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Center for Computational Systems Medicine level3
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Fusion Gene Summary

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Fusion Gene Sample Information

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Fusion ORF Analysis

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Fusion Amino Acid Sequences

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Fusion Protein Functional Features

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Fusion Protein Structure

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pLDDT scores

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Ramachandran Plot of Fusion Protein Structure

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Potential Active Site Information

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Potentially Interacting Small Molecules through Virtual Screening

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Biochemical Features of Small Molecules with ADME

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Drug Toxicity Information

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Fusion Protein-Protein Interaction

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Related drugs with this fusion protein

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Related disease with this fusion protein

Fusion Protein:ETV6-ABL1

Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ETV6-ABL1
FusionPDB ID: 27697
FusionGDB2.0 ID: 27697
HgeneTgene
Gene symbol

ETV6

ABL1

Gene ID

2120

25

Gene nameETS variant transcription factor 6ABL proto-oncogene 1, non-receptor tyrosine kinase
SynonymsTEL|TEL/ABL|THC5ABL|BCR-ABL|CHDSKM|JTK7|bcr/abl|c-ABL|c-ABL1|p150|v-abl
Cytomap

12p13.2

9q34.12

Type of geneprotein-codingprotein-coding
Descriptiontranscription factor ETV6ETS translocation variant 6ETS variant 6ETS-related protein Tel1TEL1 oncogeneets variant gene 6 (TEL oncogene)tyrosine-protein kinase ABL1ABL protooncogene 1 nonreceptor tyrosine kinaseAbelson tyrosine-protein kinase 1bcr/c-abl oncogene proteinc-abl oncogene 1, receptor tyrosine kinaseproto-oncogene c-Ablproto-oncogene tyrosine-protein kinase ABL1truncated
Modification date2020031320200327
UniProtAcc

P41212

P00519

Ensembl transtripts involved in fusion geneENST idsENST00000396373, ENST00000544715, 
ENST00000318560, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score59 X 37 X 25=5457521 X 149 X 8=25032
# samples 58154
** MAII scorelog2(58/54575*10)=-6.55604351475058
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(154/25032*10)=-4.02277130765866
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context (manual curation of fusion genes in FusionPDB)

PubMed: ETV6 [Title/Abstract] AND ABL1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ETV6(12006495)-ABL1(133729449), # samples:2
Anticipated loss of major functional domain due to fusion event.ETV6-ABL1 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
ETV6-ABL1 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
ETV6-ABL1 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
ETV6-ABL1 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneETV6

GO:0000122

negative regulation of transcription by RNA polymerase II

10514502

TgeneABL1

GO:0006974

cellular response to DNA damage stimulus

15657060

TgeneABL1

GO:0006975

DNA damage induced protein phosphorylation

18280240

TgeneABL1

GO:0018108

peptidyl-tyrosine phosphorylation

7590236|9144171|10713049|11121037

TgeneABL1

GO:0038083

peptidyl-tyrosine autophosphorylation

10518561

TgeneABL1

GO:0042770

signal transduction in response to DNA damage

9037071|15657060

TgeneABL1

GO:0043065

positive regulation of apoptotic process

9037071

TgeneABL1

GO:0046777

protein autophosphorylation

10713049

TgeneABL1

GO:0050731

positive regulation of peptidyl-tyrosine phosphorylation

15657060

TgeneABL1

GO:0051353

positive regulation of oxidoreductase activity

12893824

TgeneABL1

GO:0051444

negative regulation of ubiquitin-protein transferase activity

20823226

TgeneABL1

GO:0070301

cellular response to hydrogen peroxide

10713049

TgeneABL1

GO:0071103

DNA conformation change

9558345

TgeneABL1

GO:0071901

negative regulation of protein serine/threonine kinase activity

11121037

TgeneABL1

GO:1990051

activation of protein kinase C activity

10713049

TgeneABL1

GO:2001020

regulation of response to DNA damage stimulus

9461559


check buttonFusion 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.
all structure

check buttonFusion gene breakpoints across ABL1 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Gene Sample Information

check buttonFusion gene information from FusionGDB2.0.
check button Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4acute undifferentiated leukemia;acute myeloid leukemia;acute myeloblastic leukemia;acute myeloblastic leukemia with maturation;chronic myeloid leukemia;atypical chronic myeloid leukemia; acute lymphoblastic leukemia/lymphoblastic lymphoma;de novo acute noZ35761ETV6chr12

12006495

ABL1chr9

133729449
ChimerKB3..ETV6chr12

12022903

+ABL1chr9

133729450

+
ChiTaRS5.0N/AZ35761ETV6chr12

12006495

+ABL1chr9

133729449

+


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Fusion ORF Analysis


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)
ENST00000396373ETV6chr1212022903+ENST00000318560ABL1chr9133729450+6589128327445961440
ENST00000396373ETV6chr1212006495ENST00000318560ABL1chr9133729449604373727440501258

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000396373ENST00000318560ETV6chr1212006495ABL1chr91337294490.0026299010.9973701

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Fusion Amino Acid Sequences


check button For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

>27697_27697_1_ETV6-ABL1_ETV6_chr12_12006495_ENST00000396373_ABL1_chr9_133729449_ENST00000318560_length(amino acids)=1258AA_BP=154
MSETPAQCSIKQERISYTPPESPVPSYASSTPLHVPVPRALRMEEDSIRLPAHLRLQPIYWSRDDVAQWLKWAENEFSLRPIDSNTFEMN
GKALLLLTKEDFRYRSPHSGDVLYELLQHILKQRKPRILFSPFFHPGNSIHTQPEVILHQNHEEEALQRPVASDFEPQGLSEAARWNSKE
NLLAGPSENDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKNGQGWVPSNYITPVNSLEKHSWYHGPVSRNAAEYLLS
SGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHHSTVADGLITTLHYPAPKRNKPTVYGVSPNY
DKWEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTYGN
LLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPESLA
YNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQESSI
SDEVEKELGKQGVRGAVSTLLQAPELPTKTRTSRRAAEHRDTTDVPEMPHSKGQGESDPLDHEPAVSPLLPRKERGPPEGGLNEDERLLP
KDKKTNLFSALIKKKKKTAPTPPKRSSSFREMDGQPERRGAGEEEGRDISNGALAFTPLDTADPAKSPKPSNGAGVPNGALRESGGSGFR
SPHLWKKSSTLTSSRLATGEEEGGGSSSKRFLRSCSASCVPHGAKDTEWRSVTLPRDLQSTGRQFDSSTFGGHKSEKPALPRKRAGENRS
DQVTRGTVTPPPRLVKKNEEAADEVFKDIMESSPGSSPPNLTPKPLRRQVTVAPASGLPHKEEAGKGSALGTPAAAEPVTPTSKAGSGAP
GGTSKGPAEESRVRRHKHSSESPGRDKGKLSRLKPAPPPPPAASAGKAGGKPSQSPSQEAAGEAVLGAKTKATSLVDAVNSDAAKPSQPG
EGLKKPVLPATPKPQSAKPSGTPISPAPVPSTLPSASSALAGDQPSSTAFIPLISTRVSLRKTRQPPERIASGAITKGVVLDSTEALCLA

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

>27697_27697_2_ETV6-ABL1_ETV6_chr12_12022903_ENST00000396373_ABL1_chr9_133729450_ENST00000318560_length(amino acids)=1440AA_BP=336
MSETPAQCSIKQERISYTPPESPVPSYASSTPLHVPVPRALRMEEDSIRLPAHLRLQPIYWSRDDVAQWLKWAENEFSLRPIDSNTFEMN
GKALLLLTKEDFRYRSPHSGDVLYELLQHILKQRKPRILFSPFFHPGNSIHTQPEVILHQNHEEDNCVQRTPRPSVDNVHHNPPTIELLH
RSRSPITTNHRPSPDPEQRPLRSPLDNMIRRLSPAERAQGPRPHQENNHQESYPLSVSPMENNHCPASSESHPKPSSPRQESTRVIQLMP
SPIMHPLILNPRHSVDFKQSRLSEDGLHREGKPINLSHREDLAYMNHIMVSVSPPEEHAMPIGRIAEALQRPVASDFEPQGLSEAARWNS
KENLLAGPSENDPNLFVALYDFVASGDNTLSITKGEKLRVLGYNHNGEWCEAQTKNGQGWVPSNYITPVNSLEKHSWYHGPVSRNAAEYL
LSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSESRFNTLAELVHHHSTVADGLITTLHYPAPKRNKPTVYGVSP
NYDKWEMERTDITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMTY
GNLLDYLRECNRQEVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPIKWTAPES
LAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIHQAFETMFQES
SISDEVEKELGKQGVRGAVSTLLQAPELPTKTRTSRRAAEHRDTTDVPEMPHSKGQGESDPLDHEPAVSPLLPRKERGPPEGGLNEDERL
LPKDKKTNLFSALIKKKKKTAPTPPKRSSSFREMDGQPERRGAGEEEGRDISNGALAFTPLDTADPAKSPKPSNGAGVPNGALRESGGSG
FRSPHLWKKSSTLTSSRLATGEEEGGGSSSKRFLRSCSASCVPHGAKDTEWRSVTLPRDLQSTGRQFDSSTFGGHKSEKPALPRKRAGEN
RSDQVTRGTVTPPPRLVKKNEEAADEVFKDIMESSPGSSPPNLTPKPLRRQVTVAPASGLPHKEEAGKGSALGTPAAAEPVTPTSKAGSG
APGGTSKGPAEESRVRRHKHSSESPGRDKGKLSRLKPAPPPPPAASAGKAGGKPSQSPSQEAAGEAVLGAKTKATSLVDAVNSDAAKPSQ
PGEGLKKPVLPATPKPQSAKPSGTPISPAPVPSTLPSASSALAGDQPSSTAFIPLISTRVSLRKTRQPPERIASGAITKGVVLDSTEALC
LAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNKFAFREAINKLENNLRELQICPATAGSGPAATQDFSKLLSSVKEISDIVQR

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

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Fusion Protein Functional Features


check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr12:12006495/chr9:133729449)
- 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.
FGviewer

check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
ETV6

P41212

ABL1

P00519

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 a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 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. Regulates T-cell differentiation in a TBX21-dependent manner. Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}.

check buttonRetention 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 protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneETV6chr12:12006495chr9:133729449ENST00000396373+4840_124154.33333333333334453.0DomainPNT
TgeneABL1chr12:12006495chr9:133729449ENST00000318560011605_60926.3333333333333321131.0Compositional biasNote=Poly-Lys
TgeneABL1chr12:12006495chr9:133729449ENST00000318560011782_101926.3333333333333321131.0Compositional biasNote=Pro-rich
TgeneABL1chr12:12006495chr9:133729449ENST00000318560011897_90326.3333333333333321131.0Compositional biasNote=Poly-Pro
TgeneABL1chr12:12006495chr9:133729449ENST00000318560011127_21726.3333333333333321131.0DomainSH2
TgeneABL1chr12:12006495chr9:133729449ENST00000318560011242_49326.3333333333333321131.0DomainProtein kinase
TgeneABL1chr12:12006495chr9:133729449ENST0000031856001161_12126.3333333333333321131.0DomainSH3
TgeneABL1chr12:12006495chr9:133729449ENST000003185600111090_110026.3333333333333321131.0MotifNuclear export signal
TgeneABL1chr12:12006495chr9:133729449ENST00000318560011381_40526.3333333333333321131.0MotifNote=Kinase activation loop
TgeneABL1chr12:12006495chr9:133729449ENST00000318560011709_71526.3333333333333321131.0MotifNuclear localization signal 2
TgeneABL1chr12:12006495chr9:133729449ENST00000318560011762_76926.3333333333333321131.0MotifNuclear localization signal 3
TgeneABL1chr12:12006495chr9:133729449ENST00000318560011248_25626.3333333333333321131.0Nucleotide bindingNote=ATP
TgeneABL1chr12:12006495chr9:133729449ENST00000318560011316_32226.3333333333333321131.0Nucleotide bindingNote=ATP
TgeneABL1chr12:12006495chr9:133729449ENST00000318560011869_96826.3333333333333321131.0RegionDNA-binding
TgeneABL1chr12:12006495chr9:133729449ENST00000318560011953_113026.3333333333333321131.0RegionNote=F-actin-binding

- Not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
HgeneETV6chr12:12006495chr9:133729449ENST00000396373+48339_420154.33333333333334453.0DNA bindingETS
TgeneABL1chr12:12006495chr9:133729449ENST0000031856001118_2226.3333333333333321131.0Compositional biasNote=Poly-Ser
TgeneABL1chr12:12006495chr9:133729449ENST000003185600111_6026.3333333333333321131.0RegionNote=CAP


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Fusion Protein Structures

check button PDB and CIF files of the predicted 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.
Fusion protein PDB link (fusion AA seq ID in FusionPDB)HgeneHchrHbpHstrandTgeneTchrTbpTstrandAA seqLen(AA seq)
PDB file (926)CIF file (926) >>>926.cifETV6chr1212022903+ABL1chr9133729450+
MSETPAQCSIKQERISYTPPESPVPSYASSTPLHVPVPRALRMEEDSIRL
PAHLRLQPIYWSRDDVAQWLKWAENEFSLRPIDSNTFEMNGKALLLLTKE
DFRYRSPHSGDVLYELLQHILKQRKPRILFSPFFHPGNSIHTQPEVILHQ
NHEEDNCVQRTPRPSVDNVHHNPPTIELLHRSRSPITTNHRPSPDPEQRP
LRSPLDNMIRRLSPAERAQGPRPHQENNHQESYPLSVSPMENNHCPASSE
SHPKPSSPRQESTRVIQLMPSPIMHPLILNPRHSVDFKQSRLSEDGLHRE
GKPINLSHREDLAYMNHIMVSVSPPEEHAMPIGRIAEALQRPVASDFEPQ
GLSEAARWNSKENLLAGPSENDPNLFVALYDFVASGDNTLSITKGEKLRV
LGYNHNGEWCEAQTKNGQGWVPSNYITPVNSLEKHSWYHGPVSRNAAEYL
LSSGINGSFLVRESESSPGQRSISLRYEGRVYHYRINTASDGKLYVSSES
RFNTLAELVHHHSTVADGLITTLHYPAPKRNKPTVYGVSPNYDKWEMERT
DITMKHKLGGGQYGEVYEGVWKKYSLTVAVKTLKEDTMEVEEFLKEAAVM
KEIKHPNLVQLLGVCTREPPFYIITEFMTYGNLLDYLRECNRQEVNAVVL
LYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTG
DTYTAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPY
PGIDLSQVYELLEKDYRMERPEGCPEKVYELMRACWQWNPSDRPSFAEIH
QAFETMFQESSISDEVEKELGKQGVRGAVSTLLQAPELPTKTRTSRRAAE
HRDTTDVPEMPHSKGQGESDPLDHEPAVSPLLPRKERGPPEGGLNEDERL
LPKDKKTNLFSALIKKKKKTAPTPPKRSSSFREMDGQPERRGAGEEEGRD
ISNGALAFTPLDTADPAKSPKPSNGAGVPNGALRESGGSGFRSPHLWKKS
STLTSSRLATGEEEGGGSSSKRFLRSCSASCVPHGAKDTEWRSVTLPRDL
QSTGRQFDSSTFGGHKSEKPALPRKRAGENRSDQVTRGTVTPPPRLVKKN
EEAADEVFKDIMESSPGSSPPNLTPKPLRRQVTVAPASGLPHKEEAGKGS
ALGTPAAAEPVTPTSKAGSGAPGGTSKGPAEESRVRRHKHSSESPGRDKG
KLSRLKPAPPPPPAASAGKAGGKPSQSPSQEAAGEAVLGAKTKATSLVDA
VNSDAAKPSQPGEGLKKPVLPATPKPQSAKPSGTPISPAPVPSTLPSASS
ALAGDQPSSTAFIPLISTRVSLRKTRQPPERIASGAITKGVVLDSTEALC
LAISRNSEQMASHSAVLEAGKNLYTFCVSYVDSIQQMRNKFAFREAINKL
1440
3D view using mol* of 926 (AA BP:)


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pLDDT score distribution

check button pLDDT score distribution of the predicted wild-type structures of two partner proteins from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
ETV6_pLDDT.png
all structure
all structure
ABL1_pLDDT.png
all structure
all structure

check button pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
ETV6_ABL1_926_pLDDT_and_active_sites.png (AA BP:)
all structure
ETV6_ABL1_926_violinplot.png (AA BP:)
all structure


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Ramachandran Plot of Fusion Protein Structure


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.
Fusion AA seq ID in FusionPDB and their Ramachandran plots

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Potential Active Site Information


check button The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.
Fusion AA seq ID in FusionPDBSite scoreSizeD scoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues
9261.061901.1061800.5160.7581.0531.5310.7372.0761.027Chain A: 642,643,646,647,650,651,654,739,740,742,7
43,744,745,747,771,772,773,774,775,778,803,812,816
,820

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Potentially Interacting Small Molecules through Virtual Screening


check button The FDA-approved small molecule library molecules were subjected to virtual screening using the Glide.
Fusion AA seq ID in FusionPDBZINC IDDrugBank IDDrug nameDocking scoreGlide gscore
926ZINC000001530638DB00472Fluoxetine-8.87535-8.87585
926ZINC000000000850DB00744Zileuton-8.66624-8.68484
926ZINC000000020243DB00861Diflunisal-8.62048-8.62048
926ZINC000011681534DB04861Nebivolol-8.43116-8.45096
926ZINC000043206370DB11793Niraparib-8.29133-8.29133
926ZINC000035342789DB00323Tolcapone-6.65588-8.19288
926ZINC000004213946DB04861Nebivolol-8.16276-8.18256
926ZINC000000001644DB06795Mafenide-8.14513-8.17473
926ZINC000000085733DB00181Baclofen-8.08837-8.08837
926AvapritinibDB00181-6.91248-8.00548
926AsciminibDB00181-7.53678-8.00178
926ZINC000000004321DB00909Zonisamide-7.99504-7.99644
926ZINC000003816287DB06626Axitinib-7.9681-7.9713
926ZINC000000897258DB00983Formoterol-7.95725-7.96945
926ZINC000000083315DB00150Tryptophan-7.90933-7.90933
926ZINC000005844788DB04861Nebivolol-7.88702-7.90682
926ZINC000003872994DB01026Ketoconazole-7.5428-7.8675
926ZINC000000537822DB00502Haloperidol-7.82221-7.83561
926ZINC000000018635DB00998Frovatriptan-7.83256-7.83306
926ZINC000000006481DB00740Riluzole-7.81985-7.81985

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check button Drug information from DrugBank of the top 20 interacting small molecules.
ZINC IDDrugBank IDDrug nameDrug typeSMILESDrug group
ZINC000001530638DB00472FluoxetineSmall moleculeCNCCC(OC1=CC=C(C=C1)C(F)(F)F)C1=CC=CC=C1Approved|Vet_approved
ZINC000000020243DB00861DiflunisalSmall moleculeOC(=O)C1=C(O)C=CC(=C1)C1=C(F)C=C(F)C=C1Approved|Investigational
ZINC000011681534DB04861NebivololSmall moleculeOC(CNCC(O)C1CCC2=C(O1)C=CC(F)=C2)C1CCC2=C(O1)C=CC(F)=C2Approved|Investigational
ZINC000043206370DB11793NiraparibSmall moleculeNC(=O)C1=CC=CC2=CN(N=C12)C1=CC=C(C=C1)[C@@H]1CCCNC1Approved|Investigational
ZINC000035342789DB00323TolcaponeSmall moleculeCC1=CC=C(C=C1)C(=O)C1=CC(=C(O)C(O)=C1)[N+]([O-])=OApproved|Withdrawn
ZINC000000001644DB06795MafenideSmall moleculeNCC1=CC=C(C=C1)S(N)(=O)=OApproved|Vet_approved
ZINC000000085733DB00181BaclofenSmall moleculeNCC(CC(O)=O)C1=CC=C(Cl)C=C1Approved
ZINC000000004321DB00909ZonisamideSmall moleculeNS(=O)(=O)CC1=NOC2=CC=CC=C12Approved|Investigational
ZINC000000897258DB00983FormoterolSmall moleculeCOC1=CC=C(CC(C)NCC(O)C2=CC(NC=O)=C(O)C=C2)C=C1Approved|Investigational
ZINC000000083315DB00150TryptophanSmall moleculeN[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=OApproved|Nutraceutical|Withdrawn
ZINC000000537822DB00502HaloperidolSmall moleculeOC1(CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1)C1=CC=C(Cl)C=C1Approved
ZINC000000018635DB00998FrovatriptanSmall moleculeCN[C@@H]1CCC2=C(C1)C1=C(N2)C=CC(=C1)C(N)=OApproved|Investigational
ZINC000000006481DB00740RiluzoleSmall moleculeNC1=NC2=C(S1)C=C(OC(F)(F)F)C=C2Approved|Investigational

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Biochemical Features of Small Molecules


check button ADME (Absorption, Distribution, Metabolism, and Excretion) of drugs using QikProp(v3.9)
ZINC IDmol_MWdipoleSASAFOSAFISAPISAWPSAvolumedonorHBaccptHBIPHuman Oral AbsorptionPercent Human Oral AbsorptionRule Of FiveRule Of Three
ZINC000001530638309.3314.533597.054163.84824.069291.6117.5371015.41212.259.42310000
ZINC000000000850236.2885.297457.64285.783137.035198.52336.3755.01533.78.91375.35100
ZINC000000000850236.2885.297450.83785.532135.419201.89327.994746.83933.78.57376.55500
ZINC000000020243250.2018.261459.0810144.436231.00583.64751.87911.759.879386.60100
ZINC000011681534405.4412.335727.789280.70885.7267.62193.761272.95136.49.228395.43300
ZINC000011681534405.4416.385707.131273.32277.744262.30193.7651256.16536.49.073396.54300
ZINC000043206370320.3933.754607.688185.794143.417278.47601055.805358.546376.7200
ZINC000035342789273.2453.817507.14288.195223.7195.2470847.54824.59.508367.93400
ZINC000035342789273.2455.603506.16988.195222.204195.7690846.89124.59.828368.23300
ZINC000035342789273.2453.5506.84288.2223.976194.6650847.73424.59.758367.88100
ZINC000004213946405.4415.213712.775270.54687.695260.77393.7611260.0136.49.251394.55500
ZINC000004213946405.4413.313660.255261.06875.583229.84493.761216.09336.49.124395.53300
ZINC000000001644186.2287.234386.68948.38203.852132.6441.813608.20845.59.936246.46100
ZINC000000001644186.2288.543384.51348.79201.796132.1141.813604.74745.59.902246.800
ZINC000000085733213.6633.613420.9180.54149.736119.12871.506697.141339.549248.77600
ZINC000000004321212.2236.978398.51740.32185.554172.6440642.453269.667365.95900
ZINC000003816287386.476.702685.418106.992114.211433.50130.7151211.93124.58.542310001
ZINC000000897258344.417.083674.489258.736187.926227.82601168.66647.28.855265.22200
ZINC000000897258344.414.982586.764251.201138.136197.42601091.39147.28.677373.27800
ZINC000000083315204.2283.132419.18346.221166.648206.3140687.589438.088242.50601
ZINC000005844788405.4411.102724.6273.70387.795269.33993.7621272.25736.49.305394.99500
ZINC000005844788405.4413.204688.14293.00460.761240.61593.761244.95936.49.151310000
ZINC000003872994531.4382.643843.259319.7980.343323.603119.5231551.55108.258.241392.5310
ZINC000003872994531.4386.575844.887311.95681.254336.082115.5941549.96608.258.233392.40510
ZINC000003872994531.4385.578860.223333.68678.629331.472116.4371569.56508.259.26392.88110
ZINC000003872994531.4385.486858.441334.02479.024328.466116.9271566.07508.259.254392.76510
ZINC000000537822375.873.194684.196209.60368.864287.369118.361199.71414.759.391310000
ZINC000000537822375.872.935674.977199.70483.514273.376118.3821195.36414.759.357310000
ZINC000000537822375.874.967684.834209.15469.652287.663118.3651206.22314.759.266310000
ZINC000000018635243.3087.2492.762217.467154.534120.7610833.223448.296366.4100
ZINC000000006481234.1965.283393.4351.90387.083133.293171.157623.3228.622310000


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Drug Toxicity Information


check button Toxicity information of individual drugs using eToxPred
ZINC IDSmileSurface AccessibilityToxicity
ZINC000001530638CNCC[C@@H](Oc1ccc(C(F)(F)F)cc1)c1ccccc10.2349576480.361924168
ZINC000000000850C[C@@H](c1cc2ccccc2s1)N(O)C(N)=O0.1363358820.223511692
ZINC000000020243O=C(O)c1cc(-c2ccc(F)cc2F)ccc1O0.4404093730.371648269
ZINC000011681534O[C@H](CNC[C@@H](O)[C@@H]1CCc2cc(F)ccc2O1)[C@@H]1CCc2cc(F)ccc2O10.0555500820.198725964
ZINC000043206370NC(=O)c1cccc2cn(-c3ccc([C@@H]4CCCNC4)cc3)nc120.158103060.243905197
ZINC000035342789Cc1ccc(C(=O)c2cc(O)c(O)c([N+](=O)[O-])c2)cc10.3597350140.498165074
ZINC000004213946O[C@@H](CNC[C@@H](O)[C@@H]1CCc2cc(F)ccc2O1)[C@@H]1CCc2cc(F)ccc2O10.0555500820.198725964
ZINC000000001644NCc1ccc(S(N)(=O)=O)cc10.4977746040.389970963
ZINC000000085733NC[C@@H](CC(=O)O)c1ccc(Cl)cc10.2512033360.372196692
ZINC000000004321NS(=O)(=O)Cc1noc2ccccc120.2545692540.46155884
ZINC000003816287CNC(=O)c1ccccc1Sc1ccc2c(/C=C/c3ccccn3)n[nH]c2c10.198742650.230949688
ZINC000000897258COc1ccc(C[C@@H](C)NC[C@@H](O)c2ccc(O)c(NC=O)c2)cc10.1338630780.246482573
ZINC000000083315N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O0.2723590650.412747788
ZINC000005844788O[C@@H](CNC[C@@H](O)[C@H]1CCc2cc(F)ccc2O1)[C@@H]1CCc2cc(F)ccc2O10.0555500820.198725964
ZINC000003872994CC(=O)N1CCN(c2ccc(OC[C@H]3CO[C@@](Cn4ccnc4)(c4ccc(Cl)cc4Cl)O3)cc2)CC10.0873932720.387082142
ZINC000000537822O=C(CCCN1CCC(O)(c2ccc(Cl)cc2)CC1)c1ccc(F)cc10.3253894170.260800529
ZINC000000018635CN[C@@H]1CCc2[nH]c3ccc(C(N)=O)cc3c2C10.156787310.476568578
ZINC000000006481Nc1nc2ccc(OC(F)(F)F)cc2s10.2910020260.384188974


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Fusion Protein-Protein Interaction


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page.


check button Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160)
GenePPI interactors
ETV6KAT5, GAB2, ETV6, GRB2, CRKL, ACTA1, HDAC9, FLI1, FBXL6, SKP1, L3MBTL1, IRF8, NCOR1, SIN3A, HDAC3, UBE2I, ELAVL1, PDGFRB, SUMO1, SOCS1, SOCS3, TRAF3, SOX2, HDAC6, PIN1, AP1M1, WDYHV1, LRP6, LRP5, NID2, ETV7, USP7, VPS26B, NFATC2, EGLN3, NKX2-1, TRAF2, AXIN1, ESR2, LMNA, TP53BP1, BRCA1, MDC1, KIAA1429, WWP2, ESR1, BRD4, NFE2L2, MAD2L1, B4GALT2, KLHL9, KLHL13, SUMO2, ARHGAP32, SEC16A, XPOT, PIAS2, CEP152, NUP214, NUP62, NUP98, SEC13, RBM11, ECH1, ZNF146, TRIP6, CEP85, NUP54, TAB3, ALMS1, CEP192, PPIL4, RQCD1, SDCCAG3, NUP88, TBL1Y, KIAA1671, C2orf44, GRPEL1, TNRC6C, MID1IP1, CYLD, ZMYM2, LIMD1, SPATA2, TNRC6B, TIMM13, FLOT1, LGALS3BP, FLOT2, HNRNPUL1,


check button Protein-protein interactors based on sequence similarity (STRING)
GeneSTRING network
ETV6all structure
ABL1all structure


check button - Retained interactions in fusion protein (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost interactions due to fusion (protein functional feature from UniProt).
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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Related Drugs to ETV6-ABL1


check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID
ETV6ABL1Nilotinib Or DasatinibPubMed32279331

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Related Diseases to ETV6-ABL1


check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID
ETV6ABL1Myeloid NeoplasmsPubMed32279331
ETV6ABL1Breast Invasive Ductal CarcinomaMyCancerGenome
ETV6ABL1Invasive Breast CarcinomaMyCancerGenome
ETV6ABL1Lung AdenocarcinomaMyCancerGenome
ETV6ABL1Appendix AdenocarcinomaMyCancerGenome
ETV6ABL1AstrocytomaMyCancerGenome

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneETV6C4015537THROMBOCYTOPENIA 54CTD_human;GENOMICS_ENGLAND;UNIPROT
HgeneETV6C0023485Precursor B-Cell Lymphoblastic Leukemia-Lymphoma3CTD_human
HgeneETV6C0040034Thrombocytopenia3CTD_human;GENOMICS_ENGLAND
HgeneETV6C0023480Leukemia, Myelomonocytic, Chronic2ORPHANET
HgeneETV6C1332965Congenital Mesoblastic Nephroma2ORPHANET
HgeneETV6C0006413Burkitt Lymphoma1ORPHANET
HgeneETV6C0013146Drug abuse1CTD_human
HgeneETV6C0013170Drug habituation1CTD_human
HgeneETV6C0013222Drug Use Disorders1CTD_human
HgeneETV6C0023452Childhood Acute Lymphoblastic Leukemia1CTD_human
HgeneETV6C0023453L2 Acute Lymphoblastic Leukemia1CTD_human
HgeneETV6C0023467Leukemia, Myelocytic, Acute1CGI;CTD_human;GENOMICS_ENGLAND
HgeneETV6C0029231Organic Mental Disorders, Substance-Induced1CTD_human
HgeneETV6C0038580Substance Dependence1CTD_human
HgeneETV6C0038586Substance Use Disorders1CTD_human
HgeneETV6C0087031Juvenile-Onset Still Disease1CTD_human
HgeneETV6C0236969Substance-Related Disorders1CTD_human
HgeneETV6C0238463Papillary thyroid carcinoma1ORPHANET
HgeneETV6C0376544Hematopoietic Neoplasms1CTD_human
HgeneETV6C0376545Hematologic Neoplasms1CTD_human
HgeneETV6C0740858Substance abuse problem1CTD_human
HgeneETV6C1292769Precursor B-cell lymphoblastic leukemia1ORPHANET
HgeneETV6C1510472Drug Dependence1CTD_human
HgeneETV6C1832388Platelet Disorder, Familial, with Associated Myeloid Malignancy1ORPHANET
HgeneETV6C1838656Macrocytosis, Familial1CTD_human
HgeneETV6C1961102Precursor Cell Lymphoblastic Leukemia Lymphoma1CTD_human
HgeneETV6C3495559Juvenile arthritis1CTD_human
HgeneETV6C3714758Juvenile psoriatic arthritis1CTD_human
HgeneETV6C4316881Prescription Drug Abuse1CTD_human
HgeneETV6C4552091Polyarthritis, Juvenile, Rheumatoid Factor Negative1CTD_human
HgeneETV6C4704862Polyarthritis, Juvenile, Rheumatoid Factor Positive1CTD_human
TgeneABL1C0023473Myeloid Leukemia, Chronic3CGI;CTD_human;ORPHANET
TgeneABL1C0023452Childhood Acute Lymphoblastic Leukemia2CTD_human
TgeneABL1C0023453L2 Acute Lymphoblastic Leukemia2CTD_human
TgeneABL1C1961102Precursor Cell Lymphoblastic Leukemia Lymphoma2CGI;CTD_human
TgeneABL1C0001418Adenocarcinoma1CTD_human
TgeneABL1C0003706Arachnodactyly1GENOMICS_ENGLAND
TgeneABL1C0005941Bone Diseases, Developmental1CTD_human
TgeneABL1C0006142Malignant neoplasm of breast1CTD_human
TgeneABL1C0006413Burkitt Lymphoma1ORPHANET
TgeneABL1C0014859Esophageal Neoplasms1CTD_human
TgeneABL1C0015544Failure to Thrive1CTD_human
TgeneABL1C0018798Congenital Heart Defects1CTD_human
TgeneABL1C0023903Liver neoplasms1CTD_human
TgeneABL1C0027659Neoplasms, Experimental1CTD_human
TgeneABL1C0032927Precancerous Conditions1CTD_human
TgeneABL1C0039075Syndactyly1GENOMICS_ENGLAND
TgeneABL1C0151491Congenital musculoskeletal anomalies1CTD_human
TgeneABL1C0205641Adenocarcinoma, Basal Cell1CTD_human
TgeneABL1C0205642Adenocarcinoma, Oxyphilic1CTD_human
TgeneABL1C0205643Carcinoma, Cribriform1CTD_human
TgeneABL1C0205644Carcinoma, Granular Cell1CTD_human
TgeneABL1C0205645Adenocarcinoma, Tubular1CTD_human
TgeneABL1C0265610Clinodactyly of fingers1GENOMICS_ENGLAND
TgeneABL1C0282313Condition, Preneoplastic1CTD_human
TgeneABL1C0345904Malignant neoplasm of liver1CTD_human
TgeneABL1C0546837Malignant neoplasm of esophagus1CTD_human
TgeneABL1C0596263Carcinogenesis1CTD_human
TgeneABL1C0678222Breast Carcinoma1CTD_human
TgeneABL1C1257931Mammary Neoplasms, Human1CTD_human
TgeneABL1C1292769Precursor B-cell lymphoblastic leukemia1ORPHANET
TgeneABL1C1458155Mammary Neoplasms1CTD_human
TgeneABL1C1961099Precursor T-Cell Lymphoblastic Leukemia-Lymphoma1CGI;ORPHANET
TgeneABL1C4539857CONGENITAL HEART DEFECTS AND SKELETAL MALFORMATIONS SYNDROME1GENOMICS_ENGLAND;UNIPROT
TgeneABL1C4551485Clinodactyly1GENOMICS_ENGLAND
TgeneABL1C4704874Mammary Carcinoma, Human1CTD_human