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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:ETV6_ABL2

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: ETV6_ABL2
	KinaseFusionDB ID: KFG2173
	FusionGDB2.0 ID: KFG2173
		Hgene	Tgene
	Gene symbol	ETV6	ABL2
	Gene ID	2120	27
	Gene name	ETS variant transcription factor 6	ABL proto-oncogene 2, non-receptor tyrosine kinase
	Synonyms	TEL\|TEL/ABL\|THC5	ABLL\|ARG
	Cytomap	12p13.2	1q25.2
	Type of gene	protein-coding	protein-coding
	Description	transcription factor ETV6ETS-related protein Tel1ETV6-RUNX1 fusion proteinTEL1 oncogeneets variant gene 6 (TEL oncogene)	tyrosine-protein kinase ABL2Abelson tyrosine-protein kinase 2abelson-related gene proteinc-abl oncogene 2, non-receptor tyrosine kinasetyrosine-protein kinase ARGv-abl Abelson murine leukemia viral oncogene homolog 2
	Modification date	20240305	20240411
	UniProtAcc	P41212	P42684
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000396373, ENST00000544715,	ENST00000344730, ENST00000367623, ENST00000392043, ENST00000408940, ENST00000504405, ENST00000507173, ENST00000511413, ENST00000512653, ENST00000502732,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: ETV6 [Title/Abstract] AND ABL2 [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	ETV6	GO:0000122	negative regulation of transcription by RNA polymerase II	10514502
Tgene	ABL2	GO:0018108	peptidyl-tyrosine phosphorylation	15886098
Tgene	ABL2	GO:0051353	positive regulation of oxidoreductase activity	12893824

Kinase Fusion gene breakpoints across ETV6 (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 ABL2 (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	.	ETV6	chr12	12022903	ABL2	chr1	179102509
ChimerKB4	.	ETV6	chr12	12022903	ABL2	chr1	179102509

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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)
ENST00000396373	ENST00000502732	ETV6	chr12	12022903	ABL2	chr1	179102509	13066	1466

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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

>ENST00000396373_ENST00000502732_ETV6_chr12_12022903_ABL2_chr1_179102509_length(amino acids)=1466
MSETPAQCSIKQERISYTPPESPVPSYASSTPLHVPVPRALRMEEDSIRLPAHLRLQPIYWSRDDVAQWLKWAENEFSLRPIDSNTFEMN
GKALLLLTKEDFRYRSPHSGDVLYELLQHILKQRKPRILFSPFFHPGNSIHTQPEVILHQNHEEDNCVQRTPRPSVDNVHHNPPTIELLH
RSRSPITTNHRPSPDPEQRPLRSPLDNMIRRLSPAERAQGPRPHQENNHQESYPLSVSPMENNHCPASSESHPKPSSPRQESTRVIQLMP
SPIMHPLILNPRHSVDFKQSRLSEDGLHREGKPINLSHREDLAYMNHIMVSVSPPEEHAMPIGRIADHFASCVEDGFEGDKTGGSSPEAL
HRPYGCDVEPQALNEAIRWSSKENLLGATESDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNQNGEWSEVRSKNGQGWVPSNYITPVN
SLEKHSWYHGPVSRSAAEYLLSSLINGSFLVRESESSPGQLSISLRYEGRVYHYRINTTADGKVYVTAESRFSTLAELVHHHSTVADGLV
TTLHYPAPKCNKPTVYGVSPIHDKWEMERTDITMKHKLGGGQYGEVYVGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQ
LLGVCTLEPPFYIVTEYMPYGNLLDYLRECNREEVTAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHVVKVADFGLSRLMTG
DTYTAHAGAKFPIKWTAPESLAYNTFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYDLLEKGYRMEQPEGCPPKVYELMRACWKWSP
ADRPSFAETHQAFETMFHDSSISEEVAEELGRAASSSSVVPYLPRLPILPSKTRTLKKQVENKENIEGAQDATENSASSLAPGFIRGAQA
SSGSPALPRKQRDKSPSSLLEDAKETCFTRDRKGGFFSSFMKKRNAPTPPKRSSSFREMENQPHKKYELTGNFSSVASLQHADGFSFTPA
QQEANLVPPKCYGGSFAQRNLCNDDGGGGGGSGTAGGGWSGITGFFTPRLIKKTLGLRAGKPTASDDTSKPFPRSNSTSSMSSGLPEQDR
MAMTLPRNCQRSKLQLERTVSTSSQPEENVDRANDMLPKKSEESAAPSRERPKAKLLPRGATALPLRTPSGDLAITEKDPPGVGVAGVAA
APKGKEKNGGARLGMAGVPEDGEQPGWPSPAKAAPVLPTTHNHKVPVLISPTLKHTPADVQLIGTDSQGNKFKLLSEHQVTSSGDKDRPR
RVKPKCAPPPPPVMRLLQHPSICSDPTEEPTALTAGQSTSETQEGGKKAALGAVPISGKAGRPVMPPPQVPLPTSSISPAKMANGTAGTK
VALRKTKQAAEKISADKISKEALLECADLLSSALTEPVPNSQLVDTGHQLLDYCSGYVDCIPQTRNKFAFREAVSKLELSLQELQVSSAA

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

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:/chr1:)
- 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
ETV6 P41212	ABL2 P42684
FUNCTION: Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'. Plays a role in hematopoiesis and malignant transformation. {ECO:0000269\|PubMed:25581430}.	FUNCTION: Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). {ECO:0000250\|UniProtKB:Q4JIM5, ECO:0000269\|PubMed:15735735, ECO:0000269\|PubMed:15886098, ECO:0000269\|PubMed:16678104, ECO:0000269\|PubMed:17306540, ECO:0000269\|PubMed:18945674}.

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	ETV6	12022903	ABL2	179102509	ENST00000396373	0	10	288_539	0	543	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	11	288_539	0	1147	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	11	288_539	0	1162	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	12	288_539	0	1044	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	12	288_539	0	1059	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	12	288_539	37	1168	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	12	288_539	52	1183	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	13	288_539	37	1065	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	13	288_539	52	1080	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	10	173_263	0	543	Domain	Note=SH2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00191
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	11	173_263	0	1147	Domain	Note=SH2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00191
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	11	173_263	0	1162	Domain	Note=SH2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00191
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	12	173_263	0	1044	Domain	Note=SH2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00191
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	12	173_263	0	1059	Domain	Note=SH2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00191
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	12	173_263	37	1168	Domain	Note=SH2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00191
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	12	173_263	52	1183	Domain	Note=SH2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00191
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	13	173_263	37	1065	Domain	Note=SH2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00191
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	13	173_263	52	1080	Domain	Note=SH2;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00191
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	10	107_167	0	543	Domain	Note=SH3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00192
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	11	107_167	0	1147	Domain	Note=SH3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00192
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	11	107_167	0	1162	Domain	Note=SH3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00192
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	12	107_167	0	1044	Domain	Note=SH3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00192
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	12	107_167	0	1059	Domain	Note=SH3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00192
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	12	107_167	37	1168	Domain	Note=SH3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00192
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	12	107_167	52	1183	Domain	Note=SH3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00192
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	13	107_167	37	1065	Domain	Note=SH3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00192
Tgene	ETV6	12022903	ABL2	179102509	ENST00000396373	0	13	107_167	52	1080	Domain	Note=SH3;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00192

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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 >>>176_ETV6_ABL2	ENST00000396373	ENST00000502732	ETV6	chr12	12022903	ABL2	chr1	179102509	MSETPAQCSIKQERISYTPPESPVPSYASSTPLHVPVPRALRMEEDSIRLPAHLRLQPIYWSRDDVAQWLKWAENEFSLRPIDSNTFEMN GKALLLLTKEDFRYRSPHSGDVLYELLQHILKQRKPRILFSPFFHPGNSIHTQPEVILHQNHEEDNCVQRTPRPSVDNVHHNPPTIELLH RSRSPITTNHRPSPDPEQRPLRSPLDNMIRRLSPAERAQGPRPHQENNHQESYPLSVSPMENNHCPASSESHPKPSSPRQESTRVIQLMP SPIMHPLILNPRHSVDFKQSRLSEDGLHREGKPINLSHREDLAYMNHIMVSVSPPEEHAMPIGRIADHFASCVEDGFEGDKTGGSSPEAL HRPYGCDVEPQALNEAIRWSSKENLLGATESDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNQNGEWSEVRSKNGQGWVPSNYITPVN SLEKHSWYHGPVSRSAAEYLLSSLINGSFLVRESESSPGQLSISLRYEGRVYHYRINTTADGKVYVTAESRFSTLAELVHHHSTVADGLV TTLHYPAPKCNKPTVYGVSPIHDKWEMERTDITMKHKLGGGQYGEVYVGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQ LLGVCTLEPPFYIVTEYMPYGNLLDYLRECNREEVTAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHVVKVADFGLSRLMTG DTYTAHAGAKFPIKWTAPESLAYNTFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYDLLEKGYRMEQPEGCPPKVYELMRACWKWSP ADRPSFAETHQAFETMFHDSSISEEVAEELGRAASSSSVVPYLPRLPILPSKTRTLKKQVENKENIEGAQDATENSASSLAPGFIRGAQA SSGSPALPRKQRDKSPSSLLEDAKETCFTRDRKGGFFSSFMKKRNAPTPPKRSSSFREMENQPHKKYELTGNFSSVASLQHADGFSFTPA QQEANLVPPKCYGGSFAQRNLCNDDGGGGGGSGTAGGGWSGITGFFTPRLIKKTLGLRAGKPTASDDTSKPFPRSNSTSSMSSGLPEQDR MAMTLPRNCQRSKLQLERTVSTSSQPEENVDRANDMLPKKSEESAAPSRERPKAKLLPRGATALPLRTPSGDLAITEKDPPGVGVAGVAA APKGKEKNGGARLGMAGVPEDGEQPGWPSPAKAAPVLPTTHNHKVPVLISPTLKHTPADVQLIGTDSQGNKFKLLSEHQVTSSGDKDRPR RVKPKCAPPPPPVMRLLQHPSICSDPTEEPTALTAGQSTSETQEGGKKAALGAVPISGKAGRPVMPPPQVPLPTSSISPAKMANGTAGTK VALRKTKQAAEKISADKISKEALLECADLLSSALTEPVPNSQLVDTGHQLLDYCSGYVDCIPQTRNKFAFREAVSKLELSLQELQVSSAA	1466
3D view using mol* of 176_ETV6_ABL2

PDB file >>>TKFP_313_ETV6_ABL2	ENST00000396373	ENST00000502732	ETV6	chr12	12022903	ABL2	chr1	179102509	MSETPAQCSIKQERISYTPPESPVPSYASSTPLHVPVPRALRMEEDSIRLPAHLRLQPIYWSRDDVAQWLKWAENEFSLRPIDSNTFEMN GKALLLLTKEDFRYRSPHSGDVLYELLQHILKQRKPRILFSPFFHPGNSIHTQPEVILHQNHEEDNCVQRTPRPSVDNVHHNPPTIELLH RSRSPITTNHRPSPDPEQRPLRSPLDNMIRRLSPAERAQGPRPHQENNHQESYPLSVSPMENNHCPASSESHPKPSSPRQESTRVIQLMP SPIMHPLILNPRHSVDFKQSRLSEDGLHREGKPINLSHREDLAYMNHIMVSVSPPEEHAMPIGRIADHFASCVEDGFEGDKTGGSSPEAL HRPYGCDVEPQALNEAIRWSSKENLLGATESDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNQNGEWSEVRSKNGQGWVPSNYITPVN SLEKHSWYHGPVSRSAAEYLLSSLINGSFLVRESESSPGQLSISLRYEGRVYHYRINTTADGKVYVTAESRFSTLAELVHHHSTVADGLV TTLHYPAPKCNKPTVYGVSPIHDKWEMERTDITMKHKLGGGQYGEVYVGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQ LLGVCTLEPPFYIVTEYMPYGNLLDYLRECNREEVTAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHVVKVADFGLSRLMTG DTYTAHAGAKFPIKWTAPESLAYNTFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYDLLEKGYRMEQPEGCPPKVYELMRACWKWSP ADRPSFAETHQAFETMFHDSSISEEVAEELGRAASSSSVVPYLPRLPILPSKTRTLKKQVENKENIEGAQDATENSASSLAPGFIRGAQA SSGSPALPRKQRDKSPSSLLEDAKETCFTRDRKGGFFSSFMKKRNAPTPPKRSSSFREMENQPHKKYELTGNFSSVASLQHADGFSFTPA QQEANLVPPKCYGGSFAQRNLCNDDGGGGGGSGTAGGGWSGITGFFTPRLIKKTLGLRAGKPTASDDTSKPFPRSNSTSSMSSGLPEQDR MAMTLPRNCQRSKLQLERTVSTSSQPEENVDRANDMLPKKSEESAAPSRERPKAKLLPRGATALPLRTPSGDLAITEKDPPGVGVAGVAA APKGKEKNGGARLGMAGVPEDGEQPGWPSPAKAAPVLPTTHNHKVPVLISPTLKHTPADVQLIGTDSQGNKFKLLSEHQVTSSGDKDRPR RVKPKCAPPPPPVMRLLQHPSICSDPTEEPTALTAGQSTSETQEGGKKAALGAVPISGKAGRPVMPPPQVPLPTSSISPAKMANGTAGTK VALRKTKQAAEKISADKISKEALLECADLLSSALTEPVPNSQLVDTGHQLLDYCSGYVDCIPQTRNKFAFREAVSKLELSLQELQVSSAA	1466_ETV6_ABL2

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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

ETV6_ABL2 does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/176_ETV6_ABL2.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.

176_ETV6_ABL2.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.

176_ETV6_ABL2_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
176_ETV6_ABL2-DOCK_HTVS_1-001	Larotrectinib	-8.374410000000001	-8.374410000000001	-47.9165
176_ETV6_ABL2-DOCK_HTVS_1-001	Lapatinib	-7.4858899999999995	-7.5746899999999995	-63.5579
176_ETV6_ABL2-DOCK_HTVS_1-001	Nilotinib	-7.34479	-8.269589999999999	-51.0727
176_ETV6_ABL2-DOCK_HTVS_1-001	Nilotinib	-7.34479	-8.269589999999999	-51.0727
176_ETV6_ABL2-DOCK_HTVS_1-001	Pazopanib	-7.197589999999999	-7.20449	-49.8288
176_ETV6_ABL2-DOCK_HTVS_1-001	Pazopanib	-7.197589999999999	-7.20449	-49.8288
176_ETV6_ABL2-DOCK_HTVS_1-001	Gefitinib	-7.12568	-7.54068	-41.8216
176_ETV6_ABL2-DOCK_HTVS_1-001	Gefitinib	-7.12568	-7.54068	-41.8216
176_ETV6_ABL2-DOCK_HTVS_1-001	Tucatinib	-6.954460000000001	-7.3296600000000005	-51.5894
176_ETV6_ABL2-DOCK_HTVS_1-001	Imatinib	-6.87064	-7.07724	-44.6977
176_ETV6_ABL2-DOCK_HTVS_1-001	Imatinib	-6.87064	-7.07724	-44.6977
176_ETV6_ABL2-DOCK_HTVS_1-001	Imatinib	-6.87064	-7.07724	-44.6977
176_ETV6_ABL2-DOCK_HTVS_1-001	Acalabrutinib	-6.7388	-6.7529	-54.5237
176_ETV6_ABL2-DOCK_HTVS_1-001	Acalabrutinib	-6.7388	-6.7529	-54.5237
176_ETV6_ABL2-DOCK_HTVS_1-001	Dacomitinib	-6.71161	-8.461210000000001	-47.0167
176_ETV6_ABL2-DOCK_HTVS_1-001	Dacomitinib	-6.71161	-8.461210000000001	-47.0167
176_ETV6_ABL2-DOCK_HTVS_1-001	Dacomitinib	-6.71081	-8.461210000000001	-47.0167
176_ETV6_ABL2-DOCK_HTVS_1-001	Avapritinib	-6.48682	-6.8181199999999995	-44.9969
176_ETV6_ABL2-DOCK_HTVS_1-001	Avapritinib	-6.48682	-6.8181199999999995	-44.9969
176_ETV6_ABL2-DOCK_HTVS_1-001	Avapritinib	-6.48682	-6.8181199999999995	-44.9969

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Kinase-Substrate Information of ETV6_ABL2

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
ABL2	P42684	human	CAT	P04040	Y231	NANGEAVyCkFHYkT	Catalase
ABL2	P42684	human	HRAS	P01112	Y137	AQDLARSyGIPYIEt	Ras
ABL2	P42684	human	CRK	P46108	Y221	GGPEPGPyAQPsVNt
ABL2	P42684	human	MAPT	P10636-8	Y310	GGsVQIVykPVDLsk	Tubulin-binding
ABL2	P42684	human	ABL2	P42684	Y439	RLMtGDtytAHAGAk	PK_Tyr_Ser-Thr
ABL2	P42684	human	PDGFRB	P09619	Y686	IITEyCRyGDLVDyL	PK_Tyr_Ser-Thr
ABL2	P42684	human	GPX1	P07203	Y98	EILNSLkyVRPGGGF	GSHPx
ABL2	P42684	human	MICAL2	O94851	Y463	INkNFEQyTLDPGTR
ABL2	P42684	human	LGALS3	P17931	Y79	GAPAPGVyPGPPSGP
ABL2	P42684	human	MICAL2	O94851	Y488	PHQVKHLyITKELEH
ABL2	P42684	human	ABL2	P42684	Y261	GLVTTLHyPAPKCNK
ABL2	P42684	human	CEBPB	P17676	Y78	RAIDFsPyLEPLGAP
ABL2	P42684	human	IRF3	Q14653	Y292	rLGHCHTyWAVSEEL	IRF-3
ABL2	P42684	human	CAT	P04040	Y386	yRARVANyQRDGPMC	Catalase
ABL2	P42684	human	PSMA7	O14818	Y153	QTDPsGtyHAWkANA	Proteasome
ABL2	P42684	human	LGALS3	P17931	Y118	AGPLIVPyNLPLPGG	Gal-bind_lectin
ABL2	P42684	human	MAPT	P10636-8	Y394	DHGAEIVyKsPVVsG
ABL2	P42684	human	WWTR1	Q9GZV5	Y321	sGLGLGCySVPTtPE
ABL2	P42684	human	MAPT	P10636-8	Y197	KsGDRsGyssPGsPG
ABL2	P42684	human	ITGB1	P05556	Y783	DtGENPIyksAVttV	Integrin_b_cyt
ABL2	P42684	human	SIVA1	O15304	Y34	RGVCAERySQEVFEk	Siva
ABL2	P42684	human	MICAL2	O94851	Y445	LAERESLyRLLPQTT

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
ABL2	ID	Description	0.00e+00
ABL2	GO:0010863	positive regulation of phospholipase C activity	1.90e-03
ABL2	GO:1900274	regulation of phospholipase C activity	1.90e-03
ABL2	GO:0010518	positive regulation of phospholipase activity	2.54e-03
ABL2	GO:0010517	regulation of phospholipase activity	2.82e-03
ABL2	GO:0060193	positive regulation of lipase activity	2.82e-03
ABL2	GO:0000302	response to reactive oxygen species	2.92e-03
ABL2	GO:1903829	positive regulation of protein localization	3.11e-03
ABL2	GO:0043086	negative regulation of catalytic activity	3.11e-03
ABL2	GO:0072593	reactive oxygen species metabolic process	3.11e-03
ABL2	GO:0060191	regulation of lipase activity	3.11e-03
ABL2	GO:0009650	UV protection	3.67e-03
ABL2	GO:0090280	positive regulation of calcium ion import	5.18e-03
ABL2	GO:0042542	response to hydrogen peroxide	5.18e-03
ABL2	GO:1905477	positive regulation of protein localization to membrane	5.24e-03
ABL2	GO:0032956	regulation of actin cytoskeleton organization	6.73e-03
ABL2	GO:0071675	regulation of mononuclear cell migration	6.73e-03
ABL2	GO:0007265	Ras protein signal transduction	6.73e-03
ABL2	GO:0010288	response to lead ion	6.73e-03
ABL2	GO:0035024	negative regulation of Rho protein signal transduction	6.73e-03
ABL2	GO:1902473	regulation of protein localization to synapse	7.03e-03
ABL2	GO:0061041	regulation of wound healing	7.26e-03
ABL2	GO:1904375	regulation of protein localization to cell periphery	7.56e-03
ABL2	GO:0032970	regulation of actin filament-based process	7.89e-03
ABL2	GO:0033598	mammary gland epithelial cell proliferation	7.89e-03
ABL2	GO:0090218	positive regulation of lipid kinase activity	7.89e-03
ABL2	GO:0050900	leukocyte migration	8.69e-03
ABL2	GO:0006979	response to oxidative stress	8.70e-03
ABL2	GO:0030010	establishment of cell polarity	8.72e-03
ABL2	GO:0007159	leukocyte cell-cell adhesion	9.38e-03
ABL2	GO:0042744	hydrogen peroxide catabolic process	9.38e-03
ABL2	GO:0042060	wound healing	9.38e-03
ABL2	GO:0009314	response to radiation	9.40e-03
ABL2	GO:0090279	regulation of calcium ion import	9.40e-03
ABL2	GO:0051897	positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	9.40e-03
ABL2	GO:1903034	regulation of response to wounding	9.45e-03
ABL2	GO:1905475	regulation of protein localization to membrane	1.05e-02
ABL2	GO:0046578	regulation of Ras protein signal transduction	1.05e-02
ABL2	GO:0006935	chemotaxis	1.11e-02
ABL2	GO:0042330	taxis	1.11e-02
ABL2	GO:0043550	regulation of lipid kinase activity	1.12e-02
ABL2	GO:0055001	muscle cell development	1.15e-02
ABL2	GO:0007264	small GTPase mediated signal transduction	1.22e-02
ABL2	GO:0050777	negative regulation of immune response	1.26e-02
ABL2	GO:0071674	mononuclear cell migration	1.27e-02
ABL2	GO:1990090	cellular response to nerve growth factor stimulus	1.34e-02
ABL2	GO:0051346	negative regulation of hydrolase activity	1.34e-02
ABL2	GO:0043666	regulation of phosphoprotein phosphatase activity	1.34e-02
ABL2	GO:0046580	negative regulation of Ras protein signal transduction	1.34e-02
ABL2	GO:0070509	calcium ion import	1.34e-02

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Related Drugs to ETV6_ABL2

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 ETV6-ABL2 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 ETV6_ABL2

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

Hgene	Tgene	Disease	Source	PMID
ETV6	ABL2	Breast Invasive Ductal Carcinoma	MyCancerGenome
ETV6	ABL2	Invasive Breast Carcinoma	MyCancerGenome
ETV6	ABL2	Lung Adenocarcinoma	MyCancerGenome
ETV6	ABL2	Appendix Adenocarcinoma	MyCancerGenome
ETV6	ABL2	Colon Adenocarcinoma	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
Hgene	ETV6	C4015537	THROMBOCYTOPENIA 5	4	CTD_human;GENOMICS_ENGLAND;UNIPROT
Hgene	ETV6	C0023485	Precursor B-Cell Lymphoblastic Leukemia-Lymphoma	3	CTD_human
Hgene	ETV6	C0040034	Thrombocytopenia	3	CTD_human;GENOMICS_ENGLAND
Hgene	ETV6	C0023480	Leukemia, Myelomonocytic, Chronic	2	ORPHANET
Hgene	ETV6	C1332965	Congenital Mesoblastic Nephroma	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