CDK2AP2

Summary

CDK2AP2 (cyclin dependent kinase 2 associated protein 2, HGNC:30833) is a protein-coding gene on chromosome 11q13.2, encoding Cyclin-dependent kinase 2-associated protein 2 (O75956). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin.

This gene encodes a protein that interacts with cyclin-dependent kinase 2 associated protein 1. Pseudogenes associated with this gene are located on chromosomes 7 and 9. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 10263 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 19 total
• Druggable target: yes
• MANE Select transcript: NM_005851

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30833
Approved symbol	CDK2AP2
Name	cyclin dependent kinase 2 associated protein 2
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	DOC-1R, p14
Ensembl gene	ENSG00000167797
Ensembl biotype	protein_coding
OMIM	620061
Entrez	10263

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000301488, ENST00000525402, ENST00000526447, ENST00000531178, ENST00000531506, ENST00000890089, ENST00000935009, ENST00000935010

RefSeq mRNA: 2 — MANE Select: NM_005851 NM_001271849, NM_005851

CCDS: CCDS8169

Canonical transcript exons

ENST00000301488 — 4 exons

Exon	Start	End
ENSE00001167405	67506497	67507012
ENSE00001167412	67508001	67508162
ENSE00003556699	67507365	67507497
ENSE00003605861	67507592	67507689

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 98.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.1117 / max 394.6260, expressed in 1816 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120947	25.4096	1803
120950	10.3253	1791
120946	5.9386	1676
120944	5.2430	1666
120945	3.6403	1527
120948	2.2660	1336
120942	1.1723	657
120949	0.7017	431
120943	0.4149	211

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.54	gold quality
apex of heart	UBERON:0002098	98.02	gold quality
right lobe of thyroid gland	UBERON:0001119	97.90	gold quality
right lobe of liver	UBERON:0001114	97.68	gold quality
right coronary artery	UBERON:0001625	97.63	gold quality
granulocyte	CL:0000094	97.60	gold quality
thoracic aorta	UBERON:0001515	97.54	gold quality
ascending aorta	UBERON:0001496	97.53	gold quality
left coronary artery	UBERON:0001626	97.44	gold quality
left lobe of thyroid gland	UBERON:0001120	97.34	gold quality
aorta	UBERON:0000947	97.29	gold quality
popliteal artery	UBERON:0002250	97.20	gold quality
descending thoracic aorta	UBERON:0002345	97.20	gold quality
endometrium epithelium	UBERON:0004811	97.19	gold quality
tibial artery	UBERON:0007610	97.18	gold quality
oocyte	CL:0000023	97.13	gold quality
coronary artery	UBERON:0001621	97.09	gold quality
body of pancreas	UBERON:0001150	97.05	gold quality
tibial nerve	UBERON:0001323	96.99	gold quality
lower esophagus	UBERON:0013473	96.87	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.87	gold quality
heart left ventricle	UBERON:0002084	96.84	gold quality
metanephros cortex	UBERON:0010533	96.74	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.62	gold quality
cardiac ventricle	UBERON:0002082	96.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.46	gold quality
thyroid gland	UBERON:0002046	96.31	gold quality
body of stomach	UBERON:0001161	96.30	gold quality
lower esophagus mucosa	UBERON:0035834	96.19	gold quality
adenohypophysis	UBERON:0002196	96.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	33.87
E-MTAB-6701	yes	18.19
E-HCAD-11	yes	18.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting CDK2AP2, 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-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-3945	98.68	64.21	553
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-4761-3P	96.27	66.26	524
HSA-MIR-4743-5P	88.08	64.31	91

Literature-anchored findings (GeneRIF, showing 3)

• antitumor effects of DOC-1R may be mediated by negatively regulating G1 phase progression and G1/S transition through inhibiting CDK2 expression and activation (PMID:23781148)
• Our findings suggest that alteration of p16, p14, p27, p21, and p53 status may contribute to carcinogenesis and the clinical behavior of HPV-negative adenocarcinoma of the uterine cervix (PMID:25675191)
• Novel circular RNA hsa_circ_0036683 suppresses proliferation and migration by mediating the miR-4664-3p/CDK2AP2 axis in non-small cell lung cancer. (PMID:39113208)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk2ap2	ENSDARG00000103145
mus_musculus	Cdk2ap2	ENSMUSG00000024856
rattus_norvegicus	Cdk2ap2	ENSRNOG00000018391
drosophila_melanogaster	CDK2AP1	FBGN0030269
caenorhabditis_elegans		WBGENE00012807

Paralogs (1): CDK2AP1 (ENSG00000111328)

Protein

Protein identifiers

Cyclin-dependent kinase 2-associated protein 2 — O75956 (reviewed: O75956)

Alternative names: DOC-1-related protein

All UniProt accessions (4): E9PKR4, E9PQJ3, O75956, Q6IAV4

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Inhibits cell cycle G1/S phase transition by repressing CDK2 expression and activation; represses CDK2 activation by inhibiting its interaction with cyclin E and A. Plays a role in regulating the self-renewal of embryonic stem cells (ESCs) and in maintaining cell survival during terminal differentiation of ESCs. Regulates microtubule organization of metaphase II oocytes.

Subunit / interactions. 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 CDK2AP1. Interacts with CDK2. Interacts with MAPK1.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated by MAPK1 and CDK2.

Similarity. Belongs to the CDK2AP family.

RefSeq proteins (2): NP_001258778, NP_005842* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017266	DOC_1/2	Family

Pfam: PF09806

UniProt features (8 total): helix 3, region of interest 2, chain 1, compositionally biased region 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2M1L	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75956-F1	75.81	0.38

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: 231 (showing top): ATF_B, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, TGCGCANK_UNKNOWN, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCANCTGNY_MYOD_Q6, GOBP_CELL_CYCLE_PHASE_TRANSITION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, AREB6_01, CREBP1_Q2, ACTGCAG_MIR173P, chr11q13, CREB_Q4, GOBP_STEM_CELL_DIVISION

GO Biological Process (3): regulation of microtubule cytoskeleton organization (GO:0070507), regulation of stem cell division (GO:2000035), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134)

GO Molecular Function (2): protein binding (GO:0005515), kinase activity (GO:0016301)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), microtubule (GO:0005874), NuRD complex (GO:0016581)

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
microtubule cytoskeleton organization	1
regulation of microtubule-based process	1
regulation of cytoskeleton organization	1
stem cell division	1
regulation of cell division	1
G1/S transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
histone deacetylase complex	1
transcription regulator complex	1
CHD-type complex	1

Protein interactions and networks

STRING

736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK2AP2	CDK2	P24941	505
CDK2AP2	CDK2AP1	O14519	432
CDK2AP2	TMEM217	Q8N7C4	405
CDK2AP2	CCDC86	Q9H6F5	385
CDK2AP2	ZMYND8	Q9ULU4	384
CDK2AP2	MANF	P55145	371
CDK2AP2	SLU7	O95391	361
CDK2AP2	ZFP14	Q9HCL3	355
CDK2AP2	TMEM217B	A0A494BZU4	338
CDK2AP2	SPATA17	Q96L03	335
CDK2AP2	GNL3L	Q9NVN8	333
CDK2AP2	RNF150	Q9ULK6	325
CDK2AP2	SLC35D4	Q24JQ0	314
CDK2AP2	SPATA19	Q7Z5L4	313
CDK2AP2	TMEM169	Q96HH4	309

IntAct

25 interactions, top by confidence:

A	B	Type	Score
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
CDK2AP2	MRFAP1L1	psi-mi:“MI:0915”(physical association)	0.560
CDK2AP2		psi-mi:“MI:0915”(physical association)	0.560
CDK2AP2	A2M	psi-mi:“MI:0915”(physical association)	0.370
CDK2AP2	DBN1	psi-mi:“MI:0915”(physical association)	0.370
EED	CDK2AP2	psi-mi:“MI:0915”(physical association)	0.370
EEF1G	CDK2AP2	psi-mi:“MI:0915”(physical association)	0.370
HSF4	CDK2AP2	psi-mi:“MI:0915”(physical association)	0.370
CDK2AP2	IKZF1	psi-mi:“MI:0915”(physical association)	0.370
CDK2AP2	MBTPS1	psi-mi:“MI:0915”(physical association)	0.370
CDK2AP2	PYCR1	psi-mi:“MI:0915”(physical association)	0.370
RCC1	CDK2AP2	psi-mi:“MI:0915”(physical association)	0.370
CDK2AP2	RPLP1	psi-mi:“MI:0915”(physical association)	0.370
TRA2A	CDK2AP2	psi-mi:“MI:0915”(physical association)	0.370
YIF1A	CDK2AP2	psi-mi:“MI:0915”(physical association)	0.370
CDK2AP2	ZBTB48	psi-mi:“MI:0915”(physical association)	0.370
MTA3	CDK2AP2	psi-mi:“MI:0914”(association)	0.350
HDAC2		psi-mi:“MI:0914”(association)	0.350
CDK2AP2	MRFAP1L1	psi-mi:“MI:0915”(physical association)	0.000
CDK2AP2	fadE	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (54): MRFAP1L1 (Two-hybrid), MRFAP1L1 (Two-hybrid), CDK2AP2 (Affinity Capture-MS), CDK2AP2 (Affinity Capture-RNA), CDK2AP2 (Affinity Capture-MS), CDK2AP2 (Affinity Capture-MS), CDK2AP2 (Affinity Capture-MS), MBD2 (Affinity Capture-MS), MTA1 (Affinity Capture-MS), MTA2 (Affinity Capture-MS), MTA3 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), CHD4 (Affinity Capture-MS), GATAD2A (Affinity Capture-MS), GATAD2B (Affinity Capture-MS)

ESM2 similar proteins: A0A0D1CVX2, A0A0D1E6R6, A0A1D1V3Z0, A5HBE1, B5YWI0, B6KEU8, B6KJ32, B7UM99, C6UYL8, D1FQ14, D3QW22, G5EHI7, K9N4Q4, O00834, O00933, O46203, O75956, O84462, P03093, P03095, P05686, P06651, P0C9Z8, P0DJ90, P0DJ91, P0DJ92, P0DOJ1, P0DOJ2, P0DOJ3, P20290, P23117, P23118, P24608, P35939, P90661, Q06428, Q27002, Q27003, Q2KEJ2, Q3L6L8

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

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 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 PTEN gene transcription	5	63.7×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

412 predictions. Top by Δscore:

Variant	Effect	Δscore
11:67507359:ACTT:A	donor_loss	1.0000
11:67507360:CTTA:C	donor_loss	1.0000
11:67507361:TTA:T	donor_loss	1.0000
11:67507362:TA:T	donor_loss	1.0000
11:67507363:A:AC	donor_gain	1.0000
11:67507364:C:CC	donor_gain	1.0000
11:67507364:C:T	donor_loss	1.0000
11:67507364:CCT:C	donor_gain	1.0000
11:67507364:CCTCT:C	donor_gain	1.0000
11:67507493:ATCGC:A	acceptor_gain	1.0000
11:67507494:TCGC:T	acceptor_gain	1.0000
11:67507495:CGC:C	acceptor_gain	1.0000
11:67507495:CGCC:C	acceptor_gain	1.0000
11:67507496:GC:G	acceptor_gain	1.0000
11:67507497:CCTA:C	acceptor_gain	1.0000
11:67507498:C:CC	acceptor_gain	1.0000
11:67507498:C:T	acceptor_gain	1.0000
11:67507499:T:G	acceptor_loss	1.0000
11:67507500:A:AC	acceptor_gain	1.0000
11:67507500:A:C	acceptor_gain	1.0000
11:67507504:C:CT	acceptor_gain	1.0000
11:67507505:A:T	acceptor_gain	1.0000
11:67507588:TCACC:T	donor_loss	1.0000
11:67507589:CA:C	donor_loss	1.0000
11:67507590:A:AC	donor_gain	1.0000
11:67507591:C:CC	donor_gain	1.0000
11:67507591:CCTG:C	donor_gain	1.0000
11:67507590:ACCTG:A	donor_gain	0.9900
11:67507591:CCTGC:C	donor_gain	0.9900
11:67507686:CTTC:C	acceptor_gain	0.9900

AlphaMissense

795 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:67506974:C:G	A118P	1.000
11:67506976:A:G	L117P	1.000
11:67506978:G:C	C116W	1.000
11:67506979:C:T	C116Y	1.000
11:67506980:A:G	C116R	1.000
11:67506984:T:A	R114S	1.000
11:67506984:T:G	R114S	1.000
11:67506985:C:A	R114I	1.000
11:67506985:C:G	R114T	1.000
11:67506991:A:G	L112P	1.000
11:67506995:C:G	A111P	1.000
11:67506997:C:A	R110L	1.000
11:67506997:C:G	R110P	1.000
11:67506998:G:A	R110W	1.000
11:67507000:G:T	A109D	1.000
11:67507001:C:G	A109P	1.000
11:67507004:G:C	H108D	1.000
11:67507009:A:C	I106S	1.000
11:67507009:A:G	I106T	1.000
11:67507009:A:T	I106N	1.000
11:67507365:C:G	G105R	1.000
11:67507366:T:A	R104S	1.000
11:67507366:T:G	R104S	1.000
11:67507367:C:A	R104I	1.000
11:67507367:C:G	R104T	1.000
11:67507369:C:A	K103N	1.000
11:67507369:C:G	K103N	1.000
11:67507370:T:A	K103M	1.000
11:67507370:T:G	K103T	1.000
11:67507371:T:C	K103E	1.000

dbSNP variants (sampled 300 via entrez): RS1000237982 (11:67506625 G>A), RS1001087835 (11:67508677 G>A), RS1001408108 (11:67506914 G>C), RS1001616827 (11:67509056 C>A,T), RS1002006168 (11:67507225 A>G), RS1003073960 (11:67508648 C>A,T), RS1004011293 (11:67510082 T>A,C), RS1004376072 (11:67506347 G>A,T), RS1005552231 (11:67507963 C>A,G,T), RS1006143025 (11:67507269 T>C), RS1006503306 (11:67507721 G>A), RS1007067952 (11:67508352 CG>C), RS1007529988 (11:67508142 C>T), RS1007671902 (11:67508172 G>A,C), RS1008122353 (11:67509145 C>T)

Disease associations

OMIM: gene MIM:620061 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6010 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	4
bisphenol A	affects expression, decreases expression	2
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Cisplatin	decreases expression, increases expression	2
Nickel	increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tunicamycin	increases expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Thapsigargin	increases expression	2
dicrotophos	increases expression	1
beauvericin	decreases expression	1
methyleugenol	decreases expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
licochalcone B	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	affects cotreatment, increases expression	1
Fluvastatin	increases expression, affects cotreatment	1
Air Pollutants	increases abundance, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL966739	Binding	Inhibition of Cdk2	Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling. — Proc Natl Acad Sci U S A

Clinical trials (associated diseases)

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