Affinage

CDK13

Cyclin-dependent kinase 13 · UniProt Q14004

Length
1512 aa
Mass
164.9 kDa
Annotated
2026-04-28
76 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDK13 is a cyclin-dependent kinase that, in complex with Cyclin K, phosphorylates the RNA polymerase II C-terminal domain (CTD) at Ser2 and Ser5 to drive transcription elongation and processivity, functioning largely redundantly with CDK12 to sustain global RNAPII activity and coordinate DNA replication fork progression (PMID:26748711, PMID:32917631, PMID:41882177). Beyond CTD phosphorylation, CDK13 directly phosphorylates diverse non-CTD substrates—including the nuclear RNA surveillance factor ZC3H14, translation initiation factors 4E-BP1 and eIF4B, RNA methyltransferases NSUN5 and METTL16, the RNA-binding protein RBM39, the splicing factor ASF/SF2, and the HIV restriction factor SERINC5—thereby linking transcriptional elongation to mRNA processing, epitranscriptomic modification, nuclear RNA quality control, and translational regulation (PMID:37079685, PMID:36882522, PMID:37845385, PMID:41680470, PMID:41997449, PMID:34380030, PMID:18480452). Loss of CDK13 or combined CDK12/CDK13 inhibition triggers premature intronic polyadenylation that suppresses DNA damage response gene expression, generating a BRCAness phenotype and synthetic lethality exploitable in CDK12-mutant cancers (PMID:31668947, PMID:39368479). CDK13 knockout in mice causes embryonic lethality with cardiac, renal, and craniofacial defects, and de novo CDK13 mutations are associated with congenital heart disease and neurodevelopmental abnormalities (PMID:31440507, PMID:24999027).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2006 Medium

    Initial characterization established that CDK13 localizes to nuclear speckles via its RS domain and directly modulates pre-mRNA splicing, revealing it as a nuclear kinase connected to RNA processing rather than cell-cycle control.

    Evidence Immunofluorescence, yeast two-hybrid, and splicing reporter assays in mammalian cells

    PMID:16721827

    Open questions at the time
    • Endogenous substrates mediating splicing effects were not identified
    • RS-domain-dependent localization not tested by mutagenesis in an endogenous context
  2. 2007 Medium

    Discovery that CDK13 interacts with L-type cyclins and dose-dependently alters splice-site selection established it as a regulator of alternative splicing counteracted by SR proteins.

    Evidence Co-immunoprecipitation and E1a minigene splicing reporter in HEK293T cells

    PMID:17261272

    Open questions at the time
    • Whether Cyclin L is a physiological partner in vivo versus overexpression artifact was unclear
    • Kinase activity requirement for splicing modulation not tested
  3. 2008 Medium

    Identification of CDK13 as an HIV-1 Tat-interacting kinase that phosphorylates ASF/SF2 and promotes viral mRNA splicing linked CDK13 kinase activity to a specific splicing substrate and viral life cycle modulation.

    Evidence In vivo/in vitro co-IP with HIV-1 Tat, in vitro kinase assay on ASF/SF2, viral production assays

    PMID:18480452

    Open questions at the time
    • Phosphorylation site on ASF/SF2 not mapped
    • Whether endogenous CDK13 kinase activity (not overexpression) is limiting for viral splicing was unresolved
  4. 2014 Medium

    Demonstration that CDK13 knockdown reduces CDK5 expression and impairs axonal elongation in neurons provided the first evidence of a neurodevelopmental role and identified a downstream transcriptional target.

    Evidence siRNA knockdown in P19 cells and primary cortical neurons, CDK5 overexpression rescue

    PMID:24999027

    Open questions at the time
    • Whether CDK5 is a direct transcriptional target or indirect consequence of global transcriptional changes was unknown
    • No in vivo neurodevelopmental phenotyping in knockout animals
  5. 2015 High

    Structural determination of CDK13/Cyclin K at 2.0 Å and biochemical demonstration that it phosphorylates RNAPII CTD at Ser2 and Ser5 (preferring Ser7-primed substrates) established CDK13 as a bona fide CTD kinase with defined substrate specificity.

    Evidence X-ray crystallography, in vitro kinase assays with recombinant proteins and CTD peptides, mutagenesis

    PMID:26748711

    Open questions at the time
    • In vivo CTD phosphorylation contribution relative to CDK12 was not resolved
    • No structural basis for non-CTD substrate recognition
  6. 2015 High

    Proteomic and transcriptomic profiling showed CDK13 associates with RNA processing factors and preferentially regulates snoRNA gene expression, distinguishing its gene-specific targets from CDK12's DNA damage response gene regulation.

    Evidence Flag-IP/MS, RNA-seq upon siRNA knockdown in HCT116 cells

    PMID:25561469

    Open questions at the time
    • Direct versus indirect effects on snoRNA expression not distinguished
    • Whether CDK13 occupies snoRNA gene loci was untested
  7. 2016 High

    Development of covalent inhibitor THZ531 targeting CDK12/CDK13 and demonstration that dual inhibition causes loss of elongating RNAPII provided a pharmacological tool and confirmed the kinases' essential role in transcription elongation.

    Evidence Co-crystallization of inhibitor with CDK12-CycK, cell-based transcriptomic analysis

    PMID:27571479

    Open questions at the time
    • THZ531 does not discriminate CDK12 from CDK13, preventing assignment of individual contributions
    • Cysteine targeted is outside the kinase domain—off-target binding not fully excluded
  8. 2019 Medium

    CDK13 knockout mice die by E16.5 with heart, kidney, and palate defects, establishing CDK13 as essential for mammalian embryonic development.

    Evidence Gene trap knockout mouse, histological and morphological phenotyping

    PMID:31440507

    Open questions at the time
    • Molecular mechanism underlying each organ-specific defect not determined
    • Conditional tissue-specific knockouts not performed
  9. 2019 High

    Dual CDK12/13 inhibition was shown to trigger intronic polyadenylation of DNA damage response genes, creating a BRCAness phenotype that synergizes with PARP inhibitors, opening a therapeutic strategy in cancer.

    Evidence SR-4835 inhibitor treatment combined with siRNA, RNA-seq, drug combination assays in cancer cells

    PMID:31668947

    Open questions at the time
    • Individual contributions of CDK13 versus CDK12 to intronic polyadenylation not deconvolved
    • In vivo therapeutic window not established
  10. 2020 High

    Using analog-sensitive alleles, CDK12 and CDK13 were shown to be substantially redundant for global RNAPII processivity, with single CDK13 inhibition producing only modest effects but dual inhibition causing potent transcriptional collapse and cell death.

    Evidence CRISPR analog-sensitive kinase alleles, ChIP-seq, RNA-seq in human cells

    PMID:32917631

    Open questions at the time
    • Whether certain gene sets are uniquely CDK13-dependent in vivo was not resolved
    • Redundancy not tested across diverse cell lineages
  11. 2021 High

    HIV-1 Nef was found to recruit the CycK/CDK13 complex to phosphorylate the restriction factor SERINC5 at Ser360, enabling Nef-mediated SERINC5 internalization and degradation—identifying a non-CTD substrate with direct viral pathogenesis relevance.

    Evidence AP/MS, co-IP, site-directed mutagenesis, cell-surface staining

    PMID:34380030

    Open questions at the time
    • Structural basis for Nef-mediated CDK13 recruitment unknown
    • Whether other CDKs can substitute for CDK13 in this context untested
  12. 2023 High

    CDK13 was identified as the kinase for ZC3H14, whose phosphorylation activates nuclear RNA surveillance; oncogenic CDK13 mutations that fail to phosphorylate ZC3H14 stabilize aberrant transcripts and accelerate melanoma, directly linking CDK13 kinase activity to RNA quality control and tumor suppression.

    Evidence Kinase assays, zebrafish melanoma model, RNA stability measurements, genetic rescue

    PMID:37079685

    Open questions at the time
    • Full spectrum of transcripts stabilized by loss of ZC3H14 phosphorylation not catalogued
    • Whether CDK12 also phosphorylates ZC3H14 not addressed
  13. 2023 High

    Direct phosphorylation of translation initiation factors 4E-BP1 (Thr46) and eIF4B (Ser422) by CDK13 revealed a new role for this kinase in cap-dependent translation, with CDK13 inhibition reducing MYC synthesis and synergizing with mTOR inhibition.

    Evidence In vitro kinase assay, phosphoproteomics, polysome profiling, drug combination in colorectal cancer cells

    PMID:36882522

    Open questions at the time
    • Relative quantitative contribution of CDK13 versus mTORC1 to steady-state 4E-BP1 phosphorylation in vivo unclear
    • Generalizability beyond colorectal cancer not tested
  14. 2023 High

    CDK13 phosphorylation of NSUN5 at Ser327 was shown to augment m5C RNA modification of ACC1 mRNA, linking CDK13 kinase activity to epitranscriptomic regulation, mRNA stability, and lipid metabolism in prostate cancer.

    Evidence Co-IP/MS, in vitro kinase assay, m5C-RIP, nuclear export assay in prostate cancer cells

    PMID:37845385

    Open questions at the time
    • How many other NSUN5 substrate mRNAs are regulated via CDK13-dependent phosphorylation is unknown
    • Whether CDK12 contributes to NSUN5 phosphorylation not tested
  15. 2024 High

    CDK13 inactivation in the context of CDK12 loss induces transcription-replication conflicts and genomic instability, establishing a synthetic lethal relationship exploitable with CDK13 inhibitors/degraders in CDK12-mutant cancers.

    Evidence CRISPR KO in murine prostate epithelium, organoid and patient-derived xenograft models, CDK13 degrader treatment, genomic instability assays

    PMID:39368479

    Open questions at the time
    • Molecular mechanism by which RNAPII processivity loss leads to replication fork arrest not fully defined
    • Therapeutic index in patients not established
  16. 2026 High

    CDK13 phosphorylation of METTL16 at Ser329 was shown to enhance m6A modification of ACLY mRNA (read by YTHDC2), driving lipogenesis in renal carcinoma, extending CDK13's epitranscriptomic reach to m6A in addition to m5C.

    Evidence In vitro kinase assay, m6A-seq, site-directed mutagenesis, xenograft model in clear cell renal carcinoma

    PMID:41680470

    Open questions at the time
    • Genome-wide scope of CDK13-METTL16-dependent m6A sites not mapped
    • Whether this pathway operates in normal kidney physiology unknown
  17. 2026 High

    CDK13 phosphorylation of RBM39 at Ser117 was shown to enhance RBM39 binding to and stabilization of RAD50 mRNA, increasing DNA repair capacity and conferring cisplatin resistance in endometrial cancer, adding another non-CTD substrate linking CDK13 to genome maintenance.

    Evidence In vitro kinase assay, site-directed mutagenesis, RIP, mRNA stability assay, xenograft

    PMID:41997449

    Open questions at the time
    • Whether RBM39 phosphorylation by CDK13 affects splicing globally or is transcript-specific unknown
    • Contribution relative to CDK12 not assessed
  18. 2026 High

    CDK12/CDK13 inhibition in glioblastoma stem cells was shown to arrest DNA replication forks independently of canonical replication stress pathways, directly coupling RNAPII elongation to replication fork dynamics.

    Evidence THZ531 treatment, ChIP-seq for pSer2-RNAPII, DNA fiber assay, RNA-seq, xenograft

    PMID:41882177

    Open questions at the time
    • Precise molecular intermediaries connecting RNAPII stalling to fork arrest unidentified
    • CDK13-specific versus CDK12-specific contributions to fork dynamics not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the structural basis for CDK13's recognition of its expanding repertoire of non-CTD substrates, (2) which gene-specific transcriptional or RNA processing functions are uniquely CDK13-dependent versus redundant with CDK12 in vivo, and (3) the direct mechanistic link between RNAPII processivity loss and replication fork arrest.
  • No structural model for CDK13 bound to any non-CTD substrate
  • Tissue-specific conditional knockout studies lacking for most organ systems
  • Direct versus indirect effects on splicing, RNA surveillance, and translation not fully deconvolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0140657 ATP-dependent activity 2
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2 GO:0005730 nucleolus 2
Pathway
R-HSA-1643685 Disease 7 R-HSA-8953854 Metabolism of RNA 6 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-73894 DNA Repair 3 R-HSA-1266738 Developmental Biology 2 R-HSA-69306 DNA Replication 2 R-HSA-392499 Metabolism of proteins 1
Partners
CCNKE2F5METTL16NSUN5RBM39SERINC5SRSF1ZC3H14
Complex memberships
CDK13/Cyclin K

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 CDK13 forms a complex with Cyclin K and phosphorylates both Ser2 and Ser5 of the RNA polymerase II CTD, with a preference for substrates pre-phosphorylated at Ser7; crystal structure of CDK13/CyclinK resolved at 2.0 Å showing a C-terminal extension helix with a polybasic cluster and DCHEL motif interacting with bound ATP. Crystal structure (2.0 Å), in vitro kinase assay with recombinant proteins, mutagenesis Cell reports High 26748711
2015 CDK13 associates with Cyclin K and numerous RNA processing factors; CDK13 knockdown in HCT116 cells preferentially affects expression of snoRNA genes and leads to defects in RNA processing, distinct from CDK12 which affects DNA damage response genes. Flag-tag immunopurification, mass spectrometry, RNA-seq, siRNA knockdown Molecular and cellular biology High 25561469
2016 CDK13 (and CDK12) can be covalently inhibited by THZ531, which irreversibly targets a cysteine located outside the kinase domain; CDK12-cyclin K co-crystal with THZ531 defines the binding mode; inhibition causes loss of elongating and hyperphosphorylated RNA Pol II and decreased expression of DNA damage response genes. Co-crystallization, covalent inhibitor design, cell-based transcriptomic analysis Nature chemical biology High 27571479
2007 CDK13 (then called CDC2L5) interacts with L-type cyclins (Cyclin L1/L2) via its kinase domain, and CDK13 and L-type cyclins mutually modulate each other's subcellular localization; overexpression of CDK13 alters alternative splicing of E1a minigene reporter in a dose-dependent manner, with effects counteracted by SR proteins SF2/ASF and SC35. Co-immunoprecipitation, subcellular localization imaging, minigene splicing reporter assay, overexpression in HEK293T cells Biochemical and biophysical research communications Medium 17261272
2006 CDK13 (CDC2L5) localizes to the nucleoplasm, concentrated in nuclear speckles, dependent on its N-terminal RS domain; it directly interacts with the ASF/SF2-associated protein p32 and its overexpression disturbs constitutive splicing and switches alternative splice site selection. Subcellular fractionation, immunofluorescence, yeast two-hybrid and direct protein interaction assay, splicing reporter assay Journal of cellular biochemistry Medium 16721827
2008 CDK13 interacts with HIV-1 Tat both in vivo and in vitro; CDK13 increases HIV-1 mRNA splicing, favors production of the doubly-spliced Nef protein, and suppresses viral production; CDK13 mediates its effect on splicing through phosphorylation of ASF/SF2. Co-immunoprecipitation (in vivo and in vitro), siRNA knockdown, overexpression, viral production assay, in vitro kinase assay Journal of virology Medium 18480452
2019 CDK12 and CDK13 phosphorylate the CTD of RNA polymerase II; inhibition or loss of CDK12/CDK13 triggers intronic polyadenylation site cleavage that suppresses expression of core DNA damage response proteins, provoking a BRCAness phenotype with DNA repair deficiency synergizing with PARP inhibitors. Selective dual inhibitor (SR-4835), siRNA knockdown, RNA-seq, cell viability and combination drug assays Cancer cell High 31668947
2020 CDK13 and CDK12 are substantially redundant regulators of global RNA Pol II processivity and transcription elongation; dual analog-sensitive inhibition of both kinases results in loss of POLII CTD phosphorylation, greatly reduced POLII elongation rates and processivity, and widespread use of alternative 3' polyadenylation sites, causing potent cell death; single inhibition of CDK13 alone produces only modest transcriptional and viability changes. CRISPR-Cas9 analog-sensitive kinase alleles, chemical-genetic inhibition, ChIP-seq, RNA-seq, cell viability assays Science advances High 32917631
2014 CDK13 (and CDK12) regulate axonal elongation in neurons through a common signaling pathway that modulates CDK5 expression; knockdown of CDK13 in P19 cells and primary cortical neurons reduces CDK5 mRNA and protein levels and shortens axonal length; overexpression of CDK5 partially rescues the neurite outgrowth defect. siRNA knockdown, in situ hybridization, Western blot, microarray, conditional knockout mouse, neurite outgrowth assay, rescue overexpression Experimental neurology Medium 24999027
2021 HIV-1 Nef recruits the Cyclin K/CDK13 complex; CDK13 phosphorylates SERINC5 at serine 360 (S360), which is required for Nef-mediated downregulation of SERINC5 from the cell surface and its degradation via endocytic machinery; S360 phosphorylation enhances direct binding between Nef and SERINC5. Affinity purification/mass spectrometry, co-immunoprecipitation, chimeric protein assay, site-directed mutagenesis, cell surface staining Cell reports High 34380030
2016 CDK13 is enriched in the perinucleolar compartment (PNC) and co-localizes throughout the cell cycle with the PNC component PTB; neither Cyclin K nor Cyclin L accumulate in PNC; overexpression of CDK13 increases PNC prevalence, suggesting CDK13 contributes to PNC formation. Immunofluorescence, live-cell imaging, cell cycle staging, overexpression PloS one Medium 26886422
2021 An ADAR1-dependent A-to-I RNA editing event in the CDK13 coding region (c.308A>G) promotes cancer hallmarks in thyroid cancer; this editing increases the nucleolar abundance of the CDK13 protein and contributes to global changes in splicing. Whole transcriptome sequencing, siRNA knockdown, subcellular localization analysis, functional cancer cell assays Molecular cancer Medium 34496885
2023 CDK13 is required for phosphorylation of ZC3H14; ZC3H14 phosphorylation is necessary and sufficient to promote nuclear RNA degradation (surveillance); oncogenic CDK13 mutations fail to activate nuclear RNA surveillance, leading to aberrant stabilization and translation of protein-coding transcripts that accelerate melanoma. Genetic mutation analysis, zebrafish melanoma model, biochemical phosphorylation assays, RNA stability assays, forced aberrant RNA expression Science (New York, N.Y.) High 37079685
2023 CDK13 directly phosphorylates translation initiation factors 4E-BP1 at Thr46 and eIF4B at Ser422; pharmacological or genetic CDK13 inhibition disrupts mRNA translation and reduces MYC oncoprotein synthesis in colorectal cancer cells; CDK13 inhibition combined with mTORC1 inhibitor rapamycin further dephosphorylates these factors and blocks protein synthesis. In vitro kinase assay, phosphoproteomics, polysome profiling, siRNA knockdown, pharmacological inhibition, cell viability assay Oncogene High 36882522
2023 CDK13 interacts with RNA-methyltransferase NSUN5 and phosphorylates it at Ser327; phosphorylated NSUN5 catalyzes m5C modification of ACC1 mRNA; m5C-modified ACC1 mRNA binds ALYREF to enhance mRNA stability and nuclear export, increasing ACC1 expression and lipid deposition in prostate cancer cells. Co-immunoprecipitation with mass spectrometry, in vitro kinase assay, site-directed mutagenesis, m5C RNA immunoprecipitation, nuclear export assay, gain/loss-of-function assays Cell death and differentiation High 37845385
2023 CDK13 inhibition (by AR-A014418 targeting CDK13) represses transcription of PD-L1; CDK13-specific inhibition reduces PD-L1 transcription, while CDK12-specific inhibition enhances intronic polyadenylation of PD-L1; dual CDK12/13 inhibition dramatically suppresses full-length PD-L1 expression. In vitro kinase assay with recombinant proteins, RNAi, overexpression, RNA-seq, flow cytometry, western blot Journal for immunotherapy of cancer Medium 37164450
2023 The CDK12/13 inhibitor SR-4835 binding allosterically destabilizes CDK12/CDK13-Cyclin K interactions, thereby inhibiting kinase activity through an unusual allosteric mechanism distinct from direct active site blocking. Structural mass spectrometry (lysine reactivity profiling, native MS), small molecule inhibitor binding studies Journal of the American Chemical Society Medium 37207290
2021 CDK13 interacts with E2F5 (identified by co-immunoprecipitation/mass spectrometry), and this interaction promotes cell proliferation; transcriptional activation of endogenous CDK13 promotes E2F5 protein expression by facilitating circCDK13 formation, which in turn sponges miR-212-5p/449a to relieve repression of E2F5. Co-immunoprecipitation with mass spectrometry, CRISPR-Cas9 endogenous activation, loss/gain-of-function assays, luciferase reporter assays Journal of experimental & clinical cancer research : CR Medium 33390186
2024 CDK13 inactivation (in the context of CDK12 loss) causes genomic instability by inducing transcription-replication conflicts; CDK12-mutant cancer organoids and patient-derived xenografts are specifically sensitive to CDK13 inhibition or degradation, demonstrating synthetic lethality between CDK12 and CDK13. CRISPR knockout in murine prostate epithelium, organoid models, patient-derived xenografts, CDK13 inhibitor/degrader treatment, genomic instability assays Cell reports. Medicine High 39368479
2019 CDK13 knockout in mice causes embryonic lethality by E16.5, with defects including incomplete secondary palate formation, kidney failure, and congenital heart defects causing circulatory insufficiency, demonstrating an essential developmental role for CDK13. Gene trap knockout mouse, embryo phenotyping, histology, imaging Frontiers in cell and developmental biology Medium 31440507
2026 CDK13 directly phosphorylates METTL16 at Ser329, augmenting its catalytic activity to install m6A modifications on ACLY mRNA; m6A marks on ACLY mRNA are recognized by YTHDC2 reader protein, leading to mRNA stabilization, increased acetyl-CoA production, and lipogenesis in clear cell renal carcinoma. Phosphoproteomic analysis, in vitro kinase assay, site-directed mutagenesis, m6A-seq, RNA immunoprecipitation, pharmacological inhibition, in vivo xenograft Experimental & molecular medicine High 41680470
2026 CDK13 directly phosphorylates RBM39 at serine 117; this phosphorylation enhances RBM39 binding to and stabilization of RAD50 mRNA, increasing RAD50 protein levels and DNA repair capacity, thereby driving cisplatin resistance in endometrial cancer. Phosphoproteomic analysis, in vitro kinase assay, site-directed mutagenesis, RNA immunoprecipitation, mRNA stability assay, in vivo xenograft The Journal of biological chemistry High 41997449
2026 CDK12/CDK13 inhibition in glioblastoma stem cells causes rapid genome-wide loss of RNAPII CTD serine-2 phosphorylation, abolishing transcriptional elongation; CDK12/13 inhibition also arrests DNA replication fork progression in a manner distinct from other transcriptional CDK inhibitors, directly linking RNAPII elongation to replication fork dynamics. Chemical inhibition with THZ531, ChIP-seq for pSer2-RNAPII, DNA fiber assay, RNA-seq, xenograft mouse model EMBO molecular medicine High 41882177
2023 Cyclin O (CCNO) interacts with CDK13 (identified by co-immunoprecipitation) and promotes cancer cell proliferation signaling activation; CDK13 inhibitor effectively inhibits the oncological effect of CCNO overexpression. Co-immunoprecipitation, western blot, CDK13 inhibitor treatment, xenograft model Journal of thoracic disease Low 37197505

Source papers

Stage 0 corpus · 76 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors. Nature chemical biology 280 27571479
2019 Therapeutic Targeting of CDK12/CDK13 in Triple-Negative Breast Cancer. Cancer cell 237 31668947
2015 Characterization of human cyclin-dependent kinase 12 (CDK12) and CDK13 complexes in C-terminal domain phosphorylation, gene transcription, and RNA processing. Molecular and cellular biology 164 25561469
2020 CDK13 cooperates with CDK12 to control global RNA polymerase II processivity. Science advances 131 32917631
2015 Structural and Functional Analysis of the Cdk13/Cyclin K Complex. Cell reports 126 26748711
2012 Cyclin K goes with Cdk12 and Cdk13. Cell division 95 22512864
2018 Human CDK12 and CDK13, multi-tasking CTD kinases for the new millenium. Transcription 83 30319007
2012 Frequent amplification of CENPF, GMNN and CDK13 genes in hepatocellular carcinomas. PloS one 79 22912832
2000 Protein-only inheritance in yeast: something to get [PSI+]-ched about. Trends in cell biology 68 10675903
2023 CDK13 promotes lipid deposition and prostate cancer progression by stimulating NSUN5-mediated m5C modification of ACC1 mRNA. Cell death and differentiation 67 37845385
2002 Bacillus subtilis CheD is a chemoreceptor modification enzyme required for chemotaxis. The Journal of biological chemistry 59 12011078
2022 Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13. Journal of medicinal chemistry 56 35938508
2007 CDK13/CDC2L5 interacts with L-type cyclins and regulates alternative splicing. Biochemical and biophysical research communications 56 17261272
2006 CDC2L5, a Cdk-like kinase with RS domain, interacts with the ASF/SF2-associated protein p32 and affects splicing in vivo. Journal of cellular biochemistry 53 16721827
2001 CheC is related to the family of flagellar switch proteins and acts independently from CheD to control chemotaxis in Bacillus subtilis. Molecular microbiology 51 11722727
1998 Isolation and characterization of two novel metalloproteinase genes linked to the Cdc2L locus on human chromosome 1p36.3. Genomics 51 9740677
2007 Autosomal recessive CHED associated with novel compound heterozygous mutations in SLC4A11. Cornea 48 17667634
2021 CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 contributes to prostate carcinogenesis. Journal of experimental & clinical cancer research : CR 47 33390186
2008 CDK13, a new potential human immunodeficiency virus type 1 inhibitory factor regulating viral mRNA splicing. Journal of virology 47 18480452
1999 Abnormalities in the p34cdc2-related PITSLRE protein kinase gene complex (CDC2L) on chromosome band 1p36 in melanoma. Cancer genetics and cytogenetics 47 9973934
2021 An ADAR1-dependent RNA editing event in the cyclin-dependent kinase CDK13 promotes thyroid cancer hallmarks. Molecular cancer 46 34496885
2023 Oncogenic CDK13 mutations impede nuclear RNA surveillance. Science (New York, N.Y.) 40 37079685
2017 Phenotypic and molecular characterisation of CDK13-related congenital heart defects, dysmorphic facial features and intellectual developmental disorders. Genome medicine 40 28807008
2009 Mutational spectrum of SLC4A11 in autosomal recessive CHED in Saudi Arabia. Investigative ophthalmology & visual science 38 19369245
2023 Dual inhibition of CDK12 and CDK13 uncovers actionable vulnerabilities in patient-derived ovarian cancer organoids. Journal of experimental & clinical cancer research : CR 37 37202753
2017 Heterozygous mutations affecting the protein kinase domain of CDK13 cause a syndromic form of developmental delay and intellectual disability. Journal of medical genetics 36 29021403
1999 Homozygosity mapping and linkage analysis demonstrate that autosomal recessive congenital hereditary endothelial dystrophy (CHED) and autosomal dominant CHED are genetically distinct. The British journal of ophthalmology 36 10209448
2022 Dual Inhibition of CDK12/CDK13 Targets Both Tumor and Immune Cells in Ovarian Cancer. Cancer research 32 35857807
1995 Results of penetrating keratoplasty in CHED. Congenital hereditary endothelial dystrophy. Cornea 30 7712731
2007 The CheC phosphatase regulates chemotactic adaptation through CheD. The Journal of biological chemistry 29 17908686
2014 Cdk12 and Cdk13 regulate axonal elongation through a common signaling pathway that modulates Cdk5 expression. Experimental neurology 28 24999027
2024 CDK12 loss drives prostate cancer progression, transcription-replication conflicts, and synthetic lethality with paralog CDK13. Cell reports. Medicine 25 39368479
1985 Genetics of methyl-accepting chemotaxis proteins in Escherichia coli: cheD mutations affect the structure and function of the Tsr transducer. Journal of bacteriology 25 3155720
2016 Borrelia burgdorferi CheD Promotes Various Functions in Chemotaxis and the Pathogenic Life Cycle of the Spirochete. Infection and immunity 24 27021244
2018 De novo variants in CDK13 associated with syndromic ID/DD: Molecular and clinical delineation of 15 individuals and a further review. Clinical genetics 21 29393965
2018 CDK13-related disorder. Advances in genetics 21 30904094
2019 Insight into the molecular mechanism of LINC00152/miR-215/CDK13 axis in hepatocellular carcinoma progression. Journal of cellular biochemistry 19 31297882
2016 CDK13, a Kinase Involved in Pre-mRNA Splicing, Is a Component of the Perinucleolar Compartment. PloS one 19 26886422
2007 Haploinsufficiency of the cdc2l gene contributes to skin cancer development in mice. Carcinogenesis 19 17389615
2023 CDK13 phosphorylates the translation machinery and promotes tumorigenic protein synthesis. Oncogene 16 36882522
2019 Mouse Model of Congenital Heart Defects, Dysmorphic Facial Features and Intellectual Developmental Disorders as a Result of Non-functional CDK13. Frontiers in cell and developmental biology 16 31440507
2022 CDK13-related disorder: Report of a series of 18 previously unpublished individuals and description of an epigenetic signature. Genetics in medicine : official journal of the American College of Medical Genetics 15 35063350
2019 Observation of nine previously reported and 10 non-reported SLC4A11 mutations among 20 Iranian CHED probands and identification of an MPDZ mutation as possible cause of CHED and FECD in one family. The British journal of ophthalmology 15 31420327
1985 Aberrant regulation of methylesterase activity in cheD chemotaxis mutants of Escherichia coli. Journal of bacteriology 15 3917995
2021 HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity. Cell reports 14 34380030
2012 Elucidation of the multiple roles of CheD in Bacillus subtilis chemotaxis. Molecular microbiology 13 22931217
2004 Analysis of chimeric chemoreceptors in Bacillus subtilis reveals a role for CheD in the function of the McpC HAMP domain. Journal of bacteriology 13 15317802
2021 CDK13-Mediated Cell Cycle Disorder Promotes Tumorigenesis of High HMGA2 Expression Gastric Cancer. Frontiers in molecular biosciences 12 34513922
2017 Redefining the phenotypic spectrum of de novo heterozygous CDK13 variants: Three patients without cardiac defects. European journal of medical genetics 12 29222009
2012 The importance of the interaction of CheD with CheC and the chemoreceptors compared to its enzymatic activity during chemotaxis in Bacillus subtilis. PloS one 12 23226535
2011 Functional Imaging of Pheochromocytoma with Ga-DOTATOC and C-HED in a Genetically Defined Rat Model of Multiple Endocrine Neoplasia. International journal of molecular imaging 12 21755051
1999 Exclusion of AR-CHED from the chromosome 20 region containing the PPMD and AD-CHED loci. Ophthalmic genetics 12 10617922
2023 MYC up-regulation confers vulnerability to dual inhibition of CDK12 and CDK13 in high-risk Group 3 medulloblastoma. Journal of experimental & clinical cancer research : CR 10 37599362
2023 Structural Mass Spectrometry Probes the Inhibitor-Induced Allosteric Activation of CDK12/CDK13-Cyclin K Dissociation. Journal of the American Chemical Society 8 37207290
2019 One-month-old girl presenting with pseudohypoaldosteronism leading to the diagnosis of CDK13-related disorder: a case report and review of the literature. Journal of medical case reports 8 31883531
2023 AR-A014418 regulates intronic polyadenylation and transcription of PD-L1 through inhibiting CDK12 and CDK13 in tumor cells. Journal for immunotherapy of cancer 7 37164450
2022 The utility of DNA methylation signatures in directing genome sequencing workflow: Kabuki syndrome and CDK13-related disorder. American journal of medical genetics. Part A 6 35043535
2021 SLC4A11 mutations causative of congenital hereditary endothelial dystrophy (CHED) progressing to Harboyan syndrome in consanguineous Pakistani families. Molecular biology reports 6 34637099
2024 Physiological and pathological roles of the transcriptional kinases CDK12 and CDK13 in the central nervous system. Cell death and differentiation 5 39533070
2021 Wolfram-like syndrome with bicuspid aortic valve due to a homozygous missense variant in CDK13. Journal of human genetics 5 33879837
2023 A Prenatal Presentation of CDK13-Related Disorder with a Novel Pathogenic Variant. Case reports in genetics 4 37351084
2024 Investigation of the functional impact of CHED- and FECD4-associated SLC4A11 mutations in human corneal endothelial cells. PloS one 3 38252645
2025 CDK13-Related Disorder: Novel Insights From A Series of 27 Cases and Recommendations for Clinical Management. Clinical genetics 2 39971730
2024 ARID1A loss promotes RNA editing of CDK13 in an ADAR1-dependent manner. BMC biology 2 38835016
2024 Methionine restriction promotes cisplatin sensitivity of gastric cancer resistant cells by down-regulating circ-CDK13 level. Experimental cell research 2 39488295
2023 Cyclin O promotes lung cancer progression and cetuximab resistance via cell cycle regulation and CDK13 interaction. Journal of thoracic disease 1 37197505
2023 12-year follow-up of the first endothelial keratoplasty without Descemet stripping in a 3-month newborn with Congenital Hereditary Endothelial Dystrophy (CHED). BMC ophthalmology 1 37880638
2026 CDK12 and CDK13 in oncology: from RNA regulation to therapeutic targeting. Cellular oncology (Dordrecht, Netherlands) 0 41491919
2026 CDK13 drives clear cell renal carcinoma through METTL16-mediated m6A modification of ACLY mRNA. Experimental & molecular medicine 0 41680470
2026 Roles of CDK12/CDK13 and development of inhibitors and degraders. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 0 41687544
2026 CDK12/CDK13 inhibition disrupts transcriptional elongation and replication fork progression in glioblastoma. EMBO molecular medicine 0 41882177
2026 Sex differences in congenital hereditary endothelial dystrophy (CHED) and Slc4a11-/- mouse model of CHED. Biology of sex differences 0 41896991
2026 Phosphorylation of RBM39 by CDK13 stabilizes RAD50 mRNA to drive cisplatin resistance in endometrial cancer. The Journal of biological chemistry 0 41997449
2025 Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignature. Clinical epigenetics 0 39800774
2025 CheD is a Key Protein Involved in Regulating the Chemotaxis and Pathogenic Life Cycle of Agrobacterium fabrum. Current microbiology 0 41057670
2023 Deciphering congenital heart defects, facial dysmorphism and intellectual developmental disorder (CHDFIDD) associated with constitutional CDK13 pathogenic variants - case report and literature review. Annals of agricultural and environmental medicine : AAEM 0 38549490