGGFMSN RFVETNLFLEEIQIKEPAEKQKFFQELSKSLDAFPEDFCRHKVLPQLLTAFEFGNAGAVVLTPLFKVGKFLSAEEYQQKIIPVVVKMFSS TDRAMRIRLLQQMEQFIQYLDEPTVNTQIFPHVVHGFLDTNPAIREQTVKIHDEEVLRLLYEEAKGNVLAARYPCDVEDCEALGALVCRV QLGPYQPGRPAACDLREKLDSFLPAHLCKRGQSLFAALRGRGARAGPGEQGLLNAYRQVQEVSSDGGCEAALGTHYRAYLLKCHELPFYG CAFFHGEVDKPAQGFLHRGGRKPVSVAISLEGVHVIDSREKHVLLGLRFQELSWDHTSPEEEEPILWLEFDGDSEGTPVNKLLKIYSKQA ELMSSLIEYCIELSQAAEPAGPQDSATGSPSDPSSSLAPVQRPKLRRQGSVVSSRIQHLSTIDYVEDGKGIRRVKPKRTTSFFSRQLSLG	736_SCYL1_FRMD8
3D view using mol* of HKFP_369_SCYL1_FRMD8

PDB file >>>HKFP_370_SCYL1_FRMD8	ENST00000525364	ENST00000317568	SCYL1	chr11	65300276	FRMD8	chr11	65172335	MWFFARDPVRDFPFELIPEPPEGGLPGPWALHRGRKKATGSPVSIFVYDVKPGAEEQTQVAKAAFKRFKTLRHPNILAYIDGLETEKCLH VVTEAVTPLGIYLKARVEAGGLKELEISWGLHQIVKALSFLVNDCSLIHNNVCMAAVFVDRAGEWKLGGLDYMYSAQGNGGGPPRKGIPE LEQYDPPELADSSGRVVREKWSADMWRLGCLIWEVFNGPLPRAAALRNPGKIPKTLVPHYCELVGANPKVRPNPARFLQNCRAPGGFMSN RFVETNLFLEEIQIKEPAEKQKFFQELSKSLDAFPEDFCRHKVLPQLLTAFEFGNAGAVVLTPLFKVGKFLSAEEYQQKIIPVVVKMFSS TDRAMRIRLLQQMEQFIQYLDEPTVNTQIFPHVVHGFLDTNPAIREQTVKAELMSSLIEYCIELSQAAEPAGPQDSATGSPSDPSSSLAP	517_SCYL1_FRMD8
3D view using mol* of HKFP_370_SCYL1_FRMD8

PDB file >>>HKFP_371_SCYL1_FRMD8	ENST00000525364	ENST00000317568	SCYL1	chr11	65300276	FRMD8	chr11	65172334	MWFFARDPVRDFPFELIPEPPEGGLPGPWALHRGRKKATGSPVSIFVYDVKPGAEEQTQVAKAAFKRFKTLRHPNILAYIDGLETEKCLH VVTEAVTPLGIYLKARVEAGGLKELEISWGLHQIVKALSFLVNDCSLIHNNVCMAAVFVDRAGEWKLGGLDYMYSAQGNGGGPPRKGIPE LEQYDPPELADSSGRVVREKWSADMWRLGCLIWEVFNGPLPRAAALRNPGKIPKTLVPHYCELVGANPKVRPNPARFLQNCRAPGGFMSN RFVETNLFLEEIQIKEPAEKQKFFQELSKSLDAFPEDFCRHKVLPQLLTAFEFGNAGAVVLTPLFKVGKFLSAEEYQQKIIPVVVKMFSS TDRAMRIRLLQQMEQFIQYLDEPTVNTQIFPHVVHGFLDTNPAIREQTVKAELMSSLIEYCIELSQAAEPAGPQDSATGSPSDPSSSLAP	517_SCYL1_FRMD8

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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

./secondary_str/HKFP_369_SCYL1_FRMD8_vs_HKFP_370_SCYL1_FRMD8.png

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

SCYL1_FRMD8 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.

HKFP_369_SCYL1_FRMD8.png

HKFP_370_SCYL1_FRMD8.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
HKFP_369_SCYL1_FRMD8	1.04	160	1.072	570.752	0.59	0.727	0.91	0.665	0.932	0.714	0.722	Chain A: 361,363,366,394,395,397,398,399,400,405,4 06,409,420,423,424,427,433,530,534,536,537,539,540 ,541,542,543,568,569,570,571,636,639,640,643,644,6 46,647,672
HKFP_370_SCYL1_FRMD8	1.061	242	1.111	770.035	0.551	0.721	0.91	1.095	0.802	1.365	1.65	Chain A: 373,377,378,380,381,382,385,389,390,393,3 97,402,405,406,409,410,411,412,413,415,416,418,419 ,422,423,426,429,455,456,457,458,459,460,461,462,4 63,464,466,467,470,473,475,482

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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.

HKFP_368_SCYL1_FRMD8_ramachandran.png

HKFP_369_SCYL1_FRMD8_ramachandran.png

HKFP_370_SCYL1_FRMD8_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
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Palbociclib	-9.80758	-10.2771	-61.7275
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Palbociclib	-9.80758	-10.2771	-61.7275
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Palbociclib	-9.80758	-10.2771	-61.7275
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Palbociclib	-9.59996	-10.0069	-55.04600000000001
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Avapritinib	-9.15318	-9.48448	-55.7691
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Avapritinib	-9.15318	-9.48448	-55.7691
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Avapritinib	-9.15318	-9.48448	-55.7691
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Avapritinib	-9.15318	-9.48448	-55.7691
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Lapatinib	-9.15094	-9.23974	-66.3738
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Larotrectinib	-9.13613	-9.13613	-47.7019
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Mobocertinib	-8.963339999999997	-8.971039999999997	-44.1815
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Larotrectinib	-8.931980000000003	-8.931980000000003	-47.8525
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Afatinib	-8.90855	-9.09085	-59.2907
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Afatinib	-8.90855	-9.09085	-59.2907
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Afatinib	-8.90715	-9.09085	-59.2907
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Ribociclib	-8.83437	-8.903369999999997	-52.9686
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Ribociclib	-8.83437	-8.903369999999997	-52.9686
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Futibatinib	-8.827	-8.827	-58.3497
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Midostaurin	-8.77825	-8.77825	-33.5028
HKFP_368_SCYL1_FRMD8-DOCK_HTVS_1-001	Afatinib	-8.71613	-8.898430000000003	-56.5274
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Lapatinib	-6.3619900000000005	-6.4507900000000005	-44.2089
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Axitinib	-6.15032	-6.1535199999999985	-41.9533
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Larotrectinib	-6.08748	-6.08748	-42.9181
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Regorafenib	-5.67848	-5.67848	-41.7752
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Sunitinib	-5.56597	-5.57017	-39.8774
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Avapritinib	-5.55716	-5.88846	-40.1819
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Avapritinib	-5.55716	-5.88846	-40.1819
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Avapritinib	-5.55716	-5.88846	-40.1819
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Avapritinib	-5.55716	-5.88846	-40.1819
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Pexidartinib	-5.53504	-5.7518400000000005	-42.205
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Pexidartinib	-5.53504	-5.7518400000000005	-42.205
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Capmatinib	-5.508369999999998	-5.51397	-43.9799
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Lenvatinib	-5.48882	-5.48882	-36.038
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Netarsudil	-5.40635	-5.41745	-41.6588
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Netarsudil	-5.40635	-5.41745	-41.6588
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Infigratinib	-5.39724	-5.96404	-24.7357
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Infigratinib	-5.39724	-5.96404	-24.7357
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Infigratinib	-5.39724	-5.96404	-24.7357
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Encorafenib	-5.36135	-5.74985	-52.1246
HKFP_369_SCYL1_FRMD8_vsw_5-DOCK_HTVS_1-001	Neratinib	-5.33009	-5.51599	-50.8147
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Tepotinib	-5.65046	-5.65156	-32.9424
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Palbociclib	-5.59576	-6.00266	-43.8503
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Palbociclib	-5.59576	-6.00266	-43.8503
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Tepotinib	-5.59432	-5.59542	-35.999
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Tepotinib	-5.55203	-5.55313	-37.5779
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Palbociclib	-5.4856300000000005	-5.892530000000002	-42.9721
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Regorafenib	-5.1957	-5.1957	-43.2777
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Pralsetinib	-5.14604	-5.23754	-40.1547
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Pralsetinib	-5.08032	-5.1718199999999985	-38.7791
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Upadacitinib	-4.9908800000000015	-4.99188	-40.9972
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Sorafenib	-4.97043	-4.9825300000000015	-43.2469
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Sorafenib	-4.97043	-4.9825300000000015	-43.2469
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Ibrutinib	-4.94059	-4.94059	-41.9706
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Tivozanib	-4.8598300000000005	-4.8598300000000005	-46.3514
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Asciminib	-4.82262	-5.28762	-29.7901
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Pazopanib	-4.81163	-4.81853	-43.0599
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Pazopanib	-4.81163	-4.81853	-43.0599
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Belumosudil	-4.695130000000002	-4.7028300000000005	-52.0225
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Sunitinib	-4.64311	-4.64731	-42.0775
HKFP_370_SCYL1_FRMD8_vsw_6-DOCK_HTVS_1-001	Asciminib	-4.5658400000000015	-4.92894	-40.8266
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Lapatinib	-5.9728900000000005	-6.0616900000000005	-54.9957
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Lapatinib	-5.35849	-5.44729	-54.8155
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Tepotinib	-5.300330000000001	-5.30143	-43.2438
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Tepotinib	-5.255780000000001	-5.256880000000001	-42.2675
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Tofacitinib	-5.21633	-5.22783	-14.8165
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Tofacitinib	-5.21633	-5.22783	-14.8165
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Nilotinib	-5.11796	-6.0427599999999995	-41.4292
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Nilotinib	-5.11796	-6.0427599999999995	-41.4292
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Nilotinib	-4.99679	-5.1363900000000005	-39.1924
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Nilotinib	-4.99679	-5.1363900000000005	-39.1924
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Ruxolitinib	-4.9110000000000005	-4.9110000000000005	-33.9118
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Tofacitinib	-4.55998	-4.57148	-28.9791
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Tofacitinib	-4.55998	-4.57148	-28.9791
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Tofacitinib	-4.548780000000001	-4.5602800000000006	-26.9562
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Tofacitinib	-4.548780000000001	-4.5602800000000006	-26.9562
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Sorafenib	-4.52524	-4.53734	-36.7755
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Sorafenib	-4.52524	-4.53734	-36.7755
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Upadacitinib	-4.4926900000000005	-4.49369	-35.6228
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Midostaurin	-4.33104	-4.33104	-18.9284
312_SCYL1_FRMD8-DOCK_HTVS_1-001	Selpercatinib	-4.27003	-4.30053	-42.5329

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Kinase-Substrate Information of SCYL1_FRMD8

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 SCYL1_FRMD8

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 SCYL1-FRMD8 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 SCYL1_FRMD8

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