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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:MDM2_CDK6

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: MDM2_CDK6
KinaseFusionDB ID: KFG3739
FusionGDB2.0 ID: KFG3739
HgeneTgene
Gene symbol

MDM2

CDK6

Gene ID

4193

1021

Gene nameMDM2 proto-oncogenecyclin dependent kinase 6
SynonymsACTFS|HDMX|LSKB|hdm2MCPH12|PLSTIRE
Cytomap

12q15

7q21.2

Type of geneprotein-codingprotein-coding
DescriptionE3 ubiquitin-protein ligase Mdm2MDM2 oncogene, E3 ubiquitin protein ligaseMDM2 proto-oncogene, E3 ubiquitin protein ligaseMdm2, p53 E3 ubiquitin protein ligase homologMdm2, transformed 3T3 cell double minute 2, p53 binding proteindouble minute 2, humcyclin-dependent kinase 6cell division protein kinase 6serine/threonine-protein kinase PLSTIRE
Modification date2024040720240416
UniProtAcc

Q00987

Q00534

Ensembl transtripts involved in fusion geneENST idsENST00000462284, ENST00000356290, 
ENST00000540827, ENST00000258149, 
ENST00000428863, ENST00000393412, 
ENST00000258148, ENST00000544561, 
ENST00000393410, ENST00000393413, 
ENST00000517852, ENST00000545204, 
ENST00000350057, ENST00000360430, 
ENST00000299252, ENST00000348801, 
ENST00000478070, ENST00000544125, 
ENST00000265734, ENST00000424848, 
ENST00000491250, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: MDM2 [Title/Abstract] AND CDK6 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)
check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneMDM2

GO:0000122

negative regulation of transcription by RNA polymerase II

9271120|17310983

HgeneMDM2

GO:0006511

ubiquitin-dependent protein catabolic process

11278372|15314173|16173922|17310983

HgeneMDM2

GO:0006915

apoptotic process

30879903

HgeneMDM2

GO:0016567

protein ubiquitination

9450543|15878855|19656744|20153724

HgeneMDM2

GO:0031648

protein destabilization

9529249|10360174|15314173

HgeneMDM2

GO:0032436

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

11278372

HgeneMDM2

GO:0034504

protein localization to nucleus

10360174

HgeneMDM2

GO:0042176

regulation of protein catabolic process

9153395

HgeneMDM2

GO:0043518

negative regulation of DNA damage response, signal transduction by p53 class mediator

9529249|10360174

HgeneMDM2

GO:0045184

establishment of protein localization

10360174

HgeneMDM2

GO:0045892

negative regulation of DNA-templated transcription

9271120

HgeneMDM2

GO:0051726

regulation of cell cycle

9529249

HgeneMDM2

GO:0065003

protein-containing complex assembly

10608892|12915590

HgeneMDM2

GO:0071480

cellular response to gamma radiation

16213212

HgeneMDM2

GO:0072717

cellular response to actinomycin D

15314173

HgeneMDM2

GO:1901797

negative regulation of signal transduction by p53 class mediator

16173922

TgeneCDK6

GO:0000082

G1/S transition of mitotic cell cycle

8114739

TgeneCDK6

GO:0001954

positive regulation of cell-matrix adhesion

10205165

TgeneCDK6

GO:0003323

type B pancreatic cell development

20668294

TgeneCDK6

GO:0006468

protein phosphorylation

8114739

TgeneCDK6

GO:0010468

regulation of gene expression

15254224

TgeneCDK6

GO:0045638

negative regulation of myeloid cell differentiation

17431401

TgeneCDK6

GO:0045656

negative regulation of monocyte differentiation

26542173

TgeneCDK6

GO:0045668

negative regulation of osteoblast differentiation

15254224

TgeneCDK6

GO:0045786

negative regulation of cell cycle

14985467

TgeneCDK6

GO:2000773

negative regulation of cellular senescence

17420273


check buttonKinase Fusion gene breakpoints across MDM2 (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 CDK6 (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
CCLECCF-STTG1MDM2chr12

69203072

CDK6chr7

92252400

CCLECCF-STTG1MDM2chr12

69207408

CDK6chr7

92300849

CCLECCF-STTG1MDM2chr12

69203072

CDK6chr7

92300849

CCLECCF-STTG1MDM2chr12

69207408

CDK6chr7

92463004

CCLECCF-STTG1MDM2chr12

69210725

CDK6chr7

92252400

CCLECCF-STTG1MDM2chr12

69202271

CDK6chr7

92355107

CCLECCF-STTG1MDM2chr12

69202271

CDK6chr7

92404145

CCLECCF-STTG1MDM2chr12

69202271

CDK6chr7

92463004

CCLECCF-STTG1MDM2chr12

69203072

CDK6chr7

92463004

CCLECCF-STTG1MDM2chr12

69214154

CDK6chr7

92463004

CCLECCF-STTG1MDM2chr12

69218431

CDK6chr7

92300849

CCLECCF-STTG1MDM2chr12

69218431

CDK6chr7

92355107

CCLECCF-STTG1MDM2chr12

69222711

CDK6chr7

92355107

CCLECCF-STTG1MDM2chr12

69222711

CDK6chr7

92463004



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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/chr12:/chr7:)
- 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
MDM2

Q00987

CDK6

Q00534

FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome (PubMed:29681526). Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also a component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation (PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells (By similarity). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (By similarity). Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 leading to its cytosolic retention rather than mitochondrial localization resulting in decreased supercomplex assembly (interactions between complex I and complex III), decreased complex I activity, ROS production, and apoptosis (PubMed:30879903). {ECO:0000250|UniProtKB:P23804, ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15632057, ECO:0000269|PubMed:16337594, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19098711, ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:22128911, ECO:0000269|PubMed:29681526, ECO:0000269|PubMed:30879903}.FUNCTION: Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663). {ECO:0000269|PubMed:12833137, ECO:0000269|PubMed:14985467, ECO:0000269|PubMed:15254224, ECO:0000269|PubMed:15809340, ECO:0000269|PubMed:17420273, ECO:0000269|PubMed:17431401, ECO:0000269|PubMed:20333249, ECO:0000269|PubMed:20668294, ECO:0000269|PubMed:23918663, ECO:0000269|PubMed:8114739}.

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 MDM2_CDK6


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
CDK6Q00534humanRB1P06400S780strPPtLsPIPHIPrRb_C
CDK6Q00534humanTFEBP19484S467KASsRRssFsMEEGDDUF3371
CDK6Q00534humanRBL2Q08999T401SKALRIStPLtGVRY
CDK6Q00534humanTFEBP19484T331RVHGLPttsPsGMNMDUF3371
CDK6Q00534humanFOXM1Q08050T510EDSSQsPtPRPKKSy
CDK6Q00534humanRUNX1Q01196-8S276DTRQIQPsPPWSYDQ
CDK6Q00534humanRUNX1Q01196-8S48TPPSTALsPGKMSEA
CDK6Q00534humanFOXM1Q08050T611ETLPISstPSkSVLP
CDK6Q00534humanTSC2P49815S1452LPSssPRsPsGLrPr
CDK6Q00534humanFOXM1Q08050S508sWEDSSQsPtPRPKK
CDK6Q00534humanEGLN2Q96KS0S130EDGGDAPsPsKRPWA
CDK6Q00534humanRUNX1Q01196-8T300sPSVHPAtPIsPGRA
CDK6Q00534humanPKMP14618-2S37MCRLDIDsPPITARN
CDK6Q00534humanFOXM1Q08050S522KSySGLRsPtRCVSE
CDK6Q00534humanRB1P06400T826LPtPtkMtPRsRILVRb_C
CDK6Q00534humanRUNX1Q01196-8S424SMVGGERsPPRILPPRunxI
CDK6Q00534humanRBL2Q08999S672tLyDRySsPPAsTtR
CDK6Q00534humanRB1P06400S795sPykFPssPLrIPGGRb_C
CDK6Q00534humanCELF1Q92879S302TSSGSsPsSSSSNSV
CDK6Q00534humanRB1P06400T252PINGsPRtPRRGQNR
CDK6Q00534humanPFKFB3Q16875S467NsVtPLAsPEPtKKP
CDK6Q00534humanRB1P06400S788PIPHIPrsPykFPssRb_C
CDK6Q00534humanFOXM1Q08050T627tPEsWRLtPPAKVGG
CDK6Q00534humanRB1P06400S249AVIPINGsPRtPRRG
CDK6Q00534humanPFKFB3Q16875T463LMRRNsVtPLAsPEP
CDK6Q00534humanRBL2Q08999S1035NMDAPPLsPyPFVRt
CDK6Q00534humanNPM1P06748T199VkKsIrDtPAkNAQK
CDK6Q00534humanRB1P06400S612MyLsPVRsPKKKGsT
CDK6Q00534humanFOXM1Q08050S704IDVPKPGsPEPQVSG
CDK6Q00534humanTFEBP19484S142AGNsAPNsPMAMLHIMITF_TFEB_C_3_N
CDK6Q00534humanRUNX1Q01196-8S303VHPAtPIsPGRASGM
CDK6Q00534humanCDKN1BP46527T187NAGsVEQtPKKPGLR
CDK6Q00534humanPKMP14618S37MCRLDIDsPPItARN
CDK6Q00534humanCDKN1AP38936S130sGEQAEGsPGGPGDs
CDK6Q00534humanFOXM1Q08050S489PPLEEWPsPAPSFkE
CDK6Q00534humanTFEBP19484S114HIsPAQGsPkPPPAAMITF_TFEB_C_3_N
CDK6Q00534humanTFE3P19532S246PTGSAPNsPMALLTIMITF_TFEB_C_3_N
CDK6Q00534humanFLNAP21333S2152tRRRRAPsVANVGsHFilamin
CDK6Q00534humanELAVL1Q15717S202LLsQLyHsPArrFGG
CDK6Q00534humanRB1P06400T821kIsEGLPtPtkMtPRRb_C
CDK6Q00534humanRPRMQ9NS64S98LVKDRRPsKEVEAVV
CDK6Q00534humanCDKN1BP46527S10NVRVSNGsPsLErMD
CDK6Q00534humanFOXM1Q08050T600EVGGPFKtPIkETLP
CDK6Q00534humanTP53P04637R249CMGGMNRrPILTIITP53
CDK6Q00534humanRB1P06400S807PGGNIyIsPLksPykRb_C
CDK6Q00534humanFLNAP21333S1459kCsGPGLsPGMVRANFilamin
CDK6Q00534humanFOXM1Q08050T620SkSVLPRtPEsWRLt
CDK6Q00534humanRUNX1Q01196-8S293QYLGSIAsPSVHPAt
CDK6Q00534humanTSC2P49815S1217MSLENPLsPFSSDIN
CDK6Q00534humanRB1P06400S811IyIsPLksPykIsEGRb_C
CDK6Q00534humanFOXM1Q08050S451LLFGEGFsPLLPVQT


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
CDK6IDDescription0.00e+00
CDK6GO:0030330DNA damage respons6.21e-09
CDK6GO:0051169nuclear transport3.85e-06
CDK6GO:2000134negative regulation of G1/S transition of mitotic cell cycle3.85e-06
CDK6GO:1902807negative regulation of cell cycle G1/S phase transition5.10e-06
CDK6GO:0051348negative regulation of transferase activity7.96e-06
CDK6GO:0034504protein localization to nucleus4.18e-05
CDK6GO:0006606protein import into nucleus4.18e-05
CDK6GO:0010948negative regulation of cell cycle process4.18e-05
CDK6GO:0051170import into nucleus4.18e-05
CDK6GO:0072331signal transduction by p53 class mediator4.51e-05
CDK6GO:0006469negative regulation of protein kinase activity4.51e-05
CDK6GO:0006977DNA damage respons5.89e-07
CDK6GO:0042772DNA damage respons6.99e-07
CDK6GO:0033673negative regulation of kinase activity4.75e-05
CDK6GO:1901991negative regulation of mitotic cell cycle phase transition4.75e-05
CDK6GO:0045936negative regulation of phosphate metabolic process4.75e-05
CDK6GO:0010563negative regulation of phosphorus metabolic process4.75e-05
CDK6GO:1902806regulation of cell cycle G1/S phase transition5.93e-05
CDK6GO:0045786negative regulation of cell cycle6.78e-05
CDK6GO:0001558regulation of cell growth7.48e-05
CDK6GO:0031571mitotic G1 DNA damage checkpoint signaling1.08e-04
CDK6GO:0044819mitotic G1/S transition checkpoint signaling1.08e-04
CDK6GO:1901987regulation of cell cycle phase transition1.08e-04
CDK6GO:0045930negative regulation of mitotic cell cycle1.08e-04
CDK6GO:0000082G1/S transition of mitotic cell cycle1.13e-04
CDK6GO:0090398cellular senescence1.13e-04
CDK6GO:0044772mitotic cell cycle phase transition1.16e-04
CDK6GO:0043086negative regulation of catalytic activity1.27e-04
CDK6GO:0016049cell growth1.50e-04
CDK6GO:1901988negative regulation of cell cycle phase transition1.53e-04
CDK6GO:0044843cell cycle G1/S phase transition1.54e-04
CDK6GO:0001933negative regulation of protein phosphorylation2.27e-04
CDK6GO:0042326negative regulation of phosphorylation3.14e-04
CDK6GO:0044839cell cycle G2/M phase transition3.48e-04
CDK6GO:1901990regulation of mitotic cell cycle phase transition4.44e-04
CDK6GO:0009267cellular response to starvation5.82e-04
CDK6GO:0030308negative regulation of cell growth7.03e-04
CDK6GO:0031099regeneration7.15e-04
CDK6GO:0031400negative regulation of protein modification process1.09e-03
CDK6GO:0042594response to starvation1.13e-03
CDK6GO:0042246tissue regeneration1.13e-03
CDK6GO:0072594establishment of protein localization to organelle1.27e-03
CDK6GO:0060965negative regulation of miRNA-mediated gene silencing1.27e-03
CDK6GO:0071236cellular response to antibiotic1.27e-03
CDK6GO:0044773mitotic DNA damage checkpoint signaling1.38e-03
CDK6GO:0060149negative regulation of post-transcriptional gene silencing1.38e-03
CDK6GO:0060967negative regulation of gene silencing by regulatory ncRNA1.38e-03
CDK6GO:1900369negative regulation of post-transcriptional gene silencing by regulatory ncRNA1.38e-03
CDK6GO:0044774mitotic DNA integrity checkpoint signaling1.49e-03

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Related Drugs to MDM2_CDK6


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 MDM2-CDK6 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 MDM2_CDK6


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
TgeneCDK6C0004238Atrial Fibrillation2CTD_human
TgeneCDK6C0025149Medulloblastoma2CTD_human
TgeneCDK6C0205833Medullomyoblastoma2CTD_human
TgeneCDK6C0235480Paroxysmal atrial fibrillation2CTD_human
TgeneCDK6C0278510Childhood Medulloblastoma2CTD_human
TgeneCDK6C0278876Adult Medulloblastoma2CTD_human
TgeneCDK6C0751291Desmoplastic Medulloblastoma2CTD_human
TgeneCDK6C1275668Melanotic medulloblastoma2CTD_human
TgeneCDK6C2585653Persistent atrial fibrillation2CTD_human
TgeneCDK6C3468561familial atrial fibrillation2CTD_human


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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