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Center for Computational Systems Medicine
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Kinase Fusion Gene Summary

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Kinase Fusion Gene Sample Information

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Kinase Fusion ORF Analysis

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Kinase Fusion Amino Acid Sequences

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Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

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Kinase Fusion Protein Structures

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Comparison of Fusion Protein Isoforms

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

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pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.

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Ramachandran Plot of Kinase Fusion Protein Structure

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Potential Active Site Information

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Virtual Screening Results

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Kinase-Substrate Information

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Related Drugs with This Kinase Fusion Protein

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Related Disease with This Kinase Fusion Protein

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Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:TNK1_CHD3

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: TNK1_CHD3
KinaseFusionDB ID: KFG6658
FusionGDB2.0 ID: KFG6658
HgeneTgene
Gene symbol

TNK1

CHD3

Gene ID

8711

1107

Gene nametyrosine kinase non receptor 1chromodomain helicase DNA binding protein 3
SynonymsKOS1Mi-2a|Mi2-ALPHA|SNIBCPS|ZFH
Cytomap

17p13.1

17p13.1

Type of geneprotein-codingprotein-coding
Descriptionnon-receptor tyrosine-protein kinase TNK1CD38 negative kinase 1chromodomain-helicase-DNA-binding protein 3ATP-dependent helicase CHD3CHD-3hZFHmi-2 autoantigen 240 kDa proteinzinc finger helicasezinc-finger helicase (Snf2-like)
Modification date2024041120240411
UniProtAcc

Q13470

Q12873

Ensembl transtripts involved in fusion geneENST idsENST00000311668, ENST00000570896, 
ENST00000576812, 
ENST00000570758, 
ENST00000330494, ENST00000358181, 
ENST00000380358, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: TNK1 [Title/Abstract] AND CHD3 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TNK1(7290776)-CHD3(7814782), # samples:2
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneTNK1

GO:0046777

protein autophosphorylation

10873601

TgeneCHD3

GO:0000122

negative regulation of transcription by RNA polymerase II

27068747

TgeneCHD3

GO:0006338

chromatin remodeling

9790534

TgeneCHD3

GO:0007051

spindle organization

17626165

TgeneCHD3

GO:0007098

centrosome cycle

17626165


check buttonKinase Fusion gene breakpoints across TNK1 (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 buttonKinase Fusion gene breakpoints across CHD3 (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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Kinase Fusion Gene Sample Information

check buttonKinase Fusion gene information.
check button 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.
SourceSampleHgeneHchrHbpTgeneTchrTbp
ChimerDB4TCGA-XJ-A83H-01ATNK1chr17

7290776

CHD3chr17

7814782



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Kinase Fusion ORF Analysis


check buttonKinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.
HenstTenstHgeneHchrHbpTgeneTchrTbpSeq length
(transcript)
Seq length
(amino acids)
ENST00000570896ENST00000380358TNK1chr177290776CHD3chr1778147823220532

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Kinase Fusion Amino Acid Sequences


check button 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

>ENST00000570896_ENST00000380358_TNK1_chr17_7290776_CHD3_chr17_7814782_length(amino acids)=532
MLPEAGSLWLLKLLRDIQLAQFYWPILEELNVTRPEHFDFVKPEDLDGIGMGRPAQRRLSEALKRLRSGPKSKNWVYKILGGFAPEHKEP
TLPSDSPRHLPEPEGGLKCLIPEGAVCRGELLGSGCFGVVHRGLWTLPSGKSVPVAVKSLRVGPEGPMGTELGDFLREVSVMMNLEHPHV
LRLHGLVLGQPLQMVMELAPLGSLHARLTAPAPTPPLLVALLCLFLRQLAGAMAYLGARGLVHRDLATRNLLLASPRTIKVADFGLVRPL
GGARGRYVMGGPRPIPYAWCAPESLRHGAFSSASDVWMFGVTLWEMFSGGEEPWAGVPPYLILQRLEDRARLPRPPLCSRALYSLALRCW
APHPADRPSFSHLEGLLQEAGPSEACCVRDVTEPGALRMETGDPITVIEGSPDSTIWKGQNGRTFKVGSFPASAVTLADAGGLPATRPVH

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Multiple Sequence Alignment of All Fusion Protein Isoforms



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Kinase 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/chr17:7290776/chr17:7814782)
- 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
TNK1

Q13470

CHD3

Q12873

FUNCTION: Involved in negative regulation of cell growth. Has tumor suppressor properties. Plays a negative regulatory role in the Ras-MAPK pathway. May function in signaling pathways utilized broadly during fetal development and more selectively in adult tissues and in cells of the lymphohematopoietic system. Could specifically be involved in phospholipid signal transduction. {ECO:0000269|PubMed:10873601, ECO:0000269|PubMed:18974114}.FUNCTION: ATP-dependent helicase that binds and distorts nucleosomal DNA (PubMed:28977666). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:9804427, PubMed:30397230, PubMed:16428440, PubMed:28977666). Involved in transcriptional repression as part of the NuRD complex (PubMed:27068747). Required for anchoring centrosomal pericentrin in both interphase and mitosis, for spindle organization and centrosome integrity (PubMed:17626165). {ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:17626165, ECO:0000269|PubMed:27068747, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:30397230, ECO:0000269|PubMed:9804427}.

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.

check button - Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt).
492497492492497492
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote
HgeneTNK17290776CHD37814782ENST000005708961013116_3771662DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
HgeneTNK17290776CHD37814782ENST000005708961013116_3771667DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
HgeneTNK17290776CHD37814782ENST000005708961114116_3771662DomainNote=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159
HgeneTNK17290776CHD37814782ENST000005708961013380_4451662DomainNote=SH3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00192
HgeneTNK17290776CHD37814782ENST000005708961013380_4451667DomainNote=SH3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00192
HgeneTNK17290776CHD37814782ENST000005708961114380_4451662DomainNote=SH3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00192


check button - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


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Kinase Fusion Protein Structures

check button 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)HenstTenstHgeneHchrHbpTgeneTchrTbpAA seqLen(AA seq)
PDB file >>>285_TNK1_CHD3ENST00000570896ENST00000380358TNK1chr177290776CHD3chr177814782
MLPEAGSLWLLKLLRDIQLAQFYWPILEELNVTRPEHFDFVKPEDLDGIGMGRPAQRRLSEALKRLRSGPKSKNWVYKILGGFAPEHKEP
TLPSDSPRHLPEPEGGLKCLIPEGAVCRGELLGSGCFGVVHRGLWTLPSGKSVPVAVKSLRVGPEGPMGTELGDFLREVSVMMNLEHPHV
LRLHGLVLGQPLQMVMELAPLGSLHARLTAPAPTPPLLVALLCLFLRQLAGAMAYLGARGLVHRDLATRNLLLASPRTIKVADFGLVRPL
GGARGRYVMGGPRPIPYAWCAPESLRHGAFSSASDVWMFGVTLWEMFSGGEEPWAGVPPYLILQRLEDRARLPRPPLCSRALYSLALRCW
APHPADRPSFSHLEGLLQEAGPSEACCVRDVTEPGALRMETGDPITVIEGSPDSTIWKGQNGRTFKVGSFPASAVTLADAGGLPATRPVH
532
3D view using mol* of 285_TNK1_CHD3
PDB file >>>HKFP_412_TNK1_CHD3ENST00000570896ENST00000380358TNK1chr177290776CHD3chr177814782
MLPEAGSLWLLKLLRDIQLAQFYWPILEELNVTRPEHFDFVKPEDLDGIGMGRPAQRRLSEALKRLRSGPKSKNWVYKILGGFAPEHKEP
TLPSDSPRHLPEPEGGLKCLIPEGAVCRGELLGSGCFGVVHRGLWTLPSGKSVPVAVKSLRVGPEGPMGTELGDFLREVSVMMNLEHPHV
LRLHGLVLGQPLQMVMELAPLGSLHARLTAPAPTPPLLVALLCLFLRQLAGAMAYLGARGLVHRDLATRNLLLASPRTIKVADFGLVRPL
GGARGRYVMGGPRPIPYAWCAPESLRHGAFSSASDVWMFGVTLWEMFSGGEEPWAGVPPYLILQRLEDRARLPRPPLCSRALYSLALRCW
APHPADRPSFSHLEGLLQEAGPSEACCVRDVTEPGALRMETGDPITVIEGSPDSTIWKGQNGRTFKVGSFPASAVTLADAGGLPATRPVH
532_TNK1_CHD3


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Comparison of Fusion Protein Isoforms

check button Superimpose the 3D Structures Among All Fusion Protein Isoforms
* Download the pdb file and open it from the molstar online viewer.

check button 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

TNK1_CHD3 does not have any known PDB structures.

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pLDDT score distribution

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.
* The blue color at the bottom marks the best active site residues.


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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.
Kinase Fusion AA seq ID in KinaseFusionDBSite scoreSizeDscoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues

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Ramachandran Plot of Kinase 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.

285_TNK1_CHD3_ramachandran.png
all structure TNK1-CHD3

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Virtual Screening Results


check button 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
all structure TNK1-CHD3
3'-kinase fusion protein case

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check button 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 infoDrugDocking scoreGlide g scoreGlide energy
285_TNK1_CHD3-DOCK_HTVS_1-001Dacomitinib-7.77026-7.87926-53.2201
285_TNK1_CHD3-DOCK_HTVS_1-001Dacomitinib-7.768619999999999-7.87692-53.0467
285_TNK1_CHD3-DOCK_HTVS_1-001Dacomitinib-7.768619999999999-7.87692-53.0467
285_TNK1_CHD3-DOCK_HTVS_1-001Larotrectinib-7.54921-7.54921-44.6149
285_TNK1_CHD3-DOCK_HTVS_1-001Baricitinib-7.43553-7.43553-36.5068
285_TNK1_CHD3-DOCK_HTVS_1-001Nilotinib-7.363810000000001-8.28861-63.7848
285_TNK1_CHD3-DOCK_HTVS_1-001Nilotinib-7.363810000000001-8.28861-63.7848
285_TNK1_CHD3-DOCK_HTVS_1-001Neratinib-7.26138-7.4436800000000005-61.3693
285_TNK1_CHD3-DOCK_HTVS_1-001Neratinib-7.26138-7.4436800000000005-61.3693
285_TNK1_CHD3-DOCK_HTVS_1-001Lapatinib-7.253830000000001-7.342630000000001-63.526
285_TNK1_CHD3-DOCK_HTVS_1-001Neratinib-7.19525-7.38115-56.5041
285_TNK1_CHD3-DOCK_HTVS_1-001Midostaurin-7.18659-7.18659-49.3443
285_TNK1_CHD3-DOCK_HTVS_1-001Netarsudil-6.92242-6.93352-51.3487
285_TNK1_CHD3-DOCK_HTVS_1-001Netarsudil-6.92242-6.93352-51.3487
285_TNK1_CHD3-DOCK_HTVS_1-001Tepotinib-6.9055100000000005-6.906610000000001-54.0215
285_TNK1_CHD3-DOCK_HTVS_1-001Osimertinib-6.836760000000001-6.844460000000001-49.5846
285_TNK1_CHD3-DOCK_HTVS_1-001Nilotinib-6.81468-6.954280000000001-54.1377
285_TNK1_CHD3-DOCK_HTVS_1-001Nilotinib-6.81468-6.954280000000001-54.1377
285_TNK1_CHD3-DOCK_HTVS_1-001Lapatinib-6.80064-7.96904-67.0879
285_TNK1_CHD3-DOCK_HTVS_1-001Lapatinib-6.80064-7.96904-67.0879

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Kinase-Substrate Information of TNK1_CHD3


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
TNK1Q13470humanTNK1Q13470Y277LGGARGRyVMGGPRPPK_Tyr_Ser-Thr


check button Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

check button Enriched GO biological processes of the phosphorylation target genes of the kinase
KinaseGOIDGO termP.adjust
TNK1IDDescription0.00e+00
TNK1GO:0046777protein autophosphorylation1.05e-02

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Related Drugs to TNK1_CHD3


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

check button Distribution of the number of studies mentioning TNK1-CHD3 and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1Fusion gene - drug pair 2PMIDPublication dateDOIStudy title

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Related Diseases to TNK1_CHD3


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

check button Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)
MeSH IDMeSH term

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource


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Clinical Trials of the Found Drugs/Small Molecules


check button Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)

check button Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion GeneKinase InhibitorNCT IDStudy StatusPhasesDisease# EnrolmentDate