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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:MELK_CAMK2D

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: MELK_CAMK2D
KinaseFusionDB ID: KFG3769
FusionGDB2.0 ID: KFG3769
HgeneTgene
Gene symbol

MELK

CAMK2D

Gene ID

9833

817

Gene namematernal embryonic leucine zipper kinasecalcium/calmodulin dependent protein kinase II delta
SynonymsHPK38CAMKD
Cytomap

9p13.2

4q26

Type of geneprotein-codingprotein-coding
Descriptionmaternal embryonic leucine zipper kinasepEg3 kinaseprotein kinase Eg3protein kinase PK38tyrosine-protein kinase MELKcalcium/calmodulin-dependent protein kinase type II subunit deltaCaM kinase II delta subunitCaM-kinase II delta chainCaMK-II delta subunitcalcium/calmodulin-dependent protein kinase (CaM kinase) II deltacalcium/calmodulin-dependent protein kinase typ
Modification date2024040320240407
UniProtAcc

Q14680

Q13557

Ensembl transtripts involved in fusion geneENST idsENST00000298048, ENST00000487398, 
ENST00000536329, ENST00000536860, 
ENST00000536987, ENST00000538311, 
ENST00000541717, ENST00000543751, 
ENST00000545008, 
ENST00000296402, 
ENST00000394524, ENST00000394526, 
ENST00000418639, ENST00000429180, 
ENST00000454265, ENST00000342666, 
ENST00000379773, ENST00000394522, 
ENST00000505990, ENST00000508738, 
ENST00000509907, ENST00000511664, 
ENST00000514328, ENST00000515496, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: MELK [Title/Abstract] AND CAMK2D [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MELK(36616841)-CAMK2D(114373574), # 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
HgeneMELK

GO:0006915

apoptotic process

17280616

HgeneMELK

GO:0008283

cell population proliferation

17280616

HgeneMELK

GO:0046777

protein autophosphorylation

16216881

TgeneCAMK2D

GO:0003254

regulation of membrane depolarization

22514276

TgeneCAMK2D

GO:0006468

protein phosphorylation

17179159|23283722

TgeneCAMK2D

GO:0018105

peptidyl-serine phosphorylation

22514276|23283722

TgeneCAMK2D

GO:0018107

peptidyl-threonine phosphorylation

22514276|23283722

TgeneCAMK2D

GO:0046777

protein autophosphorylation

22514276

TgeneCAMK2D

GO:1901897

regulation of relaxation of cardiac muscle

23283722

TgeneCAMK2D

GO:1902306

negative regulation of sodium ion transmembrane transport

22514276

TgeneCAMK2D

GO:2000650

negative regulation of sodium ion transmembrane transporter activity

22514276


check buttonKinase Fusion gene breakpoints across MELK (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 CAMK2D (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
ChiTaRS5.0BI492715MELKchr9

36616841

CAMK2Dchr4

114373574



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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/:36616841/:114373574)
- 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
MELK

Q14680

CAMK2D

Q13557

FUNCTION: Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis. {ECO:0000269|PubMed:11802789, ECO:0000269|PubMed:12400006, ECO:0000269|PubMed:14699119, ECO:0000269|PubMed:15908796, ECO:0000269|PubMed:16216881, ECO:0000269|PubMed:17280616}.FUNCTION: Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and K(+) channel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Contributes to cardiac decompensation and heart failure by regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program (PubMed:17179159). Is essential for left ventricular remodeling responses to myocardial infarction. In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca(2+) influx to myocytes by binding and phosphorylating the L-type Ca(2+) channel subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca(2+) uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis (PubMed:16690701). May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q6PHZ2, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:17179159}.

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 MELK_CAMK2D


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
CAMK2DQ13557humanHDAC4P56524S210YGKTQHSsLDQSsPP
CAMK2DQ13557humanSCN5AQ14524T594LHGkKNStVDCNGVVNa_trans_cytopl
CAMK2DQ13557humanKCNQ1P51787T482sMPHFMRtNsFAEDL
CAMK2DQ13557humanKCNJ11Q14654T224MQVVRKTtSPEGEVVIRK_C
CAMK2DQ13557humanANKRD28O15084S1011TNTskTVsFEALPIM
CAMK2DQ13557humanRNF8O76064S157LRTKRkFsLDELAGP
CAMK2DQ13557humanTTNQ8WZ42T11922EVEVPTVtKRERKIP
CAMK2DQ13557humanCACNB2Q08289-2T499RGLSRQEtFDSETQE
CAMK2DQ13557humanKCNQ1P51787S484PHFMRtNsFAEDLDLKCNQ_channel
CAMK2DQ13557humanCEACAM1P13688-8S459LHFGKtGsSGPLQ__
CAMK2DQ13557humanTTNQ8WZ42S12022RRKLRPGsGGEKPPD
CAMK2DQ13557humanSCN5AQ14524S516LsLTrGLsRTsMKPRNa_trans_cytopl
CAMK2DQ13557humanTTNQ8WZ42T11932ERKIPEPtKVPEIKP
CAMK2DQ13557humanTTNQ8WZ42T11969PPVEPEPtPIAAPVT
CAMK2DQ13557humanCAMK2DQ13557T287sMMHRQEtVDCLKKF
CAMK2DQ13557humanOCLNQ16625S471LDDyREEsEEyMAAAOccludin_ELL
CAMK2DQ13557humanCAMK2BQ13554T287sMMHRQEtVECLKKF
CAMK2DQ13557humanCEACAM1P13688-8T457CFLHFGKtGsSGPLQ
CAMK2DQ13557humanTTNQ8WZ42S11878KEEVVLKsVLRKRPE
CAMK2DQ13557-8humanTPD52P55327S176kNsPtFksFEEkVENTPD52
MELKQ14680humanCDC25BP30305S169VLRNItNsQAPDGRRM-inducer_phosp
MELKQ14680humanMELKQ14680T539RGLDkVItVLtRsKR
MELKQ14680humanMELKQ14680T387DLSTGAAtPRTsQFT
MELKQ14680humanMELKQ14680T494TGtDkLMtGVIsPER
MELKQ14680humanMELKQ14680S431ENVytPKsAVkNEEy
MELKQ14680humanMELKQ14680T398sQFTkYWtEsNGVEs
MELKQ14680humanMELKQ14680T167NkDyHLQtCCGsLAYPkinase
MELKQ14680humanMELKQ14680S171HLQtCCGsLAYAAPEPkinase
MELKQ14680humanCDC25BP30305S323QRLFRsPsMPCsVIRM-inducer_phosp
MELKQ14680humanMELKQ14680S405tEsNGVEsksLtPAL
MELKQ14680humanMELKQ14680T409GVEsksLtPALCRtP
MELKQ14680humanMELKQ14680S356DIKSNNWsLEDVTAs
MELKQ14680humanMELKQ14680Y438sAVkNEEyFMFPEPK
MELKQ14680humanMELKQ14680S529KGAkVFGsLERGLDk
MELKQ14680humanMELKQ14680Y367VTAsDKNyVAGLIDY
MELKQ14680humanEIF4BP23588S406RPRERHPsWRsEEtQ
MELKQ14680humanEZH2Q15910S220RPPRKFPsDKIFEAIPRC2_HTH_1
MELKQ14680humanMELKQ14680S505sPERRCRsVELDLNQ
MELKQ14680humanMELKQ14680S407sNGVEsksLtPALCR
MELKQ14680humanMELKQ14680S336PVRLRLssFsCGQAs
MELKQ14680humanMELKQ14680S343sFsCGQAsAtPFtDI
MELKQ14680humanMELKQ14680S391GAAtPRTsQFTkYWt
MELKQ14680humanEIF4BP23588S422RERsRtGsEssQtGt
MELKQ14680humanMELKQ14680Y163kPKGNkDyHLQtCCGPkinase
MELKQ14680humanMELKQ14680S253VDPKKRIsMkNLLNHPkinase
MELKQ14680humanMELKQ14680T56sDLPRIktEIEALkNPkinase


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
CAMK2DIDDescription0.00e+00
CAMK2DGO:0003012muscle system process2.29e-06
CAMK2DGO:0086091regulation of heart rate by cardiac conduction2.54e-06
CAMK2DGO:0060048cardiac muscle contraction3.64e-06
CAMK2DGO:0001508action potential3.64e-06
CAMK2DGO:0086065cell communication involved in cardiac conduction5.79e-06
CAMK2DGO:0006941striated muscle contraction8.17e-06
CAMK2DGO:0086001cardiac muscle cell action potential1.09e-05
CAMK2DGO:0086003cardiac muscle cell contraction1.09e-05
CAMK2DGO:0086014atrial cardiac muscle cell action potential1.28e-05
CAMK2DGO:0086026atrial cardiac muscle cell to AV node cell signaling1.28e-05
CAMK2DGO:0086066atrial cardiac muscle cell to AV node cell communication1.28e-05
CAMK2DGO:0060047heart contraction1.44e-05
CAMK2DGO:0043502regulation of muscle adaptation1.44e-05
CAMK2DGO:0090257regulation of muscle system process1.44e-05
CAMK2DGO:0061337cardiac conduction1.47e-05
CAMK2DGO:0003015heart process1.47e-05
CAMK2DGO:0002027regulation of heart rate1.68e-05
CAMK2DGO:0070252actin-mediated cell contraction1.78e-05
CAMK2DGO:0043500muscle adaptation2.70e-05
CAMK2DGO:0030048actin filament-based movement4.11e-05
CAMK2DGO:0086019cell-cell signaling involved in cardiac conduction4.11e-05
CAMK2DGO:0006936muscle contraction5.19e-05
CAMK2DGO:0010959regulation of metal ion transport9.21e-05
CAMK2DGO:0086002cardiac muscle cell action potential involved in contraction1.38e-04
CAMK2DGO:0042391regulation of membrane potential1.38e-04
CAMK2DGO:0034765regulation of monoatomic ion transmembrane transport1.55e-04
CAMK2DGO:0008016regulation of heart contraction1.82e-04
CAMK2DGO:0055117regulation of cardiac muscle contraction3.86e-04
CAMK2DGO:1903522regulation of blood circulation3.88e-04
CAMK2DGO:0051899membrane depolarization3.88e-04
CAMK2DGO:0086016AV node cell action potential4.57e-04
CAMK2DGO:0086027AV node cell to bundle of His cell signaling4.57e-04
CAMK2DGO:0099624atrial cardiac muscle cell membrane repolarization4.57e-04
CAMK2DGO:0014854response to inactivity5.17e-04
CAMK2DGO:0086067AV node cell to bundle of His cell communication5.17e-04
CAMK2DGO:0014874response to stimulus involved in regulation of muscle adaptation5.81e-04
CAMK2DGO:0003300cardiac muscle hypertrophy5.81e-04
CAMK2DGO:0006942regulation of striated muscle contraction5.81e-04
CAMK2DGO:0014897striated muscle hypertrophy6.19e-04
CAMK2DGO:1904062regulation of monoatomic cation transmembrane transport6.25e-04
CAMK2DGO:0014896muscle hypertrophy6.25e-04
CAMK2DGO:1902514regulation of calcium ion transmembrane transport via high voltage-gated calcium channel8.86e-04
CAMK2DGO:1902074response to salt1.05e-03
CAMK2DGO:0061577calcium ion transmembrane transport via high voltage-gated calcium channel1.06e-03
CAMK2DGO:0098659inorganic cation import across plasma membrane1.27e-03
CAMK2DGO:0099587inorganic ion import across plasma membrane1.27e-03
CAMK2DGO:0086012membrane depolarization during cardiac muscle cell action potential1.34e-03
CAMK2DGO:0051592response to calcium ion1.41e-03
CAMK2DGO:0060307regulation of ventricular cardiac muscle cell membrane repolarization1.41e-03

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Related Drugs to MELK_CAMK2D


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 MELK-CAMK2D 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 MELK_CAMK2D


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