CDK10

Summary

CDK10 (cyclin dependent kinase 10, HGNC:1770) is a protein-coding gene on chromosome 16q24.3, encoding Cyclin-dependent kinase 10 (Q15131). Cyclin-dependent kinase that phosphorylates the transcription factor ETS2 (in vitro) and positively controls its proteasomal degradation (in cells).

The protein encoded by this gene belongs to the CDK subfamily of the Ser/Thr protein kinase family. The CDK subfamily members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and are known to be essential for cell cycle progression. This kinase has been shown to play a role in cellular proliferation and its function is limited to cell cycle G2-M phase. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8558 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Al Kaissi syndrome (Strong, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 183 total — 15 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 56
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_052988

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1770
Approved symbol	CDK10
Name	cyclin dependent kinase 10
Location	16q24.3
Locus type	gene with protein product
Status	Approved
Aliases	PISSLRE
Ensembl gene	ENSG00000185324
Ensembl biotype	protein_coding
OMIM	603464
Entrez	8558

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 10 protein_coding, 8 retained_intron, 6 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000331006, ENST00000353379, ENST00000378277, ENST00000472018, ENST00000502547, ENST00000503560, ENST00000504473, ENST00000505473, ENST00000505733, ENST00000507205, ENST00000508723, ENST00000510811, ENST00000511415, ENST00000512912, ENST00000514965, ENST00000561477, ENST00000564192, ENST00000565470, ENST00000567932, ENST00000568456, ENST00000851880, ENST00000851881, ENST00000851882, ENST00000851883, ENST00000851884, ENST00000941355

RefSeq mRNA: 4 — MANE Select: NM_052988 NM_001098533, NM_001160367, NM_052987, NM_052988

CCDS: CCDS10984, CCDS32514

Canonical transcript exons

ENST00000353379 — 13 exons

Exon	Start	End
ENSE00001813668	89695595	89696354
ENSE00002415535	89686689	89686797
ENSE00003501712	89694173	89694232
ENSE00003523308	89691443	89691545
ENSE00003545643	89691806	89691887
ENSE00003574345	89694665	89694788
ENSE00003592590	89695293	89695345
ENSE00003595012	89690553	89690624
ENSE00003602207	89689252	89689324
ENSE00003616794	89694931	89695070
ENSE00003629008	89693274	89693326
ENSE00003649319	89693398	89693467
ENSE00003661383	89692449	89692516

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.5845 / max 141.9341, expressed in 1740 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155633	17.5392	1738
155634	0.0453	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.78	gold quality
right lobe of thyroid gland	UBERON:0001119	98.62	gold quality
left lobe of thyroid gland	UBERON:0001120	98.48	gold quality
adenohypophysis	UBERON:0002196	98.32	gold quality
body of pancreas	UBERON:0001150	98.14	gold quality
metanephros cortex	UBERON:0010533	97.92	gold quality
right lobe of liver	UBERON:0001114	97.85	gold quality
granulocyte	CL:0000094	97.76	gold quality
thyroid gland	UBERON:0002046	97.74	gold quality
mucosa of transverse colon	UBERON:0004991	97.65	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.59	gold quality
transverse colon	UBERON:0001157	97.49	gold quality
pituitary gland	UBERON:0000007	97.41	gold quality
apex of heart	UBERON:0002098	97.35	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.29	gold quality
body of stomach	UBERON:0001161	97.27	gold quality
lower esophagus mucosa	UBERON:0035834	97.20	gold quality
endocervix	UBERON:0000458	97.09	gold quality
right frontal lobe	UBERON:0002810	97.01	gold quality
left ovary	UBERON:0002119	96.86	gold quality
right adrenal gland cortex	UBERON:0035827	96.83	gold quality
right ovary	UBERON:0002118	96.81	gold quality
skin of abdomen	UBERON:0001416	96.76	gold quality
right adrenal gland	UBERON:0001233	96.75	gold quality
cerebellar hemisphere	UBERON:0002245	96.68	gold quality
body of uterus	UBERON:0009853	96.61	gold quality
cerebellar cortex	UBERON:0002129	96.52	gold quality
minor salivary gland	UBERON:0001830	96.51	gold quality
upper lobe of left lung	UBERON:0008952	96.45	gold quality
left adrenal gland cortex	UBERON:0035825	96.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting CDK10, 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-10401-5P	99.99	65.79	948
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-1343-5P	96.48	66.06	1506

Literature-anchored findings (GeneRIF, showing 23)

• CDK10 is not a target for aberrant DNA methylation in breast cancer. (PMID:19846932)
• Data show that peptidyl-prolyl isomerase Pin1 silencing in SKBR-3 and MCF7 cells increased the cyclin-dependent kinase 10 (CDK10) expression. (PMID:22158035)
• CDK10 plays a crucial role in the growth and survivability of biliary tract cancer. (PMID:22209942)
• reduced Cdk10 expression is closely linked to hepatocellular carcinoma development and progression (PMID:22326270)
• Data suggest that reactivation of CDK10 might be utilized as a novel epigenetic strategy for the treatment of nasopharyngeal carcinomas (NPC) patients. (PMID:23740091)
• CDK10/cyclin M is a protein kinase that controls ETS2 degradation and is deficient in STAR syndrome. (PMID:24218572)
• Results found that CDK10 mRNA expression was up-regulated in advanced breast neoplasm and positively correlated with C1orf63, which was consistent with the relationship of protein expression between C1orf63 and CDK10. (PMID:26209438)
• Down-regulated CDK10 expression frequently occurs in breast cancers and correlates with disease progression and poor survival (PMID:26392360)
• CDK10/CycM is a key regulator of actin dynamics and a suppressor of ciliogenesis through phosphorylation of PKN2 and promotion of RhoA signaling. (PMID:27104747)
• The findings of this study indicate that CDK10 plays a role in the pathogenesis in colorectal cancer and may be a potential therapeutic target for treatment. (PMID:28663269)
• CDK10 Mutations are associated with Severe Growth Retardation, Spine Malformations, and Developmental Delays. (PMID:28886341)
• These findings underscore the importance of CDK10 for the regulation of ciliogenesis. CDK10 defect is likely associated with a new form of ciliopathy phenotype; additional patients may further validate this association (PMID:29130579)
• the results of the present study indicated that CDK10 expression may serve as a novel prognostic biomarker that holds therapeutic promise for gastric cancer. (PMID:29512714)
• The present study illustrated that downregulation of CDK10 expression activated Snaildriven EMT and consequently promoted glioma metastasis, suggesting that CDK10 may serve as a potential molecular target for glioma therapy. (PMID:29845196)
• Association of Cyclin Dependent Kinase 10 and Transcription Factor 2 during Human Corneal Epithelial Wound Healing in vitro model. (PMID:31413335)
• Gene expression network analysis of lymph node involvement in colon cancer identifies AHSA2, CDK10, and CWC22 as possible prognostic markers. (PMID:32345988)
• Functional characterization of CDK10 and cyclin M truncated variants causing severe developmental disorders. (PMID:34369103)
• A large Canadian cohort provides insights into the genetic architecture of human hair colour. (PMID:34737440)
• Functional characterization of the human Cdk10/Cyclin Q complex. (PMID:35291876)
• A sib-pair with Al Kaissi syndrome caused by homozygosity for a novel CDK10 splice variant. (PMID:36503922)
• CDK10, CDK11, FOXO1, and FOXO3 Gene Expression in Alzheimer’s Disease Encephalic Samples. (PMID:36988771)
• CDK10 suppresses metastasis of lung adenocarcinoma through inhibition of the ETS2/c-Raf/p-MEK/p-ERK signaling loop. (PMID:37737453)
• RNF115 aggravates tumor progression through regulation of CDK10 degradation in thyroid carcinoma. (PMID:38376606)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk10	ENSDARG00000034256
mus_musculus	Cdk10	ENSMUSG00000033862
rattus_norvegicus	Cdk10	ENSRNOG00000016088
drosophila_melanogaster	Cdc2rk	FBGN0013435

Paralogs (26): CDKL3 (ENSG00000006837), CDKL5 (ENSG00000008086), CDK11A (ENSG00000008128), CDK14 (ENSG00000058091), CDK17 (ENSG00000059758), CDK13 (ENSG00000065883), CDKL1 (ENSG00000100490), CDK16 (ENSG00000102225), CDK6 (ENSG00000105810), PRP4K (ENSG00000112739), CDK18 (ENSG00000117266), CDK2 (ENSG00000123374), CDK8 (ENSG00000132964), CDK7 (ENSG00000134058), CDK4 (ENSG00000135446), CDK9 (ENSG00000136807), CDK15 (ENSG00000138395), CDKL2 (ENSG00000138769), CDK19 (ENSG00000155111), CDK20 (ENSG00000156345), CDK5 (ENSG00000164885), CDK12 (ENSG00000167258), CDK1 (ENSG00000170312), CDKL4 (ENSG00000205111), CDK11B (ENSG00000248333), CDK3 (ENSG00000250506)

Protein

Protein identifiers

Cyclin-dependent kinase 10 — Q15131 (reviewed: Q15131)

Alternative names: Cell division protein kinase 10, Serine/threonine-protein kinase PISSLRE

All UniProt accessions (8): Q15131, D6RA59, D6REZ2, D6RHH3, F8W872, H3BSN8, H3BT74, Q9UHL7

UniProt curated annotations — full annotation on UniProt →

Function. Cyclin-dependent kinase that phosphorylates the transcription factor ETS2 (in vitro) and positively controls its proteasomal degradation (in cells). Involved in the regulation of actin cytoskeleton organization through the phosphorylation of actin dynamics regulators such as PKN2. Is a negative regulator of ciliogenesis through phosphorylation of PKN2 and promotion of RhoA signaling.

Subunit / interactions. Heterodimer with CCNQ, the interaction is required for kinase activity. Interacts with ETS2. Interacts with PRK2.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium basal body.

Disease relevance. Al Kaissi syndrome (ALKAS) [MIM:617694] An autosomal recessive developmental disorder characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delay. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (7)

UniProt ID	Names	Canonical?
Q15131-1	1	yes
Q15131-2	2
Q15131-3	3
Q15131-4	4
Q15131-5	5
Q15131-6	6
Q15131-7	7

RefSeq proteins (4): NP_001092003, NP_001153839, NP_443713, NP_443714* (*=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
IPR044093	STKc_CDK10	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), 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 (19 total): splice variant 8, sequence variant 4, binding site 2, chain 1, domain 1, region of interest 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15131-F1	86.27	0.62

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): 163 (proton acceptor)

Ligand- & substrate-binding residues (2): 45–53; 68

Post-translational modifications (1): 196

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 271 (showing top): GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POSITIVE_REGULATION_OF_G1_S_TRANSITION_OF_MITOTIC_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_ORGANELLE_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, NIKOLSKY_BREAST_CANCER_16Q24_AMPLICON, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CILIUM_ORGANIZATION

GO Biological Process (10): traversing start control point of mitotic cell cycle (GO:0007089), negative regulation of cell population proliferation (GO:0008285), peptidyl-threonine phosphorylation (GO:0018107), cell projection organization (GO:0030030), regulation of actin cytoskeleton organization (GO:0032956), positive regulation of MAPK cascade (GO:0043410), negative regulation of cilium assembly (GO:1902018), regulation of cell cycle G2/M phase transition (GO:1902749), protein phosphorylation (GO:0006468), regulation of mitotic cell cycle (GO:0007346)

GO Molecular Function (10): 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), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), cyclin-dependent protein kinase activity (GO:0097472)

GO Cellular Component (6): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), nucleus (GO:0005634), ciliary basal body (GO:0036064), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	3
regulation of cell cycle	2
cellular anatomical structure	2
positive regulation of G1/S transition of mitotic cell cycle	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
protein phosphorylation	1
peptidyl-threonine modification	1
cellular component organization	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
cilium assembly	1
negative regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
negative regulation of organelle assembly	1
cell cycle G2/M phase transition	1
regulation of cell cycle phase transition	1
phosphorylation	1
protein modification process	1
mitotic cell cycle	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
cyclin binding	1
serine/threonine protein kinase complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1202 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK10	ETS2	P15036	874
CDK10	ZNF276	Q8N554	806
CDK10	CCNQ	Q8N1B3	776
CDK10	GALNS	P34059	725
CDK10	CCNL2	Q96S94	723
CDK10	SPG7	Q9UQ90	695
CDK10	CCNG2	Q16589	597
CDK10	DEF8	Q6ZN54	567
CDK10	APRT	P07741	549
CDK10	FANCA	O15360	548
CDK10	PRPF3	O43395	538
CDK10	CCNK	O75909	529
CDK10	SPATA33	Q96N06	528
CDK10	KRT7	P08729	514
CDK10	SLC35E3	Q7Z769	512

IntAct

25 interactions, top by confidence:

A	B	Type	Score
FKBP5	IKBKB	psi-mi:“MI:0914”(association)	0.640
CDK10	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.640
HSP90AB1	CDK10	psi-mi:“MI:0915”(physical association)	0.640
PIN1	CDK10	psi-mi:“MI:0915”(physical association)	0.590
CDK10	PIN1	psi-mi:“MI:0915”(physical association)	0.590
ETS2	CDK10	psi-mi:“MI:0915”(physical association)	0.520
CDK10	HSPA8	psi-mi:“MI:0914”(association)	0.500
CDK10	HSPA8	psi-mi:“MI:0915”(physical association)	0.500
CCNQ	CDK10	psi-mi:“MI:0915”(physical association)	0.400
CDK10	CCT2	psi-mi:“MI:0915”(physical association)	0.400
Pin1	CDK10	psi-mi:“MI:0915”(physical association)	0.400
SEMG2	CDK10	psi-mi:“MI:0915”(physical association)	0.400
CDK10	CCR4	psi-mi:“MI:0915”(physical association)	0.370
PRKD2		psi-mi:“MI:0914”(association)	0.350
Wdr48	DMWD	psi-mi:“MI:0914”(association)	0.350
	CDK10	psi-mi:“MI:0914”(association)	0.350
CDK10	PDCD5	psi-mi:“MI:0914”(association)	0.350
TTC14	AMPD3	psi-mi:“MI:0914”(association)	0.350
CDC37	MAP2K7	psi-mi:“MI:0914”(association)	0.350
ARGLU1	PIAS2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (66): CDK10 (Two-hybrid), PLS1 (Affinity Capture-MS), RNASEH2A (Affinity Capture-MS), FAM84B (Affinity Capture-MS), CDK10 (Affinity Capture-MS), CDK10 (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), ACTB (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CDK10 (Biochemical Activity), ETS2 (Reconstituted Complex), CDK10 (Affinity Capture-Western), ETS2 (Affinity Capture-Western)

ESM2 similar proteins: A3EZ54, B0Y8W7, B9VVJ6, G1XJZ4, G4N0Z0, O15726, O19175, O42781, O62846, P21708, P22612, P24100, P26696, P27361, P28482, P35507, P35509, P42168, P46196, P48729, P54367, P63085, P63086, P67827, P67828, P67829, P67962, P67963, P68180, P68181, P68182, P93101, P97633, Q00859, Q09892, Q15131, Q3UMM4, Q4KM47, Q4PKS0, Q4PNJ1

Diamond homologs: A2X6X1, A2XUW1, A8XA58, B5DE93, D2H526, E1BB50, E1BB52, O55076, O60145, O74456, O96821, P00546, P06493, P11440, P13863, P21127, P23111, P23437, P23572, P23573, P24033, P24100, P24788, P24923, P24941, P29618, P29619, P34112, P34117, P34556, P35567, P38973, P39951, P43063, P43450, P46551, P46892, P48734, P48963, P51958

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CDK10	“down-regulates quantity by destabilization”	ETS2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	5	30.4×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	9
Uncertain significance	101
Likely benign	24
Benign	3

Top pathogenic / likely-pathogenic (24)

Variant ID	HGVS	Classification
1706570	NM_052988.5(CDK10):c.872G>A (p.Trp291Ter)	Pathogenic
1802200	NM_052988.5(CDK10):c.716_728del (p.Leu239fs)	Pathogenic
2422419	NC_000016.9:g.(?89712474)(89866066_?)del	Pathogenic
2580182	NM_052988.5(CDK10):c.625CTG[1] (p.Leu211del)	Pathogenic
2580183	NM_052988.5(CDK10):c.792G>A (p.Pro264=)	Pathogenic
2580186	NM_052988.4:c.(87+1_88-1)_(232+1_233-1)del	Pathogenic
2580187	NM_052988.5(CDK10):c.161-1G>C	Pathogenic
2580188	NM_052988.5(CDK10):c.226A>T (p.Lys76Ter)	Pathogenic
2580189	NM_052988.5(CDK10):c.452T>C (p.Leu151Pro)	Pathogenic
2580190	NM_052988.5(CDK10):c.461T>C (p.Leu154Pro)	Pathogenic
2580191	NM_052988.5(CDK10):c.503del (p.Asn168fs)	Pathogenic
440755	NM_052988.5(CDK10):c.88-870_232+368del	Pathogenic
440757	NM_052988.5(CDK10):c.608+1G>A	Pathogenic
916087	NM_052988.5(CDK10):c.664_665del (p.Met222fs)	Pathogenic
986083	NM_052988.5(CDK10):c.178del (p.Gln60fs)	Pathogenic
1180852	NM_052988.5(CDK10):c.202A>T (p.Lys68Ter)	Likely pathogenic
1684275	NM_052988.5(CDK10):c.299_300dup (p.Leu101fs)	Likely pathogenic
3235695	NM_052988.5(CDK10):c.669G>A (p.Trp223Ter)	Likely pathogenic
3779035	NM_052988.5(CDK10):c.613C>T (p.Arg205Ter)	Likely pathogenic
402153	NM_052988.5(CDK10):c.725C>G (p.Thr242Ser)	Likely pathogenic
4077143	NM_052988.5(CDK10):c.161-2A>G	Likely pathogenic
440756	NM_052988.5(CDK10):c.139del (p.Glu47fs)	Likely pathogenic
4686730	NM_052988.5(CDK10):c.846C>G (p.Tyr282Ter)	Likely pathogenic
813896	NM_052988.5(CDK10):c.550_556del (p.Leu184fs)	Likely pathogenic

SpliceAI

2507 predictions. Top by Δscore:

Variant	Effect	Δscore
16:89686760:G:GG	donor_gain	1.0000
16:89686765:G:GT	donor_gain	1.0000
16:89686796:GG:G	donor_gain	1.0000
16:89686797:GG:G	donor_gain	1.0000
16:89689323:GT:G	donor_gain	1.0000
16:89690549:CCA:C	acceptor_loss	1.0000
16:89690550:CAGAT:C	acceptor_loss	1.0000
16:89690551:A:AG	acceptor_gain	1.0000
16:89690551:AG:A	acceptor_loss	1.0000
16:89690551:AGATC:A	acceptor_gain	1.0000
16:89690552:G:GA	acceptor_gain	1.0000
16:89690552:GA:G	acceptor_gain	1.0000
16:89690552:GATC:G	acceptor_gain	1.0000
16:89690552:GATCG:G	acceptor_gain	1.0000
16:89690620:GGATG:G	donor_gain	1.0000
16:89690621:G:GT	donor_gain	1.0000
16:89691438:CCCA:C	acceptor_loss	1.0000
16:89691439:CCAG:C	acceptor_loss	1.0000
16:89691440:CA:C	acceptor_loss	1.0000
16:89691441:A:AC	acceptor_loss	1.0000
16:89691441:A:AG	acceptor_gain	1.0000
16:89691441:AG:A	acceptor_gain	1.0000
16:89691442:G:GA	acceptor_gain	1.0000
16:89691442:GG:G	acceptor_gain	1.0000
16:89691442:GGC:G	acceptor_gain	1.0000
16:89691442:GGCA:G	acceptor_gain	1.0000
16:89691442:GGCAT:G	acceptor_gain	1.0000
16:89691517:G:GT	donor_gain	1.0000
16:89691543:GAG:G	donor_gain	1.0000
16:89691544:AGG:A	donor_loss	1.0000

AlphaMissense

2343 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:89690596:G:C	K68N	1.000
16:89690596:G:T	K68N	1.000
16:89689279:T:C	F39L	0.999
16:89689281:T:A	F39L	0.999
16:89689281:T:G	F39L	0.999
16:89689306:G:C	G48R	0.999
16:89689316:G:A	G51D	0.999
16:89690556:G:C	R55P	0.999
16:89690589:C:A	A66E	0.999
16:89690592:T:C	L67P	0.999
16:89690594:A:G	K68E	0.999
16:89691810:T:C	F114L	0.999
16:89691812:C:A	F114L	0.999
16:89691812:C:G	F114L	0.999
16:89693276:A:C	D163A	0.999
16:89693276:A:T	D163V	0.999
16:89693400:G:C	D181H	0.999
16:89693401:A:C	D181A	0.999
16:89693401:A:T	D181V	0.999
16:89693402:T:A	D181E	0.999
16:89693402:T:G	D181E	0.999
16:89689280:T:C	F39S	0.998
16:89689306:G:T	G48C	0.998
16:89689315:G:C	G51R	0.998
16:89689316:G:T	G51V	0.998
16:89689321:G:A	V53M	0.998
16:89689322:T:A	V53E	0.998
16:89690558:G:C	A56P	0.998
16:89690559:C:A	A56D	0.998
16:89690594:A:C	K68Q	0.998

dbSNP variants (sampled 300 via entrez): RS1000199180 (16:89687994 T>C), RS1000247057 (16:89690589 C>G), RS1000362158 (16:89690844 C>T), RS1000406312 (16:89684761 A>C), RS1000426325 (16:89686656 G>A), RS1000629665 (16:89695108 C>A,G,T), RS1000882085 (16:89686484 C>A,G), RS1001138258 (16:89690623 T>C), RS1001363097 (16:89696790 A>G,T), RS1001438702 (16:89686558 T>A), RS1001924192 (16:89692924 T>G), RS1002033043 (16:89689725 C>A), RS1002155905 (16:89685461 G>A), RS1002261530 (16:89694438 C>G,T), RS1002475378 (16:89692281 T>C)

Disease associations

OMIM: gene MIM:603464 | disease phenotypes: MIM:617694, MIM:227650, MIM:148050

GenCC curated gene-disease

Disease	Classification	Inheritance
Al Kaissi syndrome	Strong	Autosomal recessive

Mondo (3): Al Kaissi syndrome (MONDO:0044324), Fanconi anemia (MONDO:0019391), KBG syndrome (MONDO:0007846)

Orphanet (2): Fanconi anemia (Orphanet:84), KBG syndrome (Orphanet:2332)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000325	Triangular face
HP:0000331	Short chin
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000473	Torticollis
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000664	Synophrys
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000960	Sacral dimple
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002702_26	Height	4.000000e-23
GCST004142_15	Melanoma	2.000000e-09
GCST006986_36	Red vs. brown/black hair color	2.000000e-308
GCST006988_185	Blond vs. brown/black hair color	2.000000e-49
GCST006989_44	Brown vs. black hair color	2.000000e-08
GCST008759_18	Intake of total sugars	9.000000e-06
GCST010083_322	Hemoglobin levels	3.000000e-22
GCST010304_7	Cutaneous malignant melanoma	8.000000e-13
GCST010703_280	Brain morphology (MOSTest)	2.000000e-15
GCST012226_393	Waist circumference adjusted for body mass index	3.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0003924	hair color
EFO:0010158	sugar consumption measurement
EFO:0004509	hemoglobin measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D005199	Fanconi Anemia	C15.378.050.085.080.280; C15.378.190.223.500.500.280; C16.320.077.280; C18.452.284.280
C537015	KBG syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1795191 (SINGLE PROTEIN), CHEMBL3559691 (PROTEIN FAMILY), CHEMBL5483186 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,095 (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
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL495727	AT-9283	2	1,376
CHEMBL1276127	INDIRUBIN	2	181

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CDK10 subfamily

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.05	Kd	9	nM	AT-9283
6.96	IC50	110	nM	MOLIBRESIB
5.77	IC50	1700	nM	CHEMBL6162267
5.66	IC50	2200	nM	INDIRUBIN
5.10	Kd	8020	nM	CHEMBL4445812

PubChem BioAssay actives

4 with measured affinity, of 187 total; 4 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
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	1424938: 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	0.0090	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178578: Inhibition of CDK10 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.1100	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
6-[(3,4-dichlorobenzoyl)amino]-N-(1,3-thiazol-2-yl)naphthalene-2-carboxamide	1577061: Binding affinity to wild-type human full-length CDK10 (M1 to P360 residues) expressed in mammalian expression system measured after 1 hr by kinomescan method	kd	8.0200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Doxorubicin	affects expression, increases expression	2
Cadmium Chloride	decreases expression	2
Particulate Matter	affects cotreatment, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
propionaldehyde	decreases expression	1
bisphenol A	affects expression	1
methylselenic acid	decreases expression	1
kojic acid	decreases expression	1
terbufos	increases methylation	1
trichostatin A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ochratoxin A	affects cotreatment, decreases expression	1
potassium chromate(VI)	increases expression	1
nickel sulfate	increases expression	1
pentanal	decreases expression	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	increases expression	1
Aldehydes	decreases expression	1
Benzo(a)pyrene	affects methylation	1

ChEMBL screening assays

59 unique, capped per target: 59 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1837575	Binding	Inhibition of human CDK10 in HL60 cells lysate at 10 uM using post probe-labeling by LC-MS/MS analysis relative to control	Synthesis and structure-activity relationship of 4-quinolone-3-carboxylic acid based inhibitors of glycogen synthase kinase-3β. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2TZ	Abcam HEK293T CDK10 KO	Transformed cell line	Female
CVCL_SI19	HAP1 CDK10 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06465641	PHASE4	RECRUITING	Methylphenidate in KBG Syndrome: N-of-1 Series
NCT06519786	PHASE3	UNKNOWN	Safety and Efficacy of Metformin for Treatment of Cytopenia in Children and Adolescents With Fanconi Anemia
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00001749	PHASE2	COMPLETED	Medical Treatment for Diamond Blackfan Anemia
NCT00004787	PHASE2	COMPLETED	Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
NCT00053989	PHASE2	COMPLETED	NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders
NCT00084695	PHASE2	UNKNOWN	Umbilical Cord Blood for Stem Cell Transplantation in Treating Young Patients With Malignant or Nonmalignant Diseases
NCT00258427	PHASE2	COMPLETED	Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia
NCT00453388	PHASE2	COMPLETED	Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia
NCT01071239	PHASE2	COMPLETED	Hematopoietic Stem Cell Transplant for Fanconi Anemia
NCT02143830	PHASE2	RECRUITING	HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy
NCT02931071	PHASE2	COMPLETED	Clinical Phase II Trial to Evaluate CD34+ Cells Mobilization and Collection in Patients With Fanconi Anemia for Subsequent Transduction With a Lentiviral Vector Carring FANCA Gene. FANCOSTEM-1
NCT03206086	PHASE2	ACTIVE_NOT_RECRUITING	Eltrombopag for People With Fanconi Anemia
NCT03398824	PHASE2	COMPLETED	Pilot Study of Metformin for Patients With Fanconi Anemia
NCT03476330	PHASE2	COMPLETED	Quercetin Chemoprevention for Squamous Cell Carcinoma in Patients With Fanconi Anemia
NCT03579875	PHASE2	RECRUITING	Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
NCT03600909	PHASE2	TERMINATED	A Study of the Effect of Blood Stem Cell Transplant After Chemotherapy Alone in Patients With Fanconi Anemia
NCT04232085	PHASE2	RECRUITING	Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures
NCT06045052	PHASE2	COMPLETED	Eltrombopag for Treatment of Fanconi Anemia
NCT00001399	PHASE1	COMPLETED	Gene Therapy for the Treatment of Fanconi’s Anemia Type C
NCT00005896	PHASE1	UNKNOWN	Phase I Pilot Study of CD34 Enriched, Fanconi’s Anemia Complementation Group C Gene Transduced Autologous Peripheral Blood Stem Cell Transplantation in Patients With Fanconi’s Anemia
NCT00006127	PHASE1	UNKNOWN	Phase I Study of Amifostine in Patients With Bone Marrow Failure Related to Fanconi’s Anemia
NCT00093743	PHASE1	COMPLETED	Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia
NCT00243399	PHASE1	COMPLETED	Oxandrolone for the Treatment of Bone Marrow Aplasia in Fanconi Anemia
NCT00272857	PHASE1	COMPLETED	Bone Marrow Cell Gene Transfer in Individuals With Fanconi Anemia
NCT00317876	PHASE1	COMPLETED	Cyclophosphamide in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Fanconi’s Anemia
NCT00586274	PHASE1	TERMINATED	Use of Rft5-Dga to Deplete Alloreactive Cells for Pts With Fanconi Anemia After Haploidentical SCT
NCT01331018	PHASE1	TERMINATED	Gene Therapy for Fanconi Anemia
NCT01720147	PHASE1	COMPLETED	Quercetin in Children With Fanconi Anemia; a Pilot Study
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00352976	PHASE2/PHASE3	COMPLETED	TBI Dose De-escalation for Fanconi Anemia
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00005898	PHASE1/PHASE2	COMPLETED	Phase I/II Study of Total Body Irradiation, Cyclophosphamide, and Fludarabine Followed by Alternate Donor Hematopoietic Cell Transplantation in Patients With Fanconi’s Anemia
NCT00167206	PHASE1/PHASE2	TERMINATED	Stem Cell Transplantation for Fanconi Anemia
NCT00305708	PHASE1/PHASE2	COMPLETED	Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission
NCT00479115	PHASE1/PHASE2	COMPLETED	Mobilization and Collection of Peripheral Blood Stem Cells in Patients With Fanconi Anemia Using G-CSF and AMD3100
NCT00590460	PHASE1/PHASE2	TERMINATED	Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Fanconi Anemia
NCT00630253	PHASE1/PHASE2	COMPLETED	Cytoxan, Fludara, and Antithymocyte Globulin Conditioning Followed By Stem Cell Transplant in Treating Fanconi Anemia
NCT01001598	PHASE1/PHASE2	TERMINATED	Safety and Efficacy Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita
NCT02065869	PHASE1/PHASE2	TERMINATED	Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant