CDK11B

Summary

CDK11B (cyclin dependent kinase 11B, HGNC:1729) is a protein-coding gene on chromosome 1p36.33, encoding Cyclin-dependent kinase 11B (P21127). Cyclin-dependent protein kinase that acts as a regulator of transcription and pre-mRNA splicing. It is a selective cancer dependency (DepMap: 80.0% of cell lines).

This gene encodes a member of the serine/threonine protein kinase family. Members of this kinase family are known to be essential for eukaryotic cell cycle control. Due to a segmental duplication, this gene shares very high sequence identity with a neighboring gene. These two genes are frequently deleted or altered in neuroblastoma. The protein kinase encoded by this gene can be cleaved by caspases and may play a role in cell apoptosis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 984 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 35 total
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 80.0% of screened cell lines
• MANE Select transcript: NM_033486

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1729
Approved symbol	CDK11B
Name	cyclin dependent kinase 11B
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Aliases	CDK11-p110, CDK11-p58, CDK11-p46
Ensembl gene	ENSG00000248333
Ensembl biotype	protein_coding
OMIM	176873
Entrez	984

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 16 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000340677, ENST00000341028, ENST00000341832, ENST00000407249, ENST00000611150, ENST00000615951, ENST00000626918, ENST00000629289, ENST00000629312, ENST00000892873, ENST00000892874, ENST00000892875, ENST00000892876, ENST00000892877, ENST00000931742, ENST00000931743, ENST00000931744, ENST00000931745, ENST00000931746

RefSeq mRNA: 6 — MANE Select: NM_033486 NM_001291345, NM_001787, NM_033486, NM_033487, NM_033489, NM_033490

CCDS: CCDS72682, CCDS72683, CCDS72684

Canonical transcript exons

ENST00000341832 — 20 exons

Exon	Start	End
ENSE00001603328	1641048	1641113
ENSE00001609289	1642386	1642508
ENSE00001609765	1641662	1641820
ENSE00001615731	1636682	1636798
ENSE00001617779	1637408	1637513
ENSE00001642055	1636333	1636481
ENSE00001648532	1640277	1640452
ENSE00001649685	1638500	1638590
ENSE00001658779	1636897	1637004
ENSE00001673993	1637081	1637202
ENSE00001761950	1635937	1636126
ENSE00001772575	1637762	1637883
ENSE00001780919	1641906	1642001
ENSE00003633361	1655369	1655484
ENSE00003713782	1652439	1652566
ENSE00003719976	1635225	1635856
ENSE00003730225	1657375	1657498
ENSE00003743744	1649499	1649637
ENSE00003754733	1645126	1645262
ENSE00003906595	1658914	1659004

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.5190 / max 1248.7644, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9812	34.2100	1818
9814	2.4930	1223
9813	0.8160	448

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.48	gold quality
gastrocnemius	UBERON:0001388	95.58	gold quality
muscle of leg	UBERON:0001383	94.93	gold quality
mucosa of stomach	UBERON:0001199	94.25	gold quality
left testis	UBERON:0004533	94.15	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.98	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.96	gold quality
right testis	UBERON:0004534	93.93	gold quality
lower esophagus	UBERON:0013473	93.93	gold quality
granulocyte	CL:0000094	93.73	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.51	gold quality
mucosa of transverse colon	UBERON:0004991	93.48	gold quality
transverse colon	UBERON:0001157	93.45	gold quality
small intestine	UBERON:0002108	93.45	gold quality
testis	UBERON:0000473	93.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.14	gold quality
right lung	UBERON:0002167	93.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.01	gold quality
spleen	UBERON:0002106	92.98	gold quality
skeletal muscle tissue	UBERON:0001134	92.97	gold quality
colon	UBERON:0001155	92.80	gold quality
fundus of stomach	UBERON:0001160	92.76	gold quality
skin of leg	UBERON:0001511	92.65	gold quality
apex of heart	UBERON:0002098	92.56	gold quality
heart left ventricle	UBERON:0002084	92.52	gold quality
substantia nigra	UBERON:0002038	92.47	gold quality
blood	UBERON:0000178	92.43	gold quality
intestine	UBERON:0000160	92.40	gold quality
zone of skin	UBERON:0000014	92.37	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	29.13
E-ANND-3	yes	5.67
E-GEOD-106540	no	196.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ETS1, MYC, NFE2L1, POU2F3

miRNA regulators (miRDB)

19 targeting CDK11B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-4671-5P	97.10	65.70	93
HSA-MIR-7847-3P	96.63	64.58	952

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 80.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 35)

• interaction with cyclin D3 (PMID:12082095)
• CDK11p110 and casein kinase 2 negatively regulate tyrosine hydroxylase[TH] catecholamine biosynthetic activity since phosphoserine 19 of TH requires 14-3-3 binding for optimal enzyme activity and a decreased rate of dephosphorylation (PMID:14675149)
• the PITSLRE IRES interacts with the Unr protein, which is more prominently expressed at the G2/M stage of the cell cycle (PMID:15330758)
• These data suggest that cyclin D3/CDK11p58 signaling is involved in the negative regulation of AR function. (PMID:17698582)
• Although hCDK11 has nearly 80% amino acid sequence identity to hCDK8, siRNA-knockdown study revealed that hCDK8 and hCDK11 possess opposing functions in viral activator VP16-dependent transcriptional regulation. (PMID:18651850)
• CDK11(p58) is involved in the negative regulation of VDR. (PMID:19538938)
• eIF3f mediates restriction of HIV-1 expression through a set of factors that includes eIF3f, the SR protein 9G8, and the cyclin-dependent kinase 11 (CDK11). (PMID:19854136)
• Thr-370 is responsible for the autophosphorylation, dimerization, and kinase activity of CDK11(p58). Moreover, Thr-370 mutants might affect CDK11(p58)-mediated signaling pathways. (PMID:21078675)
• CDK11(p58), which accumulates only in the vicinity of mitotic centrosomes, directly interacts with the centriole-associated protein kinase Plk4 that regulates centriole number in cells. (PMID:21297952)
• Taken together, these results provide evidence for the novel role of CDK11p46 in the regulation of translation and cell apoptosis. (PMID:21371428)
• These data suggest that CDK11 may play a vital role in cell cycle re-entry in Alzheimer disease neurons in an APP-dependent manner. (PMID:21461981)
• Since PITSLRE/CDK11 regulates autophagy in both Drosophila and human cells, this kinase represents a novel phylogenetically conserved component of the autophagy machinery. (PMID:21808150)
• We have identified a correlation between two exon 7 mutations of the CDC2L1 gene and keloid disease. (PMID:22188294)
• CDK11 signaling is essential in osteosarcoma cell growth and survival, further elucidating the regulatory mechanisms controlling the expression of CDK11 and ultimately develop a CDK11 inhibitor that may provide therapeutic benefit against osteosarcoma. (PMID:22791884)
• CHK2 kinase constitutively phosphorylates CDK11(p110) in a DNA damage-independent manner. (PMID:23178491)
• CDK11 is critical for the growth and proliferation of liposarcoma cells. (PMID:24007862)
• CDK11(p58) kinase activity appears to be involved in early events in the establishment of the centromere protection machinery. (PMID:24436071)
• Data indicate that CDK11p58 is an anti-metastatic gene in ERalpha-positive breast cancer and that the regulation of integrin beta3 by CDK11p58 via the repression of ERalpha signaling may constitute part of a signaling pathway underlying breast cancer invasion. (PMID:25106495)
• silencing induces cell death in osteosarcoma (PMID:25348612)
• Hepsin suppressed CDK11p58 internal ribosome entry site activity in prostate cancer cells by modulating UNR expression and eIF-2alpha phosphorylation. (PMID:25576733)
• CDK11 and CK2 expression are individually essential for breast cancer cell survival, including TNBC. (PMID:25837326)
• Real-time PCR and dual-luciferase assay showed CDK11(p58) inhibited the mRNA levels of VEGF and the promoter activity of VEGF (PMID:26470709)
• CDK11 was found associated with the TREX/THOC, which recruited this kinase to DNA. Once at the viral genome, CDK11 phosphorylated serines at position 2 in the CTD of RNAPII, which increased levels of cleavage and polyadenylation factors at the HIV 3’ end. In its absence, cleavage of viral transcripts was greatly attenuated. (PMID:26567509)
• CDK11 has a role in human cancers [review] (PMID:27049727)
• we showed high expression of CDK11 in metastatic and recurrent ovarian cancer and demonstrated that CDK11 is essential for ovarian cancer cell growth and survival in vitro and in vivo. (PMID:27207777)
• These findings suggest that CDK11 is involved in the regulation of AR pathway and AR can be a potential novel prognostic marker and therapeutic target for osteosarcoma treatment. (PMID:28262798)
• DNA methylation exists in the CDC2L1 gene promoter region in keloid tissue fibroblasts. DNA methylation of the CDC2L1 gene promoter region dramatically inhibits the expression of CDK11p58 protein in keloid tissues. (PMID:29204684)
• These results provided evidence that CDK11(p110) play a critical role in the tumorigenicity of esophageal squamous cell carcinoma cells, which suggests that CDK11(p110) may be a promising therapeutic target in esophageal squamous cell carcinoma. (PMID:30722725)
• Transcriptional activation of CBFbeta by CDK11(p110) is necessary to promote osteosarcoma cell proliferation (PMID:31610798)
• A cyclin-dependent kinase, CDK11/p58, represses cap-dependent translation during mitosis. (PMID:32030451)
• CDK11 is required for transcription of replication-dependent histone genes. (PMID:32367068)
• CDK11 negatively regulates Wnt/beta-catenin signaling in the endosomal compartment by affecting microtubule stability. (PMID:32587772)
• Therapeutic potential of CDK11 in cancer. (PMID:36855776)
• CDK10, CDK11, FOXO1, and FOXO3 Gene Expression in Alzheimer’s Disease Encephalic Samples. (PMID:36988771)
• CDK11 facilitates centromeric transcription to maintain centromeric cohesion during mitosis. (PMID:38019613)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk11b	ENSDARG00000102546
mus_musculus	Cdk11b	ENSMUSG00000029062
rattus_norvegicus	AABR07040938.1	ENSRNOG00000005402
rattus_norvegicus	Cdk11b	ENSRNOG00000017213
drosophila_melanogaster	Pitslre	FBGN0016696

Paralogs (26): CDKL3 (ENSG00000006837), CDKL5 (ENSG00000008086), CDK11A (ENSG00000008128), CDK14 (ENSG00000058091), CDK17 (ENSG00000059758), CDK13 (ENSG00000065883), CDKL1 (ENSG00000100490), CDK16 (ENSG00000102225), CDK6 (ENSG00000105810), PRP4K (ENSG00000112739), CDK18 (ENSG00000117266), CDK2 (ENSG00000123374), CDK8 (ENSG00000132964), CDK7 (ENSG00000134058), CDK4 (ENSG00000135446), CDK9 (ENSG00000136807), CDK15 (ENSG00000138395), CDKL2 (ENSG00000138769), CDK19 (ENSG00000155111), CDK20 (ENSG00000156345), CDK5 (ENSG00000164885), CDK12 (ENSG00000167258), CDK1 (ENSG00000170312), CDK10 (ENSG00000185324), CDKL4 (ENSG00000205111), CDK3 (ENSG00000250506)

Protein

Protein identifiers

Cyclin-dependent kinase 11B — P21127 (reviewed: P21127)

Alternative names: Cell division cycle 2-like protein kinase 1, Cell division protein kinase 11B, Galactosyltransferase-associated protein kinase p58/GTA, PITSLRE serine/threonine-protein kinase CDC2L1, p58 CLK-1

All UniProt accessions (6): A0A087WYI9, A0A087X1I0, A0A0D9SEI3, A0A0D9SEN2, A0A0D9SER5, P21127

UniProt curated annotations — full annotation on UniProt →

Function. Cyclin-dependent protein kinase that acts as a regulator of transcription and pre-mRNA splicing. Acts as a key regulator of pre-mRNA splicing by mediating phosphorylation of SF3B1, enabling the association between SF3B1 and U5 and U6 snRNAs in the activated spliceosome, thereby promoting spliceosome assembly. Also acts as a regulator of transcription by phosphorylating ‘Ser-2’ of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A. Involved in replication-dependent transcription of histone genes: binds to histone genes and phosphorylates POLR2A at ‘Ser-2’ of the CTD to specifically control transcriptional elongation of histones and recruitment of 3’-end processing factors. Part of a transcription checkpoint upstream of CDK9, which regulates promoter-proximal pausing by RNA polymerase II, a transcription halt following transcription initiation, but prior to elongation. Probably regulates promoter-proximal pausing by mediating phosphorylation of POLR2A at ‘Ser-2’ of the CTD. Isoform expressed in a non-cell cycle-dependent manner. Isoform specifically expressed during the G2-M phases of the cell cycle. Phosphorylates ‘Ser-2’ of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A. Promotes centromeric transcription to maintain centromeric cohesion during mitosis.

Subunit / interactions. Associates with cyclin-L1 (CCNL1) or cyclin-L2 (CCNL2) to form an active cyclin-L-CDK11 cyclin-dependent protein kinase complex. Interacts with SAP30BP; promoting assenbly of the cyclin-L-CDK11 cyclin-dependent protein kinase complex. Interacts with CASP8AP2/FLASH; promoting 3’ end cleavage of histone pre-mRNAs. Associates with cyclin-L1 (CCNL1) or cyclin-L2 (CCNL2) to form an active cyclin-L-CDK11 cyclin-dependent protein kinase complex. Interacts with SFRS7. Forms complexes with pre-mRNA-splicing factors, including at least SRSF1, SRSF2 and SRSF7/SLU7. Interacts with isoform 5 of MYO18A. The cleaved p110 isoform, p110C, binds to the serine/threonine kinase PAK1 and RANBP9. p110C interacts with RNPS1. Associates with cyclin-D3 (CCND3) to form an active cyclin-dependent protein kinase complex. (Microbial infection) Interacts with human herpes virus 1 (HHV-1) transcriptional regulator ICP22.

Subcellular location. Nucleus. Chromosome. Cytoplasm Nucleus Nucleus. Centromere.

Tissue specificity. Expressed ubiquitously. Some evidence of isoform-specific tissue distribution.

Post-translational modifications. During FAS- or TNF-induced apoptosis, isoform SV9 is cleaved by caspases to produce p110C, a fragment that contains the C-terminal kinase domain. Phosphorylation at Ser-115 creates a binding site for 14-3-3 proteins. p110C can be autophosphorylated.

Activity regulation. Phosphorylation at Thr-448 or Tyr-449 inactivates the enzyme, while phosphorylation at Thr-595 activates it. CDK11 (CDK11A and/or CDK11B) is specifically inhibited by the anticancer agent OTS964.

Induction. Induced in G2/M phase of the cell cycle.

Miscellaneous. Duplicated gene. CDK11A and CDK11B encode almost identical protein kinases of 110 kDa that contain at their C-termini the open reading frame of a smaller 58 kDa isoform which is expressed following IRES-mediated alternative initiation of translation. Many references talk about ‘p110 isoforms’ but it is not yet known if this refers to CDK11A and/or CDK11B or one/some of the isoforms of each. Produced by alternative initiation at Met-357 of isoform SV9 via an internal ribosomal entry site (IRES).

Similarity. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Isoforms (10)

UniProt ID	Names	Canonical?
P21127-1	SV9, CDK11-p110	yes
P21127-2	SV1, Alpha 2-1
P21127-3	2, Alpha 2-2
P21127-4	3, Alpha 1
P21127-5	SV4
P21127-6	SV5
P21127-8	8, Alpha 2-3
P21127-9	SV10
P21127-10	SV11, Alpha 2-4
P21127-12	7, CDK11-p58

RefSeq proteins (6): NP_001278274, NP_001778, NP_277021, NP_277022, NP_277024, NP_277025 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR045267	CDK11/PITSLRE_STKc	Domain
IPR050108	CDK	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.22 — cyclin-dependent kinase (BRENDA: 49 organisms, 441 substrates, 555 inhibitors, 8 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ADAQHATPPKKKRKVEDPKDF	0.046–0.521	2
ATP	0.0052–0.017	2
FIN1	0.003	1
PKTPKKAKKL	0.0029	1

Catalyzed reactions (Rhea), 3 shown:

• [DNA-directed RNA polymerase] + ATP = phospho-[DNA-directed RNA polymerase] + ADP + H(+) (RHEA:10216)
• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (98 total): sequence conflict 16, modified residue 13, helix 13, sequence variant 11, strand 10, compositionally biased region 9, splice variant 9, turn 5, mutagenesis site 4, binding site 2, region of interest 2, chain 1, domain 1, active site 1, cross-link 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9QKZ	ELECTRON MICROSCOPY	2.3
9QKT	ELECTRON MICROSCOPY	2.4
9QL1	ELECTRON MICROSCOPY	2.4
7UKZ	X-RAY DIFFRACTION	2.6
9I9I	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21127-F1	65.24	0.23

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 562 (proton acceptor)

Ligand- & substrate-binding residues (2): 444–452; 467

Post-translational modifications (14): 47, 72, 115, 283, 448, 449, 482, 488, 589, 594, 595, 751, 752, 641

Mutagenesis-validated functional residues (4):

Position	Phenotype
445	does not affect binding to anticancer agent ots964.
516	decreased binding to anticancer agent ots964.
579	enhanced binding to anticancer agent ots964.
579	induces resistance to inhibition by anticancer agent ots964.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-1640170	Cell Cycle
R-HSA-380287	Centrosome maturation
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 145 (showing top): GOBP_CHROMOSOME_ORGANIZATION, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_GROWTH, NKX61_01, KESHELAVA_MULTIPLE_DRUG_RESISTANCE, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_SISTER_CHROMATID_COHESION, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CENTROSOME_CYCLE, GOBP_RNA_SPLICING, HP1SITEFACTOR_Q6, GOBP_MITOTIC_CELL_CYCLE, BIOCARTA_HIVNEF_PATHWAY, NKX22_01

GO Biological Process (11): mitotic cell cycle (GO:0000278), regulation of cell growth (GO:0001558), regulation of DNA-templated transcription (GO:0006355), protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), regulation of apoptotic process (GO:0042981), regulation of RNA splicing (GO:0043484), regulation of centrosome cycle (GO:0046605), regulation of mRNA processing (GO:0050684), regulation of cell cycle (GO:0051726), mitotic sister chromatid cohesion, centromeric (GO:0071962)

GO Molecular Function (10): RNA binding (GO:0003723), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), cyclin-dependent protein serine/threonine kinase activity (GO:0004693), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Centrosome maturation	1
G2/M Transition	1
Cell Cycle, Mitotic	1
Mitotic G2-G2/M phases	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell cycle	2
regulation of cellular component organization	2
regulation of gene expression	2
protein kinase activity	2
mitotic nuclear division	1
cell growth	1
regulation of growth	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
apoptotic process	1
regulation of programmed cell death	1
RNA splicing	1
regulation of primary metabolic process	1
centrosome cycle	1
regulation of cell cycle process	1
regulation of microtubule-based process	1
mRNA processing	1
regulation of mRNA metabolic process	1
regulation of cellular process	1
mitotic sister chromatid cohesion	1
centromeric sister chromatid cohesion	1
nucleic acid binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein serine/threonine kinase activity	1
cyclin-dependent protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
serine/threonine protein kinase complex	1

Protein interactions and networks

STRING

1596 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK11B	MMP23B	O75900	858
CDK11B	MMP21	Q8N119	763
CDK11B	CCNL1	Q9UK58	603
CDK11B	RNPS1	Q15287	603
CDK11B	CDK13	Q14004	560
CDK11B	SUFU	Q9UMX1	543
CDK11B	EVI5	O60447	494
CDK11B	TBC1D1	Q86TI0	493
CDK11B	EIF4B	P23588	492
CDK11B	SFN	P31947	490
CDK11B	CCNL2	Q96S94	473
CDK11B	NBPF1	Q3BBV0	447
CDK11B	PTPRZ1	P23471	434
CDK11B	ID3	Q02535	431
CDK11B	VPS37B	Q9H9H4	426

IntAct

103 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
CSNK2A1	EIF3J	psi-mi:“MI:0914”(association)	0.810
CSNK2A2	EIF3J	psi-mi:“MI:0914”(association)	0.790
NRP1	CSNK2A2	psi-mi:“MI:0914”(association)	0.790
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
CDK11B	KAT7	psi-mi:“MI:0915”(physical association)	0.730
CDK11B	KAT7	psi-mi:“MI:0403”(colocalization)	0.730
KAT7	CDK11B	psi-mi:“MI:0407”(direct interaction)	0.730
KAT7	CDK11B	psi-mi:“MI:0915”(physical association)	0.730
PAK1	CDK11B	psi-mi:“MI:0915”(physical association)	0.690
CDK11B	PAK1	psi-mi:“MI:0915”(physical association)	0.690
CSNK2B	RPS6KA5	psi-mi:“MI:0914”(association)	0.660
CSNK2B	NMT2	psi-mi:“MI:0914”(association)	0.660
CDK11B	CDC37	psi-mi:“MI:0914”(association)	0.640
FKBP5	IKBKB	psi-mi:“MI:0914”(association)	0.640
CSNK2A2	PES1	psi-mi:“MI:0914”(association)	0.640
YWHAE	RGS12	psi-mi:“MI:0914”(association)	0.610
YWHAE	SRSF10	psi-mi:“MI:0914”(association)	0.560
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
CCNL1	CDK11B	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530

BioGRID (244): CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDK11B (Affinity Capture-MS)

ESM2 similar proteins: A2X6X1, A2XUW1, A9RVK2, B9FMJ3, F4HRJ4, F4I114, F4ICB6, O08678, O08679, O45818, P21127, P24788, P27448, P78362, Q03141, Q05512, Q08DZ2, Q09437, Q13523, Q23357, Q39008, Q40541, Q5R814, Q5RKH1, Q5Z9J0, Q5ZCI1, Q61136, Q6K5F8, Q6L5D4, Q6L5F7, Q6Z829, Q7KZI7, Q7XUF4, Q8H0U8, Q8RX66, Q8VHF0, Q8VHJ5, Q96VK3, Q9C9U4, Q9C9U5

Diamond homologs: A1CL96, A1D624, A2QU77, A2X6X1, A2XUW1, A3LUB9, A4QXX4, A8XA58, O13958, O55076, O61847, O96821, P00546, P06493, P0C661, P0CS76, P0CS77, P11440, P21127, P23111, P23437, P23572, P24033, P24100, P24788, P24923, P24941, P29618, P29619, P34112, P34117, P34556, P35567, P39073, P39951, P43063, P43450, P46892, P48734, P48963

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
CDK11A	up-regulates	CDK11B	phosphorylation
CDK11B	unknown	EIF3F	phosphorylation
CDK7	“up-regulates activity”	CDK11B	phosphorylation
CHEK2	“up-regulates activity”	CDK11B	phosphorylation
CDK11B	“up-regulates activity”	SRSF1	phosphorylation
CDK11B	“up-regulates activity”	RBM17	phosphorylation
CDK11B	“up-regulates activity”	PRPF4	phosphorylation
CDK11B	“up-regulates activity”	THRAP3	phosphorylation
CDK11B	down-regulates	EIF3F	phosphorylation
CDK11B	“form complex”	CyclinD3/CDK11B	binding
CDK11B	“up-regulates activity”	EIF3F	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signal transduction by L1	5	31.3×	2e-04
Negative epigenetic regulation of rRNA expression	5	15.6×	3e-03
Regulation of PTEN stability and activity	5	11.1×	7e-03
Toll Like Receptor TLR6:TLR2 Cascade	5	10.6×	7e-03
Toll Like Receptor 2 (TLR2) Cascade	5	10.4×	7e-03
Toll Like Receptor TLR1:TLR2 Cascade	5	10.1×	7e-03
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	5	9.2×	9e-03
Regulation of TP53 Activity through Phosphorylation	6	8.5×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

35 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3170 predictions. Top by Δscore:

Variant	Effect	Δscore
1:1635959:C:A	donor_gain	1.0000
1:1636327:GCTCA:G	donor_loss	1.0000
1:1636328:CTCA:C	donor_loss	1.0000
1:1636329:TCA:T	donor_loss	1.0000
1:1636330:CA:C	donor_loss	1.0000
1:1636331:A:AC	donor_gain	1.0000
1:1636332:C:CC	donor_gain	1.0000
1:1636477:AGATC:A	acceptor_gain	1.0000
1:1636478:GATC:G	acceptor_gain	1.0000
1:1636480:TC:T	acceptor_gain	1.0000
1:1636481:CC:C	acceptor_gain	1.0000
1:1636482:C:CC	acceptor_gain	1.0000
1:1636677:CCCA:C	donor_loss	1.0000
1:1636717:T:TA	donor_gain	1.0000
1:1636718:C:A	donor_gain	1.0000
1:1636794:TATTC:T	acceptor_gain	1.0000
1:1636796:TTC:T	acceptor_gain	1.0000
1:1636796:TTCCT:T	acceptor_loss	1.0000
1:1636797:TC:T	acceptor_gain	1.0000
1:1636798:CC:C	acceptor_gain	1.0000
1:1636798:CCTAA:C	acceptor_loss	1.0000
1:1636799:C:CC	acceptor_gain	1.0000
1:1636800:T:C	acceptor_loss	1.0000
1:1636894:CACC:C	donor_loss	1.0000
1:1636895:A:AC	donor_gain	1.0000
1:1636895:AC:A	donor_gain	1.0000
1:1636896:C:CA	donor_gain	1.0000
1:1636896:CC:C	donor_gain	1.0000
1:1637000:CCCAC:C	acceptor_gain	1.0000
1:1637001:CCAC:C	acceptor_gain	1.0000

AlphaMissense

5176 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:1635767:G:C	F795L	1.000
1:1635767:G:T	F795L	1.000
1:1635769:A:G	F795L	1.000
1:1635774:A:G	L793P	1.000
1:1635774:A:T	L793H	1.000
1:1635779:G:C	F791L	1.000
1:1635779:G:T	F791L	1.000
1:1635780:A:C	F791C	1.000
1:1635780:A:G	F791S	1.000
1:1635781:A:G	F791L	1.000
1:1635827:G:C	F775L	1.000
1:1635827:G:T	F775L	1.000
1:1635828:A:G	F775S	1.000
1:1635829:A:G	F775L	1.000
1:1635976:G:C	S752R	1.000
1:1635976:G:T	S752R	1.000
1:1635978:T:G	S752R	1.000
1:1636013:G:T	A740D	1.000
1:1636018:C:A	W738C	1.000
1:1636018:C:G	W738C	1.000
1:1636020:A:G	W738R	1.000
1:1636020:A:T	W738R	1.000
1:1636342:A:G	L699P	1.000
1:1636352:C:G	G696R	1.000
1:1636454:A:G	W662R	1.000
1:1636454:A:T	W662R	1.000
1:1636468:G:T	P657H	1.000
1:1636474:C:T	G655E	1.000
1:1636475:C:A	G655W	1.000
1:1636475:C:G	G655R	1.000

dbSNP variants (sampled 300 via entrez): RS1000008651 (1:1642062 C>A,G,T), RS1000037479 (1:1654834 AT>A), RS1000078484 (1:1641171 C>T), RS1000423450 (1:1636319 T>A), RS1000704026 (1:1659339 G>A), RS1000755909 (1:1659120 TAA>T,TA), RS1000969548 (1:1654141 C>T), RS1001050829 (1:1640022 C>T), RS1001083477 (1:1639913 A>G), RS1001570136 (1:1648990 C>T), RS1001708798 (1:1658294 G>A), RS1001761199 (1:1657405 C>T), RS1002051568 (1:1639237 G>A,C), RS1002082875 (1:1639079 T>C), RS1002640050 (1:1645996 A>C)

Disease associations

OMIM: gene MIM:176873 | disease phenotypes: MIM:113477, MIM:615373

GenCC curated gene-disease

Mondo (2): Brachymorphism-onychodysplasia-dysphalangism syndrome (MONDO:0007230), left ventricular noncompaction 8 (MONDO:0014152)

Orphanet (3): Brachymorphism-onychodysplasia-dysphalangism syndrome (Orphanet:1292), Familial isolated dilated cardiomyopathy (Orphanet:154), Left ventricular noncompaction (Orphanet:54260)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_34	Body mass index	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536242	Brachymorphism-onychodysplasia-dysphalangism syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL3559691 (PROTEIN FAMILY), CHEMBL5483188 (PROTEIN COMPLEX), CHEMBL5808 (SINGLE PROTEIN), CHEMBL6066064 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 47,286 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL1276127	INDIRUBIN	2	181
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL215152	DEFOSBARASERTIB	2	372
CHEMBL384304	RG-547	2	93
CHEMBL445813	AT-7519	2	2,614
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL296468	BMS-387032	1	2,075
CHEMBL574738	AST-487	1	451

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — PITSLRE subfamily

Binding affinities (BindingDB)

9 measured of 9 human assays (9 total across all organisms); most potent 9 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[2-(cyclopropanecarbonylamino)-[1,3]thiazolo[5,4-b]pyridin-5-yl]-N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	KD	57 nM	US-8765747: Fused 2-aminothiazole compounds
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea	KD	450 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
BMS-387072	KD	1800 nM
2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide	KD	1900 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
2-methylsulfanyl-6-[4-[3-[3-(trifluoromethyl)anilino]-1H-1,2,4-triazol-5-yl]phenoxy]pyrimidin-4-amine	KD	7500 nM	US-9260417: Therapeutic methods and compositions involving allosteric kinase inhibition

ChEMBL bioactivities

28 potent at pChembl≥5 of 28 total, top 22 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.08	Kd	8.4	nM	AT-7519
7.70	IC50	20	nM	MOLIBRESIB
7.50	Kd	32	nM	CHEMBL2148124
7.47	Kd	34	nM	MOLIBRESIB
7.44	IC50	36	nM	CHEMBL4101411
7.01	Kd	98	nM	BMS-387032
6.82	Kd	150	nM	JNJ-7706621
6.54	Kd	290	nM	TOZASERTIB
6.43	Kd	370	nM	CHEMBL4553037
6.38	Kd	420	nM	CHEMBL4799297
6.38	Kd	420	nM	BMS-345541
6.33	Kd	470	nM	CHEMBL4571241
6.19	Kd	640	nM	FORETINIB
6.12	Kd	760	nM	CRIZOTINIB
5.92	Kd	1200	nM	DEFOSBARASERTIB
5.89	Kd	1300	nM	CHEMBL2425628
5.89	Kd	1300	nM	LINIFANIB
5.85	Kd	1400	nM	AST-487
5.68	Kd	2100	nM	PAZOPANIB
5.66	IC50	2200	nM	INDIRUBIN
5.64	Kd	2300	nM	RG-547
5.12	Kd	7500	nM	CHEMBL3932957

PubChem BioAssay actives

25 with measured affinity, of 334 total; 18 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	624708: Binding constant for CDC2L1 kinase domain	kd	0.0084	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178491: Inhibition of CDC2L1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0200	uM
1-[4-[4-amino-3-[4-(2-morpholin-4-ylethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]phenyl]-3-(5-tert-butyl-1,2-oxazol-3-yl)urea	1476233: Inhibition of human GST-tagged CDK11 by Z’Lyte assay	ic50	0.0360	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	435395: Binding constant for CDC2L1 kinase domain	kd	0.0980	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435395: Binding constant for CDC2L1 kinase domain	kd	0.1500	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435395: Binding constant for CDC2L1 kinase domain	kd	0.2900	uM
(4R)-4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-pyrimidin-5-yl-3,4-dihydro-1H-isoquinoline-7-carboxamide	1625887: Binding affinity to wild type human partial length CDK11 (1 to 360 residues) expressed in bacterial expression system preincubated for 1 hr measured after 30 mins by qPCR method	kd	0.3700	uM
N’-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine	624708: Binding constant for CDC2L1 kinase domain	kd	0.4200	uM
N-[4-(6,7-dimethoxyquinazolin-4-yl)oxy-3-fluorophenyl]-6-ethyl-1,2-dimethyl-4-oxoquinoline-3-carboxamide	1626957: Binding affinity to human CDK11	kd	0.4700	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	624708: Binding constant for CDC2L1 kinase domain	kd	0.6400	uM
Crizotinib	624708: Binding constant for CDC2L1 kinase domain	kd	0.7600	uM
2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide	435395: Binding constant for CDC2L1 kinase domain	kd	1.2000	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	435395: Binding constant for CDC2L1 kinase domain	kd	1.3000	uM
(4-hydroxypiperidin-1-yl)-[4-[[4-[4-(3-methylsulfonylpropoxy)indol-1-yl]pyrimidin-2-yl]amino]cyclohexyl]methanone	769529: Binding affinity to CDC2L1 (unknown origin)	kd	1.3000	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435395: Binding constant for CDC2L1 kinase domain	kd	1.4000	uM
Pazopanib	435395: Binding constant for CDC2L1 kinase domain	kd	2.1000	uM
2-(2-hydroxy-1H-indol-3-yl)indol-3-one	1378312: Inhibition of recombinant human CDK expressed in baculovirus infected sf9 cells after 10 mins by SDS-PAGE based autoradiography	ic50	2.2000	uM
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone	624708: Binding constant for CDC2L1 kinase domain	kd	2.3000	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
Aflatoxin B1	increases methylation	2
Particulate Matter	increases abundance, increases expression	2
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
potassium perchlorate	increases expression	1
cobaltous chloride	increases expression	1
aflatoxin B2	increases methylation	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	decreases methylation	1
Arsenic Trioxide	decreases expression	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	increases phosphorylation	1
Ivermectin	decreases expression	1
Phthalic Acids	affects methylation	1
Quercetin	decreases phosphorylation	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Copper Sulfate	increases expression	1
Chlorodiphenyl (54% Chlorine)	increases expression	1

ChEMBL screening assays

158 unique, capped per target: 158 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1064257	Binding	Inhibition of CDK in human A2780 cells assessed as reduction of RNAP2 phosphorylation at Ser2 site at 5 uM after 6 hrs by Western bloting	Design, synthesis, and evaluation of 2-methyl- and 2-amino-N-aryl-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amines as ring-constrained 2-anilino-4-(thiazol-5-yl)pyrimidine cyclin-dependent kinase inhibitors. — J Med Chem

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04132739	Not specified	TERMINATED	Piloting Diet and Exercise Interventions in Older Hispanics With Diabetes