CDK15

Summary

CDK15 (cyclin dependent kinase 15, HGNC:14434) is a protein-coding gene on chromosome 2q33.1, encoding Cyclin-dependent kinase 15 (Q96Q40). Serine/threonine-protein kinase that acts like an antiapoptotic protein that counters TRAIL/TNFSF10-induced apoptosis by inducing phosphorylation of BIRC5 at ‘Thr-34’.

Enables protein serine/threonine kinase activity. Predicted to be involved in regulation of cell cycle phase transition. Predicted to be part of cyclin-dependent protein kinase holoenzyme complex. Predicted to be active in cytosol and nucleus.

Source: NCBI Gene 65061 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 66 total
• GTEx eGene: eQTL in 7 tissues, sQTL in 1 (q < 0.05)
• ChEMBL bioactivity: 13 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.29 (unconstrained)
• MANE Select transcript: NM_001366386
• Notable: 66 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14434
Approved symbol	CDK15
Name	cyclin dependent kinase 15
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	PFTAIRE2
Ensembl gene	ENSG00000138395
Ensembl biotype	protein_coding
OMIM	616147
Entrez	65061

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000652192

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 2, TSL 4: 3

ENST00000652192, ENST00000260967, ENST00000410091, ENST00000434439, ENST00000450471, ENST00000451080, ENST00000460149, ENST00000466337, ENST00000488419, ENST00000493754

RefSeq mRNA: 4 — MANE Select: NM_001366386 NM_001261435, NM_001261436, NM_001366386, NM_139158

CCDS: CCDS2350, CCDS58746, CCDS58747, CCDS92927

Canonical transcript exons

ENST00000652192 — 14 exons

Exon	Start	End
ENSE00000000297	201806537	201806787
ENSE00003474063	201847381	201847474
ENSE00003476429	201812483	201812562
ENSE00003523928	201833848	201833971
ENSE00003580487	201872278	201872326
ENSE00003589424	201880028	201880167
ENSE00003611693	201807494	201807643
ENSE00003617898	201890785	201890927
ENSE00003632123	201854874	201854937
ENSE00003632778	201807858	201807952
ENSE00003640314	201823665	201823727
ENSE00003659051	201822809	201822903
ENSE00003689329	201835643	201835763
ENSE00004805940	201893301	201895550

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 92.19.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4219 / max 161.6394, expressed in 341 samples.

Highest expression (Bgee): corpus epididymis, mucosa of paranasal sinus, epithelial cell of pancreas, kidney epithelium, sperm.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CDK15 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 7 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

8 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	2.2e-27	+0.35	2:201838784:T:A
Breast Mammary Tissue	sqtl	3.5e-03	+1.56	2:201988005:G:A
Adipose Visceral Omentum	eqtl	5.3e-03	-0.50	2:201814371:C:T
Testis	eqtl	1.3e-02	+0.14	2:201876341:G:A
Artery Tibial	eqtl	2.0e-02	-0.12	2:201867072:A:G
Pituitary	eqtl	2.1e-02	+0.40	2:201535163:T:C
Lung	eqtl	3.5e-02	+0.66	2:201638728:C:T
Brain Cerebellum	eqtl	3.7e-02	-0.36	2:201860450:T:C

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
24688	0.9696	311
24685	0.3935	26
24689	0.0375	13
24684	0.0121	6
24686	0.0092	5

Top tissues by expression

showing 100 of 219 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	92.19	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.55	gold quality
epithelial cell of pancreas	CL:0000083	85.61	gold quality
kidney epithelium	UBERON:0004819	84.66	gold quality
sperm	CL:0000019	84.58	gold quality
germinal epithelium of ovary	UBERON:0001304	83.30	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.14	gold quality
secondary oocyte	CL:0000655	82.39	gold quality
buccal mucosa cell	CL:0002336	81.19	gold quality
cardiac muscle of right atrium	UBERON:0003379	79.33	gold quality
lower lobe of lung	UBERON:0008949	79.11	silver quality
upper arm skin	UBERON:0004263	79.01	gold quality
cauda epididymis	UBERON:0004360	78.25	gold quality
left ventricle myocardium	UBERON:0006566	78.11	gold quality
superficial temporal artery	UBERON:0001614	77.52	gold quality
left ovary	UBERON:0002119	72.39	gold quality
oocyte	CL:0000023	72.15	gold quality
right ovary	UBERON:0002118	72.09	gold quality
ovary	UBERON:0000992	70.80	gold quality
caput epididymis	UBERON:0004358	69.90	silver quality
myocardium	UBERON:0002349	69.81	gold quality
nasal cavity epithelium	UBERON:0005384	69.70	gold quality
stromal cell of endometrium	CL:0002255	69.53	gold quality
gall bladder	UBERON:0002110	69.31	gold quality
epithelium of nasopharynx	UBERON:0001951	68.36	gold quality
parietal pleura	UBERON:0002400	67.74	silver quality
endothelial cell	CL:0000115	65.48	gold quality
deltoid	UBERON:0001476	65.30	gold quality
muscle tissue	UBERON:0002385	64.35	gold quality
layer of synovial tissue	UBERON:0007616	63.17	silver quality
heart right ventricle	UBERON:0002080	63.10	gold quality
skeletal muscle tissue	UBERON:0001134	62.78	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	62.59	gold quality
vena cava	UBERON:0004087	62.45	gold quality
descending thoracic aorta	UBERON:0002345	62.34	gold quality
thoracic aorta	UBERON:0001515	62.26	gold quality
epithelium of mammary gland	UBERON:0003244	62.22	gold quality
pancreatic ductal cell	CL:0002079	62.17	silver quality
mammary duct	UBERON:0001765	62.05	gold quality
cardia of stomach	UBERON:0001162	61.86	silver quality
ascending aorta	UBERON:0001496	61.78	gold quality
smooth muscle tissue	UBERON:0001135	61.36	gold quality
skin of hip	UBERON:0001554	61.22	gold quality
lower esophagus mucosa	UBERON:0035834	61.17	gold quality
aorta	UBERON:0000947	60.96	gold quality
urinary bladder	UBERON:0001255	60.87	gold quality
colonic epithelium	UBERON:0000397	60.82	silver quality
rectum	UBERON:0001052	60.82	gold quality
parotid gland	UBERON:0001831	60.42	gold quality
mucosa of stomach	UBERON:0001199	60.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	60.16	gold quality
lower esophagus	UBERON:0013473	60.02	gold quality
lower esophagus muscularis layer	UBERON:0035833	60.02	gold quality
gingival epithelium	UBERON:0001949	60.01	gold quality
popliteal artery	UBERON:0002250	60.00	gold quality
cerebellar vermis	UBERON:0004720	59.99	gold quality
tibial artery	UBERON:0007610	59.94	gold quality
lateral globus pallidus	UBERON:0002476	59.87	gold quality
dorsal root ganglion	UBERON:0000044	59.76	silver quality
hindlimb stylopod muscle	UBERON:0004252	59.69	gold quality
trachea	UBERON:0003126	59.50	gold quality
subcutaneous adipose tissue	UBERON:0002190	59.43	gold quality
lung	UBERON:0002048	59.28	gold quality
mammary gland	UBERON:0001911	59.25	gold quality
thoracic mammary gland	UBERON:0005200	59.23	gold quality
nipple	UBERON:0002030	59.18	gold quality
pharyngeal mucosa	UBERON:0000355	59.17	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	59.11	gold quality
inferior vagus X ganglion	UBERON:0005363	59.05	gold quality
peritoneum	UBERON:0002358	58.88	gold quality
omental fat pad	UBERON:0010414	58.88	gold quality
tibialis anterior	UBERON:0001385	58.64	silver quality
adipose tissue of abdominal region	UBERON:0007808	58.60	gold quality
fundus of stomach	UBERON:0001160	58.37	gold quality
esophagus squamous epithelium	UBERON:0006920	58.35	gold quality
thymus	UBERON:0002370	58.30	gold quality
synovial joint	UBERON:0002217	58.26	gold quality
pericardium	UBERON:0002407	58.09	silver quality
body of stomach	UBERON:0001161	58.07	gold quality
upper lobe of lung	UBERON:0008948	57.92	gold quality
right lung	UBERON:0002167	57.88	gold quality
gingiva	UBERON:0001828	57.74	gold quality
urethra	UBERON:0000057	57.71	gold quality
pylorus	UBERON:0001166	57.47	gold quality
pons	UBERON:0000988	57.45	gold quality
testis	UBERON:0000473	57.43	gold quality
penis	UBERON:0000989	57.28	gold quality
substantia nigra pars reticulata	UBERON:0001966	57.24	gold quality
tibia	UBERON:0000979	57.03	gold quality
lateral nuclear group of thalamus	UBERON:0002736	56.94	gold quality
caecum	UBERON:0001153	56.92	gold quality
stomach	UBERON:0000945	56.88	gold quality
seminal vesicle	UBERON:0000998	56.84	gold quality
cartilage tissue	UBERON:0002418	56.83	gold quality
tibial nerve	UBERON:0001323	56.82	gold quality
trabecular bone tissue	UBERON:0002483	56.72	gold quality
renal medulla	UBERON:0000362	56.71	gold quality
female reproductive system	UBERON:0000474	56.68	gold quality
small intestine	UBERON:0002108	56.59	gold quality
substantia nigra pars compacta	UBERON:0001965	56.58	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	11.61
E-CURD-112	yes	10.38
E-MTAB-9801	yes	7.17
E-ANND-3	yes	5.46

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 68 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Epididymis	tissue	14.4
Thalamus	tissue	8.5
Superior colliculi	tissue	8.1
Midbrain	tissue	8.0
Pons	tissue	7.3
Spinal cord	tissue	6.8
Medulla oblongata	tissue	6.4
Corpus callosum	tissue	6.0
Putamen	tissue	5.9
Hypothalamus	tissue	5.6
Substantia nigra	tissue	5.2
Basal ganglia	tissue	5.1
Periaqueductal gray	tissue	5.1
Cerebellum	tissue	4.8
Septum	tissue	4.8
Ventral forebrain	tissue	4.7
Hippocampal formation	tissue	4.1
Amygdala	tissue	4.0
Ovary	tissue	3.9
Cerebral cortex	tissue	3.8
Somatosensory cortex	tissue	3.8
Occipital cortex	tissue	3.7
Insular cortex	tissue	3.7
Entorhinal cortex	tissue	3.6
Prefrontal cortex	tissue	3.5
Retrosplenial cortex	tissue	3.5
Temporal cortex	tissue	3.4
Motor cortex	tissue	3.3
Retrosplenial and cingulate cortex	tissue	3.2
Olfactory bulb	tissue	3.0
Caudate putamen	tissue	2.2
Testis	tissue	1.8
Gallbladder	tissue	1.7
Postcentral gyrus	tissue	1.7
Frontal cortex	tissue	1.6
Lung	tissue	1.0
Hippocampus	tissue	1.0
Cervix	tissue	0.8
Skeletal muscle	tissue	0.8
Nucleus accumbens	tissue	0.7
Locus coeruleus	tissue	0.7
Skin 1	tissue	0.6
Breast	tissue	0.6
Rectum	tissue	0.6
Endometrium 1	tissue	0.6
Tongue	tissue	0.6
Small intestine	tissue	0.6
Stomach 1	tissue	0.5
Adipose tissue	tissue	0.5
Esophagus	tissue	0.5
Urinary bladder	tissue	0.5
Choroid plexus	tissue	0.5
Prostate	tissue	0.5
Vagina	tissue	0.4
Smooth muscle	tissue	0.4
Colon	tissue	0.4
Fallopian tube	tissue	0.4
Seminal vesicle	tissue	0.3
Kidney	tissue	0.3
Duodenum	tissue	0.3

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Dorsal spinal cord (6.8), Ventral spinal cord (6.6), White matter (6.0), Vermis (5.8), Flocculonodular lobe (4.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CDK15 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 101 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-885-5P	99.59	68.59	879

Functional genomics

gnomAD constraint: pLI 5.44e-19, LOEUF 1.29, missense Z 0.169 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000652192 — one region, missense o/e 1.03.

Literature-anchored findings (GeneRIF, showing 3)

• In summary, our results suggest that ALS2CR7 confers TRAIL resistance to cancer cells via phosphorylation of survivin. (PMID:24866247)
• Cyclin-dependent kinase 15 upregulation is correlated with poor prognosis for patients with breast cancer. (PMID:34162268)
• CDK15 promotes colorectal cancer progression via phosphorylating PAK4 and regulating beta-catenin/ MEK-ERK signaling pathway. (PMID:34262144)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk15	ENSDARG00000006093
mus_musculus	Cdk15	ENSMUSG00000026023
rattus_norvegicus	Cdk15	ENSRNOG00000022899

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), CDKL2 (ENSG00000138769), CDK19 (ENSG00000155111), CDK20 (ENSG00000156345), CDK5 (ENSG00000164885), CDK12 (ENSG00000167258), CDK1 (ENSG00000170312), CDK10 (ENSG00000185324), CDKL4 (ENSG00000205111), CDK11B (ENSG00000248333), CDK3 (ENSG00000250506)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:3583944) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating free fatty acids level	1
increased heart weight	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q02399	100.0%	Diamond
Callithrix jacchus	B0VXE8	99.8%	Diamond
Plecturocebus moloch	B0VXL7	99.5%	Diamond
Dasypus novemcinctus	C0RW22	99.3%	Diamond
Oryctolagus cuniculus	B6A7Q3	98.8%	Diamond
Pongo abelii	Q5RD01	98.7%	Diamond
Petunia x hybrida	P43290	96.7%	Diamond
Xenopus tropicalis	A4IIW7	93.6%	Diamond
Saccharomyces cerevisiae S288C	P17157	91.3%	Diamond
Nakaseomyces glabratus CBS 138	Q6FKD4	91.3%	Diamond
Debaryomyces hansenii CBS767	Q6BRY2	90.9%	Diamond
Candida albicans	Q9HGY5	90.9%	Diamond
Xenopus laevis	Q6DJM7	89.6%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q92241	83.8%	Diamond
Eremothecium gossypii ATCC 10895	Q751E8	81.7%	Diamond
Yarrowia lipolytica CLIB122	Q6C7U8	79.2%	Diamond
Schizosaccharomyces pombe 972h-	O74456	70.7%	Diamond
Caenorhabditis elegans	Q8I7M8	63.5%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SRF5	52.8%	Diamond
Dictyostelium discoideum	Q54UL8	47.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ALS2	protein-coding	57679
MPP4	protein-coding	58538
TMEM237	protein-coding	65062
FZD7	protein-coding	8324
CATSPERT	protein-coding	151254
KIAA2012	protein-coding	100652824

Protein

Protein identifiers

Cyclin-dependent kinase 15 — Q96Q40 (reviewed: Q96Q40)

Alternative names: Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 7 protein, Cell division protein kinase 15, Serine/threonine-protein kinase ALS2CR7, Serine/threonine-protein kinase PFTAIRE-2

All UniProt accessions (2): F8WDP7, Q96Q40

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that acts like an antiapoptotic protein that counters TRAIL/TNFSF10-induced apoptosis by inducing phosphorylation of BIRC5 at ‘Thr-34’.

Miscellaneous. May be due to competing acceptor splice site.

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q96Q40-1	1	yes
Q96Q40-3	3
Q96Q40-4	4
Q96Q40-5	5
Q96Q40-6	6

RefSeq proteins (4): NP_001248364, NP_001248365, NP_001353315, NP_631897 (=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
IPR042761	CDK15_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)

• 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 (16 total): splice variant 6, sequence variant 5, binding site 2, chain 1, domain 1, active site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96Q40-F1	72.75	0.43

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, CMGC Ser/Thr protein kinases, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; nucleoplasm

Antibody reliability (HPA): IH uncertain · IF approved

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)

Position	Role
224	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
109–117	ATP
132	ATP

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 77 (showing top): GOBP_CELL_CYCLE_PHASE_TRANSITION, TGACCTY_ERR1_Q2, TGCTGAY_UNKNOWN, GOBP_REGULATION_OF_CELL_CYCLE, AACTTT_UNKNOWN, P300_01, GOBP_REGULATION_OF_CELL_CYCLE_PHASE_TRANSITION, CTGYNNCTYTAA_UNKNOWN, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GOCC_TRANSFERASE_COMPLEX, GOCC_PROTEIN_KINASE_COMPLEX, GOBP_CELL_CYCLE_PROCESS, GOCC_CYCLIN_DEPENDENT_PROTEIN_KINASE_HOLOENZYME_COMPLEX, GOMF_CYCLIN_BINDING

GO Biological Process (2): regulation of cell cycle phase transition (GO:1901987), protein phosphorylation (GO:0006468)

GO Molecular Function (11): protein serine/threonine kinase activity (GO:0004674), cyclin-dependent protein serine/threonine kinase activity (GO:0004693), ATP binding (GO:0005524), cyclin binding (GO:0030332), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (4): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

25 GO namespaces:

Category	Terms
protein kinase activity	2
cellular anatomical structure	2
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
anion binding	1
protein binding	1
cation 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
serine/threonine protein kinase complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
protein serine/threonine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,198 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK15	CCNY	Q8ND76	589
CDK15	HEATR6	Q6AI08	370
CDK15	TRARG1	Q8IXB3	370
CDK15	TEKT3	Q9BXF9	370
CDK15	FSIP2	Q5CZC0	370
CDK15	CLMP	Q9H6B4	367
CDK15	MIPOL1	Q8TD10	357
CDK15	LRTM1	Q9HBL6	350
CDK15	CCNYL1	Q8N7R7	342
CDK15	GLB1L3	Q8NCI6	325
CDK15	ARHGAP28	Q9P2N2	317
CDK15	SERPINB12	Q96P63	312
CDK15	PLPPR5	Q32ZL2	304
CDK15	KATNB1	Q9BVA0	299
CDK15	DDX6	P26196	298

IntAct

Human interaction partners of CDK15 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

9 partners by confidence:

Partner	Interaction type	MIscore	Records
FKBP5	physical association	0.670	1
HSP90AA1	association	0.560	2
HSP90AB1	physical association	0.520	2
CDC37	physical association	0.400	2
DNMT3B	physical association	0.400	1
A2ML1	association	0.350	1
NDUFA4	association	0.350	1
TUSC2	association	0.350	1
CDK2	physical association	0.000	1

BioGRID (201 interactions; top human partners by supporting records): FKBP5 (Affinity Capture-MS; 4 records), HSP90AA1 (Affinity Capture-MS; 4 records), CDK18 (Affinity Capture-MS; 3 records), HSP90AA5P (Affinity Capture-MS; 3 records), HSP90AB3P (Affinity Capture-MS; 3 records), HSP90AB4P (Affinity Capture-MS; 3 records), A2ML1 (Affinity Capture-MS; 2 records), ACPP (Affinity Capture-MS; 2 records), AIM1 (Affinity Capture-MS; 2 records), AKR1B10 (Affinity Capture-MS; 2 records), ALDH1A3 (Affinity Capture-MS; 2 records), ANKRD22 (Affinity Capture-MS; 2 records), ARHGAP1 (Affinity Capture-MS; 2 records), C3 (Affinity Capture-MS; 2 records), CALML5 (Affinity Capture-MS; 2 records)

Disease & clinical

Genetic variants

Variant evidence for CDK15: 66 ClinVar records (0 pathogenic / likely pathogenic); 5 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 42 predictions of 1,452):

Position(s)	Effect	Δscore	Sites
2:201812563–201812564	donor_loss	1.0000	5
2:201822807–201822808	acceptor_loss	1.0000	6
2:201822904–201822905	donor_loss	1.0000	5
2:201833972–201833973	donor_loss	1.0000	5
2:201812481–201812482	acceptor_loss	0.9900	6
2:201833846–201833847	acceptor_loss	0.9900	6
2:201835641–201835642	acceptor_loss	0.9900	6
2:201882612	donor_gain	0.9900
2:201807629	donor_gain	0.9800
2:201822905	donor_loss	0.9800

AlphaMissense

919 missense substitutions predicted likely pathogenic (of 2,845 scored), across 216 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D224	8	0.996	0.999
N229	8	0.993	0.997
D282	8	0.992	0.995
D242	8	0.990	0.998
H222	8	0.983	0.997
F243	8	0.979	0.995
D166	8	0.968	0.995
H216	8	0.964	0.991
H158	8	0.951	0.986
F300	8	0.942	0.985
D184	8	0.928	0.976
F178	8	0.916	0.963
F387	8	0.887	0.976
F176	8	0.779	0.981
E149	7	0.992	0.997
W284	7	0.988	0.997
K132	7	0.985	0.999
R223	7	0.980	0.999
W325	7	0.971	0.996
E292	7	0.969	0.994

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Skin Cutaneous Melanoma)

Disease associations

OMIM: gene MIM:616147 | disease phenotypes:

GWAS associations

5 associations:

Study	Trait	p-value
GCST006979_280	Heel bone mineral density	2e-21
GCST006979_281	Heel bone mineral density	6e-16
GCST006288_518	Heel bone mineral density	4e-13
GCST006288_55	Heel bone mineral density	2e-9
GCST90020026_589	Hip index	2e-9

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3559691 (PROTEIN FAMILY), CHEMBL5483184 (PROTEIN COMPLEX), CHEMBL5856 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 145,150 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

13 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL1336	SORAFENIB	4	87,476
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL300138	ENZASTAURIN	3	3,401
CHEMBL603469	LESTAURTINIB	3
CHEMBL445813	AT-7519	2	2,733
CHEMBL1230609	FORETINIB	2	3,230
CHEMBL1276127	INDIRUBIN	2	183
CHEMBL384304	RG-547	2	93
CHEMBL574738	AST-487	1	468
CHEMBL296468	BMS-387032	1	2,127
CHEMBL1908397	KW-2449	1	655

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — TAIRE subfamily

Binding affinities (BindingDB)

20 measured of 76 human assays (77 total across all organisms); most potent 20 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
CEP-701	KD	3.4 nM
Staurosporine, 8	IC50	6.5 nM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	KI	15 nM	US-10981896: Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase
CHEMBL1240703	KD	15 nM
2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide	IC50	17 nM
PKC-412	KD	110 nM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	KD	120 nM	US-9145414: 1,2,4-triazine-6-carboxamide derivative
CHEMBL1908397	KD	650 nM
CHEMBL4160662	IC50	679 nM
4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide	KD	740 nM
(9S)-9-[(dimethylamino)methyl]-6,7,10,11-tetrahydro-9H,18H-5,21:12,17-di(metheno)dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecine-18,20(19H)-dione	IC50	743 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
CHEMBL6167007	IC50	2260 nM
3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol	KD	2400 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
SUNITINIB MALATE	KD	3500 nM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide	KD	3900 nM	US-20250129067: PLATELET-DERIVED GROWTH FACTOR RECEPTOR (PDGFR) ALPHA INHIBITORS AND USES THEREOF
(4-chlorophenyl)-[4-(4-pyridylmethyl)phthalazin-1-yl]amine	KD	8800 nM

ChEMBL bioactivities

20 potent at pChembl≥5 of 20 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.14	Kd	7.2	nM	RG-547
7.50	Kd	32	nM	FORETINIB
7.21	Kd	62	nM	AT-7519
7.08	Kd	84	nM	AST-487
6.58	Kd	260	nM	STAUROSPORINE
6.48	Kd	330	nM	ALVOCIDIB
6.29	Kd	510	nM	PHA-665752
6.13	Kd	740	nM	BMS-387032
5.89	Kd	1300	nM	LESTAURTINIB
5.80	Kd	1600	nM	BOSUTINIB
5.68	Kd	2100	nM	TAE-684
5.68	Kd	2100	nM	CHEMBL379218
5.66	IC50	2200	nM	INDIRUBIN
5.58	Kd	2600	nM	KW-2449
5.54	Kd	2900	nM	SORAFENIB
5.52	IC50	3024	nM	CHEMBL4160662
5.31	Kd	4900	nM	ENZASTAURIN
5.07	Kd	8600	nM	FEDRATINIB

PubChem BioAssay actives

20 with measured affinity, of 209 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-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.0072	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	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.0320	uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.0620	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.0840	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	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.2600	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.3300	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	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.5100	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.7400	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	507668: Binding affinity to PFTAIRE2	kd	1.3000	uM
Bosutinib	624718: Binding constant for PFTAIRE2 kinase domain	kd	1.6000	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624718: Binding constant for PFTAIRE2 kinase domain	kd	2.1000	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	624718: Binding constant for PFTAIRE2 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-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624718: Binding constant for PFTAIRE2 kinase domain	kd	2.6000	uM
Sorafenib	507668: Binding affinity to PFTAIRE2	kd	2.9000	uM
3-benzyl-1-[4-[(5-cyano-2-pyridinyl)amino]cyclohexyl]-1-[4-(1-methyl-6-oxo-3-pyridinyl)phenyl]urea	2246324: Inhibition of CDK15/Cyclin Y (unknown origin) by ADP-Glo kinase assay	ic50	3.0240	uM
3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione	624718: Binding constant for PFTAIRE2 kinase domain	kd	4.9000	uM
Fedratinib	624718: Binding constant for PFTAIRE2 kinase domain	kd	8.6000	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	affects methylation	2
Nickel	decreases expression	2
Smoke	increases expression	2
aristolochic acid I	increases expression	1
bisphenol A	increases methylation	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	increases expression	1
Cadmium	decreases expression, increases abundance	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Malathion	increases expression	1
Methapyrilene	increases methylation	1
Niclosamide	decreases expression	1
Valproic Acid	decreases methylation	1
Vanadates	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
p-Chloromercuribenzoic Acid	decreases expression	1

ChEMBL screening assays

95 unique, capped per target: 95 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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CDK15 across ~30M SureChEMBL compounds — explore on Sugi Predict.