CDK18

Summary

CDK18 (cyclin dependent kinase 18, HGNC:8751) is a protein-coding gene on chromosome 1q32.1, encoding Cyclin-dependent kinase 18 (Q07002). May play a role in signal transduction cascades in terminally differentiated cells.

Predicted to enable cyclin-dependent protein serine/threonine kinase activity. Involved in positive regulation of myelination. Located in mitochondrion.

Source: NCBI Gene 5129 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 112 total
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_212502

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8751
Approved symbol	CDK18
Name	cyclin dependent kinase 18
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	PCTAIRE3
Ensembl gene	ENSG00000117266
Ensembl biotype	protein_coding
OMIM	169190
Entrez	5129

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 22 protein_coding, 14 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000360066, ENST00000419301, ENST00000429964, ENST00000443813, ENST00000459862, ENST00000462976, ENST00000468954, ENST00000476153, ENST00000478560, ENST00000484080, ENST00000489617, ENST00000504162, ENST00000504648, ENST00000505932, ENST00000506215, ENST00000506489, ENST00000506784, ENST00000507067, ENST00000507240, ENST00000512008, ENST00000512922, ENST00000515494, ENST00000515514, ENST00000906020, ENST00000906021, ENST00000906022, ENST00000906023, ENST00000906024, ENST00000906025, ENST00000906026, ENST00000906027, ENST00000906028, ENST00000906029, ENST00000906030, ENST00000906031, ENST00000927129, ENST00000927130, ENST00000942641, ENST00000942642, ENST00000942643

RefSeq mRNA: 3 — MANE Select: NM_212502 NM_002596, NM_212502, NM_212503

CCDS: CCDS1454, CCDS44300

Canonical transcript exons

ENST00000429964 — 16 exons

Exon	Start	End
ENSE00001294726	205523147	205523297
ENSE00001707236	205504669	205504796
ENSE00002050539	205531344	205532790
ENSE00003468213	205528999	205529096
ENSE00003502117	205530628	205530705
ENSE00003528100	205527794	205527917
ENSE00003530517	205526775	205526837
ENSE00003564505	205530259	205530349
ENSE00003572179	205524232	205524357
ENSE00003627867	205526367	205526461
ENSE00003627928	205529521	205529563
ENSE00003631350	205525139	205525195
ENSE00003634172	205529324	205529429
ENSE00003635543	205523483	205523625
ENSE00003640183	205528048	205528168
ENSE00003646089	205526065	205526179

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 99.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.7644 / max 700.3668, expressed in 1185 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8037	9.7055	1068
8033	0.9227	418
8036	0.5178	302
8041	0.3263	150
8043	0.3221	137
8034	0.3204	125
8035	0.2734	157
8038	0.1971	108
8040	0.1476	63
8042	0.0316	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.50	gold quality
spinal cord	UBERON:0002240	99.24	gold quality
inferior vagus X ganglion	UBERON:0005363	98.96	gold quality
apex of heart	UBERON:0002098	98.93	gold quality
middle frontal gyrus	UBERON:0002702	97.91	gold quality
subthalamic nucleus	UBERON:0001906	97.68	gold quality
right atrium auricular region	UBERON:0006631	97.47	gold quality
corpus callosum	UBERON:0002336	97.24	gold quality
cardiac atrium	UBERON:0002081	97.04	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.83	gold quality
heart left ventricle	UBERON:0002084	96.82	gold quality
ventral tegmental area	UBERON:0002691	96.64	gold quality
superior vestibular nucleus	UBERON:0007227	96.63	gold quality
medulla oblongata	UBERON:0001896	96.56	gold quality
cardiac ventricle	UBERON:0002082	96.47	gold quality
dorsal plus ventral thalamus	UBERON:0001897	95.44	gold quality
pons	UBERON:0000988	95.41	gold quality
lateral globus pallidus	UBERON:0002476	95.40	gold quality
midbrain	UBERON:0001891	95.36	gold quality
substantia nigra	UBERON:0002038	95.16	gold quality
right frontal lobe	UBERON:0002810	95.16	gold quality
heart	UBERON:0000948	95.02	gold quality
substantia nigra pars compacta	UBERON:0001965	94.95	gold quality
amygdala	UBERON:0001876	94.83	gold quality
putamen	UBERON:0001874	94.79	gold quality
inferior olivary complex	UBERON:0002127	94.39	gold quality
hypothalamus	UBERON:0001898	94.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.69	gold quality
cingulate cortex	UBERON:0003027	93.64	gold quality
anterior cingulate cortex	UBERON:0009835	93.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	62.87
E-ANND-3	yes	4.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

80 targeting CDK18, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6134	99.63	65.68	1537

Literature-anchored findings (GeneRIF, showing 7)

• Expression of PCTAIRE 3a (474 amino acids) was evident throughout the brain and in the majority of tissues analyzed, while spliced isoform PCTAIRE 3b (504 amino acids) was limited to several subcortical nuclei of the basal gangli and the spinal cord. (PMID:15019984)
• PCTAIRE 3 is aassociated kinase that modulates tau phosphorylation in Alzeheimer’s disease. (PMID:16766195)
• Increased levels of PCTAIRE3 is associated with Alzheimer’s disease. (PMID:26885753)
• these data reveal a rate-limiting role for CDK18 in replication stress signalling and establish it as a novel regulator of genome integrity. (PMID:27382066)
• CDK18 knockdown or ATR inhibition in glioblastoma stem-like cells suppressed homologous recombination. (PMID:31266951)
• Cyclin-Dependent Kinase 18 Controls Trafficking of Aquaporin-2 and Its Abundance through Ubiquitin Ligase STUB1, Which Functions as an AKAP. (PMID:32164329)
• Genome-wide association study of early ischaemic stroke risk in Brazilian individuals with sickle cell disease implicates ADAMTS2 and CDK18 and uncovers novel loci. (PMID:36602125)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk18	ENSDARG00000012204
mus_musculus	Cdk18	ENSMUSG00000026437
rattus_norvegicus	Cdk18	ENSRNOG00000008137

Paralogs (26): CDKL3 (ENSG00000006837), CDKL5 (ENSG00000008086), CDK11A (ENSG00000008128), CDK14 (ENSG00000058091), CDK17 (ENSG00000059758), CDK13 (ENSG00000065883), CDKL1 (ENSG00000100490), CDK16 (ENSG00000102225), CDK6 (ENSG00000105810), PRP4K (ENSG00000112739), 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 18 — Q07002 (reviewed: Q07002)

Alternative names: Cell division protein kinase 18, PCTAIRE-motif protein kinase 3, Serine/threonine-protein kinase PCTAIRE-3

All UniProt accessions (3): A0A0A0MSJ6, D6R9B0, Q07002

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in signal transduction cascades in terminally differentiated cells.

Tissue specificity. Isoform 2 expression is limited to several subcortical nuclei of the basal gangli and the spinal cord. Isoform 1 is widely expressed.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q07002-2	1, 3a	yes
Q07002-3	2, 3b

RefSeq proteins (3): NP_002587, NP_997667, NP_997668 (=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 (21 total): modified residue 8, sequence variant 3, sequence conflict 3, binding site 2, chain 1, domain 1, splice variant 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q07002-F1	73.28	0.45

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): 265 (proton acceptor)

Ligand- & substrate-binding residues (2): 150–158; 173

Post-translational modifications (8): 117, 132, 440, 443, 14, 74, 89, 98

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_MYELINATION, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, CAGCTG_AP4_Q5, WOTTON_RUNX_TARGETS_UP, RODRIGUES_NTN1_TARGETS_DN, MODULE_66, GOBP_ENSHEATHMENT_OF_NEURONS, TGCTGAY_UNKNOWN, GOBP_REGULATION_OF_CELL_CYCLE, ZIC1_01, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_PROCESS

GO Biological Process (3): positive regulation of myelination (GO:0031643), regulation of cell cycle phase transition (GO:1901987), protein phosphorylation (GO:0006468)

GO Molecular Function (9): 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), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
intracellular membrane-bounded organelle	2
regulation of myelination	1
positive regulation of nervous system process	1
myelination	1
positive regulation of cellular process	1
regulation of cell cycle process	1
cell cycle phase transition	1
phosphorylation	1
protein modification process	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
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2949 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK18	TDRD7	Q8NHU6	795
CDK18	CABLES1	Q8TDN4	754
CDK18	CCNH	P51946	628
CDK18	RAD9A	Q99638	564
CDK18	CCNY	Q8ND76	550
CDK18	CCDC180	Q9P1Z9	549
CDK18	CCNL2	Q96S94	544
CDK18	RAB2A	P08886	521
CDK18	GORASP2	Q9H8Y8	481
CDK18	PTPN1	P18031	471
CDK18	EPS15	P42566	445
CDK18	UBA1	P22314	439
CDK18	RAB6B	Q9NRW1	438
CDK18	SUMF2	Q8NBJ7	424
CDK18	CCNC	P24863	417

IntAct

337 interactions, top by confidence:

A	B	Type	Score
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
CDK18	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720
CDK18	KRT31	psi-mi:“MI:0915”(physical association)	0.720
GOLGA2	CDK18	psi-mi:“MI:0915”(physical association)	0.720
KRT31	CDK18	psi-mi:“MI:0915”(physical association)	0.720
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
CDK18	CCDC102B	psi-mi:“MI:0915”(physical association)	0.560
CCNDBP1	CDK18	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	CDK18	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	CDK18	psi-mi:“MI:0915”(physical association)	0.560
KRT40	CDK18	psi-mi:“MI:0915”(physical association)	0.560
PNMA1	CDK18	psi-mi:“MI:0915”(physical association)	0.560
MIPOL1	CDK18	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	CDK18	psi-mi:“MI:0915”(physical association)	0.560
CDK18	KIFC3	psi-mi:“MI:0915”(physical association)	0.560
CDK18	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
TSGA10	CDK18	psi-mi:“MI:0915”(physical association)	0.560
CDK18	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.560
CDK18	TRIM27	psi-mi:“MI:0915”(physical association)	0.560
CDK18	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
CDK18	KRT40	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (188): CDK18 (Two-hybrid), CDK18 (Two-hybrid), CDK18 (Two-hybrid), TRIM27 (Two-hybrid), PNMA1 (Two-hybrid), MTUS2 (Two-hybrid), CCNDBP1 (Two-hybrid), TRIM54 (Two-hybrid), CCDC102B (Two-hybrid), TSGA10 (Two-hybrid), LZTS2 (Two-hybrid), KRT40 (Two-hybrid), MIPOL1 (Two-hybrid), CDK18 (Affinity Capture-MS), CDK18 (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

6 interactions.

A	Effect	B	Mechanism
CDK18	“down-regulates activity”	PTK2
CDK18	“down-regulates quantity by destabilization”	AQP2	phosphorylation
CDK18	unknown	RB1	phosphorylation
PKA	“up-regulates activity”	CDK18	phosphorylation
PRKACA	“up-regulates activity”	CDK18	phosphorylation
CDK18	“form complex”	CyclinA2/CDK18	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	90.4×	2e-10
Activation of BAD and translocation to mitochondria	6	87.8×	4e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	77.5×	7e-09
Activation of BH3-only proteins	6	57.3×	4e-08
RHO GTPases activate PKNs	6	36.6×	5e-07
Intrinsic Pathway for Apoptosis	6	33.8×	8e-07
SARS-CoV-1-host interactions	6	20.3×	1e-05
Apoptosis	6	19.4×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	8	41.3×	8e-09
morphogenesis of an epithelium	5	24.2×	2e-04
intermediate filament organization	7	23.7×	4e-06
epithelial cell differentiation	5	12.4×	5e-03
intracellular protein localization	8	11.8×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2501 predictions. Top by Δscore:

Variant	Effect	Δscore
1:205523290:G:GT	donor_gain	1.0000
1:205523294:GAGA:G	donor_gain	1.0000
1:205523296:GA:G	donor_gain	1.0000
1:205523298:G:GG	donor_gain	1.0000
1:205523303:GGGTC:G	donor_gain	1.0000
1:205523624:AGGTA:A	donor_loss	1.0000
1:205523625:GGTAA:G	donor_loss	1.0000
1:205523626:GTA:G	donor_loss	1.0000
1:205523627:T:A	donor_loss	1.0000
1:205524225:A:AG	acceptor_gain	1.0000
1:205524227:CACA:C	acceptor_loss	1.0000
1:205524229:CAGG:C	acceptor_loss	1.0000
1:205524230:A:AG	acceptor_gain	1.0000
1:205524230:AG:A	acceptor_gain	1.0000
1:205524230:AGG:A	acceptor_loss	1.0000
1:205524231:G:A	acceptor_loss	1.0000
1:205524231:G:GA	acceptor_gain	1.0000
1:205524231:GG:G	acceptor_gain	1.0000
1:205524231:GGAC:G	acceptor_gain	1.0000
1:205524358:G:GG	donor_gain	1.0000
1:205524360:G:GG	donor_loss	1.0000
1:205525137:A:AG	acceptor_gain	1.0000
1:205525138:G:GT	acceptor_gain	1.0000
1:205525138:GTC:G	acceptor_gain	1.0000
1:205525138:GTCA:G	acceptor_gain	1.0000
1:205525193:GAG:G	donor_gain	1.0000
1:205525194:AGGTA:A	donor_loss	1.0000
1:205525195:GGTAA:G	donor_loss	1.0000
1:205525196:GTA:G	donor_loss	1.0000
1:205525197:T:A	donor_loss	1.0000

AlphaMissense

3104 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:205525151:T:C	F138L	1.000
1:205525153:T:A	F138L	1.000
1:205525153:T:G	F138L	1.000
1:205525169:T:G	Y144D	1.000
1:205525191:G:A	G151E	1.000
1:205526065:G:A	G153S	1.000
1:205526065:G:C	G153R	1.000
1:205526065:G:T	G153C	1.000
1:205526066:G:A	G153D	1.000
1:205526075:C:A	A156D	1.000
1:205526081:T:A	V158D	1.000
1:205526089:G:A	G161R	1.000
1:205526089:G:C	G161R	1.000
1:205526089:G:T	G161W	1.000
1:205526090:G:A	G161E	1.000
1:205526120:C:A	A171D	1.000
1:205526123:T:C	L172P	1.000
1:205526125:A:C	K173Q	1.000
1:205526125:A:G	K173E	1.000
1:205526126:A:T	K173I	1.000
1:205526127:A:C	K173N	1.000
1:205526127:A:T	K173N	1.000
1:205526168:C:A	A187D	1.000
1:205526174:G:C	R189P	1.000
1:205526176:G:A	E190K	1.000
1:205526177:A:T	E190V	1.000
1:205526178:G:C	E190D	1.000
1:205526178:G:T	E190D	1.000
1:205526373:T:C	L193P	1.000
1:205526376:T:C	L194P	1.000

dbSNP variants (sampled 300 via entrez): RS1000039710 (1:205524035 C>T), RS1000137140 (1:205531460 C>T), RS1000403035 (1:205516207 C>T), RS1000424825 (1:205509288 G>A), RS1000472479 (1:205504585 G>C), RS1000514024 (1:205505022 G>T), RS1000545697 (1:205504866 A>G), RS1000575439 (1:205506569 T>A), RS1000754829 (1:205509074 A>C,G), RS1000806285 (1:205510418 A>G,T), RS1000894344 (1:205527540 G>A,C), RS1001052721 (1:205505393 T>C), RS1001155333 (1:205510726 C>G,T), RS1001159595 (1:205511537 A>G,T), RS1001180098 (1:205516638 G>C)

Disease associations

OMIM: gene MIM:169190 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002450_2	Plasma omega-6 polyunsaturated fatty acid levels (gamma-linolenic acid)	5.000000e-07
GCST006281_18	Coronary artery disease in type 1 diabetes	9.000000e-06
GCST006281_21	Coronary artery disease in type 1 diabetes	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005680	omega-6 polyunsaturated fatty acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3559691 (PROTEIN FAMILY), CHEMBL4106161 (PROTEIN COMPLEX), CHEMBL5316 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 143,474 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL1276127	INDIRUBIN	2	181
CHEMBL5199065	ISTISOCICLIB	2	21
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1721885	SU-014813	2	363
CHEMBL384304	RG-547	2	93
CHEMBL445813	AT-7519	2	2,614
CHEMBL521851	PICTILISIB	2	6,071
CHEMBL296468	BMS-387032	1	2,075
CHEMBL3128043	PF-03758309	1	233
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 — TAIRE subfamily

Binding affinities (BindingDB)

6 measured of 6 human assays (6 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 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
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

34 potent at pChembl≥5 of 36 total, top 28 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.38	IC50	4.2	nM	CHEMBL6144731
7.85	Kd	14	nM	AT-7519
7.70	Kd	20	nM	RG-547
7.36	Kd	44	nM	BMS-387032
7.29	IC50	51.1	nM	STAUROSPORINE
7.27	Kd	54	nM	AST-487
7.18	IC50	66.3	nM	STAUROSPORINE
7.17	Kd	67	nM	PF-03758309
7.15	IC50	70.9	nM	STAUROSPORINE
6.96	Kd	110	nM	CHEMBL1082152
6.60	Kd	250	nM	FORETINIB
6.57	Kd	270	nM	STAUROSPORINE
6.29	Kd	510	nM	NINTEDANIB
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.96	Kd	1100	nM	ALVOCIDIB
5.82	Kd	1500	nM	PHA-665752
5.77	Kd	1700	nM	SUNITINIB
5.68	Kd	2100	nM	JNJ-7706621
5.66	IC50	2200	nM	INDIRUBIN
5.57	Kd	2700	nM	FEDRATINIB
5.50	Kd	3200	nM	SU-014813
5.34	Kd	4600	nM	PICTILISIB
5.31	IC50	4900	nM	CHEMBL3656841
5.11	IC50	7700	nM	CHEMBL4160662
5.11	Kd	7700	nM	CHEMBL379218
5.08	Kd	8400	nM	DOVITINIB

PubChem BioAssay actives

29 with measured affinity, of 359 total; 20 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	624874: Binding constant for PCTK3 kinase domain	kd	0.0140	uM
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone	624874: Binding constant for PCTK3 kinase domain	kd	0.0200	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	435826: Binding constant for full-length PCTK3	kd	0.0440	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	1531622: Inhibition of human CDK18/cyclin-Y using RB protein as substrate by [gamma-33P]-ATP assay	ic50	0.0511	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435826: Binding constant for full-length PCTK3	kd	0.0540	uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	1424943: 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	0.0670	uM
3-[3-(2,3-dihydroxypropylamino)phenyl]-4-(5-fluoro-1-methylindol-3-yl)pyrrole-2,5-dione	465272: Inhibition of PCTK3	kd	0.1100	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	624874: Binding constant for PCTK3 kinase domain	kd	0.2500	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624874: Binding constant for PCTK3 kinase domain	kd	0.5100	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	435826: Binding constant for full-length PCTK3	kd	1.1000	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	624874: Binding constant for PCTK3 kinase domain	kd	1.5000	uM
Sunitinib	435826: Binding constant for full-length PCTK3	kd	1.7000	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435826: Binding constant for full-length PCTK3	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
Fedratinib	624874: Binding constant for PCTK3 kinase domain	kd	2.7000	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	624874: Binding constant for PCTK3 kinase domain	kd	3.2000	uM
4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine	624874: Binding constant for PCTK3 kinase domain	kd	4.6000	uM
4-[[[6-[5-chloro-2-[[4-[[(2R)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	1921486: Inhibition of CDK18 (unknown origin) by Kinomescan method	ic50	4.9000	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624874: Binding constant for PCTK3 kinase domain	kd	7.7000	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	624874: Binding constant for PCTK3 kinase domain	kd	8.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance	3
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
lead acetate	decreases expression	1
methylselenic acid	increases expression	1
sodium arsenate	increases abundance, increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
afimoxifene	increases expression	1
sulforaphane	decreases expression	1
cupric chloride	decreases expression	1
1-hydroxypyrene	affects cotreatment, decreases methylation	1
CGP 52608	affects binding, increases reaction	1
JP8 aviation fuel	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Oxygen	increases expression	1

ChEMBL screening assays

194 unique, capped per target: 194 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

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SI28	HAP1 CDK18 (-) 1	Cancer cell line	Male
CVCL_SI29	HAP1 CDK18 (-) 2	Cancer cell line	Male
CVCL_SI30	HAP1 CDK18 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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