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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:CDK9_PTMS

Kinase Fusion Protein Summary

check button Kinase Fusion gene summary
Kinase Fusion partner gene informationKinase Fusion gene name: CDK9_PTMS
KinaseFusionDB ID: KFG1209
FusionGDB2.0 ID: KFG1209
HgeneTgene
Gene symbol

CDK9

PTMS

Gene ID

1025

5763

Gene namecyclin dependent kinase 9parathymosin
SynonymsC-2k|CDC2L4|CTK1|PITALRE|TAKParaT
Cytomap

9q34.11

12p13.31

Type of geneprotein-codingprotein-coding
Descriptioncyclin-dependent kinase 9CDC2-related kinasecell division cycle 2-like protein kinase 4cell division protein kinase 9serine/threonine protein kinase PITALREtat-associated kinase complex catalytic subunitparathymosin
Modification date2024041620240305
UniProtAcc

P50750

P20962

Ensembl transtripts involved in fusion geneENST idsENST00000373265, ENST00000373264, 
ENST00000480353, 		ENST00000389462, 
ENST00000309083, ENST00000538057, 
Context (manual curation of fusion genes in KinaseFusionDB)

PubMed: CDK9 [Title/Abstract] AND PTMS [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
HgeneCDK9

GO:0006282

regulation of DNA repair

20493174

HgeneCDK9

GO:0006366

transcription by RNA polymerase II

28426094

HgeneCDK9

GO:0006468

protein phosphorylation

16109376

HgeneCDK9

GO:0031297

replication fork processing

20930849

HgeneCDK9

GO:0032968

positive regulation of transcription elongation by RNA polymerase II

9499409|14701750|30134174

HgeneCDK9

GO:0043923

positive regulation by host of viral transcription

10866664

HgeneCDK9

GO:0045944

positive regulation of transcription by RNA polymerase II

29335245

HgeneCDK9

GO:0051647

nucleus localization

12942536

HgeneCDK9

GO:0051726

regulation of cell cycle

20930849

HgeneCDK9

GO:0071345

cellular response to cytokine stimulus

17956865

HgeneCDK9

GO:0120186

negative regulation of protein localization to chromatin

14701750

HgeneCDK9

GO:0120187

positive regulation of protein localization to chromatin

29335245

HgeneCDK9

GO:0140673

transcription elongation-coupled chromatin remodeling

19844166


check buttonKinase Fusion gene breakpoints across CDK9 (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 PTMS (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
CCLESW403CDK9chr9

130551773

PTMSchr12

6879723



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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/:/:)
- 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
CDK9

P50750

PTMS

P20962

FUNCTION: Protein kinase involved in the regulation of transcription (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094, PubMed:29335245). Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094, PubMed:30134174). This complex is inactive when in the 7SK snRNP complex form (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094). Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR and the negative elongation factors DSIF and NELFE (PubMed:9857195, PubMed:10912001, PubMed:11112772, PubMed:12037670, PubMed:20081228, PubMed:20980437, PubMed:21127351). Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling) (PubMed:17956865, PubMed:18362169). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis (PubMed:10393184, PubMed:11112772). P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export (PubMed:15564463, PubMed:19575011, PubMed:19844166). Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing (PubMed:15564463, PubMed:19575011, PubMed:19844166). The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro (PubMed:21127351). Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage (PubMed:20493174). In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6 (PubMed:20493174). Promotes cardiac myocyte enlargement (PubMed:20081228). RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription (PubMed:21127351). AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect (PubMed:9857195, PubMed:10912001, PubMed:11112772). The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation (PubMed:12037670). Catalyzes phosphorylation of KAT5, promoting KAT5 recruitment to chromatin and histone acetyltransferase activity (PubMed:29335245). {ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10574912, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11145967, ECO:0000269|PubMed:11575923, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:11884399, ECO:0000269|PubMed:12037670, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15564463, ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:17956865, ECO:0000269|PubMed:18362169, ECO:0000269|PubMed:19575011, ECO:0000269|PubMed:19844166, ECO:0000269|PubMed:20081228, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:20930849, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:28426094, ECO:0000269|PubMed:29335245, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:9857195}.FUNCTION: Parathymosin may mediate immune function by blocking the effect of prothymosin alpha which confers resistance to certain opportunistic infections.

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 CDK9_PTMS


check button Phosphorylation target of the kinase
(phosphosite, 03-17-2024)
KinaseKinase UniProt AccKinase speciesSubstrateSubstrate UniProt AccSubstrate phosphorylated residuesSubstrate phosphorylated sites (+/-7AA)Domain
CDK9P50750humanSIRT1Q96EB6S47DGPGLERsPGEPGGA
CDK9P50750humanACTL6AO96019S233kEAVREGsPANWkRkActin
CDK9P50750humanSMAD1Q15797S195PNSSYPNsPGSSSSt
CDK9P50750humanSMAD1Q15797S187NSHPFPHsPNSSYPN
CDK9P50750humanCDK9P50750T186NSQPNRYtNRVVTLWPkinase
CDK9P50750humanOGFOD1Q8N543S256FEPPIPRsPHIPQDH
CDK9P50750humanTP73O15350T86AASASPYtPEHAASV
CDK9P50750humanSUPT5HO00267T784MyGsGsrtPMyGsQt
CDK9P50750humanH1-1Q02539S183KPKKVAKsPAKAKAV
CDK9P50750humanPOLR2AP24928T1525TPWNQGAtPAYGAWS
CDK9P50750humanBORAQ6PGQ7S325sPYIDGCsPIKNWsP
CDK9P50750humanSUPT5HO00267T775tPMyGsQtPMyGsGs
CDK9P50750humanPPARGP37231S112AIkVEPAsPPYYSEK
CDK9P50750humanCDK9P50750S353GsQItQQstNQsRNP
CDK9P50750humanSUPT5HO00267T768MtStyGRtPMyGsQt
CDK9P50750humanSMAD1Q15797S206SSStYPHsPTSSDPG
CDK9P50750humanRB1P06400S795sPykFPssPLrIPGGRb_C
CDK9P50750humanTP53P04637S392FktEGPDsD______
CDK9P50750humanTP53P04637S33LPENNVLsPLPsQAM
CDK9P50750humanCDK9P50750T363QsRNPAttNQtEFEr
CDK9P50750humanNCOA2Q15596S487GQPTSMLsPrHRMsPNCOA_u2
CDK9P50750humanSMAD1Q15797S214PTSSDPGsPFQMPAD
CDK9P50750humanSMAD3P84022T179PQSNIPEtPPPGYLS
CDK9P50750humanSMAD3P84022S213NLsPNPMsPAHNNLD
CDK9P50750humanH1-4P10412S187KPKKAPKsPAKAkAV
CDK9P50750humanSUPT5HO00267T814PLHDGsRtPAQsGAW
CDK9P50750humanRCHY1Q96PM5T217PsEYQNMtVDILCNDzinc_ribbon_6
CDK9P50750humanSMAD3P84022S208DAGsPNLsPNPMsPA
CDK9P50750humanRCHY1Q96PM5S211VAQTPMPsEYQNMtVzinc_ribbon_6
CDK9P50750humanMDM2Q00987S166SsRRRAIsEtEENsD
CDK9P50750humanSUPT5HO00267T806tPHyGsQtPLHDGsR
CDK9P50750humanPOLR2AP24928S1616TPQSPSysPtsPsYSRNA_pol_Rpb1_R
CDK9P50750humanXRN2Q9H0D6T439FtPsGILtPHALGsRXRN_M
CDK9P50750humanCDK9P50750T362NQsRNPAttNQtEFE
CDK9P50750humanSUPT5HO00267T799PLQDGsRtPHyGsQt
CDK9P50750humanSUPT5HO00267S782tPMyGsGsrtPMyGs
CDK9P50750humanSUPT5HO00267S773GRtPMyGsQtPMyGs
CDK9P50750humanPOLR2AP24928S1621SysPtsPsYSPTSPSRNA_pol_Rpb1_R
CDK9P50750humanSUPT5HO00267T791tPMyGsQtPLQDGsR
CDK9P50750humanMED1Q15648T1032SSSNRPFtPPTsTGG
CDK9P50750humanARP10275S83QQQQQETsPRQQQQQAndrogen_recep
CDK9P50750humanPOLR2AP24928T1618QSPSysPtsPsYSPTRNA_pol_Rpb1_R
CDK9P50750humanNCOA2Q15596S493LsPrHRMsPGVAGsPNCOA_u2
CDK9P50750humanPOLR2AP24928T1540PSVGSGMtPGAAGFS
CDK9P50750humanPOLR2AP24928S1619SPSysPtsPsYSPTSRNA_pol_Rpb1_R
CDK9P50750humanSUPT5HO00267S666VGGFAPMsPrISsPM
CDK9P50750humanACTL6AO96019S195LQQGIVksPLAGDFIActin
CDK9P50750humanACTL6AO96019S86RENMEAIsPLkNGMVActin
CDK9P50750humanRB1P06400S807PGGNIyIsPLksPykRb_C
CDK9P50750humanCDK9P50750S347APPRRkGsQItQQst
CDK9P50750humanAFF4Q9UHB7S388KDDLKLsssEDsDGEAF-4
CDK9P50750humanNCOA2Q15596S499MsPGVAGsPrIPPSQNCOA_u2
CDK9P50750humanRB1P06400S811IyIsPLksPykIsEGRb_C
CDK9P50750humanTP53P04637S315LPNNtsssPQPkkkP
CDK9P50750humanNCOA2Q15596S469NYALKMNsPsQSsPGNCOA_u2
CDK9P50750humanCDK9P50750T354sQItQQstNQsRNPA


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
CDK9IDDescription0.00e+00
CDK9GO:1902895positive regulation of miRNA transcription4.86e-06
CDK9GO:2000630positive regulation of miRNA metabolic process4.86e-06
CDK9GO:0035357peroxisome proliferator activated receptor signaling pathway4.86e-06
CDK9GO:1902893regulation of miRNA transcription4.86e-06
CDK9GO:0061614miRNA transcription4.86e-06
CDK9GO:2000628regulation of miRNA metabolic process1.07e-05
CDK9GO:0140747regulation of ncRNA transcription1.29e-05
CDK9GO:0010586miRNA metabolic process2.20e-05
CDK9GO:1904179positive regulation of adipose tissue development2.71e-05
CDK9GO:0009299mRNA transcription4.57e-05
CDK9GO:0098781ncRNA transcription5.81e-05
CDK9GO:0061448connective tissue development8.48e-05
CDK9GO:1904177regulation of adipose tissue development8.71e-05
CDK9GO:0072332intrinsic apoptotic signaling pathway by p53 class mediator2.66e-04
CDK9GO:1901653cellular response to peptide3.26e-04
CDK9GO:0060333type II interferon-mediated signaling pathway3.26e-04
CDK9GO:0050678regulation of epithelial cell proliferation4.62e-04
CDK9GO:0007179transforming growth factor beta receptor signaling pathway4.62e-04
CDK9GO:0065004protein-DNA complex assembly5.50e-04
CDK9GO:1902253regulation of intrinsic apoptotic signaling pathway by p53 class mediator6.52e-04
CDK9GO:0043516regulation of DNA damage respons1.13e-05
CDK9GO:0071560cellular response to transforming growth factor beta stimulus1.08e-03
CDK9GO:0042771intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator1.09e-03
CDK9GO:0071559response to transforming growth factor beta1.10e-03
CDK9GO:0001666response to hypoxia1.11e-03
CDK9GO:0042789mRNA transcription by RNA polymerase II1.11e-03
CDK9GO:0035196miRNA processing1.14e-03
CDK9GO:0071456cellular response to hypoxia1.19e-03
CDK9GO:0071375cellular response to peptide hormone stimulus1.20e-03
CDK9GO:0036293response to decreased oxygen levels1.25e-03
CDK9GO:0036294cellular response to decreased oxygen levels1.43e-03
CDK9GO:0017015regulation of transforming growth factor beta receptor signaling pathway1.43e-03
CDK9GO:0048545response to steroid hormone1.43e-03
CDK9GO:0051147regulation of muscle cell differentiation1.43e-03
CDK9GO:1903844regulation of cellular response to transforming growth factor beta stimulus1.43e-03
CDK9GO:0060612adipose tissue development1.54e-03
CDK9GO:0070482response to oxygen levels1.54e-03
CDK9GO:0045862positive regulation of proteolysis1.58e-03
CDK9GO:0050680negative regulation of epithelial cell proliferation1.58e-03
CDK9GO:0071453cellular response to oxygen levels1.58e-03
CDK9GO:0030522intracellular receptor signaling pathway1.58e-03
CDK9GO:0072331signal transduction by p53 class mediator1.58e-03
CDK9GO:0032786positive regulation of DNA-templated transcriptio4.97e-05
CDK9GO:0014745negative regulation of muscle adaptation1.83e-03
CDK9GO:0043353enucleate erythrocyte differentiation1.83e-03
CDK9GO:0009755hormone-mediated signaling pathway2.08e-03
CDK9GO:0033148positive regulation of intracellular estrogen receptor signaling pathway2.08e-03
CDK9GO:0051095regulation of helicase activity2.08e-03
CDK9GO:0071479cellular response to ionizing radiation2.08e-03

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Related Drugs to CDK9_PTMS


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 CDK9-PTMS 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 CDK9_PTMS


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