CDK2AP1

Summary

CDK2AP1 (cyclin dependent kinase 2 associated protein 1, HGNC:14002) is a protein-coding gene on chromosome 12q24.31, encoding Cyclin-dependent kinase 2-associated protein 1 (O14519). Inhibitor of cyclin-dependent kinase CDK2.

The protein encoded by this gene is a cyclin-dependent kinase 2 (CDK2) -associated protein which is thought to negatively regulate CDK2 activity by sequestering monomeric CDK2, and targeting CDK2 for proteolysis. This protein was found to also interact with DNA polymerase alpha/primase and mediate the phosphorylation of the large p180 subunit, which suggests a regulatory role in DNA replication during the S-phase of the cell cycle. This protein also forms a core subunit of the nucleosome remodeling and histone deacetylation (NURD) complex that epigenetically regulates embryonic stem cell differentiation. This gene thus plays a role in both cell-cycle and epigenetic regulation. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 8099 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 29 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_004642

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14002
Approved symbol	CDK2AP1
Name	cyclin dependent kinase 2 associated protein 1
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	DORC1, doc-1, DOC1, ST19, p12DOC-1
Ensembl gene	ENSG00000111328
Ensembl biotype	protein_coding
OMIM	602198
Entrez	8099

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000261692, ENST00000535796, ENST00000535979, ENST00000538446, ENST00000541002, ENST00000542174, ENST00000542427, ENST00000543217, ENST00000544658, ENST00000544890, ENST00000618072, ENST00000652466

RefSeq mRNA: 3 — MANE Select: NM_004642 NM_001270433, NM_001270434, NM_004642

CCDS: CCDS58289, CCDS9245

Canonical transcript exons

ENST00000261692 — 4 exons

Exon	Start	End
ENSE00000881341	123265196	123265322
ENSE00001225302	123271564	123271856
ENSE00002221858	123260976	123261803
ENSE00003606193	123267185	123267282

Expression profiles

Bgee: expression breadth ubiquitous, 304 present calls, max score 99.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 111.0389 / max 705.5640, expressed in 1822 samples.

FANTOM5 promoters (24 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133929	84.3775	1817
133928	7.8579	1647
133931	1.9885	1152
133910	1.5540	876
133927	1.4550	894
133930	1.3136	884
133911	1.2565	717
133921	1.1295	648
133935	1.0147	587
133932	0.9672	671

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.62	gold quality
tibia	UBERON:0000979	99.54	gold quality
spinal cord	UBERON:0002240	99.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.41	gold quality
ganglionic eminence	UBERON:0004023	99.40	gold quality
medial globus pallidus	UBERON:0002477	99.39	gold quality
superior vestibular nucleus	UBERON:0007227	99.38	gold quality
globus pallidus	UBERON:0001875	99.36	gold quality
medulla oblongata	UBERON:0001896	99.34	gold quality
ventricular zone	UBERON:0003053	99.34	gold quality
inferior vagus X ganglion	UBERON:0005363	99.33	gold quality
subthalamic nucleus	UBERON:0001906	99.32	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.32	gold quality
gingival epithelium	UBERON:0001949	99.27	gold quality
hair follicle	UBERON:0002073	99.27	gold quality
substantia nigra	UBERON:0002038	99.20	gold quality
midbrain	UBERON:0001891	99.19	gold quality
lateral globus pallidus	UBERON:0002476	99.18	gold quality
gingiva	UBERON:0001828	99.12	gold quality
postcentral gyrus	UBERON:0002581	99.09	gold quality
pons	UBERON:0000988	99.07	gold quality
mammary duct	UBERON:0001765	99.05	gold quality
CA1 field of hippocampus	UBERON:0003881	99.04	gold quality
hypothalamus	UBERON:0001898	99.03	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.02	gold quality
epithelium of mammary gland	UBERON:0003244	99.02	gold quality
embryo	UBERON:0000922	99.01	gold quality
ventral tegmental area	UBERON:0002691	98.99	gold quality
tendon of biceps brachii	UBERON:0008188	98.98	gold quality
cranial nerve II	UBERON:0000941	98.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	507.93
E-MTAB-11121	yes	342.44
E-ANND-3	yes	16.73
E-HCAD-13	yes	7.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, PGR

miRNA regulators (miRDB)

61 targeting CDK2AP1, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-7106-5P	99.53	67.47	3574

Literature-anchored findings (GeneRIF, showing 29)

• DOC1 has a differential expression in microsatellite-unstable human colorectal neoplasms. (PMID:13679870)
• plays a role in TGF-beta1-mediated growth suppression by modulating CDK2 activities and pRB phosphorylation (PMID:14744761)
• p12CDK2-AP1 forms nuclear homodimers in contact inhibited normal diploid cells and dimerization of p12 is a necessary process for the growth inhibition effect by p12 (PMID:15840587)
• Resistance to TGF-beta 1-induced growth suppression is due to the disruption of its signaling pathway as a consequence of reduced or lost p12(CDK2-AP1). (PMID:17217620)
• the del T poly (T) 8 observed in the 3’-UTR of the CDK2-AP1 gene in human microsatellite unstable colorectal cancer is functionally significant and results in decreased CDK2-AP1 expression (PMID:17689689)
• expression negatively associated with a more advanced depth of tumor invasion and stage in gastric carcinoma (PMID:19279387)
• p12CDK2-AP1 is associated with tumor progression and a poor prognosis in esophageal squamous cell carcinoma. (PMID:19513502)
• The expression of cdk2ap1 correlated with a reduction in cellular growth, irrespective of inhibition or stimulation of androgen receptor (AR) signaling pathways (PMID:19585490)
• Data show low or moderate methylation was found in seven selected genes BAD, BBC3, CAV1, CDK2AP1, NPM1, PRKCDBP and THEM4. (PMID:19679565)
• Results indicate that DOC-1 is a bona fide subunit of the Mi-2/NuRD chromatin remodeling complex. (PMID:20523938)
• Data support the role of cdk2ap1 as a tumor suppressor gene that can regulate squamous cell carcinoma growth in a cell autonomous manner through decreases in invasiveness and a non-cell autonomous manner through decreases in angiogenesis phenotypes. (PMID:20541561)
• CDK2AP1 is a novel multiple sclerosis susceptibility loci, and it’s risk allele correlates with diminished RNA expression of the cell cycle regulator CDK2AP1 (PMID:20555355)
• The combination of an increased expression of the antimicrobial peptide DEFA-4, the oncogene S100-A7, epidermal growth factor, and tenascin-c, and a decreased Doc-1 expression in oral leukoplakia might characterize its potency of malignant transformation. (PMID:20727496)
• Missing down-regulation of the tumor-suppressor gene DOC-1, might exert protective effects and counteract malignant transformation of benign, proliferating lesions of the oral cavity. (PMID:21187770)
• P12(CDK2AP1) is downregulated by miR-21 (PMID:21328460)
• In comparison with the healthy gingiva, the expression of Doc-1 was decreased, whereas the expression of S100A7 was upregulated in all oral lesions. (PMID:21740085)
• exerts its effect on stem cell maintenance/differentiation through epigenetic regulation [review] (PMID:21865592)
• Human cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) is dimeric in its disulfide-reduced state, with natively disordered N-terminal region (PMID:22427660)
• Low CDK2AP1 expression is common and associated with adverse prognosis in nasopharyngeal carcinoma. (PMID:22791769)
• CDK2AP1 plays an important role in modulating the growth and tumorigenesis of lung cancer cells. (PMID:23404055)
• Study reports that knockdown of CDK2AP1 by RNAi in glioma cells could effectively inhibit cell proliferation by inducing cell cycle arrest and apoptosis (PMID:24620959)
• In summary, p12CDK2AP1 expression in myxofibrosarcoma cells induces G0/G1 arrest and mitochondria dependent proapoptotic activity and down-regulation of p12CDK2AP1 by shRNAi results in up-regulation of the CDK2 transcript and protein. (PMID:24889487)
• knockdown of CDK2AP1 in primary human fibroblasts reduced proliferation and induced premature senescence, with the observed phenotype being p53 dependent (PMID:25785833)
• The simultaneous overexpression of p12CDK2-AP1 and CD82 significantly suppressed the in vivo tumor growth. (PMID:27349208)
• DOC1 re-expression in oral cancer cells causes a reversal of EMT. DOC1 promotes NURD binding to a subset of target loci. (PMID:28683324)
• Knockdown of CDK2AP1 in hESCs results in increased p53 and enhances differentiation and favors it over a self-renewal fate. (PMID:29734353)
• A compelling relationship exists between high CDK2AP1 mRNA expression and lower TNM classification of breast cancer, which is consistent with CDK2AP1 having a tumour-suppressive function. (PMID:30343278)
• The Association between Cyclin Dependent Kinase 2 Associated Protein 1 (CDK2AP1) and Molecular Subtypes of Lethal Prostate Cancer. (PMID:36362115)
• The deleted in oral cancer (DOC1 aka CDK2AP1) tumor suppressor gene is downregulated in oral squamous cell carcinoma by multiple microRNAs. (PMID:37217493)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	CDK2AP1	ENSDARG00000115248
mus_musculus	Cdk2ap1	ENSMUSG00000029394
mus_musculus	Cdk2ap1rt	ENSMUSG00000078154
rattus_norvegicus	Cdk2ap1	ENSRNOG00000001070
drosophila_melanogaster	CDK2AP1	FBGN0030269
caenorhabditis_elegans		WBGENE00012807

Paralogs (1): CDK2AP2 (ENSG00000167797)

Protein

Protein identifiers

Cyclin-dependent kinase 2-associated protein 1 — O14519 (reviewed: O14519)

Alternative names: Deleted in oral cancer 1, Putative oral cancer suppressor

All UniProt accessions (2): O14519, F5GZF0

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitor of cyclin-dependent kinase CDK2. Also acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin.

Subunit / interactions. Homodimer. Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5. The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes. Interacts with monomeric unphosphorylated CDK2. Interacts with CDK2AP2. Interacts with GATAD2A. Interacts with HDAC1. Interacts with HDAC2. Interacts with MBD2. Interacts with MBD3. Interacts with RBBP4. Interacts with RBBP7.

Subcellular location. Nucleus. Chromosome.

Post-translational modifications. Phosphorylated in vitro by IKBKE at Ser-46.

Similarity. Belongs to the CDK2AP family.

Isoforms (2)

UniProt ID	Names	Canonical?
O14519-1	1	yes
O14519-2	2

RefSeq proteins (3): NP_001257362, NP_001257363, NP_004633* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017266	DOC_1/2	Family

Pfam: PF09806

UniProt features (11 total): helix 3, turn 2, chain 1, region of interest 1, modified residue 1, disulfide bond 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2KW6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14519-F1	76.47	0.48

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): 46

Disulfide bonds (1): 105

Mutagenesis-validated functional residues (1):

Position	Phenotype
105	does not alter homodimerization.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9937850	NuRD complex assembly
R-HSA-9940951	Interaction of NuRD complexes with transcription factors

MSigDB gene sets: 272 (showing top): GOBP_REGULATION_OF_PHOSPHORYLATION, TGCACTT_MIR519C_MIR519B_MIR519A, GCANCTGNY_MYOD_Q6, GCAAGGA_MIR502, CACCAGC_MIR138, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, GOLDRATH_ANTIGEN_RESPONSE, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, EVI1_05, ONKEN_UVEAL_MELANOMA_UP, MARTINEZ_RB1_TARGETS_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GROSS_HYPOXIA_VIA_ELK3_UP

GO Biological Process (3): positive regulation of protein phosphorylation (GO:0001934), DNA-templated DNA replication (GO:0006261), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (2): DNA polymerase binding (GO:0070182), protein binding (GO:0005515)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), NuRD complex (GO:0016581), perinuclear region of cytoplasm (GO:0048471), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
CHD3, CHD4, CHD5 subfamily	1
NuRD complex assembly	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	2
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
DNA replication	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
enzyme binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
histone deacetylase complex	1
transcription regulator complex	1
CHD-type complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

942 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK2AP1	GATAD2A	Q86YP4	957
CDK2AP1	CHD3	Q12873	827
CDK2AP1	GATAD2B	Q8WXI9	798
CDK2AP1	ST20	Q9HBF5	771
CDK2AP1	RBBP4	P31149	769
CDK2AP1	MTA1	Q13330	719
CDK2AP1	HDAC1	Q13547	662
CDK2AP1	RBBP7	Q16576	625
CDK2AP1	MTA2	O94776	543
CDK2AP1	MTA3	Q9BTC8	542
CDK2AP1	SDCBP	O00560	518
CDK2AP1	ZNF687	Q8N1G0	518
CDK2AP1	APEH	P13798	507
CDK2AP1	IL24	Q13007	507
CDK2AP1	CDK2AP2	O75956	432

IntAct

89 interactions, top by confidence:

A	B	Type	Score
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
MRFAP1L1	CDK2AP1	psi-mi:“MI:0915”(physical association)	0.830
CDK2AP1	MRFAP1L1	psi-mi:“MI:0915”(physical association)	0.830
CHD3	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
GATAD2B	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
CHD4	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
GATAD2A	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
CDK2AP1	MTA2	psi-mi:“MI:0914”(association)	0.730
MBD3	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
ZNF219	CDK2AP1	psi-mi:“MI:0914”(association)	0.640
CCDC136	CDK2AP1	psi-mi:“MI:0915”(physical association)	0.560
USP20	CDK2AP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (200): CCDC136 (Two-hybrid), MRFAP1L1 (Two-hybrid), CDK2AP1 (Affinity Capture-MS), CDK2AP1 (Affinity Capture-MS), CDK2AP1 (Affinity Capture-MS), CDK2AP1 (Affinity Capture-MS), CDK2AP1 (Two-hybrid), ALDOA (Affinity Capture-MS), CHD3 (Affinity Capture-MS), CHD4 (Affinity Capture-MS), ERCC6 (Affinity Capture-MS), HDAC1 (Affinity Capture-MS), HDAC2 (Affinity Capture-MS), RBBP4 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS)

ESM2 similar proteins: A0A1V6NYZ6, A0A3G1DJJ7, A4H824, A4HWF0, B0DX25, C5DFL1, F5HCK7, F5HGQ8, G1XTZ6, O14519, O35207, O60153, O74461, P09272, P09512, P10471, P11625, P17523, P17524, P27271, P28937, P28979, P32845, P34347, P34890, P38612, P49119, P79943, P91820, Q00041, Q06658, Q08589, Q09824, Q32LJ5, Q4JQW6, Q4QFD3, Q66125, Q67621, Q6DR24, Q6GZQ5

Diamond homologs: O14519, O35207, O75956, P49119, Q58CN7, Q9CPY4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IKBKE	unknown	CDK2AP1	phosphorylation
CDK2AP1	“down-regulates activity”	CDK2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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
Regulation of TP53 Activity through Acetylation	10	123.5×	1e-17
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	11	113.2×	1e-18
RNA Polymerase I Transcription Initiation	11	66.6×	1e-16
Regulation of PTEN gene transcription	12	57.9×	3e-17
NuRD complex assembly	13	49.5×	1e-17
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	12	49.4×	2e-16
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	12	47.5×	2e-16
HDACs deacetylate histones	13	42.2×	6e-17

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	11	195.9×	9e-22
chromatin remodeling	12	20.4×	4e-11
negative regulation of transforming growth factor beta receptor signaling pathway	5	20.2×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	18
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
393913	GRCh37/hg19 12q24.31(chr12:123404920-124192840)	Likely pathogenic

SpliceAI

1092 predictions. Top by Δscore:

Variant	Effect	Δscore
12:123256811:A:AG	acceptor_gain	1.0000
12:123256812:G:GA	acceptor_gain	1.0000
12:123256812:GT:G	acceptor_gain	1.0000
12:123256812:GTGCC:G	acceptor_gain	1.0000
12:123265190:GCTT:G	donor_loss	1.0000
12:123265191:CTTA:C	donor_loss	1.0000
12:123265192:TTA:T	donor_loss	1.0000
12:123265193:TA:T	donor_loss	1.0000
12:123265194:A:AC	donor_gain	1.0000
12:123265195:C:A	donor_loss	1.0000
12:123265195:C:CC	donor_gain	1.0000
12:123265195:CCG:C	donor_gain	1.0000
12:123265195:CCGCG:C	donor_gain	1.0000
12:123265227:C:CA	donor_gain	1.0000
12:123265318:GTTCC:G	acceptor_gain	1.0000
12:123265319:TTCC:T	acceptor_gain	1.0000
12:123265320:TCC:T	acceptor_gain	1.0000
12:123265321:CC:C	acceptor_gain	1.0000
12:123265321:CCC:C	acceptor_gain	1.0000
12:123265322:CC:C	acceptor_gain	1.0000
12:123265323:C:CC	acceptor_gain	1.0000
12:123265323:C:G	acceptor_loss	1.0000
12:123265324:T:G	acceptor_loss	1.0000
12:123267180:CATA:C	donor_loss	1.0000
12:123267181:ATAC:A	donor_loss	1.0000
12:123267182:TACCT:T	donor_loss	1.0000
12:123267183:A:AT	donor_loss	1.0000
12:123267184:C:A	donor_loss	1.0000
12:123267278:CCCAG:C	acceptor_gain	1.0000
12:123267279:CCAG:C	acceptor_gain	1.0000

AlphaMissense

734 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:123261767:A:G	L106S	1.000
12:123261769:G:C	C105W	1.000
12:123261770:C:T	C105Y	1.000
12:123261771:A:G	C105R	1.000
12:123261782:A:G	L101P	1.000
12:123261787:T:A	R99S	1.000
12:123261787:T:G	R99S	1.000
12:123261788:C:A	R99I	1.000
12:123261788:C:G	R99T	1.000
12:123261791:G:T	A98D	1.000
12:123261792:C:G	A98P	1.000
12:123261800:A:C	I95S	1.000
12:123261800:A:G	I95T	1.000
12:123261800:A:T	I95N	1.000
12:123265196:C:G	G94R	1.000
12:123265200:C:A	K92N	1.000
12:123265200:C:G	K92N	1.000
12:123265201:T:A	K92M	1.000
12:123265202:T:C	K92E	1.000
12:123265204:A:G	L91P	1.000
12:123265206:C:A	R90S	1.000
12:123265206:C:G	R90S	1.000
12:123265207:C:A	R90M	1.000
12:123265211:C:T	E89K	1.000
12:123265216:G:T	A87D	1.000
12:123265221:C:A	K85N	1.000
12:123265221:C:G	K85N	1.000
12:123265223:T:C	K85E	1.000
12:123265224:G:C	S84R	1.000
12:123265224:G:T	S84R	1.000

dbSNP variants (sampled 300 via entrez): RS1000005628 (12:123262487 A>G,T), RS1000167819 (12:123262843 C>G), RS1000226178 (12:123268494 C>A), RS1000237303 (12:123262530 A>C,G), RS1000385704 (12:123268082 G>A,T), RS1000471572 (12:123272225 GC>G), RS1000813003 (12:123273739 C>A,T), RS1000906514 (12:123261291 A>T), RS1001429590 (12:123273954 C>A), RS1002223593 (12:123266188 C>T), RS1002288745 (12:123264026 T>C), RS1002298561 (12:123266069 C>T), RS1002334155 (12:123269010 T>C), RS1002890243 (12:123270827 G>A,C), RS1002995798 (12:123270851 C>G)

Disease associations

OMIM: gene MIM:602198 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST002149_20	Schizophrenia	2.000000e-08
GCST002539_19	Schizophrenia	2.000000e-14
GCST003990_9	Allergy	1.000000e-11
GCST004521_72	Autism spectrum disorder or schizophrenia	8.000000e-12
GCST005038_81	Allergic disease (asthma, hay fever or eczema)	3.000000e-13
GCST005316_380	Intelligence (MTAG)	2.000000e-08
GCST005316_462	Intelligence (MTAG)	3.000000e-10
GCST005781_6	Total cholesterol levels	3.000000e-06
GCST006409_30	Allergic rhinitis	3.000000e-24
GCST006585_860	Blood protein levels	9.000000e-06
GCST006803_10	Schizophrenia	6.000000e-16
GCST006979_1085	Heel bone mineral density	2.000000e-14
GCST007277_17	Tourette syndrome	2.000000e-06
GCST010241_101	Apolipoprotein A1 levels	5.000000e-49
GCST010703_43	Brain morphology (MOSTest)	1.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004574	total cholesterol measurement
EFO:0009270	heel bone mineral density
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5578 (SINGLE PROTEIN)

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

ChEMBL bioactivities

17 potent at pChembl≥5 of 21 total, top 17 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.75	IC50	1800	nM	CHEMBL488231
5.66	IC50	2200	nM	CHEMBL520902
5.48	IC50	3300	nM	CHEMBL488230
5.48	IC50	3300	nM	CHEMBL516784
5.44	IC50	3600	nM	CHEMBL469481
5.44	IC50	3600	nM	CHEMBL518777
5.43	IC50	3700	nM	CHEMBL527881
5.43	IC50	3700	nM	CHEMBL470288
5.32	IC50	4800	nM	CHEMBL518661
5.29	IC50	5100	nM	CHEMBL487273
5.28	IC50	5300	nM	CHEMBL520734
5.27	IC50	5400	nM	CHEMBL469686
5.26	IC50	5500	nM	CHEMBL513191
5.25	IC50	5600	nM	CHEMBL519913
5.25	IC50	5600	nM	CHEMBL517553
5.08	IC50	8400	nM	CHEMBL488287
5.06	IC50	8800	nM	CHEMBL513377

PubChem BioAssay actives

17 with measured affinity, of 33 total; 17 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-(carbamoylamino)-N-[(3S)-piperidin-3-yl]-5-pyridin-4-ylthiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	1.8000	uM
2-(carbamoylamino)-5-(4-methylsulfonylphenyl)-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	2.2000	uM
2-(carbamoylamino)-5-(4-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	3.3000	uM
2-(carbamoylamino)-N-[(3S)-piperidin-3-yl]-5-pyridin-3-ylthiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	3.3000	uM
2-(carbamoylamino)-5-[3-[2-(diethylamino)ethoxy]phenyl]-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	3.6000	uM
2-(carbamoylamino)-5-(4-cyanophenyl)-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	3.6000	uM
2-(carbamoylamino)-5-(4-chlorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	3.7000	uM
2-(carbamoylamino)-5-[4-(dimethylcarbamoyl)phenyl]-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	3.7000	uM
2-(carbamoylamino)-5-[4-[2-(diethylamino)ethoxy]phenyl]-N-piperidin-3-ylthiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	4.8000	uM
2-(carbamoylamino)-5-phenyl-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	5.1000	uM
2-(carbamoylamino)-N-[(3S)-piperidin-3-yl]-5-thiophen-3-ylthiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	5.3000	uM
2-(carbamoylamino)-N-[(3S)-piperidin-3-yl]-5-[4-(trifluoromethyl)phenyl]thiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	5.4000	uM
2-(carbamoylamino)-5-(4-methylphenyl)-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	5.5000	uM
2-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	5.6000	uM
2-(carbamoylamino)-N-[(3S)-piperidin-3-yl]-5-thiophen-2-ylthiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	5.6000	uM
2-(carbamoylamino)-5-[4-(dimethylamino)phenyl]-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	8.4000	uM
2-(carbamoylamino)-5-(3-chlorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide	343533: Inhibition of Cdk1	ic50	8.8000	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
bisphenol A	increases methylation, affects expression, affects cotreatment	2
Air Pollutants	affects methylation, decreases expression, increases abundance	2
Cisplatin	increases expression	2
Cyclosporine	decreases expression, decreases methylation	2
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
pinosylvin	decreases expression	1
K 7174	decreases expression	1
scriptaid	affects expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Metribolone	increases expression	1
Aflatoxin B1	increases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	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
CHEMBL944208	Binding	Inhibition of Cdk1	Discovery of a novel class of 2-ureido thiophene carboxamide checkpoint kinase inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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