CDK20

Summary

CDK20 (cyclin dependent kinase 20, HGNC:21420) is a protein-coding gene on chromosome 9q22.1, encoding Cyclin-dependent kinase 20 (Q8IZL9). Required for high-level Shh responses in the developing neural tube.

The protein encoded by this gene contains a kinase domain most closely related to the cyclin-dependent protein kinases. The encoded kinase may activate cyclin-dependent kinase 2 and is involved in cell growth. Alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 23552 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 129 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001039803

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21420
Approved symbol	CDK20
Name	cyclin dependent kinase 20
Location	9q22.1
Locus type	gene with protein product
Status	Approved
Aliases	p42, PNQALRE
Ensembl gene	ENSG00000156345
Ensembl biotype	protein_coding
OMIM	610076
Entrez	23552

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 17 protein_coding, 5 retained_intron

ENST00000325303, ENST00000336654, ENST00000375871, ENST00000375883, ENST00000459720, ENST00000486228, ENST00000603475, ENST00000604175, ENST00000605159, ENST00000605591, ENST00000870587, ENST00000870588, ENST00000870589, ENST00000870590, ENST00000870591, ENST00000870592, ENST00000926638, ENST00000926639, ENST00000926640, ENST00000952589, ENST00000952590, ENST00000952591

RefSeq mRNA: 5 — MANE Select: NM_001039803 NM_001039803, NM_001170639, NM_001170640, NM_012119, NM_178432

CCDS: CCDS35060, CCDS55324, CCDS65075, CCDS6677, CCDS6678

Canonical transcript exons

ENST00000325303 — 8 exons

Exon	Start	End
ENSE00001468688	87974372	87974533
ENSE00001902501	87966441	87967659
ENSE00003471288	87970776	87970897
ENSE00003501098	87971147	87971335
ENSE00003508198	87969796	87969919
ENSE00003532544	87970568	87970630
ENSE00003535476	87969194	87969349
ENSE00003694606	87973922	87974035

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 89.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2549 / max 100.4753, expressed in 1299 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101254	1.8380	968
101255	1.1224	637
101253	0.2429	62
101252	0.0515	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	89.28	gold quality
right adrenal gland cortex	UBERON:0035827	88.11	gold quality
right adrenal gland	UBERON:0001233	86.84	gold quality
adenohypophysis	UBERON:0002196	86.68	gold quality
pituitary gland	UBERON:0000007	86.32	gold quality
left adrenal gland	UBERON:0001234	86.25	gold quality
left adrenal gland cortex	UBERON:0035825	86.16	gold quality
right frontal lobe	UBERON:0002810	85.92	gold quality
prefrontal cortex	UBERON:0000451	85.52	gold quality
adrenal cortex	UBERON:0001235	85.37	gold quality
oocyte	CL:0000023	84.69	gold quality
left testis	UBERON:0004533	84.60	gold quality
mucosa of transverse colon	UBERON:0004991	84.41	gold quality
right testis	UBERON:0004534	84.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.85	gold quality
adrenal gland	UBERON:0002369	83.76	gold quality
cortical plate	UBERON:0005343	83.75	gold quality
testis	UBERON:0000473	83.16	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.13	gold quality
frontal cortex	UBERON:0001870	82.96	gold quality
nucleus accumbens	UBERON:0001882	82.74	gold quality
neocortex	UBERON:0001950	82.59	gold quality
cingulate cortex	UBERON:0003027	82.38	gold quality
anterior cingulate cortex	UBERON:0009835	82.26	gold quality
secondary oocyte	CL:0000655	82.02	gold quality
ventricular zone	UBERON:0003053	81.74	gold quality
left ovary	UBERON:0002119	81.36	gold quality
right ovary	UBERON:0002118	81.25	gold quality
endothelial cell	CL:0000115	81.20	gold quality
stromal cell of endometrium	CL:0002255	81.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

30 targeting CDK20, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6133	100.00	66.48	2064
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-1285-5P	98.01	68.71	779
HSA-MIR-5585-5P	97.95	68.80	1024
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-3928-3P	97.61	66.53	1096
HSA-MIR-10397-5P	97.31	69.06	710
HSA-MIR-4793-5P	96.88	65.90	872
HSA-MIR-6803-3P	87.24	63.68	71

Literature-anchored findings (GeneRIF, showing 11)

• identification of p42, a novel cyclin-dependent kinase-activating kinase (CAK) activity in human cells; p42 is essential for the phosphorylation of Thr-160 and activation of CDK2 and is indispensable for cell growth (PMID:14597612)
• Depletion of PNQALRE by >80% due to RNA interference (RNAi) impairs cell proliferation, but fails to arrest the cell cycle at a discrete point. (PMID:16552187)
• Overexpression of CCRK is associated with ovarian carcinoma. (PMID:19672860)
• results suggest for the first time that CCRK is involved in colorectal cancer carcinogenesis and G1/S cell cycle transition by regulating Cdk2, cyclin E and Rb. (PMID:20466538)
• Cell cycle-related kinase is a direct androgen receptor-regulated gene that drives beta-catenin/T cell factor-dependent hepatocarcinogenesis (PMID:21747169)
• Data indicate that expression of ERAS, LHX1, and CCRK is increased in aggressive subgroups of medulloblastomas. (PMID:22875024)
• In glioblastoma cells with deregulated high levels of CCRK, its depletion restores cilia through ICK and an ICK-related kinase MAK, thereby inhibiting glioblastoma cell proliferation. (PMID:23743448)
• A CCRK-EZH2 epigenetic circuitry drives hepatocarcinogenesis and associates with tumor recurrence and poor survival of patient. (PMID:25500144)
• Results delineate an immunosuppressive mechanism of the hepatoma-intrinsic CCRK signalling and highlight an overexpressed kinase target whose inhibition might empower hepatocellular carcinoma immunotherapy (PMID:28939663)
• BROMI/TBC1D32 together with CCRK/CDK20 and FAM149B1/JBTS36 contributes to intraflagellar transport turnaround involving ICK/CILK1. (PMID:35609210)
• The Role of CDK20 Protein in Carcinogenesis. (PMID:37469151)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk20	ENSDARG00000003867
mus_musculus	Cdk20	ENSMUSG00000021483
rattus_norvegicus	Cdk20	ENSRNOG00000017991
drosophila_melanogaster	CG6800	FBGN0038902

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), CDK5 (ENSG00000164885), CDK12 (ENSG00000167258), CDK1 (ENSG00000170312), CDK10 (ENSG00000185324), CDKL4 (ENSG00000205111), CDK11B (ENSG00000248333), CDK3 (ENSG00000250506)

Protein

Protein identifiers

Cyclin-dependent kinase 20 — Q8IZL9 (reviewed: Q8IZL9)

Alternative names: CDK-activating kinase p42, Cell cycle-related kinase, Cell division protein kinase 20, Cyclin-dependent protein kinase H, Cyclin-kinase-activating kinase p42

All UniProt accessions (2): Q8IZL9, A0A0S2Z5B6

UniProt curated annotations — full annotation on UniProt →

Function. Required for high-level Shh responses in the developing neural tube. Together with TBC1D32, controls the structure of the primary cilium by coordinating assembly of the ciliary membrane and axoneme, allowing GLI2 to be properly activated in response to SHH signaling. Involved in cell growth. Activates CDK2, a kinase involved in the control of the cell cycle, by phosphorylating residue ‘Thr-160’.

Subunit / interactions. Monomer. Interacts with TBC1D32. Interacts with MAK.

Subcellular location. Nucleus. Cytoplasm. Cell projection. Cilium.

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q8IZL9-1	1	yes
Q8IZL9-2	2, Cardiac CCRK
Q8IZL9-3	3
Q8IZL9-4	4
Q8IZL9-5	5

RefSeq proteins (5): NP_001034892, NP_001164110, NP_001164111, NP_036251, NP_848519 (=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
IPR048002	CDK20-like_STKc	Domain
IPR050108	CDK	Family

Pfam: PF00069

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 (17 total): splice variant 6, sequence variant 4, binding site 2, chain 1, domain 1, mutagenesis site 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZL9-F1	86.08	0.64

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): 127 (proton acceptor)

Ligand- & substrate-binding residues (2): 10–18; 33

Mutagenesis-validated functional residues (1):

Position	Phenotype
161	impairs cdk2 t-160 phosphorylation and activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 153 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, EFC_Q6, GOBP_PROTEIN_MATURATION, GOBP_REGULATION_OF_CELL_CYCLE, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, GOBP_NEGATIVE_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, CYTAGCAAY_UNKNOWN, GOBP_REGULATION_OF_PROTEIN_MATURATION

GO Biological Process (14): neural tube closure (GO:0001843), floor plate formation (GO:0021508), dorsal/ventral neural tube patterning (GO:0021904), embryonic camera-type eye development (GO:0031076), negative regulation of smoothened signaling pathway (GO:0045879), embryonic skeletal system development (GO:0048706), cell division (GO:0051301), roof of mouth development (GO:0060021), protein localization to cilium (GO:0061512), regulation of protein maturation (GO:1903317), embryonic brain development (GO:1990403), protein phosphorylation (GO:0006468), regulation of smoothened signaling pathway (GO:0008589), regulation of cell cycle (GO:0051726)

GO Molecular Function (9): 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)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229), sperm head-tail coupling apparatus (GO:0120212), cytoplasm (GO:0005737), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
sperm flagellum	3
embryonic organ development	2
smoothened signaling pathway	2
protein kinase activity	2
intracellular membrane-bounded organelle	2
primary neural tube formation	1
tube closure	1
ventral midline development	1
floor plate morphogenesis	1
anatomical structure formation involved in morphogenesis	1
dorsal/ventral pattern formation	1
neural tube patterning	1
camera-type eye development	1
regulation of smoothened signaling pathway	1
negative regulation of signal transduction	1
skeletal system development	1
chordate embryonic development	1
cellular process	1
anatomical structure development	1
protein localization to organelle	1
regulation of gene expression	1
regulation of protein metabolic process	1
protein maturation	1
phosphorylation	1
protein modification process	1
regulation of signal transduction	1
cell cycle	1
regulation of cellular 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

Protein interactions and networks

STRING

916 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK20	CCNH	P51946	907
CDK20	RAPGEF1	Q13905	585
CDK20	DPP3	Q9NY33	564
CDK20	CCNL2	Q96S94	545
CDK20	CRK	P46108	506
CDK20	GRB2	P29354	499
CDK20	IGF1R	P08069	467
CDK20	CCNK	O75909	455
CDK20	ABL1	P00519	454
CDK20	CCNC	P24863	434
CDK20	PALB2	Q86YC2	431
CDK20	NCK1	P16333	431
CDK20	TRAFD1	O14545	427
CDK20	CCNL1	Q9UK58	420
CDK20	IRS1	P35568	414

IntAct

37 interactions, top by confidence:

A	B	Type	Score
CFAP20	SFSWAP	psi-mi:“MI:0914”(association)	0.620
CDK20	TRIM2	psi-mi:“MI:0915”(physical association)	0.560
SLC9A6	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
FOXJ1	PEX14	psi-mi:“MI:0914”(association)	0.530
SLC9A6	IFNGR1	psi-mi:“MI:0914”(association)	0.530
CFAP20	KPNA4	psi-mi:“MI:0914”(association)	0.510
ACMSD	CDK20	psi-mi:“MI:0915”(physical association)	0.400
UBE2S	CDK20	psi-mi:“MI:0915”(physical association)	0.400
CDK20	MAK	psi-mi:“MI:0915”(physical association)	0.400
HAX1	GPM6B	psi-mi:“MI:0914”(association)	0.350
CDK5	CDK14	psi-mi:“MI:0914”(association)	0.350
FOXJ1	PEX14	psi-mi:“MI:0914”(association)	0.350
CFAP20	PRPF40A	psi-mi:“MI:0914”(association)	0.350
CDK7	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
CDK20	APOD	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
KLRC1	METTL15	psi-mi:“MI:0914”(association)	0.350
CDK20	RPS6KA4	psi-mi:“MI:0914”(association)	0.350
CFAP20	RABEPK	psi-mi:“MI:0914”(association)	0.350
CDK20	CDH11	psi-mi:“MI:0914”(association)	0.350
RPS7	ASGR2	psi-mi:“MI:0914”(association)	0.350

BioGRID (133): CDK20 (Affinity Capture-MS), CDK20 (Affinity Capture-MS), CDK20 (Affinity Capture-MS), CDK20 (Affinity Capture-MS), CDK20 (Affinity Capture-MS), CDK20 (Affinity Capture-MS), CDK20 (Affinity Capture-MS), CDK20 (Affinity Capture-MS), CDK20 (Affinity Capture-MS), CDK20 (Affinity Capture-MS), CDK20 (Affinity Capture-MS), CDK20 (Affinity Capture-MS), HDAC1 (Affinity Capture-MS), XYLT2 (Affinity Capture-MS), KEAP1 (Affinity Capture-MS)

ESM2 similar proteins: A8WIP6, A8XA58, G5EFV5, O13958, O61847, P06242, P17157, P20911, P23573, P25859, P34556, P50613, P50750, P51952, P51953, P54664, P54665, Q00534, Q00646, Q03147, Q06309, Q0J4I1, Q12126, Q2V419, Q38775, Q3TZA2, Q4KM34, Q4V862, Q5EAB2, Q5R7I7, Q5ZKN1, Q641Z4, Q64261, Q6FKD4, Q6GLD8, Q6ZAG3, Q7ZX42, Q8IZL9, Q8L4P8, Q8LF80

Diamond homologs: A2X6X1, A2XUW1, A2Y4B6, A8WIP6, A8XA58, G5ECH7, G5EFV5, O55076, O74456, O96821, P00546, P04551, P06242, P06493, P11440, P13863, P20911, P23111, P23437, P23572, P23573, P24033, P24100, P24923, P24941, P29618, P29619, P29620, P34112, P34117, P35567, P38973, P39951, P43063, P43450, P48609, P48734, P48963, P49615, P50613

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CDK20	up-regulates	CDK2	phosphorylation
CDK20	up-regulates	CILK1	phosphorylation
CDK20	“up-regulates activity”	EZH2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	19
Benign	14

Top pathogenic / likely-pathogenic (0)

SpliceAI

1441 predictions. Top by Δscore:

Variant	Effect	Δscore
9:87969188:CCCTA:C	donor_loss	1.0000
9:87969189:CCTAC:C	donor_loss	1.0000
9:87969190:CTAC:C	donor_loss	1.0000
9:87969191:TAC:T	donor_loss	1.0000
9:87969192:A:T	donor_loss	1.0000
9:87969345:AGCTC:A	acceptor_gain	1.0000
9:87969347:CTC:C	acceptor_gain	1.0000
9:87969348:TC:T	acceptor_gain	1.0000
9:87969349:CC:C	acceptor_gain	1.0000
9:87969349:CCTGG:C	acceptor_loss	1.0000
9:87969350:C:CC	acceptor_gain	1.0000
9:87969350:CTGGG:C	acceptor_loss	1.0000
9:87969351:T:G	acceptor_loss	1.0000
9:87969356:C:CT	acceptor_gain	1.0000
9:87969356:C:T	acceptor_gain	1.0000
9:87969357:A:T	acceptor_gain	1.0000
9:87970772:CTA:C	donor_loss	1.0000
9:87970773:TAC:T	donor_loss	1.0000
9:87970774:AC:A	donor_loss	1.0000
9:87970775:CCT:C	donor_loss	1.0000
9:87970893:AGGTC:A	acceptor_gain	1.0000
9:87970894:GGTC:G	acceptor_gain	1.0000
9:87970895:GTC:G	acceptor_gain	1.0000
9:87970896:TC:T	acceptor_gain	1.0000
9:87970897:CC:C	acceptor_gain	1.0000
9:87970897:CCT:C	acceptor_loss	1.0000
9:87970898:C:CC	acceptor_gain	1.0000
9:87970898:C:T	acceptor_gain	1.0000
9:87970899:T:G	acceptor_loss	1.0000
9:87970904:G:C	acceptor_gain	1.0000

AlphaMissense

2243 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:87974012:C:A	K33N	0.998
9:87974012:C:G	K33N	0.998
9:87970896:T:G	D127A	0.995
9:87970841:G:C	D145E	0.994
9:87970841:G:T	D145E	0.994
9:87970896:T:A	D127V	0.993
9:87970842:T:A	D145V	0.992
9:87970895:G:C	D127E	0.992
9:87970895:G:T	D127E	0.992
9:87970569:A:G	W188R	0.991
9:87970569:A:T	W188R	0.991
9:87970850:C:A	K142N	0.991
9:87970850:C:G	K142N	0.991
9:87970896:T:C	D127G	0.991
9:87974022:A:T	V30D	0.990
9:87970848:A:T	I143K	0.989
9:87971173:A:G	C118R	0.989
9:87974013:T:A	K33M	0.989
9:87974013:T:G	K33T	0.989
9:87970848:A:C	I143R	0.988
9:87970843:C:G	D145H	0.987
9:87971148:C:G	R126P	0.987
9:87969211:G:T	R276S	0.986
9:87973947:A:G	L55P	0.986
9:87973951:C:G	A54P	0.985
9:87970842:T:G	D145A	0.984
9:87969893:A:G	L197P	0.983
9:87974016:A:G	L32P	0.983
9:87970842:T:C	D145G	0.982
9:87970852:T:C	K142E	0.982

dbSNP variants (sampled 300 via entrez): RS1000098900 (9:87971971 A>G), RS1000294321 (9:87968010 A>T), RS1000745734 (9:87976006 CTT>C), RS1001550648 (9:87974635 C>G,T), RS1001956278 (9:87975367 C>G), RS1002022593 (9:87974471 C>G,T), RS1002141335 (9:87975046 GGGCC>G), RS1002441934 (9:87970999 C>T), RS1002716354 (9:87966763 A>G), RS1003064094 (9:87969133 A>G), RS1003137718 (9:87968932 G>A), RS1003172998 (9:87974293 A>C,G), RS1003230096 (9:87969611 G>A,C,T), RS1003303767 (9:87969977 C>A,T), RS1003967274 (9:87966157 G>A,C)

Disease associations

OMIM: gene MIM:610076 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (6): intellectual disability (MONDO:0001071), nephrotic syndrome (MONDO:0005377), hearing loss disorder (MONDO:0005365), attention deficit-hyperactivity disorder (MONDO:0007743), hereditary breast ovarian cancer syndrome (MONDO:0003582), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (2): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000175_1	Height	9.000000e-07

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3559690 (SINGLE PROTEIN), CHEMBL3559691 (PROTEIN FAMILY), CHEMBL5483181 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 181 (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
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 — CCRK subfamily

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.66	IC50	2200	nM	INDIRUBIN
5.10	Kd	8020	nM	CHEMBL4445812

PubChem BioAssay actives

2 with measured affinity, of 86 total; 2 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
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	1577058: Binding affinity to wild-type human full-length CDK20 (M1 to G346 residues) expressed in mammalian expression system measured after 1 hr by kinomescan method	kd	8.0200	uM

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases reaction, decreases expression	2
Benzo(a)pyrene	increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
bufotalin	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
monoisoamyl-2,3-dimercaptosuccinate	decreases expression, decreases reaction	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Ethanol	affects response to substance	1
Doxorubicin	decreases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Fenofibrate	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
Paclitaxel	decreases expression	1
Chlorodiphenyl (54% Chlorine)	increases expression	1
Particulate Matter	decreases expression	1

ChEMBL screening assays

40 unique, capped per target: 40 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4034282	Binding	Inhibition of CCRK Lysine 1 labelling site (unknown origin) at 10 uM	Developing DYRK inhibitors derived from the meridianins as a means of increasing levels of NFAT in the nucleus. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00308321	PHASE4	UNKNOWN	Long Term Tapering or Standard Steroids for Nephrotic Syndrome
NCT01021540	PHASE4	COMPLETED	Prospective Study Evaluating the Effect of Repository Corticotropin in the Treatment of Various Nephrotic Syndromes
NCT01028287	PHASE4	COMPLETED	Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN)
NCT01162005	PHASE4	COMPLETED	Therapeutic Effect of Tacrolimus on Primary Nephrotic Syndrome in Children
NCT01895894	PHASE4	COMPLETED	Mycophenolate Mofetil in Pediatric Steroid Dependent Nephrotic Syndrome
NCT02238418	PHASE4	COMPLETED	Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.
NCT02382575	PHASE4	UNKNOWN	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Resistant Nephrotic Syndrome
NCT02427880	PHASE4	COMPLETED	Role of Acetazolamide and Hydrochlorothiazide Followed by Furosemide in Treating Nephrotic Edema
NCT03210688	PHASE4	COMPLETED	Active Vitamin D And Reduced Dose Prednisolone for Treatment in Minimal Change Nephropathy
NCT03347357	PHASE4	COMPLETED	Pharmacokinetics of Tacrolimus in Children
NCT05696977	PHASE4	UNKNOWN	Effect of Obesity on Cyclosporine Blood Trough Level in Nephrotic Syndrome Patients
NCT05966818	PHASE4	UNKNOWN	Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.
NCT06026787	PHASE4	COMPLETED	Clinical Value of Adding Dapagliflozin in Patients With Nephrotic Syndrome
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00354731	PHASE3	COMPLETED	Efficacy of Pentoxifylline on Primary Nephrotic Syndrome
NCT00615667	PHASE3	COMPLETED	Prospective, Multicenter Study of the Efficacy and Tolerance of Tacrolimus on Refractory Nephrotic Syndrome (RNS)
NCT00981838	PHASE3	COMPLETED	Rituximab in Multirelapsing Minimal Change Disease (MCD) or Focal Segmental Glomerulosclerosis (FSGS)
NCT01197040	PHASE3	COMPLETED	Evaluation of Low Dose Corticosteroids Efficiency, Associated With Myfortic ® in the Treatment of Nephrotic Syndrome
NCT01309477	PHASE3	COMPLETED	The Efficacy and Tolerance of Tacrolimus Sustained-release Capsules on Refractory Nephrotic Syndrome (RNS)
NCT02132195	PHASE3	COMPLETED	Adrenocorticotropic Hormone (ACTH) for Frequently Relapsing and Steroid Dependent Nephrotic Syndrome
NCT02257697	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Refractory Nephrotic Syndrome
NCT02438982	PHASE3	COMPLETED	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Dependent Nephrotic Syndrome
NCT03141970	PHASE3	COMPLETED	Prednisolone Trial in Children Younger Than 4 Years
NCT03501459	PHASE3	UNKNOWN	Lymphocyte Markers As Predictors Of Responsiveness To Rituximab Among Patients With Idiopathic Nephrotic Syndrome
NCT05079789	PHASE3	TERMINATED	Amiloride in Nephrotic Syndrome
NCT05716880	PHASE3	RECRUITING	Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome
NCT06635720	PHASE3	ACTIVE_NOT_RECRUITING	REduced-dose Steroid PrOtocol for Childhood Nephrotic SyndromE (RESPONSE)
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00001212	PHASE2	COMPLETED	Drug Therapy in Lupus Nephropathy
NCT00001959	PHASE2	COMPLETED	Pirfenidone to Treat Kidney Disease (Focal Segmental Glomerulosclerosis)
NCT00004466	PHASE2	TERMINATED	Pilot Study of Atorvastatin in Children With Chronic Hyperlipidemia Secondary to Nephrotic Syndrome
NCT00004990	PHASE2	COMPLETED	Once-A-Month Steroid Treatment for Patients With Focal Segmental Glomerulosclerosis
NCT00977977	PHASE2	RECRUITING	Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy