CKS2

Summary

CKS2 (CDC28 protein kinase regulatory subunit 2, HGNC:2000) is a protein-coding gene on chromosome 9q22.2, encoding Cyclin-dependent kinases regulatory subunit 2 (P33552). Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function.

CKS2 protein binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function. The CKS2 mRNA is found to be expressed in different patterns through the cell cycle in HeLa cells, which reflects specialized role for the encoded protein.

Source: NCBI Gene 1164 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 13 total
• Druggable target: yes
• MANE Select transcript: NM_001827

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2000
Approved symbol	CKS2
Name	CDC28 protein kinase regulatory subunit 2
Location	9q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000123975
Ensembl biotype	protein_coding
OMIM	116901
Entrez	1164

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000314355, ENST00000940740, ENST00000940741, ENST00000940742, ENST00000940743, ENST00000940744

RefSeq mRNA: 1 — MANE Select: NM_001827 NM_001827

CCDS: CCDS6682

Canonical transcript exons

ENST00000314355 — 3 exons

Exon	Start	End
ENSE00000843533	89316373	89316703
ENSE00000843534	89315170	89315297
ENSE00001468493	89311195	89311351

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 109.4607 / max 1201.7669, expressed in 1812 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97283	109.4607	1812

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.52	gold quality
right testis	UBERON:0004534	99.21	gold quality
left testis	UBERON:0004533	99.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	98.87	gold quality
testis	UBERON:0000473	98.82	gold quality
ganglionic eminence	UBERON:0004023	98.69	gold quality
adult organism	UBERON:0007023	98.29	gold quality
embryo	UBERON:0000922	98.18	gold quality
sperm	CL:0000019	97.65	gold quality
oocyte	CL:0000023	97.56	gold quality
adrenal tissue	UBERON:0018303	97.20	gold quality
male germ cell	CL:0000015	96.84	gold quality
trabecular bone tissue	UBERON:0002483	96.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.36	gold quality
mucosa of transverse colon	UBERON:0004991	96.28	gold quality
stromal cell of endometrium	CL:0002255	95.90	gold quality
right adrenal gland cortex	UBERON:0035827	95.76	gold quality
right adrenal gland	UBERON:0001233	95.49	gold quality
thymus	UBERON:0002370	95.05	gold quality
secondary oocyte	CL:0000655	94.74	gold quality
bone marrow	UBERON:0002371	94.68	gold quality
lower esophagus mucosa	UBERON:0035834	94.55	gold quality
rectum	UBERON:0001052	94.45	gold quality
left adrenal gland	UBERON:0001234	94.30	gold quality
vermiform appendix	UBERON:0001154	93.92	gold quality
left adrenal gland cortex	UBERON:0035825	93.80	gold quality
gingival epithelium	UBERON:0001949	93.73	gold quality
amniotic fluid	UBERON:0000173	93.72	gold quality
adrenal cortex	UBERON:0001235	93.40	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.33	gold quality

Single-cell (SCXA)

Detected in 26 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-MTAB-10485	yes	2431.22
E-MTAB-8894	yes	1703.84
E-MTAB-6108	yes	1080.28
E-MTAB-9154	yes	980.05
E-MTAB-10283	yes	871.93
E-MTAB-8495	yes	853.47
E-GEOD-81383	yes	701.65
E-GEOD-99795	yes	697.39
E-MTAB-10290	yes	639.51
E-HCAD-6	yes	454.24
E-GEOD-124858	yes	338.17
E-HCAD-4	yes	155.18
E-HCAD-1	yes	42.47
E-HCAD-10	yes	38.01
E-GEOD-134144	yes	30.53

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, MYC, TP53, TP63, TP73, YBX1

miRNA regulators (miRDB)

47 targeting CKS2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-6744-5P	99.93	66.82	748
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-510-3P	99.54	70.06	2965

Literature-anchored findings (GeneRIF, showing 31)

• p53, rather than its homologues p63 and p73, may contribute to control of the first metaphase/anaphase transition of mammalian meiosis by downregulation of Cks2 expression (PMID:17336302)
• Elevated expression of Cks1 may contribute to prostate tumorigenesis by promoting proliferation, anchorage-independent growth and migration of the cells, and elevated expression of Cks2 by protecting cells from undergoing programmed cell death. (PMID:18498131)
• Data show that cyclin-dependent kinase-associated proteins Cks1 and Cks2 are essential during early embryogenesis and for cell cycle progression in somatic cells. (PMID:18625720)
• Results suggest that the cell cycle regulator CKS2 might be deeply involved in gastric cancer progression. (PMID:19034516)
• Overexpression of Cks1 and Cks2 is associated with the aggressive tumour behaviours of hepatocellular carcinoma. (PMID:19845855)
• the involvement CKS2 gene expression in bladder cancer tumorgenesis (PMID:20920335)
• CKS2 is one of the gastric cancer-related genes that correlates with biological aggressiveness and poor prognosis of gastric cancer. (PMID:21617860)
• The Cks2 gene may have potential as a biomarker for predicting superficial bladder cancer progression to muscle-invasive cancer. (PMID:21672358)
• Overexpression of Cks1 or Cks2 in human mammary epithelial and breast cancer-derived cells, as well as in other cell types, leads to override of the intra-S-phase checkpoint. (PMID:21697511)
• Study calculated DeltaCt values of CKS2 and LEPR and found that their differential expression (C-L index) was significantly higher in grade I than in grade II or III meningiomas. (PMID:21948653)
• Cks2 may serve as an independent prognostic factor in patients with cholangiocarcinoma, and play a role in the carcinogenesis of cholangiocarcinoma by facilitating cell cycle progression and Bax-mediated mitochondrial caspase-dependent apoptosis. (PMID:23121546)
• CKS2 mRNA and protein expression were increased in esophageal carcinoma. Overexpression of CKS2 was associated with higher grad, regional lymph node invasion, and neoplastic embolus. CKS2 was negatively associated with the p27(kip1) level in the tumor. (PMID:23301842)
• CKS2 mRNA expression was higher in cancer tissue than in corresponding normal tissue. Patients with positive-CKS2 protein expression had a poorer five year survival frequency than patients who did not express CKS2 protein. (PMID:24604089)
• CKS2 is up-regulated in breast cancer and associated with large tumor size, lack expression of progesterone receptor, poor tumor differentiation and survival (PMID:25674223)
• Results show that Cks1 and Cks2 promoted proliferation and prevented apoptosis of hepatocellular carcinoma HepG2 cells. (PMID:26531156)
• miR-26a inhibited proliferation and tumourigenesis of LSCC via targeting CKS2 in vitro and in vivo (PMID:29143362)
• that CKS2 play a role in tumor activation and serve as a useful potential target for the treatment of hepatocellular carcinoma (PMID:29487004)
• EGFL7 promotes hepatocellular carcinoma cell proliferation and inhibits cell apoptosis through increasing CKS2 expression by activating Wnt/b-catenin signaling. (PMID:30129142)
• Our study uncovers a novel link between regulation of cell division by nuclear pathways and OXPHOS in the mitochondrion that involves CKS2 and promotes chemoradioresistance of cervical cancer. (PMID:30856376)
• CKS2 inhibition suppressed cell proliferation and invasion ability in vitro and reduced tumor growth in vivo. CKS2 may act as a potential biomarker and therapeutic target for the treatment of BC. (PMID:30957190)
• High CKS2 expression is associated with Hepatocellular Carcinoma. (PMID:31781310)
• CKS2 modulates cell-cycle progression of tongue squamous cell carcinoma cells partly via modulating the cellular distribution of DUTPase. (PMID:33107644)
• Identification of NDRG Family Member 4 (NDRG4) and CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) as Key Prognostic Genes in Adrenocortical Carcinoma by Transcriptomic Analysis. (PMID:33667214)
• CKS2 (CDC28 protein kinase regulatory subunit 2) is a prognostic biomarker in lower grade glioma: a study based on bioinformatic analysis and immunohistochemistry. (PMID:34494924)
• High Expression of CKS2 Predicts Adverse Outcomes: A Potential Therapeutic Target for Glioma. (PMID:35663965)
• Prognostic significance of CKS2 and CD47 expression in patients with gastric cancer who underwent radical gastrectomy. (PMID:35703112)
• Errate: Identification of NDRG Family Member 4 (NDRG4) and CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) as Key Prognostic Genes in Adrenocortical Carcinoma by Transcriptomic Analysis. (PMID:35899496)
• Knockdown of replication protein A 3 induces protective autophagy and enhances cisplatin sensitivity in lung adenocarcinoma by inhibiting AKT/mTOR signaling via binding to cyclin-dependent kinases regulatory subunit 2. (PMID:35903032)
• Cyclin-Dependent Kinase Subunit 2 (CKS2) as a Prognostic Marker for Stages I-III Invasive Non-Mucinous Lung Adenocarcinoma and Its Role in Affecting Drug Sensitivity. (PMID:36010686)
• Cyclin-dependent kinase subunit2 (CKS2) promotes malignant phenotypes and epithelial-mesenchymal transition-like process in glioma by activating TGFbeta/SMAD signaling. (PMID:36284444)
• Prognostic significance of cyclin-dependent kinase subunit 2 (CKS2) in malignant tumours: a meta-analysis and bioinformatic analysis. (PMID:38296306)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	CKS2	ENSDARG00000117089
mus_musculus	Cks2	ENSMUSG00000062248
rattus_norvegicus	LOC120102505	ENSRNOG00000042804
rattus_norvegicus	Cks2l1	ENSRNOG00000051034
rattus_norvegicus	Cks2	ENSRNOG00000079240
drosophila_melanogaster	Cks85A	FBGN0037613
caenorhabditis_elegans		WBGENE00001051

Paralogs (2): NIP7 (ENSG00000132603), CKS1B (ENSG00000173207)

Protein

Protein identifiers

Cyclin-dependent kinases regulatory subunit 2 — P33552 (reviewed: P33552)

All UniProt accessions (1): P33552

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function.

Subunit / interactions. Forms a homohexamer that can probably bind six kinase subunits.

Similarity. Belongs to the CKS family.

RefSeq proteins (1): NP_001818* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000789	Cyclin-dep_kinase_reg-sub	Family
IPR036858	Cyclin-dep_kinase_reg-sub_sf	Homologous_superfamily

Pfam: PF01111

UniProt features (9 total): strand 4, helix 2, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
6GU2	X-RAY DIFFRACTION	2
5LQF	X-RAY DIFFRACTION	2.06
1CKS	X-RAY DIFFRACTION	2.1
4Y72	X-RAY DIFFRACTION	2.3
5HQ0	X-RAY DIFFRACTION	2.3
6GU6	X-RAY DIFFRACTION	2.33
6GU3	X-RAY DIFFRACTION	2.65
4YC3	X-RAY DIFFRACTION	2.7
6GU4	X-RAY DIFFRACTION	2.73
6GU7	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P33552-F1	92.83	0.88

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 4

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 444 (showing top): MODULE_52, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, GNF2_CENPF, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, PAL_PRMT5_TARGETS_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, DITTMER_PTHLH_TARGETS_UP, GENTILE_RESPONSE_CLUSTER_D3, MODULE_16, GNF2_RRM1, GOLDRATH_ANTIGEN_RESPONSE, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_2_UP

GO Biological Process (6): regulation of transcription by RNA polymerase II (GO:0006357), meiosis I (GO:0007127), regulation of mitotic cell cycle (GO:0007346), mitotic cell cycle phase transition (GO:0044772), fibroblast proliferation (GO:0048144), cell division (GO:0051301)

GO Molecular Function (7): chromatin binding (GO:0003682), protein kinase binding (GO:0019901), histone binding (GO:0042393), ubiquitin binding (GO:0043130), cyclin-dependent protein serine/threonine kinase activator activity (GO:0061575), protein binding (GO:0005515), cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538)

GO Cellular Component (2): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), SCF ubiquitin ligase complex (GO:0019005)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic cell cycle	2
binding	2
cyclin-dependent protein serine/threonine kinase activity	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
meiotic telophase I	1
meiosis I cell cycle process	1
meiotic nuclear division	1
regulation of cell cycle	1
cell cycle phase transition	1
mitotic cell cycle process	1
cell population proliferation	1
cellular process	1
kinase binding	1
protein binding	1
ubiquitin-like protein binding	1
cyclin-dependent protein serine/threonine kinase regulator activity	1
protein serine/threonine kinase activator activity	1
cyclin-dependent protein kinase regulator activity	1
serine/threonine protein kinase complex	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

1866 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CKS2	CDK1	P06493	968
CKS2	CDK2	P24941	937
CKS2	CCNB1	P14635	923
CKS2	CDC20	Q12834	900
CKS2	CCNA2	P20248	873
CKS2	SKP2	Q13309	780
CKS2	CCNA1	P78396	767
CKS2	CCNB2	O95067	759
CKS2	SKP1	P34991	711
CKS2	UBE2C	O00762	681
CKS2	CCNL2	Q96S94	671
CKS2	AURKA	O14965	642
CKS2	DLGAP5	Q15398	633
CKS2	BUB1	O43683	632
CKS2	MELK	Q14680	606

IntAct

69 interactions, top by confidence:

A	B	Type	Score
CDK2	CCNE2	psi-mi:“MI:0914”(association)	0.940
CDK2	CCNB1	psi-mi:“MI:0914”(association)	0.890
CDKN1A	CCNE2	psi-mi:“MI:0914”(association)	0.890
CDK2	CCNB2	psi-mi:“MI:0914”(association)	0.860
CDK1	CCNB2	psi-mi:“MI:0914”(association)	0.840
CDKN1B	CCNE2	psi-mi:“MI:0914”(association)	0.790
CDKN1A	CDK14	psi-mi:“MI:0914”(association)	0.770
CKS2	CDK3	psi-mi:“MI:0915”(physical association)	0.740
PKMYT1	CCNB2	psi-mi:“MI:0914”(association)	0.730
PTGR3	DBT	psi-mi:“MI:0914”(association)	0.640
CCNA2	GMNN	psi-mi:“MI:0914”(association)	0.640
CDK2	GMNN	psi-mi:“MI:0914”(association)	0.640
CKS2	GMNN	psi-mi:“MI:0914”(association)	0.530
CKS1B	GMNN	psi-mi:“MI:0914”(association)	0.530
CDK3	GMNN	psi-mi:“MI:0914”(association)	0.530
LACC1	DUSP14	psi-mi:“MI:0914”(association)	0.530
FZR1	TK1	psi-mi:“MI:0914”(association)	0.530
CKS2	CCNB2	psi-mi:“MI:0914”(association)	0.530
CDK1	GMNN	psi-mi:“MI:0914”(association)	0.530
LACC1	CKS2	psi-mi:“MI:0914”(association)	0.530
SPDYC	CDK1	psi-mi:“MI:0914”(association)	0.530
Cdk1	PHGDH	psi-mi:“MI:0914”(association)	0.500

BioGRID (109): CKS2 (Affinity Capture-Western), CKS2 (Affinity Capture-MS), CKS2 (Affinity Capture-MS), CKS2 (Affinity Capture-MS), CKS2 (Affinity Capture-MS), CKS2 (Affinity Capture-MS), CKS2 (Affinity Capture-MS), CKS2 (Affinity Capture-MS), CKS2 (Affinity Capture-MS), TSC22D4 (Two-hybrid), CDK1 (Co-fractionation), CFL1 (Co-fractionation), DUT (Co-fractionation), BLZF1 (Two-hybrid), CKS2 (Affinity Capture-MS)

ESM2 similar proteins: A0KK58, A0KXU1, A1RK88, A2XCH8, A4VJA8, A4Y6A8, A8XMF2, B0G102, G5EDM7, O04438, O23249, O94733, P00128, P0CM26, P0CM27, P12798, P16653, P20329, P20486, P23915, P28896, P28974, P33552, P37991, P55933, P56390, P61024, P61025, P84395, Q07088, Q0P5A5, Q0TBK7, Q15S25, Q17868, Q1R4Z6, Q24152, Q2KJI1, Q3M6B5, Q6C3T0, Q6PS57

Diamond homologs: A2XCH8, A8XMF2, B0G102, O23249, P08463, P20486, P33552, P41384, P55933, P56390, P61024, P61025, Q0P5A5, Q17868, Q24152, Q25330, Q2KJI1, Q6PS57, Q91879, Q9SJJ5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
TP53 Regulates Transcription of Cell Cycle Genes	7	108.8×	2e-11
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	5	102.0×	3e-08
p53-Dependent G1 DNA Damage Response	5	102.0×	3e-08
p53-Dependent G1/S DNA damage checkpoint	5	102.0×	3e-08
G1/S DNA Damage Checkpoints	5	96.0×	3e-08
Regulation of APC/C activators between G1/S and early anaphase	8	70.5×	2e-11
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	6	69.9×	7e-09
APC/C-mediated degradation of cell cycle proteins	7	67.2×	5e-10

GO biological processes:

GO term	Partners	Fold	FDR
G2/M transition of mitotic cell cycle	8	48.0×	7e-10
mitotic G2 DNA damage checkpoint signaling	5	42.6×	1e-05
G1/S transition of mitotic cell cycle	10	38.6×	3e-11
regulation of mitotic cell cycle	5	23.1×	2e-04
Ras protein signal transduction	5	19.8×	3e-04
cell division	14	12.4×	7e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

476 predictions. Top by Δscore:

Variant	Effect	Δscore
9:89311325:G:GG	donor_gain	1.0000
9:89311346:G:GG	donor_gain	1.0000
9:89315169:GGC:G	acceptor_gain	1.0000
9:89315169:GGCAT:G	acceptor_gain	1.0000
9:89315293:GCCAG:G	donor_gain	1.0000
9:89315294:CCAGG:C	donor_loss	1.0000
9:89315296:AGG:A	donor_loss	1.0000
9:89315297:GGTAA:G	donor_loss	1.0000
9:89315298:G:GA	donor_loss	1.0000
9:89315299:T:G	donor_loss	1.0000
9:89311344:GA:G	donor_gain	0.9900
9:89311352:G:GG	donor_gain	0.9900
9:89311352:GTG:G	donor_loss	0.9900
9:89314862:T:A	acceptor_gain	0.9900
9:89315166:A:G	acceptor_gain	0.9900
9:89315167:CAGGC:C	acceptor_loss	0.9900
9:89315168:A:AG	acceptor_gain	0.9900
9:89315168:A:T	acceptor_loss	0.9900
9:89315169:G:GG	acceptor_gain	0.9900
9:89316371:A:AG	acceptor_gain	0.9900
9:89316372:G:GG	acceptor_gain	0.9900
9:89311340:C:CG	donor_gain	0.9800
9:89312533:A:AG	acceptor_gain	0.9800
9:89312534:G:GG	acceptor_gain	0.9800
9:89312540:G:GA	acceptor_gain	0.9800
9:89315158:ATCTT:A	acceptor_loss	0.9800
9:89315159:T:G	acceptor_loss	0.9800
9:89315165:A:AG	acceptor_gain	0.9800
9:89316370:C:G	acceptor_gain	0.9800
9:89316370:CAG:C	acceptor_loss	0.9800

AlphaMissense

522 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:89311351:G:C	R20P	1.000
9:89315175:T:A	V22D	1.000
9:89315181:T:C	L24S	1.000
9:89315237:T:A	W43R	1.000
9:89315237:T:C	W43R	1.000
9:89315241:G:C	R44T	1.000
9:89315241:G:T	R44M	1.000
9:89315242:G:C	R44S	1.000
9:89315242:G:T	R44S	1.000
9:89315253:T:A	V48D	1.000
9:89315270:T:A	W54R	1.000
9:89315270:T:C	W54R	1.000
9:89315272:G:C	W54C	1.000
9:89315272:G:T	W54C	1.000
9:89311314:T:C	Y8H	0.999
9:89311326:T:C	Y12H	0.999
9:89311347:T:C	Y19H	0.999
9:89311351:G:T	R20L	0.999
9:89315173:T:A	H21Q	0.999
9:89315173:T:G	H21Q	0.999
9:89315249:G:C	G47R	0.999
9:89315250:G:T	G47V	0.999
9:89315260:G:C	Q50H	0.999
9:89315260:G:T	Q50H	0.999
9:89315267:G:C	G53R	0.999
9:89315268:G:T	G53V	0.999
9:89315271:G:C	W54S	0.999
9:89315271:G:T	W54L	0.999
9:89315288:C:G	H60D	0.999
9:89315290:T:A	H60Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000003178 (9:89310949 G>A,C,T), RS1000015045 (9:89316645 C>T), RS1000565726 (9:89314057 C>T), RS1000574707 (9:89315759 A>G), RS1000809341 (9:89311159 T>C), RS1002190130 (9:89316146 T>C), RS1002661527 (9:89314926 G>A), RS1002815238 (9:89310469 C>T), RS1002919156 (9:89315831 T>C), RS1002934467 (9:89314654 C>T), RS1003036595 (9:89316167 G>A), RS1003554832 (9:89310582 G>C), RS1004065524 (9:89313789 C>T), RS1004074518 (9:89311412 G>A,C,T), RS1004105715 (9:89311614 A>G)

Disease associations

OMIM: gene MIM:116901 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006192_44	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066381 (SINGLE PROTEIN)

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

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
5.21	Kd	6120	nM	CHEMBL5653589
5.14	ED50	7213	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148078: Binding affinity to human CKS2 incubated for 45 mins by Kinobead based pull down assay	kd	6.1200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects cotreatment, decreases expression, increases reaction, increases expression	4
Particulate Matter	decreases expression, increases abundance, affects cotreatment	4
sodium arsenite	decreases expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
2,3-dimethoxy-1,4-naphthoquinone	increases expression	2
chloropicrin	decreases expression, increases expression	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Nickel	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
testosterone enanthate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	increases expression, increases abundance	1
diethyl maleate	increases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione	decreases expression	1
nickel chloride	increases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
cupric chloride	increases expression	1
isobutyl alcohol	increases abundance, affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651120	Binding	Binding affinity to human CKS2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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