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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:PPM1H_DYRK2

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: PPM1H_DYRK2
KinaseFusionDB ID: KFG4813
FusionGDB2.0 ID: KFG4813
HgeneTgene
Gene symbol

PPM1H

DYRK2

Gene ID

57460

8445

Gene nameprotein phosphatase, Mg2+/Mn2+ dependent 1Hdual specificity tyrosine phosphorylation regulated kinase 2
SynonymsARHCL1|NERPP-2C|URCC2-
Cytomap

12q14.1-q14.2

12q15

Type of geneprotein-codingprotein-coding
Descriptionprotein phosphatase 1Hneurite extension-related protein phosphatase related to PP2Cprotein phosphatase 1H (PP2C domain containing)ras homolog gene family, member C like 1dual specificity tyrosine-phosphorylation-regulated kinase 2dual specificity tyrosine-(Y)-phosphorylation regulated kinase 2
Modification date2024030520240407
UniProtAcc

Q9ULR3

Q92630

Ensembl transtripts involved in fusion geneENST idsENST00000228705, ENST00000551214, 
ENST00000393555, ENST00000537632, 
ENST00000344096, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: PPM1H [Title/Abstract] AND DYRK2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PPM1H(63182006)-DYRK2(68050886), # 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
TgeneDYRK2

GO:0006468

protein phosphorylation

11311121

TgeneDYRK2

GO:0042771

intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

17349958

TgeneDYRK2

GO:0045725

positive regulation of glycogen biosynthetic process

11311121


check buttonKinase Fusion gene breakpoints across PPM1H (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 DYRK2 (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
ChimerDB4TCGA-HZ-A49I-01APPM1Hchr12

63182006

DYRK2chr12

68050886



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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/:63182006/:68050886)
- 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
PPM1H

Q9ULR3

DYRK2

Q92630

FUNCTION: Dephosphorylates CDKN1B at 'Thr-187', thus removing a signal for proteasomal degradation. {ECO:0000269|PubMed:22586611}.FUNCTION: Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro). {ECO:0000269|PubMed:11311121, ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:15910284, ECO:0000269|PubMed:16511445, ECO:0000269|PubMed:16611631, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:9748265}.

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 PPM1H_DYRK2


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
DYRK2Q92630humanSIAH2O43255S68GGGAGPVsPQHHELT
DYRK2Q92630humanCARHSP1Q9Y2V2S41LRGNVVPsPLPtRRt
DYRK2Q92630humanDCXO43602-2S306GPMRRSKsPADSANG
DYRK2Q92630humanCDC25AP30304S283PErsQEEsPPGSTKrM-inducer_phosp
DYRK2Q92630humanSIAH2O43255T119PTCRGALtPSIRNLA
DYRK2Q92630humanKATNA1O75449S42QMNKYLYsVkDTYLQ
DYRK2Q92630humanTP53P04637S46AMDDLMLsPDDIEQWTAD2
DYRK2Q92630humanCDC25AP30304S321QSLSLAssPKGTIENM-inducer_phosp
DYRK2Q92630humanCDC25AP30304S107NPMRRIHsLPQkLLGM-inducer_phosp
DYRK2Q92630humanDYRK2Q92630-2S483SVKRITEstGAItsI
DYRK2Q92630humanCDC25AP30304S18RRLLFACsPPPASQP
DYRK2Q92630humanKATNA1O75449S109VPVERRPsPGPRKRQ
DYRK2Q92630humanDYRK2Q92630-2T484VKRITEstGAItsIS
DYRK2Q92630humanDYRK2Q92630-2T32SNKRTVLttQPNGLT
DYRK2Q92630humanKATNA1O75449T133HGNRPSTtVRVHRSS
DYRK2Q92630humanPSMC4P43686T25LSVsRPQtGLsFLGP
DYRK2Q92630humanDYRK2Q92630-2T488TEstGAItsISKLPP
DYRK2Q92630humanDYRK2Q92630-2T82KVKATPMtPEQAMKQ
DYRK2Q92630humanCRMP1Q14194S522PAPsAKssPsKHQPP
DYRK2Q92630humanEIF4EBP1Q13541S65FLMECrNsPVtktPPeIF_4EBP
DYRK2Q92630humanSNAI1O95863S104GkGsQPPsPPsPAPs
DYRK2Q92630humanDYRK2Q92630-2Y309EHQRVYTyIQSRFYRPkinase
DYRK2Q92630humanH3-3AP84243T45PHryrPGtVALrEIRHistone
DYRK2Q92630humanCDC25AP30304S88DsGFCLDsPGPLDSKM-inducer_phosp
DYRK2Q92630humanHSF1Q00613S363DtEGRPPsPPPtstPVert_HS_TF
DYRK2Q92630humanNOTCH1P46531T2511VPEHPFLtPsPEsPD
DYRK2Q92630humanSIAH2O43255T26PPPQPQHtPsPAAPP
DYRK2Q92630humanCARHSP1Q9Y2V2S30tPRsRERsPsPLRGN
DYRK2Q92630humanCDC25AP30304S320HQSLSLAssPKGTIEM-inducer_phosp
DYRK2Q92630humanCARHSP1Q9Y2V2S32RsRERsPsPLRGNVV
DYRK2Q92630humanHSF1Q00613S307EPPsPPQsPRVEEAsVert_HS_TF
DYRK2Q92630humanHSF1Q00613S320AsPGRPssVDtLLsPVert_HS_TF
DYRK2Q92630humanDPYSL3Q14195S522PAGsArGsPtRPNPP
DYRK2Q92630humanDPYSL2Q16555S522PAssAktsPAkQQAP
DYRK2Q92630humanMAPTP10636-8T212tPGsRsRtPsLPtPP
DYRK2Q92630humanDYRK2Q92630-2S497ISKLPPPsssAsKLR
DYRK2Q92630humanDYRK2Q92630-2T33NKRTVLttQPNGLTT
DYRK2Q92630humanSIAH2O43255S16PsANkPCsKQPPPQP
DYRK2Q92630humanHSF1Q00613S326ssVDtLLsPTALIDsVert_HS_TF
DYRK2Q92630humanEIF4EBP1Q13541S101sQSHLRNsPEDKRAGeIF_4EBP
DYRK2Q92630humanCDC25AP30304S156KkPVRPVsRGCLHSHM-inducer_phosp
DYRK2Q92630humanCDC25AP30304S185sAPARMLsSNERDSSM-inducer_phosp
DYRK2Q92630humanTBK1Q9UHD2S527QDIDSRLsPGGSLADTBK1_CCD1
DYRK2Q92630humanDYRK2Q92630-2S489EstGAItsISKLPPP
DYRK2Q92630humanSIAH2O43255S28PQPQHtPsPAAPPAA
DYRK2Q92630humanHSF1Q00613T323GRPssVDtLLsPTALVert_HS_TF


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
DYRK2IDDescription0.00e+00
DYRK2GO:0061314Notch signaling involved in heart development2.82e-02
DYRK2GO:0003198epithelial to mesenchymal transition involved in endocardial cushion formation2.82e-02
DYRK2GO:1900034regulation of cellular response to heat2.82e-02
DYRK2GO:0060253negative regulation of glial cell proliferation2.82e-02
DYRK2GO:0008630intrinsic apoptotic signaling pathway in response to DNA damage2.82e-02
DYRK2GO:1901796regulation of signal transduction by p53 class mediator2.82e-02
DYRK2GO:0045931positive regulation of mitotic cell cycle3.63e-02
DYRK2GO:0070841inclusion body assembly3.63e-02
DYRK2GO:0061311cell surface receptor signaling pathway involved in heart development3.63e-02
DYRK2GO:0071480cellular response to gamma radiation3.63e-02
DYRK2GO:0003272endocardial cushion formation3.63e-02
DYRK2GO:0001701in utero embryonic development3.88e-02
DYRK2GO:0031069hair follicle morphogenesis3.88e-02
DYRK2GO:0060317cardiac epithelial to mesenchymal transition3.88e-02
DYRK2GO:0048730epidermis morphogenesis3.88e-02
DYRK2GO:0043254regulation of protein-containing complex assembly3.88e-02
DYRK2GO:0072331signal transduction by p53 class mediator3.88e-02
DYRK2GO:0003180aortic valve morphogenesis3.88e-02
DYRK2GO:0043516regulation of DNA damage respons5.92e-04
DYRK2GO:0003203endocardial cushion morphogenesis3.90e-02
DYRK2GO:0060251regulation of glial cell proliferation3.90e-02
DYRK2GO:1990000amyloid fibril formation3.92e-02
DYRK2GO:0003176aortic valve development3.94e-02
DYRK2GO:0042771intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator3.96e-02
DYRK2GO:0014014negative regulation of gliogenesis3.98e-02
DYRK2GO:1905314semi-lunar valve development4.06e-02
DYRK2GO:2000241regulation of reproductive process4.06e-02
DYRK2GO:0043086negative regulation of catalytic activity4.06e-02
DYRK2GO:0010665regulation of cardiac muscle cell apoptotic process4.06e-02
DYRK2GO:0010332response to gamma radiation4.06e-02
DYRK2GO:0003197endocardial cushion development4.06e-02
DYRK2GO:0010662regulation of striated muscle cell apoptotic process4.06e-02
DYRK2GO:0010823negative regulation of mitochondrion organization4.06e-02
DYRK2GO:1902692regulation of neuroblast proliferation4.10e-02
DYRK2GO:0010659cardiac muscle cell apoptotic process4.13e-02
DYRK2GO:0010658striated muscle cell apoptotic process4.32e-02
DYRK2GO:0072132mesenchyme morphogenesis4.33e-02
DYRK2GO:0010718positive regulation of epithelial to mesenchymal transition4.33e-02
DYRK2GO:0014009glial cell proliferation4.33e-02
DYRK2GO:0031122cytoplasmic microtubule organization4.33e-02
DYRK2GO:0003179heart valve morphogenesis4.51e-02
DYRK2GO:0000082G1/S transition of mitotic cell cycle4.62e-02
DYRK2GO:0034599cellular response to oxidative stress4.62e-02
DYRK2GO:0045927positive regulation of growth4.62e-02
DYRK2GO:0001649osteoblast differentiation4.62e-02
DYRK2GO:0001756somitogenesis4.62e-02
DYRK2GO:0034605cellular response to heat4.62e-02
DYRK2GO:2000379positive regulation of reactive oxygen species metabolic process4.67e-02
DYRK2GO:0003007heart morphogenesis4.67e-02

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Related Drugs to PPM1H_DYRK2


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 PPM1H-DYRK2 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 PPM1H_DYRK2


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