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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:DAPK3_NFATC1

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: DAPK3_NFATC1
KinaseFusionDB ID: KFG1614
FusionGDB2.0 ID: KFG1614
HgeneTgene
Gene symbol

DAPK3

NFATC1

Gene ID

1613

4772

Gene namedeath associated protein kinase 3nuclear factor of activated T cells 1
SynonymsDLK|ZIP|ZIPKNF-ATC|NF-ATc1.2|NFAT2|NFATc
Cytomap

19p13.3

18q23

Type of geneprotein-codingprotein-coding
Descriptiondeath-associated protein kinase 3DAP kinase 3DAP-like kinaseMYPT1 kinaseZIP-kinasezipper-interacting protein kinasenuclear factor of activated T-cells, cytoplasmic 1NFAT transcription complex cytosolic componentnuclear factor of activated T-cells 'c'nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Modification date2024030520240403
UniProtAcc

O43293

O95644

Ensembl transtripts involved in fusion geneENST idsENST00000301264, ENST00000545797, 
ENST00000253506, ENST00000318065, 
ENST00000329101, ENST00000397790, 
ENST00000427363, ENST00000542384, 
ENST00000545796, ENST00000586434, 
ENST00000587635, ENST00000590172, 
ENST00000591814, ENST00000592223, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: DAPK3 [Title/Abstract] AND NFATC1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DAPK3(3964370)-NFATC1(77272307), # samples:1
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneDAPK3

GO:0006468

protein phosphorylation

10356987

HgeneDAPK3

GO:0006915

apoptotic process

10580117

HgeneDAPK3

GO:0017148

negative regulation of translation

18995835

HgeneDAPK3

GO:0032956

regulation of actin cytoskeleton organization

23454120

HgeneDAPK3

GO:0035556

intracellular signal transduction

10356987

HgeneDAPK3

GO:0043065

positive regulation of apoptotic process

21487036

HgeneDAPK3

GO:0046777

protein autophosphorylation

18239682

HgeneDAPK3

GO:0051893

regulation of focal adhesion assembly

23454120

HgeneDAPK3

GO:0071346

cellular response to type II interferon

18995835

TgeneNFATC1

GO:0033173

calcineurin-NFAT signaling cascade

14979875

TgeneNFATC1

GO:0035556

intracellular signal transduction

14749367

TgeneNFATC1

GO:0045893

positive regulation of DNA-templated transcription

14749367

TgeneNFATC1

GO:0045893

positive regulation of DNA-templated transcription

14979875

TgeneNFATC1

GO:0045944

positive regulation of transcription by RNA polymerase II

14979875

TgeneNFATC1

GO:1905064

negative regulation of vascular associated smooth muscle cell differentiation

23853098


check buttonKinase Fusion gene breakpoints across DAPK3 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

check buttonKinase Fusion gene breakpoints across NFATC1 (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

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
ChiTaRS5.0BI045301DAPK3chr19

3964370

NFATC1chr18

77272307



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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)

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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

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/:3964370/:77272307)
- 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
DAPK3

O43293

NFATC1

O95644

FUNCTION: Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Involved in the regulation of smooth muscle contraction. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in regulation of starvation-induced autophagy. Regulates myosin phosphorylation in both smooth muscle and non-muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A; the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton. Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B. Overexpression leads to condensation of actin stress fibers into thick bundles. Involved in actin filament focal adhesion dynamics. The function in both reorganization of actin cytoskeleton and focal adhesion dissolution is modulated by RhoD. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Involved in regulation of cell cycle progression and cell proliferation. May be a tumor suppressor. {ECO:0000269|PubMed:10356987, ECO:0000269|PubMed:11384979, ECO:0000269|PubMed:11781833, ECO:0000269|PubMed:12917339, ECO:0000269|PubMed:15096528, ECO:0000269|PubMed:15367680, ECO:0000269|PubMed:16219639, ECO:0000269|PubMed:17126281, ECO:0000269|PubMed:17158456, ECO:0000269|PubMed:18084323, ECO:0000269|PubMed:18995835, ECO:0000269|PubMed:21169990, ECO:0000269|PubMed:21408167, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:21487036, ECO:0000269|PubMed:23454120}.FUNCTION: Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 or IL-4 gene transcription. Also controls gene expression in embryonic cardiac cells. Could regulate not only the activation and proliferation but also the differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells (PubMed:10358178). Required for osteoclastogenesis and regulates many genes important for osteoclast differentiation and function (By similarity). {ECO:0000250|UniProtKB:O88942, ECO:0000269|PubMed:10358178}.

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).
PartnerHgeneeneHbpTgeneeneTbpENSTBPexonTotalExonProtein feature lociBPlociTotalLenFeatureNote


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


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Kinase-Substrate Information of DAPK3_NFATC1


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
DAPK3O43293humanPPP1R14AQ96A00S12rLGKRVLsKLQsPSrPP1_inhibitor
DAPK3O43293humanDAPK3O43293T306tTRLkEytIksHssL
DAPK3O43293humanDAPK3O43293S311EytIksHssLPPNNS
DAPK3O43293humanLMO7Q8WWI1-3S863LKNLKRRsQFFEQGS
DAPK3O43293humanMYL9P24844T19KKRPQRAtsNVFAMF
DAPK3O43293humanPPP1R14AQ96A00T38QkRHARVtVkYDRREPP1_inhibitor
DAPK3O43293humanMDM2Q00987S186RQRkRHksDsIsLsF
DAPK3O43293humanCDKN1AP38936T145QGRkRRQtsMTDFyH
DAPK3O43293humanBECN1Q14457S90IPPARMMstEsANsF
DAPK3O43293humanTRIP12Q14669S312STKkRsEsPPAELPs
DAPK3O43293humanMDM2Q00987S166SsRRRAIsEtEENsD
DAPK3O43293humanRPL13AP40429S77PYHFrAPsRIFWRTVRibosomal_L13
DAPK3O43293humanMYL12BO14950S20KRPQRAtsNVFAMFD
DAPK3O43293humanTP53P04637S20PLsQEtFsDLWkLLPP53_TAD
DAPK3O43293humanDAPK3O43293T180EFKNIFGtPEFVAPEPkinase
DAPK3O43293humanMYL9P24844S20KRPQRAtsNVFAMFD
DAPK3O43293humanDAPK3O43293T225LGETKQEtLTNISAVPkinase
DAPK3O43293humanDAPK3O43293T265KDPKRRMtIAQSLEHPkinase
DAPK3O43293humanMYL12BO14950T19KKRPQRAtsNVFAMF
DAPK3O43293humanCDC14AQ9UNH5S484INSRLASsLGNLNAA
DAPK3O43293humanDAPK3O43293T299PERRRLKtTRLkEyt


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
DAPK3IDDescription0.00e+00
DAPK3GO:0006977DNA damage respons1.59e-07
DAPK3GO:0031571mitotic G1 DNA damage checkpoint signaling1.33e-04
DAPK3GO:0044819mitotic G1/S transition checkpoint signaling1.33e-04
DAPK3GO:0010332response to gamma radiation6.00e-04
DAPK3GO:0071479cellular response to ionizing radiation1.19e-03
DAPK3GO:0030330DNA damage respons1.19e-05
DAPK3GO:0044773mitotic DNA damage checkpoint signaling1.19e-03
DAPK3GO:0072332intrinsic apoptotic signaling pathway by p53 class mediator1.19e-03
DAPK3GO:2000134negative regulation of G1/S transition of mitotic cell cycle1.19e-03
DAPK3GO:0044774mitotic DNA integrity checkpoint signaling1.19e-03
DAPK3GO:0031668cellular response to extracellular stimulus1.19e-03
DAPK3GO:0034644cellular response to UV1.19e-03
DAPK3GO:0071236cellular response to antibiotic1.21e-03
DAPK3GO:1902807negative regulation of cell cycle G1/S phase transition1.23e-03
DAPK3GO:0010225response to UV-C1.47e-03
DAPK3GO:0097193intrinsic apoptotic signaling pathway1.48e-03
DAPK3GO:0070482response to oxygen levels1.70e-03
DAPK3GO:0071496cellular response to external stimulus1.70e-03
DAPK3GO:0090399replicative senescence1.70e-03
DAPK3GO:0071346cellular response to type II interferon1.70e-03
DAPK3GO:1901990regulation of mitotic cell cycle phase transition1.70e-03
DAPK3GO:0006978DNA damage respons5.64e-05
DAPK3GO:0000077DNA damage checkpoint signaling1.74e-03
DAPK3GO:0042772DNA damage respons6.30e-05
DAPK3GO:0010212response to ionizing radiation2.06e-03
DAPK3GO:0007093mitotic cell cycle checkpoint signaling2.15e-03
DAPK3GO:0034341response to type II interferon2.15e-03
DAPK3GO:2000377regulation of reactive oxygen species metabolic process2.26e-03
DAPK3GO:0009411response to UV2.42e-03
DAPK3GO:0009410response to xenobiotic stimulus2.59e-03
DAPK3GO:1901987regulation of cell cycle phase transition3.04e-03
DAPK3GO:0010165response to X-ray3.09e-03
DAPK3GO:0010039response to iron ion3.10e-03
DAPK3GO:0044772mitotic cell cycle phase transition3.10e-03
DAPK3GO:0072331signal transduction by p53 class mediator3.10e-03
DAPK3GO:0009267cellular response to starvation3.21e-03
DAPK3GO:0071478cellular response to radiation3.21e-03
DAPK3GO:0016242negative regulation of macroautophagy3.21e-03
DAPK3GO:2000045regulation of G1/S transition of mitotic cell cycle3.21e-03
DAPK3GO:0031667response to nutrient levels3.32e-03
DAPK3GO:0042770signal transduction in response to DNA damage3.35e-03
DAPK3GO:2001242regulation of intrinsic apoptotic signaling pathway3.35e-03
DAPK3GO:0000075cell cycle checkpoint signaling3.38e-03
DAPK3GO:1902253regulation of intrinsic apoptotic signaling pathway by p53 class mediator3.39e-03
DAPK3GO:1901991negative regulation of mitotic cell cycle phase transition3.45e-03
DAPK3GO:0046677response to antibiotic3.57e-03
DAPK3GO:2000279negative regulation of DNA biosynthetic process3.57e-03
DAPK3GO:0043516regulation of DNA damage respons2.57e-04
DAPK3GO:1902806regulation of cell cycle G1/S phase transition3.78e-03

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Related Drugs to DAPK3_NFATC1


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 DAPK3-NFATC1 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 DAPK3_NFATC1


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