CDK16

Summary

CDK16 (cyclin dependent kinase 16, HGNC:8749) is a protein-coding gene on chromosome Xp11.3, encoding Cyclin-dependent kinase 16 (Q00536). Protein kinase that plays a role in vesicle-mediated transport processes and exocytosis.

The protein encoded by this gene belongs to the cdc2/cdkx subfamily of the ser/thr family of protein kinases. It may play a role in signal transduction cascades in terminally differentiated cells; in exocytosis; and in transport of secretory cargo from the endoplasmic reticulum. This gene is thought to escape X inactivation. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 5127 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked complex neurodevelopmental disorder (Limited, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 163 total — 2 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 50 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006201

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8749
Approved symbol	CDK16
Name	cyclin dependent kinase 16
Location	Xp11.3
Locus type	gene with protein product
Status	Approved
Aliases	PCTAIRE, PCTAIRE1, PCTGAIRE, FLJ16665
Ensembl gene	ENSG00000102225
Ensembl biotype	protein_coding
OMIM	311550
Entrez	5127

Gene structure

Transcript identifiers

Ensembl transcripts: 54 — 45 protein_coding, 6 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000276052, ENST00000357227, ENST00000428400, ENST00000457458, ENST00000462483, ENST00000462827, ENST00000493213, ENST00000517426, ENST00000517479, ENST00000517997, ENST00000518022, ENST00000518391, ENST00000519758, ENST00000520141, ENST00000520295, ENST00000520893, ENST00000522234, ENST00000522883, ENST00000523034, ENST00000523344, ENST00000523543, ENST00000523699, ENST00000869366, ENST00000869367, ENST00000869368, ENST00000869369, ENST00000869370, ENST00000869371, ENST00000869372, ENST00000869373, ENST00000869374, ENST00000869375, ENST00000869376, ENST00000869377, ENST00000918218, ENST00000918219, ENST00000918220, ENST00000918221, ENST00000918222, ENST00000918223, ENST00000918224, ENST00000918225, ENST00000918226, ENST00000918227, ENST00000971182, ENST00000971183, ENST00000971184, ENST00000971185, ENST00000971186, ENST00000971187, ENST00000971188, ENST00000971189, ENST00000971190, ENST00000971191

RefSeq mRNA: 3 — MANE Select: NM_006201 NM_001170460, NM_006201, NM_033018

CCDS: CCDS14276, CCDS48101, CCDS55408

Canonical transcript exons

ENST00000357227 — 16 exons

Exon	Start	End
ENSE00000669267	47225965	47226027
ENSE00000669268	47226279	47226402
ENSE00000870093	47228567	47228644
ENSE00001473093	47218681	47219105
ENSE00001656967	47228731	47229997
ENSE00003501196	47226994	47227099
ENSE00003534823	47227181	47227223
ENSE00003539421	47227379	47227469
ENSE00003567331	47224834	47224890
ENSE00003591567	47224618	47224743
ENSE00003627062	47225772	47225866
ENSE00003634881	47224988	47225102
ENSE00003641371	47224385	47224518
ENSE00003647357	47226583	47226703
ENSE00003658095	47223552	47223759
ENSE00003684330	47226812	47226909

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 78.5784 / max 587.9830, expressed in 1826 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196187	70.0161	1825
196183	1.9122	1047
196182	1.6897	1048
196181	1.4762	979
196188	0.7351	244
196195	0.6197	378
196185	0.5187	190
196191	0.4027	186
196193	0.3080	140
196186	0.2688	115

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.74	gold quality
cerebellar hemisphere	UBERON:0002245	98.55	gold quality
cerebellar cortex	UBERON:0002129	98.48	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.43	gold quality
apex of heart	UBERON:0002098	98.00	gold quality
gastrocnemius	UBERON:0001388	97.86	gold quality
right frontal lobe	UBERON:0002810	97.74	gold quality
cortical plate	UBERON:0005343	97.66	gold quality
muscle of leg	UBERON:0001383	97.41	gold quality
ganglionic eminence	UBERON:0004023	97.35	gold quality
stromal cell of endometrium	CL:0002255	97.30	gold quality
cerebellum	UBERON:0002037	97.25	gold quality
lower esophagus mucosa	UBERON:0035834	97.21	gold quality
right atrium auricular region	UBERON:0006631	96.95	gold quality
prefrontal cortex	UBERON:0000451	96.83	gold quality
right lobe of thyroid gland	UBERON:0001119	96.75	gold quality
ventricular zone	UBERON:0003053	96.75	gold quality
metanephros cortex	UBERON:0010533	96.71	gold quality
left lobe of thyroid gland	UBERON:0001120	96.65	gold quality
heart left ventricle	UBERON:0002084	96.52	gold quality
cingulate cortex	UBERON:0003027	96.51	gold quality
anterior cingulate cortex	UBERON:0009835	96.45	gold quality
left testis	UBERON:0004533	96.36	gold quality
cardiac ventricle	UBERON:0002082	96.23	gold quality
muscle organ	UBERON:0001630	96.19	gold quality
skeletal muscle organ	UBERON:0014892	96.19	gold quality
right testis	UBERON:0004534	96.17	gold quality
right adrenal gland cortex	UBERON:0035827	96.17	gold quality
right adrenal gland	UBERON:0001233	96.12	gold quality
left adrenal gland cortex	UBERON:0035825	96.10	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting CDK16, 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-4692	100.00	67.32	2066
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-5682	99.89	72.56	1005

Literature-anchored findings (GeneRIF, showing 27)

• Data show that various forms of PCTAIRE-1 transfected into neuroblastoma cell lines could either promote or inhibit neurite outgrowth, suggesting a potential role for the PCTAIRE-1 gene product in the control of neurite outgrowth. (PMID:12154078)
• Pctaire1 phosphorylates N-ethylmaleimide-sensitive fusion protein (PMID:16461345)
• Cdk5-dependent phosphorylation of Pctaire1 at Ser95 plays an important role in dendrite development (PMID:21335063)
• CCNY binding to CDK16 required a region upstream of the kinase domain and was found to be inhibited by phosphorylation of serine 153, a potential PKA phosphorylation site. (PMID:22184064)
• a novel function of BRSK2 in the regulation of GSIS in beta-cells via a PCTAIRE1-dependent mechanism and suggest that BRSK2 is an attractive target for developing novel diabetic drugs. (PMID:22798068)
• Dysfunction of MKL2 and its transcriptional coactivation partner, serum response factor (SRF), was supported by a decrease in gene and protein expression of PCTAIRE1, a downstream target of MKL2:SRF heterodimer transcriptional activation (PMID:23692340)
• Pctaire1 exerts promyogenic effects by regulating myoblast migration and process formation during skeletal myogenesis (PMID:24931367)
• An unexpected role for PCTAIRE1 in regulating p27 stability, mitosis, and tumor growth. (PMID:25205104)
• PCTK1 in the proliferation and survival of medulloblastoma characterized by cMYC amplification (PMID:25402633)
• PCTK1 regulates spindle orientation through phosphorylation of Ser83 on KAP0, a regulatory subunit of protein kinase A. (PMID:25605337)
• GALNT7 and CDK16 were confirmed to be the direct targets of miR-494. These results suggested that miR-494 play an inhibitory role in the tumorigenesis of NPC (PMID:25809707)
• Activation of PCTAIRE-1 is mediated through interaction with the phosphorylated form of cyclin Y in complex with 14-3-3. (PMID:26205494)
• CDK-16 upregulation in serous EOC cells may represent a negative feedback loop to promote ovarian cell differentiation in malignantly-transformed serous epithelial ovarian cancer cells (PMID:26546806)
• PCTAIRE1 has a role in regulating p27, c-Myc levels and tumor growth in cutaneous cutaneous squamous cell carcinoma cells (PMID:28274513)
• CDK16 negatively modulates p53 signaling pathway to promote radioresistance in lung cancer cells. (PMID:29344296)
• CDK16 is significantly up-regulated in non-small cell lung cancer tumor tissue and plays a role in promoting cell proliferation. (PMID:29674275)
• Fisetin inhibits TET1 expression and reduces 5hmC modification in specific loci in the promoters of CCNY/CDK16 in HuRSCs. (PMID:30411496)
• The authors have identified AP2-associated protein kinase 1(AAK1), dynamin 1 and synaptojanin 1 as putative substrates of PCTAIRE-1. (PMID:30880224)
• Data identified PRC1 as the first substrate of the CDK16/CCNY complex and demonstrated that the proliferative function of CDK16 is mediated by PRC1 phosphorylation. (PMID:30992425)
• Study uncovered a higher expression of CDK16 in melanomas than in compound nevi and suggested that the combination of CDK16 and p27/Kip1 expression may be helpful to differentiate malignant melanoma and compound nevi. (PMID:31106900)
• High plasma PCTK1 levels are associated with non-small cell lung cancer. (PMID:31882554)
• Cyclin Y and CDK16 complex is necessary for efficient AMPK-dependent activation of autophagy. (PMID:32098961)
• circRNA 001306 enhances hepatocellular carcinoma growth by up-regulating CDK16 expression via sponging miR-584-5p. (PMID:33135290)
• Lung cancer cells expressing a shortened CDK16 3’UTR escape senescence through impaired miR-485-5p targeting. (PMID:34687270)
• CDK16 promotes the progression and metastasis of triple-negative breast cancer by phosphorylating PRC1. (PMID:35449080)
• The roles, molecular interactions, and therapeutic value of CDK16 in human cancers. (PMID:37236028)
• PCTAIRE Protein Kinase 1 (PCTK1) Suppresses Proliferation, Stemness, and Chemoresistance in Colorectal Cancer through the BMPR1B-Smad1/5/8 Signaling Pathway. (PMID:37373155)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk16	ENSDARG00000032072
mus_musculus	Cdk16	ENSMUSG00000031065
caenorhabditis_elegans		WBGENE00003961

Paralogs (26): CDKL3 (ENSG00000006837), CDKL5 (ENSG00000008086), CDK11A (ENSG00000008128), CDK14 (ENSG00000058091), CDK17 (ENSG00000059758), CDK13 (ENSG00000065883), CDKL1 (ENSG00000100490), 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), CDK11B (ENSG00000248333), CDK3 (ENSG00000250506)

Protein

Protein identifiers

Cyclin-dependent kinase 16 — Q00536 (reviewed: Q00536)

Alternative names: Cell division protein kinase 16, PCTAIRE-motif protein kinase 1, Serine/threonine-protein kinase PCTAIRE-1

All UniProt accessions (11): Q00536, A0A140VK97, E5RGN0, E5RIU4, E5RIY8, E5RJM2, E5RJQ8, H0YAZ9, H0YBX5, H0YC36, H0YC60

UniProt curated annotations — full annotation on UniProt →

Function. Protein kinase that plays a role in vesicle-mediated transport processes and exocytosis. Regulates GH1 release by brain neurons. Phosphorylates NSF, and thereby regulates NSF oligomerization. Required for normal spermatogenesis. Regulates neuron differentiation and dendrite development. Plays a role in the regulation of insulin secretion in response to changes in blood glucose levels. Can phosphorylate CCNY at ‘Ser-336’ (in vitro).

Subunit / interactions. Found in a complex containing CABLES1, CDK17 and TDRD7. Interacts with BRSK2. Identified in a complex with NSF, syntaxin-1, synaptotagmin, SYN1, SYP and CDK5R1. Interacts with YWHAH, YWHAQ and YWHAZ. Interacts with CCNY; this interaction increases the CDK16 kinase activity. Interacts with CCNYL1; this interaction mutually increases the stability of CDK16 and CCNYL1 and increases the kinase activity of CDK16. Interacts with NSF.

Subcellular location. Cytoplasm. Cytoplasmic vesicle. Secretory vesicle. Cell membrane. Synapse. Synaptosome.

Tissue specificity. Detected in pancreas islets (at protein level). Detected in brain and pancreas.

Post-translational modifications. Phosphorylation of CDK16 is essential for the binding of CCNY, but also essential for the regulation of CDK16 kinase activity. Phosphorylation of CDK16 is essential for the binding of CCNYl1, but also essential for the regulation of CDK16 kinase activity. Ser-146 and Ser-153 are the most critical sites for the binding of CCNYL1 and for modulating CDK16 kinase activity. Phosphorylation at Ser-153 inhibits kinase activity.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q00536-1	1	yes
Q00536-2	2
Q00536-3	3

RefSeq proteins (3): NP_001163931, NP_006192, NP_148978 (=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
IPR017441	Protein_kinase_ATP_BS	Binding_site
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), 2 shown:

• 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 (67 total): modified residue 20, helix 15, strand 10, mutagenesis site 6, turn 5, splice variant 2, compositionally biased region 2, binding site 2, chain 1, domain 1, region of interest 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5G6V	X-RAY DIFFRACTION	2.2
3MTL	X-RAY DIFFRACTION	2.4
9R2I	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00536-F1	72.92	0.46

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): 286 (proton acceptor)

Ligand- & substrate-binding residues (2): 171–179; 194

Post-translational modifications (20): 42, 64, 65, 78, 82, 89, 95, 110, 119, 138, 146, 153, 155, 175, 380, 391, 478, 480, 12, 36

Mutagenesis-validated functional residues (6):

Position	Phenotype
12	abolishes phosphorylation by brsk2. abolishes effect on insulin secretion.
119	strongly reduces interaction with ccny.
153	constitutively activated, due to loss of an inhibitory phosphorylation site. increases interaction with ccny.
153	abolishes interaction with ccny.
194	loss of kinase activity. abolishes effect on insulin secretion.
194	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 278 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, PAX4_01, TGCGCANK_UNKNOWN, MODULE_255, ENK_UV_RESPONSE_KERATINOCYTE_UP, SP3_Q3, GOBP_INSULIN_SECRETION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MODULE_317, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT

GO Biological Process (21): protein phosphorylation (GO:0006468), exocytosis (GO:0006887), spermatogenesis (GO:0007283), positive regulation of autophagy (GO:0010508), growth hormone secretion (GO:0030252), neuron projection development (GO:0031175), regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061178), regulation of cell cycle phase transition (GO:1901987), epidermal growth factor receptor signaling pathway (GO:0007173), positive regulation of macrophage chemotaxis (GO:0010759), cell differentiation (GO:0030154), positive regulation of telomere maintenance (GO:0032206), regulation of stress-activated MAPK cascade (GO:0032872), cellular response to amino acid starvation (GO:0034198), stress-activated MAPK cascade (GO:0051403), regulation of cytoskeleton organization (GO:0051493), response to epidermal growth factor (GO:0070849), caveolin-mediated endocytosis (GO:0072584), regulation of Golgi inheritance (GO:0090170), positive regulation of macrophage proliferation (GO:0120041), regulation of early endosome to late endosome transport (GO:2000641)

GO Molecular Function (11): 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 kinase activity (GO:0004672), MAP kinase activity (GO:0004707), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphatase binding (GO:0019902)

GO Cellular Component (18): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), cytoplasmic side of plasma membrane (GO:0009898), microtubule cytoskeleton (GO:0015630), neuron projection (GO:0043005), early endosome (GO:0005769), late endosome (GO:0005770), Golgi apparatus (GO:0005794), caveola (GO:0005901), focal adhesion (GO:0005925), membrane (GO:0016020), transport vesicle (GO:0030133), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	3
MAPK cascade	2
protein kinase activity	2
protein serine/threonine kinase activity	2
intracellular membrane-bounded organelle	2
endosome	2
endomembrane system	2
phosphorylation	1
protein modification process	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
developmental process involved in reproduction	1
male gamete generation	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
peptide hormone secretion	1
neuron development	1
plasma membrane bounded cell projection organization	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion	1
regulation of cellular localization	1
regulation of cell cycle process	1
cell cycle phase transition	1
ERBB signaling pathway	1
positive regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
regulation of granulocyte chemotaxis	1
positive regulation of macrophage migration	1
cellular developmental process	1
telomere maintenance	1
regulation of telomere maintenance	1
positive regulation of DNA metabolic process	1
positive regulation of chromosome organization	1
regulation of MAPK cascade	1
stress-activated MAPK cascade	1
regulation of stress-activated protein kinase signaling cascade	1

Protein interactions and networks

STRING

3300 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK16	CCNY	Q8ND76	916
CDK16	CCNYL1	Q8N7R7	857
CDK16	TDRD7	Q8NHU6	703
CDK16	CABLES1	Q8TDN4	637
CDK16	CCNH	P51946	575
CDK16	UBA1	P22314	497
CDK16	PABIR3	Q6P4D5	491
CDK16	VPS37B	Q9H9H4	425
CDK16	CCDC180	Q9P1Z9	425
CDK16	SFN	P31947	419
CDK16	YWHAB	P31946	414
CDK16	CCNC	P24863	407
CDK16	CDK5	Q00535	406
CDK16	SAGE1	Q9NXZ1	406
CDK16	DIAPH2	O60879	391

IntAct

129 interactions, top by confidence:

A	B	Type	Score
CDK2	CCNE2	psi-mi:“MI:0914”(association)	0.940
CDK16	CCNYL1	psi-mi:“MI:0914”(association)	0.800
CDK16	CCNYL1	psi-mi:“MI:0915”(physical association)	0.800
CDK16	YWHAE	psi-mi:“MI:0915”(physical association)	0.740
CDKN1B	CCNB2	psi-mi:“MI:0914”(association)	0.670
CDK16	CCNY	psi-mi:“MI:0915”(physical association)	0.660
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
CDK16	YWHAZ	psi-mi:“MI:0914”(association)	0.640
CDK17	CDK16	psi-mi:“MI:0915”(physical association)	0.620
CDK16	CDK17	psi-mi:“MI:0914”(association)	0.620
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
SEC23A	CDK16	psi-mi:“MI:0915”(physical association)	0.580
CDK16	SEC23A	psi-mi:“MI:0915”(physical association)	0.580
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
ZBTB14	CDK16	psi-mi:“MI:0915”(physical association)	0.560
APPBP2	CDK16	psi-mi:“MI:0915”(physical association)	0.560
CDK16	ZBTB14	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
CDK16	CCNY	psi-mi:“MI:0915”(physical association)	0.540
CCNY	CDK16	psi-mi:“MI:0217”(phosphorylation reaction)	0.540
CDK16	CCNY	psi-mi:“MI:0217”(phosphorylation reaction)	0.540

BioGRID (184): ZBTB14 (Two-hybrid), APPBP2 (Two-hybrid), ATRIP (Two-hybrid), BRCA1 (Two-hybrid), CCNYL1 (Affinity Capture-MS), PKM (Affinity Capture-MS), YWHAE (Affinity Capture-MS), YWHAZ (Affinity Capture-MS), CDK16 (Affinity Capture-MS), CCNYL1 (Affinity Capture-MS), CDK17 (Affinity Capture-MS), CDK18 (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), ICK (Affinity Capture-MS), BRCA1 (Affinity Capture-MS)

ESM2 similar proteins: A1CL96, A1D624, A2QU77, A2X0M1, A2Y4B6, A3LUB9, A4IIW7, A4QXX4, B0VXE8, B0VXL7, B6A7Q3, C0RW22, O13958, O35495, O35831, O35832, O44514, O94921, P0CS76, P0CS77, P29620, Q00536, Q00537, Q04735, Q04899, Q07002, Q0CQK1, Q0E459, Q0TWJ7, Q11179, Q1EBK0, Q1RLU9, Q2GYV9, Q2UC58, Q336M2, Q39010, Q4FCZ5, Q4WYR6, Q5BAE1, Q5RD01

Diamond homologs: A4IIW7, A8XA58, B0VXE8, B0VXL7, B6A7Q3, C0RW22, G5ECH7, O35495, O35831, O35832, O55076, O61847, O74456, O94921, O96821, P00546, P04551, P06493, P11440, P13863, P17157, P23111, P23437, P23572, P23573, P24033, P24100, P24923, P24941, P25859, P29618, P29619, P34112, P34117, P35567, P38973, P39951, P43063, P43450, P48609

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
PRKACA	down-regulates	CDK16	phosphorylation
dabrafenib	“down-regulates activity”	CDK16	“chemical inhibition”
CDK16	“down-regulates quantity by destabilization”	CDKN1B	phosphorylation
CDK16	“up-regulates activity”	PRC1	phosphorylation
CDK16	“up-regulates activity”	PRKAR1A	phosphorylation
CDK16	“down-regulates quantity”	CDKN1B	phosphorylation
CDK16	“down-regulates activity”	TP53	phosphorylation
CDK5	“up-regulates activity”	CDK16	phosphorylation
CDK16	“down-regulates activity”	NSF	phosphorylation
CDK16	“form complex”	CyclinY/CDK16	binding
CyclinY/CDK16	“up-regulates activity”	CDK16	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 120 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
Activation of BAD and translocation to mitochondria	7	66.6×	1e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	58.8×	2e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	58.8×	2e-09
Activation of BH3-only proteins	7	43.5×	1e-08
RHO GTPases activate PKNs	8	31.7×	1e-08
Intrinsic Pathway for Apoptosis	7	25.6×	4e-07
FOXO-mediated transcription	6	25.2×	3e-06
RAF activation	5	21.0×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	20.2×	3e-04
Ras protein signal transduction	6	11.3×	3e-03
G1/S transition of mitotic cell cycle	6	11.0×	3e-03
MAPK cascade	6	8.4×	8e-03
regulation of small GTPase mediated signal transduction	6	7.9×	1e-02
intracellular protein localization	8	7.7×	3e-03
protein phosphorylation	9	5.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	59
Likely benign	5
Benign	8

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3239639	NM_006201.5(CDK16):c.43C>T (p.Leu15Phe)	Likely pathogenic
694513	46,Y,inv(X)(p21.1q13.3)	Likely pathogenic

SpliceAI

1941 predictions. Top by Δscore:

Variant	Effect	Δscore
X:47219019:G:GT	donor_gain	1.0000
X:47223538:T:A	acceptor_gain	1.0000
X:47223545:T:TA	acceptor_gain	1.0000
X:47223547:CTCA:C	acceptor_loss	1.0000
X:47223549:CA:C	acceptor_loss	1.0000
X:47223550:A:AG	acceptor_gain	1.0000
X:47223550:A:G	acceptor_loss	1.0000
X:47223550:AGATC:A	acceptor_gain	1.0000
X:47223551:G:GT	acceptor_gain	1.0000
X:47223551:GA:G	acceptor_gain	1.0000
X:47223551:GAT:G	acceptor_gain	1.0000
X:47223551:GATC:G	acceptor_gain	1.0000
X:47223551:GATCG:G	acceptor_gain	1.0000
X:47223759:GGTG:G	donor_loss	1.0000
X:47224477:GTGC:G	donor_gain	1.0000
X:47224603:T:A	acceptor_gain	1.0000
X:47224609:A:AG	acceptor_gain	1.0000
X:47224609:ACCT:A	acceptor_gain	1.0000
X:47224610:C:G	acceptor_gain	1.0000
X:47224612:T:A	acceptor_gain	1.0000
X:47224613:GCTA:G	acceptor_loss	1.0000
X:47224614:CTA:C	acceptor_loss	1.0000
X:47224615:TA:T	acceptor_loss	1.0000
X:47224616:A:AG	acceptor_gain	1.0000
X:47224616:AG:A	acceptor_gain	1.0000
X:47224616:AGGA:A	acceptor_loss	1.0000
X:47224617:G:A	acceptor_gain	1.0000
X:47224617:G:GT	acceptor_gain	1.0000
X:47224617:GGA:G	acceptor_gain	1.0000
X:47224617:GGAC:G	acceptor_gain	1.0000

AlphaMissense

3222 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:47224634:T:C	L118P	1.000
X:47224640:T:A	L120Q	1.000
X:47224640:T:C	L120P	1.000
X:47224643:C:A	P121Q	1.000
X:47224720:C:A	R147S	1.000
X:47224729:C:A	R150S	1.000
X:47224732:C:A	R151S	1.000
X:47224738:A:C	S153R	1.000
X:47224740:C:A	S153R	1.000
X:47224740:C:G	S153R	1.000
X:47224742:T:C	L154P	1.000
X:47224843:G:C	G158R	1.000
X:47224844:G:A	G158D	1.000
X:47224844:G:T	G158V	1.000
X:47224846:T:A	F159I	1.000
X:47224846:T:C	F159L	1.000
X:47224846:T:G	F159V	1.000
X:47224847:T:C	F159S	1.000
X:47224847:T:G	F159C	1.000
X:47224848:T:A	F159L	1.000
X:47224848:T:G	F159L	1.000
X:47224849:G:A	G160R	1.000
X:47224849:G:C	G160R	1.000
X:47224849:G:T	G160W	1.000
X:47224850:G:A	G160E	1.000
X:47224850:G:T	G160V	1.000
X:47224862:C:T	T164I	1.000
X:47224864:T:A	Y165N	1.000
X:47224864:T:C	Y165H	1.000
X:47224864:T:G	Y165D	1.000

dbSNP variants (sampled 300 via entrez): RS1000666901 (X:47219993 A>G), RS1000864894 (X:47219643 G>C,T), RS1001370313 (X:47227353 A>G), RS1001654507 (X:47228037 A>G), RS1001675336 (X:47222486 C>A), RS1002257528 (X:47225168 T>C), RS1003359639 (X:47221952 C>T), RS1003558575 (X:47217494 A>G), RS1003675731 (X:47222492 A>G), RS1003733980 (X:47227269 T>G), RS1003836631 (X:47217214 C>A,T), RS1004550952 (X:47227943 G>T), RS1004765428 (X:47219085 G>A), RS1004939952 (X:47229109 G>A), RS1005145184 (X:47229586 C>G,T)

Disease associations

OMIM: gene MIM:311550 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability	Limited	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
X-linked complex neurodevelopmental disorder	Limited	XL

Mondo (3): oligospermia (MONDO:0001913), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000798	Oligozoospermia

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D009845	Oligospermia	C12.100.500.430.508; C12.100.750.700.508; C12.200.294.430.508

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3559691 (PROTEIN FAMILY), CHEMBL3885550 (PROTEIN COMPLEX), CHEMBL4597 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

50 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 249,039 (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
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1173055	RUCAPARIB	4	7,009
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL180022	NERATINIB	4	9,404
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL3545110	RIBOCICLIB	4	8,018
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL1276127	INDIRUBIN	2
CHEMBL1230165	SILMITASERTIB	2
CHEMBL1230609	FORETINIB	2
CHEMBL124660	TANDUTINIB	2
CHEMBL14762	SELICICLIB	2
CHEMBL1721885	SU-014813	2
CHEMBL1738757	REBASTINIB	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — TAIRE subfamily

Binding affinities (BindingDB)

12 measured of 13 human assays (13 total across all organisms); most potent 12 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide	KD	740 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-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 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
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM

ChEMBL bioactivities

106 potent at pChembl≥5 of 107 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.27	Kd	0.54	nM	RG-547
8.96	Kd	1.1	nM	AT-7519
8.55	IC50	2.8	nM	CHEMBL6144731
8.52	Kd	3	nM	RGB-286638
8.15	Kd	7.1	nM	BMS-387032
8.10	Kd	8	nM	AT-7519
8.00	IC50	10	nM	CHEMBL4580787
7.92	Kd	12	nM	CHEMBL1082152
7.89	Kd	13	nM	DABRAFENIB
7.79	IC50	16.3	nM	STAUROSPORINE
7.76	IC50	17.2	nM	STAUROSPORINE
7.68	Kd	21	nM	NINTEDANIB
7.64	Kd	23	nM	JNJ-7706621
7.62	IC50	24	nM	STAUROSPORINE
7.62	Kd	24	nM	STAUROSPORINE
7.60	Kd	25	nM	STAUROSPORINE
7.57	Kd	27	nM	LESTAURTINIB
7.50	Kd	32	nM	AT-9283
7.47	Kd	34	nM	CHEMBL3688339
7.46	Kd	35	nM	ZOTIRACICLIB
7.44	Kd	36	nM	UPROSERTIB
7.30	Kd	50	nM	ABEMACICLIB
7.25	IC50	55.6	nM	CHEMBL4848734
6.95	Kd	113	nM	BMS-387032
6.90	Kd	125	nM	DINACICLIB
6.89	Kd	130	nM	SUNITINIB
6.87	IC50	135	nM	CHEMBL5193702
6.82	Kd	150	nM	SUNITINIB
6.75	Kd	180	nM	ALVOCIDIB
6.75	Kd	180	nM	SP-600125
6.64	Kd	230	nM	TOZASERTIB
6.54	IC50	292	nM	CHEMBL4281048
6.50	Kd	314	nM	REBASTINIB
6.42	IC50	381	nM	RUCAPARIB
6.38	Kd	420	nM	AST-487
6.37	Kd	430	nM	DOVITINIB
6.36	Kd	440	nM	ALVOCIDIB
6.35	Kd	444	nM	PHA-793887
6.28	Kd	526	nM	MILCICLIB
6.25	Kd	560	nM	TAE-684
6.22	IC50	605	nM	CHEMBL3656841
6.08	Kd	830	nM	KW-2449
6.05	Kd	890	nM	FORETINIB
6.05	Kd	890	nM	BMS-345541
6.03	Kd	940	nM	SU-014813
6.00	Kd	990	nM	SELICICLIB
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.98	Kd	1055	nM	XL-228

PubChem BioAssay actives

96 with measured affinity, of 851 total; 50 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-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone	625033: Binding constant for PCTK1 kinase domain	kd	0.0005	uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	625033: Binding constant for PCTK1 kinase domain	kd	0.0011	uM
1-[3-[4-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]phenyl]-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]-3-morpholin-4-ylurea	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0030	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	435925: Binding constant for PCTK1 kinase domain	kd	0.0071	uM
N-[1-[3-[[(E)-4-(dimethylamino)but-2-enoyl]amino]phenyl]sulfonylpiperidin-4-yl]-4-[(2,4,6-trichlorobenzoyl)amino]-1H-pyrazole-5-carboxamide	1609466: Competitive irreversible inhibition of CDK16/cyclin Y (unknown origin) in presence of Km ATP	ic50	0.0100	uM
3-[3-(2,3-dihydroxypropylamino)phenyl]-4-(5-fluoro-1-methylindol-3-yl)pyrrole-2,5-dione	465264: Inhibition of PCTK1	kd	0.0120	uM
Dabrafenib	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0130	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	2198170: Inhibition of human CDK16/cyclin Y using RB Protein as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by radiometric Hot-SpotSM Kinase assay	ic50	0.0163	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625033: Binding constant for PCTK1 kinase domain	kd	0.0210	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435925: Binding constant for PCTK1 kinase domain	kd	0.0230	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507662: Binding affinity to PCTK1	kd	0.0270	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0320	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0340	uM
(16E)-14-methyl-20-oxa-5,7,14,27-tetrazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(27),3,5,8,10,12(26),16,21,23-decaene	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0350	uM
N-[(2S)-1-amino-3-(3,4-difluorophenyl)propan-2-yl]-5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)furan-2-carboxamide	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0360	uM
Abemaciclib	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0500	uM
3-acetyl-7-[[4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-yl]amino]-4-morpholin-4-ylchromen-2-one	1771108: Inhibition of human CDK16/cyclin-Y using RB protein as substrate incubated for 2 hrs by [gamma-33P]-ATP assay	ic50	0.0556	uM
2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1250	uM
Sunitinib	256588: Average Binding Constant for PCTK1; NA=Not Active at 10 uM	kd	0.1300	uM
N-[5-[[4-[[(3R,3aR,6R,6aR)-3-methoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-5-chloropyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]phenyl]prop-2-enamide	1885424: Inhibition of human CDK16/cyclin-Y protein-protein complex	ic50	0.1350	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	256588: Average Binding Constant for PCTK1; NA=Not Active at 10 uM	kd	0.1800	uM
14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1(15),2,4,6,9(16),10,12-heptaen-8-one	256588: Average Binding Constant for PCTK1; NA=Not Active at 10 uM	kd	0.1800	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435925: Binding constant for PCTK1 kinase domain	kd	0.2300	uM
4-[[[4-[5-chloro-2-[[4-(2-methoxyethylamino)cyclohexyl]amino]-4-pyridinyl]-1,3-thiazol-2-yl]amino]methyl]oxane-4-carbonitrile	1418193: Inhibition of recombinant GST-tagged inactive state of human CDK16 (108 to end residues)/cyclin Y (2 to end residues)	ic50	0.2920	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.3140	uM
Rucaparib	2116022: Inhibition of CDK16 (unknown origin) by discoverX kinomescan assay	ic50	0.3810	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435925: Binding constant for PCTK1 kinase domain	kd	0.4200	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435925: Binding constant for PCTK1 kinase domain	kd	0.4300	uM
N-[6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-3-methylbutanamide	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.4440	uM
N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,5-h]quinazoline-3-carboxamide	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.5260	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625033: Binding constant for PCTK1 kinase domain	kd	0.5600	uM
4-[[[6-[5-chloro-2-[[4-[[(2R)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	1921484: Inhibition of CDK16 (unknown origin) by Kinomescan method	ic50	0.6050	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625033: Binding constant for PCTK1 kinase domain	kd	0.8300	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	625033: Binding constant for PCTK1 kinase domain	kd	0.8900	uM
N’-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine	625033: Binding constant for PCTK1 kinase domain	kd	0.8900	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435925: Binding constant for PCTK1 kinase domain	kd	0.9400	uM
(2R)-2-[[6-(benzylamino)-9-propan-2-ylpurin-2-yl]amino]butan-1-ol	256588: Average Binding Constant for PCTK1; NA=Not Active at 10 uM	kd	0.9900	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.0550	uM
3-[3-[N-[4-[(dimethylamino)methyl]phenyl]-C-phenylcarbonimidoyl]-2-hydroxy-1H-indol-6-yl]-N-ethylprop-2-ynamide	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.0960	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	625033: Binding constant for PCTK1 kinase domain	kd	1.1000	uM
4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine	625033: Binding constant for PCTK1 kinase domain	kd	1.1000	uM
Momelotinib	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.1620	uM
Pazopanib	435925: Binding constant for PCTK1 kinase domain	kd	1.2000	uM
5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.2130	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625033: Binding constant for PCTK1 kinase domain	kd	1.5000	uM
Ponatinib	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.7290	uM
1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[2-(5-hydroxy-1H-indole-2-carbonyl)-1-benzofuran-5-yl]urea	1691310: Inhibition of human CDK16 incubated for 30 mins by Kinobead based assay	ec50	1.7680	uM
N-methyl-N-[3-[[[2-[(2-oxo-1,3-dihydroindol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]-2-pyridinyl]methanesulfonamide	1424941: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.9940	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
Neratinib	625033: Binding constant for PCTK1 kinase domain	kd	2.3000	uM

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	4
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
methylselenic acid	decreases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects expression, affects reaction	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	increases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dimethylarsinous acid	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arbutin	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Diazinon	increases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Tretinoin	increases expression	1
Vanadium	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
1-Methyl-4-phenylpyridinium	affects expression, affects reaction	1
Cyclosporine	increases expression	1

ChEMBL screening assays

259 unique, capped per target: 259 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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SI25	HAP1 CDK16 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02307994	PHASE4	UNKNOWN	Clinical Research on Effectiveness and Safety of Treatment of Severe Oligospermia or Azoospermia With uFSH
NCT05320536	PHASE4	UNKNOWN	A Clinical Study of Gulingji Capsule in the Treatment of Idiopathic Oligospermia, Asthenia, and Teratozoospermia
NCT06260007	PHASE4	RECRUITING	Efficacy and Safety Study of Products Based on Tribulus Terrestris, L. in Men With Oligospermia
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00440180	PHASE3	TERMINATED	Aromatase Inhibitors in the Treatment of Male Infertility
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT01409837	PHASE2	COMPLETED	The Effect and Safety of Lisinopril in Non-hypertensive Men With Infertility From Low Sperm Count
NCT02234206	PHASE2	COMPLETED	A Clinical Trial to Study the Safety and Efficacy of Chandrakanthi Choornam in Patients With Low Sperm Count
NCT07481370	PHASE2	ENROLLING_BY_INVITATION	Isotretinoin vs hCG for Male Infertility Due to Low or Absent Sperm
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT05158114	PHASE1	WITHDRAWN	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for Testicular Injury and Oligospermia
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills