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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:CARS_ALK

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: CARS_ALK
	KinaseFusionDB ID: KFG917
	FusionGDB2.0 ID: KFG917
		Hgene	Tgene
	Gene symbol	CARS	ALK
	Gene ID	833	238
	Gene name	cysteinyl-tRNA synthetase 1	ALK receptor tyrosine kinase
	Synonyms	CARS\|CYSRS\|MCDDBH\|MDBH\|MGC:11246	ALK1\|CD246\|NBLST3
	Cytomap	11p15.4	2p23.2-p23.1
	Type of gene	protein-coding	protein-coding
	Description	cysteine--tRNA ligase, cytoplasmiccysteine tRNA ligase 1, cytoplasmiccysteine translase	ALK tyrosine kinase receptorCD246 antigenanaplastic lymphoma receptor tyrosine kinasemutant anaplastic lymphoma kinase
	Modification date	20240403	20240411
	UniProtAcc	P49589	Q3KRA9
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000278224, ENST00000380525, ENST00000397111, ENST00000397114, ENST00000401769, ENST00000470221,	ENST00000431873, ENST00000498037, ENST00000389048,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: CARS [Title/Abstract] AND ALK [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)

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	CARS	GO:0006423	cysteinyl-tRNA aminoacylation	10908348\|17303165
Tgene	ALK	GO:0007169	cell surface receptor protein tyrosine kinase signaling pathway	25605972\|30061385\|34646012
Tgene	ALK	GO:0016310	phosphorylation	9174053
Tgene	ALK	GO:0038083	peptidyl-tyrosine autophosphorylation	30061385\|34646012
Tgene	ALK	GO:0046777	protein autophosphorylation	9174053
Tgene	ALK	GO:0046777	protein autophosphorylation	9174053

Kinase Fusion gene breakpoints across CARS (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 ALK (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
ChimerKB3	.	CARS	chr11	3033424	ALK	chr2	29446394
ChimerKB3	.	CARS	chr11	3037010	ALK	chr2	29446394
ChimerKB3	.	CARS	chr11	3038335	ALK	chr2	29445473
COSMIC	1152148	CARS	chr11	3033425	ALK	chr2	29446394
COSMIC	1152149	CARS	chr11	3032308	ALK	chr2	29446623
COSMIC	1152150	CARS	chr11	3032308	ALK	chr2	29446623

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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)
ENST00000380525	ENST00000389048	CARS	chr11	3033425	ALK	chr2	29446394	4279	1252
ENST00000380525	ENST00000389048	CARS	chr11	3033424	ALK	chr2	29446394	4279	1252
ENST00000401769	ENST00000389048	CARS	chr11	3037010	ALK	chr2	29446394	4076	614

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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

>ENST00000380525_ENST00000389048_CARS_chr11_3033425_ALK_chr2_29446394_length(amino acids)=1252
MADSSGQQAPDYRSILSISDEAARAQALNEHLSTRSYVQGYSLSQADVDAFRQLSAPPADPQLFHVARWFRHIEALLGSPCGKGQPCRLQ
ASKGRRVQPQWSPPAGTQPCRLHLYNSLTRNKEVFIPQDGKKVTWYCCGPTVYDASHMGHARSYISFDILRRVLKDYFKFDVFYCMNITD
IDDKIIKRARQNHLFEQYREKRPEAAQLLEDVQAALKPFSVKLNETTDPDKKQMLERIQHAVQLATEPLEKAVQSRLTGEEVNSCVEVLL
EEAKDLLSDWLDSTLGCDVTDNSIFSKLPKFWEGDFHRDMEALNVLPPDVLTRVSEYVPEIVNFVQKIVDNGYGYVSNGSVYFDTAKFAS
SEKHSYGKLVPEAVGDQKALQEGEGDLSISADRLSEKRSPNDFALWKASKPGEPSWPCPWGKGRPGWHIECSAMAGTLLGASMDIHGGGF
DLRFPHHDNELAQSEAYFENDCWVRYFLHTGHLTIAGCKMSKSLKNFITIKDALKKHSARQLRLAFLMHSWKDTLDYSSNTMESALQYEK
FLNEFFLNVKDILRAPVDITGQFEKWGEEEAELNKNFYDKKTAIHKALCDNVDTRTVMEEMRALVSQCNLYMAARKAVRKRPNQALLENI
ALYLTHMLKIFGAVEEDSSLGFPVGGPGTSLSLEATVMPYLQVLSEFREGVRKIAREQKVYRRKHQELQAMQMELQSPEYKLSKLRTSTI
MTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQN
IVRCIGVSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKI
GDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPV
YRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTS
SGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGS

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

>ENST00000380525_ENST00000389048_CARS_chr11_3033424_ALK_chr2_29446394_length(amino acids)=1252
MADSSGQQAPDYRSILSISDEAARAQALNEHLSTRSYVQGYSLSQADVDAFRQLSAPPADPQLFHVARWFRHIEALLGSPCGKGQPCRLQ
ASKGRRVQPQWSPPAGTQPCRLHLYNSLTRNKEVFIPQDGKKVTWYCCGPTVYDASHMGHARSYISFDILRRVLKDYFKFDVFYCMNITD
IDDKIIKRARQNHLFEQYREKRPEAAQLLEDVQAALKPFSVKLNETTDPDKKQMLERIQHAVQLATEPLEKAVQSRLTGEEVNSCVEVLL
EEAKDLLSDWLDSTLGCDVTDNSIFSKLPKFWEGDFHRDMEALNVLPPDVLTRVSEYVPEIVNFVQKIVDNGYGYVSNGSVYFDTAKFAS
SEKHSYGKLVPEAVGDQKALQEGEGDLSISADRLSEKRSPNDFALWKASKPGEPSWPCPWGKGRPGWHIECSAMAGTLLGASMDIHGGGF
DLRFPHHDNELAQSEAYFENDCWVRYFLHTGHLTIAGCKMSKSLKNFITIKDALKKHSARQLRLAFLMHSWKDTLDYSSNTMESALQYEK
FLNEFFLNVKDILRAPVDITGQFEKWGEEEAELNKNFYDKKTAIHKALCDNVDTRTVMEEMRALVSQCNLYMAARKAVRKRPNQALLENI
ALYLTHMLKIFGAVEEDSSLGFPVGGPGTSLSLEATVMPYLQVLSEFREGVRKIAREQKVYRRKHQELQAMQMELQSPEYKLSKLRTSTI
MTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQN
IVRCIGVSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKI
GDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPV
YRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTS
SGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGS

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

>ENST00000401769_ENST00000389048_CARS_chr11_3037010_ALK_chr2_29446394_length(amino acids)=614
MEPTSGPFRTDLGYHLVGCSSGKGRRVQPQWSPPAGTQPCRLHLYNSLTRNKEVFIPQDGKKVTWYCCGPTVYDASHMGHARSYISFDIL
RRVLKDYFKFDVFYCMNITDIDDKIIKRARQNHLFEQYREKRPEAAQLLEDVQAALKPFSVKLNETTDPDKKQMLERIQHAVQLATEPLE
KAVQSRLTGEEVNSCVEVLLEEAKDLLSDWLDSTLGCDVTDNSIFSKLPKFWEGDFHRDMEALNVLPPDVLTRVSEYVPEIVNFVQKIVD
NGYGYVSNGSVYFDTAKFASSEKHSYGKLVPEAVGDQKALQEGEGDLSISADRLSEKRSPNDFALWKASKPGEPSWPCPWGKGRPGWHIE
CSAMAGTLLGASMDIHGGGFDLRFPHHDNELAQSEAYFENDCWVRYFLHTGHLTIAGCKMSKSLKNFITIKDALKKHSARQLRLAFLMHS
WKDTLDYSSNTMESALQYEKFLNEFFLNVKDILRAPVDITGQFEKWGEEEAELNKNFYDKKTAIHKALCDNVDTRTVMEEMRALVSQCNL

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

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:/chr2:)
- 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
CARS P49589	ALK Q3KRA9
FUNCTION: Catalyzes the ATP-dependent ligation of cysteine to tRNA(Cys). {ECO:0000269\|PubMed:11347887, ECO:0000269\|PubMed:30824121}.	FUNCTION: Probable dioxygenase that requires molecular oxygen, alpha-ketoglutarate and iron. {ECO:0000250}.

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

CARS

3033424

ALK

29446394

ENST00000380525

1116_1392

1057

1621

Domain

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

Tgene

CARS

3033425

ALK

29446394

ENST00000380525

1116_1392

1057

1621

Domain

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

Tgene

CARS

3037010

ALK

29446394

ENST00000401769

1116_1392

1057

1621

Domain

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

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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 >>>81_CARS_ALK	ENST00000401769	ENST00000389048	CARS	chr11	3037010	ALK	chr2	29446394	MEPTSGPFRTDLGYHLVGCSSGKGRRVQPQWSPPAGTQPCRLHLYNSLTRNKEVFIPQDGKKVTWYCCGPTVYDASHMGHARSYISFDIL RRVLKDYFKFDVFYCMNITDIDDKIIKRARQNHLFEQYREKRPEAAQLLEDVQAALKPFSVKLNETTDPDKKQMLERIQHAVQLATEPLE KAVQSRLTGEEVNSCVEVLLEEAKDLLSDWLDSTLGCDVTDNSIFSKLPKFWEGDFHRDMEALNVLPPDVLTRVSEYVPEIVNFVQKIVD NGYGYVSNGSVYFDTAKFASSEKHSYGKLVPEAVGDQKALQEGEGDLSISADRLSEKRSPNDFALWKASKPGEPSWPCPWGKGRPGWHIE CSAMAGTLLGASMDIHGGGFDLRFPHHDNELAQSEAYFENDCWVRYFLHTGHLTIAGCKMSKSLKNFITIKDALKKHSARQLRLAFLMHS WKDTLDYSSNTMESALQYEKFLNEFFLNVKDILRAPVDITGQFEKWGEEEAELNKNFYDKKTAIHKALCDNVDTRTVMEEMRALVSQCNL	614
3D view using mol* of 81_CARS_ALK

PDB file >>>TKFP_136_CARS_ALK	ENST00000380525	ENST00000389048	CARS	chr11	3033425	ALK	chr2	29446394	MADSSGQQAPDYRSILSISDEAARAQALNEHLSTRSYVQGYSLSQADVDAFRQLSAPPADPQLFHVARWFRHIEALLGSPCGKGQPCRLQ ASKGRRVQPQWSPPAGTQPCRLHLYNSLTRNKEVFIPQDGKKVTWYCCGPTVYDASHMGHARSYISFDILRRVLKDYFKFDVFYCMNITD IDDKIIKRARQNHLFEQYREKRPEAAQLLEDVQAALKPFSVKLNETTDPDKKQMLERIQHAVQLATEPLEKAVQSRLTGEEVNSCVEVLL EEAKDLLSDWLDSTLGCDVTDNSIFSKLPKFWEGDFHRDMEALNVLPPDVLTRVSEYVPEIVNFVQKIVDNGYGYVSNGSVYFDTAKFAS SEKHSYGKLVPEAVGDQKALQEGEGDLSISADRLSEKRSPNDFALWKASKPGEPSWPCPWGKGRPGWHIECSAMAGTLLGASMDIHGGGF DLRFPHHDNELAQSEAYFENDCWVRYFLHTGHLTIAGCKMSKSLKNFITIKDALKKHSARQLRLAFLMHSWKDTLDYSSNTMESALQYEK FLNEFFLNVKDILRAPVDITGQFEKWGEEEAELNKNFYDKKTAIHKALCDNVDTRTVMEEMRALVSQCNLYMAARKAVRKRPNQALLENI ALYLTHMLKIFGAVEEDSSLGFPVGGPGTSLSLEATVMPYLQVLSEFREGVRKIAREQKVYRRKHQELQAMQMELQSPEYKLSKLRTSTI MTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQN IVRCIGVSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKI GDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPV YRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTS SGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGS	1252_CARS_ALK
PDB file >>>TKFP_137_CARS_ALK	ENST00000380525	ENST00000389048	CARS	chr11	3033424	ALK	chr2	29446394	MADSSGQQAPDYRSILSISDEAARAQALNEHLSTRSYVQGYSLSQADVDAFRQLSAPPADPQLFHVARWFRHIEALLGSPCGKGQPCRLQ ASKGRRVQPQWSPPAGTQPCRLHLYNSLTRNKEVFIPQDGKKVTWYCCGPTVYDASHMGHARSYISFDILRRVLKDYFKFDVFYCMNITD IDDKIIKRARQNHLFEQYREKRPEAAQLLEDVQAALKPFSVKLNETTDPDKKQMLERIQHAVQLATEPLEKAVQSRLTGEEVNSCVEVLL EEAKDLLSDWLDSTLGCDVTDNSIFSKLPKFWEGDFHRDMEALNVLPPDVLTRVSEYVPEIVNFVQKIVDNGYGYVSNGSVYFDTAKFAS SEKHSYGKLVPEAVGDQKALQEGEGDLSISADRLSEKRSPNDFALWKASKPGEPSWPCPWGKGRPGWHIECSAMAGTLLGASMDIHGGGF DLRFPHHDNELAQSEAYFENDCWVRYFLHTGHLTIAGCKMSKSLKNFITIKDALKKHSARQLRLAFLMHSWKDTLDYSSNTMESALQYEK FLNEFFLNVKDILRAPVDITGQFEKWGEEEAELNKNFYDKKTAIHKALCDNVDTRTVMEEMRALVSQCNLYMAARKAVRKRPNQALLENI ALYLTHMLKIFGAVEEDSSLGFPVGGPGTSLSLEATVMPYLQVLSEFREGVRKIAREQKVYRRKHQELQAMQMELQSPEYKLSKLRTSTI MTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQN IVRCIGVSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKI GDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPV YRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTS SGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGS	1252_CARS_ALK
PDB file >>>TKFP_138_CARS_ALK	ENST00000401769	ENST00000389048	CARS	chr11	3037010	ALK	chr2	29446394	MEPTSGPFRTDLGYHLVGCSSGKGRRVQPQWSPPAGTQPCRLHLYNSLTRNKEVFIPQDGKKVTWYCCGPTVYDASHMGHARSYISFDIL RRVLKDYFKFDVFYCMNITDIDDKIIKRARQNHLFEQYREKRPEAAQLLEDVQAALKPFSVKLNETTDPDKKQMLERIQHAVQLATEPLE KAVQSRLTGEEVNSCVEVLLEEAKDLLSDWLDSTLGCDVTDNSIFSKLPKFWEGDFHRDMEALNVLPPDVLTRVSEYVPEIVNFVQKIVD NGYGYVSNGSVYFDTAKFASSEKHSYGKLVPEAVGDQKALQEGEGDLSISADRLSEKRSPNDFALWKASKPGEPSWPCPWGKGRPGWHIE CSAMAGTLLGASMDIHGGGFDLRFPHHDNELAQSEAYFENDCWVRYFLHTGHLTIAGCKMSKSLKNFITIKDALKKHSARQLRLAFLMHS WKDTLDYSSNTMESALQYEKFLNEFFLNVKDILRAPVDITGQFEKWGEEEAELNKNFYDKKTAIHKALCDNVDTRTVMEEMRALVSQCNL	614_CARS_ALK
3D view using mol* of TKFP_138_CARS_ALK

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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.

3D view using mol* of viewer/superimpose_isoforms/TKFP_136_CARS_ALK_vs_TKFP_138_CARS_ALK_superimposed.pdb.html

Comparison of the Secondary Structures of Fusion Protein Isoforms

./secondary_str/TKFP_136_CARS_ALK_vs_TKFP_138_CARS_ALK.png

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

CARS_ALK does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/81_CARS_ALK.pngall_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/TKFP_138_CARS_ALK_updated_violin_plot.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.

81_CARS_ALK.png

TKFP_138_CARS_ALK.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
TKFP_138_CARS_ALK	1.065	295	1.056	1066.73	0.503	0.795	0.964	0.599	1.107	0.541	0.718	Chain A: 68,69,70,71,72,73,74,77,79,80,82,83,84,87 ,107,109,112,114,117,118,120,121,122,145,148,149,1 52,164,165,168,204,205,208,209,210,212,213,228,232 ,312,313,314,315,316,317,337,357,360,361,378,379,3 80,381,382,385,386,410,411,412,413,419,420,421,422 ,423,425

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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.

81_CARS_ALK_ramachandran.png

TKFP_138_CARS_ALK_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
81_CARS_ALK-DOCK_HTVS_1-001	Pralsetinib	-7.05163	-7.14313	-60.4963
81_CARS_ALK-DOCK_HTVS_1-001	Larotrectinib	-6.8300399999999994	-6.8300399999999994	-57.9763
81_CARS_ALK-DOCK_HTVS_1-001	Belumosudil	-6.45809	-6.46579	-54.1226
81_CARS_ALK-DOCK_HTVS_1-001	Belumosudil	-6.431019999999999	-6.43872	-58.0764
81_CARS_ALK-DOCK_HTVS_1-001	Tivozanib	-6.28022	-6.28022	-51.1618
81_CARS_ALK-DOCK_HTVS_1-001	Lenvatinib	-6.04542	-6.04542	-52.0039
81_CARS_ALK-DOCK_HTVS_1-001	Tofacitinib	-5.9429300000000005	-5.95443	-40.6479
81_CARS_ALK-DOCK_HTVS_1-001	Tofacitinib	-5.9429300000000005	-5.95443	-40.6479
81_CARS_ALK-DOCK_HTVS_1-001	Midostaurin	-5.89931	-5.89931	-54.4718
81_CARS_ALK-DOCK_HTVS_1-001	Tofacitinib	-5.88566	-5.8971599999999995	-41.1829
81_CARS_ALK-DOCK_HTVS_1-001	Tofacitinib	-5.88566	-5.8971599999999995	-41.1829
81_CARS_ALK-DOCK_HTVS_1-001	Pralsetinib	-5.8168	-5.9083	-60.3563
81_CARS_ALK-DOCK_HTVS_1-001	Nilotinib	-5.5254	-6.4502	-59.7425
81_CARS_ALK-DOCK_HTVS_1-001	Nilotinib	-5.5254	-6.4502	-59.7425
81_CARS_ALK-DOCK_HTVS_1-001	Tofacitinib	-5.5176099999999995	-5.52911	-39.8861
81_CARS_ALK-DOCK_HTVS_1-001	Tofacitinib	-5.5176099999999995	-5.52911	-39.8861
81_CARS_ALK-DOCK_HTVS_1-001	Pralsetinib	-5.50852	-5.60002	-57.1214
81_CARS_ALK-DOCK_HTVS_1-001	Pexidartinib	-5.490559999999999	-6.1913599999999995	-44.619
81_CARS_ALK-DOCK_HTVS_1-001	Pexidartinib	-5.490559999999999	-6.1913599999999995	-44.619
81_CARS_ALK-DOCK_HTVS_1-001	Baricitinib	-5.4888900000000005	-5.4888900000000005	-46.0658

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Kinase-Substrate Information of CARS_ALK

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
ALK	Q9UM73	human	ALK	Q9UM73	Y1604	tAPGAGHyEDTILkS
ALK	Q9UM73	human	ELP3	Q9H9T3	Y202	GHtSNNIyEAVkySE	Radical_SAM
ALK	Q9UM73	human	ALK	Q9UM73	Y1278	FGMARDIyRAsyyRK	PK_Tyr_Ser-Thr
ALK	Q9UM73	human	CDK9	P50750	Y19	FCDEVSkyEkLAkIG
ALK	Q9UM73	human	SFPQ	P23246	Y293	RRPGEktyTQRCRLF
ALK	Q9UM73	human	ATIC	P31939	Y104	RVVACNLyPFVkTVA	MGS
ALK	Q9UM73	human	SRCIN1	Q9C0H9	Y396	LVKGEGLyADPyGLL
ALK	Q9UM73	human	STAT3	P40763	Y705	DPGsAAPyLktKFIC
ALK	Q9UM73	human	PTPN11	Q06124	Y580	REDsARVyENVGLMQ
ALK	Q9UM73	human	PBK	Q96KB5	Y74	NPICNDHyRsVyQkR	Pkinase
ALK	Q9UM73	human	VASP	P50552	Y39	AFSRVQIyHNPtANs	WH1
ALK	Q9UM73	human	PTPN11	Q06124	Y542	sKRkGHEytNIKysL
ALK	Q9UM73	human	GRB2	P62993	Y160	QVPQQPtyVQALFDF

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 CARS_ALK

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 CARS-ALK 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 CARS_ALK

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

Hgene	Tgene	Disease	Source	PMID
CARS	ALK	Lung Adenocarcinoma	MyCancerGenome
CARS	ALK	Acute Myeloid Leukemia	MyCancerGenome
CARS	ALK	Cancer Of Unknown Primary	MyCancerGenome
CARS	ALK	Diffuse Large B-Cell Lymphoma	MyCancerGenome

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
Tgene	ALK	C0007131	Non-Small Cell Lung Carcinoma	28	CGI;CTD_human
Tgene	ALK	C0027819	Neuroblastoma	13	CGI;CTD_human;ORPHANET
Tgene	ALK	C0152013	Adenocarcinoma of lung (disorder)	8	CGI;CTD_human
Tgene	ALK	C2751681	NEUROBLASTOMA, SUSCEPTIBILITY TO, 3	8	CLINGEN;UNIPROT
Tgene	ALK	C0206180	Ki-1+ Anaplastic Large Cell Lymphoma	6	CGI;CTD_human
Tgene	ALK	C0334121	Inflammatory Myofibroblastic Tumor	4	CGI;CTD_human;ORPHANET
Tgene	ALK	C0018199	Granuloma, Plasma Cell	3	CTD_human
Tgene	ALK	C0007621	Neoplastic Cell Transformation	2	CTD_human
Tgene	ALK	C0027627	Neoplasm Metastasis	2	CTD_human
Tgene	ALK	C0238463	Papillary thyroid carcinoma	2	ORPHANET

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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