CDC25A

Summary

CDC25A (cell division cycle 25A, HGNC:1725) is a protein-coding gene on chromosome 3p21.31, encoding M-phase inducer phosphatase 1 (P30304). Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression. It is a selective cancer dependency (DepMap: 14.8% of cell lines).

CDC25A is a member of the CDC25 family of phosphatases. CDC25A is required for progression from G1 to the S phase of the cell cycle. It activates the cyclin-dependent kinase CDC2 by removing two phosphate groups. CDC25A is specifically degraded in response to DNA damage, which prevents cells with chromosomal abnormalities from progressing through cell division. CDC25A is an oncogene, although its exact role in oncogenesis has not been demonstrated. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 993 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 67 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 14.8% of screened cell lines
• MANE Select transcript: NM_001789

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1725
Approved symbol	CDC25A
Name	cell division cycle 25A
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164045
Ensembl biotype	protein_coding
OMIM	116947
Entrez	993

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000302506, ENST00000351231, ENST00000437972, ENST00000443342, ENST00000459900, ENST00000880434, ENST00000880435

RefSeq mRNA: 2 — MANE Select: NM_001789 NM_001789, NM_201567

CCDS: CCDS2760, CCDS2761

Canonical transcript exons

ENST00000302506 — 15 exons

Exon	Start	End
ENSE00001080839	48174284	48174457
ENSE00001080840	48183800	48183836
ENSE00001080844	48164307	48164437
ENSE00001080846	48186703	48186779
ENSE00001080848	48177371	48177442
ENSE00001080851	48180721	48180840
ENSE00001080854	48177854	48177988
ENSE00001171814	48184653	48184695
ENSE00001171824	48159344	48159455
ENSE00001293060	48157146	48159085
ENSE00003560329	48165831	48165893
ENSE00003588556	48167846	48167944
ENSE00003680580	48165636	48165734
ENSE00003787803	48182929	48183030
ENSE00003891824	48187778	48188417

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 95.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7658 / max 158.8640, expressed in 1124 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42100	8.7658	1124

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.33	gold quality
buccal mucosa cell	CL:0002336	91.53	gold quality
oocyte	CL:0000023	90.29	gold quality
embryo	UBERON:0000922	86.24	gold quality
sperm	CL:0000019	86.06	gold quality
ventricular zone	UBERON:0003053	85.60	gold quality
trabecular bone tissue	UBERON:0002483	85.30	gold quality
male germ cell	CL:0000015	84.52	silver quality
ganglionic eminence	UBERON:0004023	83.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.13	gold quality
bone marrow	UBERON:0002371	80.85	gold quality
gingival epithelium	UBERON:0001949	80.49	silver quality
esophagus squamous epithelium	UBERON:0006920	79.45	silver quality
squamous epithelium	UBERON:0006914	79.18	silver quality
adrenal tissue	UBERON:0018303	78.15	gold quality
bone marrow cell	CL:0002092	78.01	gold quality
tongue squamous epithelium	UBERON:0006919	77.87	gold quality
gingiva	UBERON:0001828	77.30	silver quality
epithelium of esophagus	UBERON:0001976	76.95	silver quality
testis	UBERON:0000473	76.51	gold quality
left testis	UBERON:0004533	75.62	gold quality
right testis	UBERON:0004534	75.42	gold quality
palpebral conjunctiva	UBERON:0001812	75.01	silver quality
eye	UBERON:0000970	74.80	silver quality
amniotic fluid	UBERON:0000173	74.13	silver quality
pigmented layer of retina	UBERON:0001782	74.04	gold quality
mucosa of transverse colon	UBERON:0004991	73.56	gold quality
cervix squamous epithelium	UBERON:0006922	73.29	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	73.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF3, CDKN1A, E2F1, E2F4, ESR1, FOXM1, HIF1A, HMGA1, LIN28A, MSC, MYC, NANOG, NFYA, SMAD3, SP1, SP3, SP4, STAT3, TP53, TP63, TP73

miRNA regulators (miRDB)

126 targeting CDC25A, 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-3163	100.00	77.23	8605
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 14.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• human papillomavirus type 16 E7 maintains elevated levels of the cdc25A tyrosine phosphatase during deregulation of cell cycle arrest (PMID:11752153)
• examination of catalytic mechanism (PMID:11805096)
• Identification of epidermal growth factor receptor as a target of Cdc25A protein phosphatase (PMID:11912208)
• propose that a dual mechanism of regulated degradation allows for fine tuning of Cdc25 A abundance in response to cell environment (PMID:12234927)
• findings indicate that Chk1 directly phosphorylates Cdc25A during an unperturbed cell cycle, and that phosphorylation of Cdc25A by Chk1 is required for cells to delay cell cycle progression in response to double-strand DNA breaks (PMID:12399544)
• description of a markedly stable form of Cdc25A, which plays a previously unrecognized role in mitosis (PMID:12411508)
• CHK1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A. (PMID:12676583)
• Cdc25A is involved in the G2/M transition in addition to its commonly accepted effect on G1/S progression (PMID:12676925)
• Overexpression of CDC25A phosphatase is associated with hypergrowth activity of hepatocellular carcinomas (PMID:12738732)
• phosphorylation of Cdc25A on Ser-75 by Chk1 and its subsequent degradation is required to delay cell cycle progression in response to UV-induced DNA lesions (PMID:12759351)
• regulation of half life in interphase by cyclin-dependent kinase 2 activity (PMID:12801928)
• regulation of human Cdc25A stability by its phosphorylation at S75 may contribute to S phase checkpoint activation (PMID:12963847)
• CDC25A that accumulated during mitosis is rapidly destroyed after DNA damage (PMID:14517313)
• Data suggest that the Chk1/Cdc25A/14-3-3 pathway functions to prevent cells from entering into mitosis prior to replicating their genomes to ensure the fidelity of the cell division process. (PMID:14559997)
• beta-TrCP has a crucial role in mediating the response to DNA damage through Cdc25A degradation (PMID:14603323)
• CDC25A regulates Raf-1/MEK/Erk activation in human prostate cancer cells (PMID:14673957)
• CDC25A is able to partially restore a functional checkpoint in response to both ionising and UV irradiation, but not a DNA replication checkpoint (PMID:14727060)
• cdc25A may contribute to the progression of thyroid lymphoma (PMID:14767575)
• Cdc25A phosphatase may interact with substrates and regulators both in the nucleus and the cytoplasm. (PMID:15572030)
• Ubiquitination and degradation of CDC25A protein depend on the TGF-beta-Smad3 pathway. (PMID:15798217)
• both genomic and non-genomic pathways of estrogen action are involved in induction of cdc25A in breast cancer cells (PMID:16598773)
• decreased CDC25A is associated with spermatogenic failure and failed sperm retrieval in infertile men (PMID:16720623)
• the Chk1-mediated S-phase checkpoint targets initiation factor Cdc45 via a Cdc25A/Cdk2-independent mechanism (PMID:16912045)
• data suggest that, as long as p53 is intact, Cdc25A transcriptional downregulation might play a role in cancer prevention (PMID:17001315)
• Caulibugulone inhibition of cellular Cdc25A and B phosphatases occurred through at least two different mechanisms, leading to pronounced cell cycle arrest. (PMID:17018577)
• Cdc14A may be involved in the cell cycle regulation of Cdc25A stability. (PMID:17172867)
• Arsenite slows S phase progression via inhibition of cdc25A dual specificity phosphatase gene transcription. (PMID:17545210)
• hypoxia inhibits the expression of CDC25A, another cell cycle gene encoding a tyrosine phosphatase that maintains CDK2 activity (PMID:17671423)
• protein kinase CK2 is involved in cell cycle regulation and indicate the mechanism by which CDC25A turnover might be regulated by Chk1 in the absence of DNA damage. (PMID:17912454)
• CDC25A is not only a major regulator of both G(1)/S and G(2)/M transition during unperturbed cell cycle progression, but also a critical checkpoint mediator.[review] (PMID:18073536)
• Glycogen synthase kinase-3beta (GSK-3beta) phosphorylates Cdc25A to promote its proteolysis in early cell-cycle phases. (PMID:18167338)
• These results suggest that CDC25A, by inhibiting hepatocellular carcinoma (HCC) growth and invasion, may be a feasible therapeutic target for human HCC. (PMID:18204780)
• restricting CDC25A can limit tumorigenesis induced by the HER2/neu-RAS oncogenic pathway without compromising normal cell division or viability [review] (PMID:18316586)
• Chk1 is the primary signal transducer linking activation of the ATM/ATR kinases to Cdc25A destruction in response to ionizing radiation. (PMID:18480045)
• CDC25A overexpression in hTERT-immortalized primary human mammary epithelial cells induces DNA damage response alterations that might enhance genomic instability. (PMID:18566993)
• Data reveal novel *NO-dependent enzymatic and translational mechanisms controlling Cdc25A, and implicate Cdc25A as a mediator of *NO-dependent apoptotic signaling. (PMID:18794133)
• A caspase-dependent cleavage of CDC25A is a central step linking cyclin-dependent kinase 2 activation with non-genotoxic apoptotic induction. (PMID:18927589)
• Metastatic HCC cells showed a defective S-M checkpoint following cisplatin treatment and potential aberrant checkpoint adaptation, which might result from deregulation of Plk1-Cdc25A pathway. (PMID:18980975)
• The authors report here that CDC25A, a cell cycle-promoting phosphatase over-expressed in a number of cancers, functions as an androgen receptor (AR) coregulator suppressing the AR transcriptional activity. (PMID:19013180)
• Chk1 affects Cdc25A via rapid phosphorylation and protein turnover, inhibition of Cdc25A transcription by p53-ATF3 is required for the maintenance of cell cycle arrest. (PMID:19060337)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdc25b	ENSDARG00000010792
danio_rerio	cdc25d	ENSDARG00000075599
mus_musculus	Cdc25a	ENSMUSG00000032477
rattus_norvegicus	Cdc25a	ENSRNOG00000020737
drosophila_melanogaster	twe	FBGN0002673
drosophila_melanogaster	stg	FBGN0003525
caenorhabditis_elegans		WBGENE00000387
caenorhabditis_elegans		WBGENE00000388

Paralogs (2): CDC25B (ENSG00000101224), CDC25C (ENSG00000158402)

Protein

Protein identifiers

M-phase inducer phosphatase 1 — P30304 (reviewed: P30304)

Alternative names: Dual specificity phosphatase Cdc25A

All UniProt accessions (5): C9JFR5, C9JH94, D8KXX0, P30304, K7N7S0

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression. Directly dephosphorylates CDK1 and stimulates its kinase activity. Also dephosphorylates CDK2 in complex with cyclin-E, in vitro.

Subunit / interactions. Interacts with CCNB1/cyclin B1. Interacts with YWHAE/14-3-3 epsilon when phosphorylated. Interacts with CUL1 specifically when CUL1 is neddylated and active. Interacts with BTRC/BTRCP1 and FBXW11/BTRCP2. Interactions with CUL1, BTRC and FBXW11 are enhanced upon DNA damage. Interacts with CHEK2; mediates CDC25A phosphorylation and degradation in response to infrared-induced DNA damages. Interacts with HSP90AB1; prevents heat shock-mediated CDC25A degradation and contributes to cell cycle progression.

Post-translational modifications. Phosphorylated by CHEK1 on Ser-76, Ser-124, Ser-178, Ser-279, Ser-293 and Thr-507 during checkpoint mediated cell cycle arrest. Also phosphorylated by CHEK2 on Ser-124, Ser-279, and Ser-293 during checkpoint mediated cell cycle arrest. Phosphorylation on Ser-178 and Thr-507 creates binding sites for YWHAE/14-3-3 epsilon which inhibits CDC25A. Phosphorylation on Ser-76, Ser-124, Ser-178, Ser-279 and Ser-293 may also promote ubiquitin-dependent proteolysis of CDC25A by the SCF complex. Phosphorylation of CDC25A at Ser-76 by CHEK1 primes it for subsequent phosphorylation at Ser-79, Ser-82 and Ser-88 by NEK11. Phosphorylation by NEK11 is required for BTRC-mediated polyubiquitination and degradation. Phosphorylation by PIM1 leads to an increase in phosphatase activity. Phosphorylated by PLK3 following DNA damage, leading to promote its ubiquitination and degradation. Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex that contains FZR1/CDH1 during G1 phase leading to its degradation by the proteasome. Ubiquitinated by a SCF complex containing BTRC and FBXW11 during S phase leading to its degradation by the proteasome. Deubiquitination by USP17L2/DUB3 leads to its stabilization.

Activity regulation. Stimulated by B-type cyclins. Stimulated by PIM1-mediated phosphorylation.

Domain organisation. The phosphodegron motif mediates interaction with specific F-box proteins when phosphorylated. Putative phosphorylation sites at Ser-79 and Ser-82 appear to be essential for this interaction.

Similarity. Belongs to the MPI phosphatase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P30304-1	1, CDC25A1	yes
P30304-2	2, CDC25A2

RefSeq proteins (2): NP_001780, NP_963861 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000751	MPI_Phosphatase	Family
IPR001763	Rhodanese-like_dom	Domain
IPR036873	Rhodanese-like_dom_sf	Homologous_superfamily

Pfam: PF00581, PF06617

Enzyme classification (BRENDA):

• EC 3.1.3.48 — protein-tyrosine-phosphatase (BRENDA: 59 organisms, 501 substrates, 1326 inhibitors, 270 Km, 165 kcat entries)

Substrate kinetics (BRENDA)

70 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-NITROPHENYL PHOSPHATE	0.0008–148	84
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.0039–0.862	27
P-NITROPHENYL PHOSPHATE	0.0024–10	20
DADEPYLIPQQG	0.0003–0.1	12
PHOSPHOTYROSINE	0.012–30	11
LYSOZYME	0.0003–0.012	5
MYELIN BASIC PROTEIN	0.0001–0.022	5
ACETYL-DADEPY-NH2	0.0228–0.219	4
ACETYL-DADEPYL-NH2	1.1–97.5	4
4,6,8-TRIMETHYL-2-OXO-2H-CHROMEN-7-YL DIHYDROGEN	0.02–0.156	3
SASASPYSASA	0.53–2.3	3
1-NAPHTHYL PHOSPHATE	1.19–1.88	2
3,6-FLUORESCEIN DIPHOSPHATE	15–19	2
4-METHYLUMBELLIFERYL PHOSPHATE	0.953–2.41	2
BOVINE SERUM ALBUMIN	0.0001–0.0003	2

Catalyzed reactions (Rhea), 1 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)

UniProt features (60 total): mutagenesis site 17, modified residue 13, strand 8, helix 7, sequence variant 3, short sequence motif 2, sequence conflict 2, turn 2, chain 1, domain 1, region of interest 1, splice variant 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1C25	X-RAY DIFFRACTION	2.3
8ROZ	ELECTRON MICROSCOPY	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30304-F1	63.93	0.32

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): 431

Post-translational modifications (13): 88, 107, 124, 178, 279, 293, 321, 507, 513, 519, 76, 79, 82

Mutagenesis-validated functional residues (17):

Position	Phenotype
76	abolishes ubiquitination and impairs chek1-dependent degradation following checkpoint activation.
79	abrogates interactions with btrc and fbxw11 and prevents ubiquitination.
81	abrogates interactions with btrc and fbxw11 and prevents ubiquitination.
82	abrogates interactions with btrc and fbxw11 and prevents ubiquitination.
124	abrogates phosphorylation by chek2 and infrared-induced degradation. increases basal stability and impairs chek1-depende
141–143	prevents ubiquitination and subsequent degradation by the apc/c ubiquitin ligase complex.
178	increases basal stability and impairs chek1-dependent degradation following checkpoint activation; when associated with
279	increases basal stability and impairs chek1-dependent degradation following checkpoint activation; when associated with
293	increases basal stability and impairs chek1-dependent degradation following checkpoint activation; when associated with
431	abolishes phosphatase activity.
507	abrogates 14-3-3 protein binding; increases binding to cyclin b1.
513	increased stability following ir treatment.
513	mimicks phosphorylation state, leading to promote degradation following ir treatment.
514	abrogates binding to ccnb1; when associated with l-520.
519	increased stability following ir treatment.
519	mimicks phosphorylation state, leading to promote degradation following ir treatment.
520	abrogates binding to ccnb1; when associated with l-514.

Function

Pathways and Gene Ontology

Reactome pathways

30 pathways

ID	Pathway
R-HSA-1362277	Transcription of E2F targets under negative control by DREAM complex
R-HSA-156711	Polo-like kinase mediated events
R-HSA-176187	Activation of ATR in response to replication stress
R-HSA-5689880	Ub-specific processing proteases
R-HSA-69202	Cyclin E associated events during G1/S transition
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-69601	Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry
R-HSA-8862803	Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models
R-HSA-69205	G1/S-Specific Transcription
R-HSA-1538133	G0 and Early G1
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-392499	Metabolism of proteins
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-453279	Mitotic G1 phase and G1/S transition
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification
R-HSA-69206	G1/S Transition
R-HSA-69242	S Phase
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69481	G2/M Checkpoints
R-HSA-69610
R-HSA-69613	p53-Independent G1/S DNA Damage Checkpoint
R-HSA-69615	G1/S DNA Damage Checkpoints
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-8863678	Neurodegenerative Diseases
R-HSA-9645723	Diseases of programmed cell death
R-HSA-9734009	Defective Intrinsic Pathway for Apoptosis

MSigDB gene sets: 415 (showing top): E2F_Q4, SA_G2_AND_M_PHASES, E2F_Q4_01, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, REACTOME_G1_S_SPECIFIC_TRANSCRIPTION, E2F4DP1_01, GOBP_REGULATION_OF_PHOSPHORYLATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, FISCHER_G1_S_CELL_CYCLE, BIOCARTA_SRCRPTP_PATHWAY, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP

GO Biological Process (13): regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079), G1/S transition of mitotic cell cycle (GO:0000082), G2/M transition of mitotic cell cycle (GO:0000086), cell population proliferation (GO:0008283), response to radiation (GO:0009314), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), positive regulation of DNA replication (GO:0045740), cell division (GO:0051301), positive regulation of G2/MI transition of meiotic cell cycle (GO:0110032), protein dephosphorylation (GO:0006470), nuclear envelope organization (GO:0006998), mitotic nuclear membrane disassembly (GO:0007077), positive regulation of cell cycle G2/M phase transition (GO:1902751)

GO Molecular Function (6): phosphoprotein phosphatase activity (GO:0004721), protein tyrosine phosphatase activity (GO:0004725), protein kinase binding (GO:0019901), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Cell Cycle, Mitotic	3
G2/M Transition	2
G1/S Transition	2
Mitotic G1 phase and G1/S transition	2
G0 and Early G1	1
G2/M Checkpoints	1
Deubiquitination	1
p53-Independent G1/S DNA Damage Checkpoint	1
S Phase	1
Neurodegenerative Diseases	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic cell cycle	3
cellular anatomical structure	3
mitotic cell cycle phase transition	2
cell cycle G2/M phase transition	2
cellular process	2
positive regulation of cell cycle G2/M phase transition	2
cyclin-dependent protein serine/threonine kinase activity	1
regulation of protein serine/threonine kinase activity	1
cell cycle G1/S phase transition	1
response to abiotic stimulus	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
DNA replication	1
regulation of DNA replication	1
positive regulation of DNA metabolic process	1
G2/MI transition of meiotic cell cycle	1
regulation of G2/MI transition of meiotic cell cycle	1
positive regulation of meiotic cell cycle phase transition	1
dephosphorylation	1
protein modification process	1
nucleus organization	1
endomembrane system organization	1
membrane organization	1
nuclear membrane disassembly	1
mitotic cell cycle process	1
positive regulation of cell cycle phase transition	1
regulation of cell cycle G2/M phase transition	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
kinase binding	1
protein binding	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC25A	CHEK2	O96017	949
CDC25A	CHEK1	O14757	944
CDC25A	CDK2	P24941	933
CDC25A	BRCA1	P38398	911
CDC25A	CDC45	O75419	896
CDC25A	CDK1	P06493	859
CDC25A	TP53	P04637	858
CDC25A	ATM	Q13315	857
CDC25A	WEE1	P30291	831
CDC25A	CDK6	Q00534	806
CDC25A	CCNB1	P14635	804
CDC25A	MYC	P01106	797
CDC25A	CCNL2	Q96S94	791
CDC25A	BOLL	Q8N9W6	773
CDC25A	E2F1	Q01094	762

IntAct

74 interactions, top by confidence:

A	B	Type	Score
YWHAB	RAF1	psi-mi:“MI:0915”(physical association)	0.960
CDC25A	FBXW11	psi-mi:“MI:0914”(association)	0.820
FBXW11	CDC25A	psi-mi:“MI:0915”(physical association)	0.820
BTRC	CDC25A	psi-mi:“MI:0915”(physical association)	0.810
BTRC	CDC25A	psi-mi:“MI:0407”(direct interaction)	0.810
BTRC	CDC25A	psi-mi:“MI:0220”(ubiquitination reaction)	0.810
KPNA4	MYC	psi-mi:“MI:0915”(physical association)	0.780
YWHAE	CDC25A	psi-mi:“MI:0915”(physical association)	0.760
YWHAB	CDC25A	psi-mi:“MI:0915”(physical association)	0.700
CDC25A	YWHAB	psi-mi:“MI:0915”(physical association)	0.700
CDC25A	YWHAZ	psi-mi:“MI:0915”(physical association)	0.660
CDC25A	YWHAZ	psi-mi:“MI:0407”(direct interaction)	0.660
FBXW11	EEF2K	psi-mi:“MI:0914”(association)	0.640
CHEK2	CDC25A	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
CDC25A	YWHAQ	psi-mi:“MI:2364”(proximity)	0.570
YWHAQ	CDC25A	psi-mi:“MI:0914”(association)	0.570
CDC25A	NAA11	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CDC25A	CHEK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (287): CDC25A (Affinity Capture-MS), CDC25A (Affinity Capture-MS), SKP1 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), CDC25A (Reconstituted Complex), CDC25A (Affinity Capture-RNA), CDC25A (Biochemical Activity), CDC25A (Biochemical Activity), CDC25A (Biochemical Activity), CDC25A (Affinity Capture-MS), CDC25A (Affinity Capture-MS), NAA10 (Two-hybrid), CDC25A (Affinity Capture-MS), CDC25A (Affinity Capture-MS), CDC25A (Proximity Label-MS)

ESM2 similar proteins: A0JM98, A1L1H3, A4IGY9, A5D7P0, A5PLL1, A7MBD1, B2RWW0, D3ZF42, O75113, O88866, P12525, P30304, P30305, P30306, P30307, P30308, P30309, P30310, P30311, P48964, P48965, P48966, P48967, P48968, P57058, Q29029, Q4G163, Q56NI9, Q5QJC4, Q5SW75, Q66JT0, Q68UT7, Q6GQJ2, Q6IE82, Q6P1H6, Q6PCM1, Q6PJP8, Q6S7F2, Q6YI93, Q76I76

Diamond homologs: A5D7P0, A7MBD1, O44552, O44628, P06652, P20483, P23748, P30303, P30304, P30305, P30306, P30307, P30308, P30309, P30310, P30311, P30634, P48964, P48965, P48966, P48967, P48968, Q03019, Q29029, Q54QM6, Q8WZK3, P54510

SIGNOR signaling

74 interactions.

A	Effect	B	Mechanism
CHEK2	“down-regulates quantity by destabilization”	CDC25A	phosphorylation
BTRC	up-regulates	CDC25A	ubiquitination
CDC25A	down-regulates	MAPK3	dephosphorylation
CDK2	down-regulates	CDC25A	phosphorylation
MAPKAPK2	down-regulates	CDC25A	phosphorylation
PLK3	down-regulates	CDC25A	phosphorylation
CHEK1	down-regulates	CDC25A	phosphorylation
CSNK1A1	down-regulates	CDC25A	phosphorylation
GSK3B	“down-regulates quantity by repression”	CDC25A	phosphorylation
NEK11	down-regulates	CDC25A	phosphorylation
CDC25A	up-regulates	CDK2	dephosphorylation
RPS6KA1	down-regulates	CDC25A	phosphorylation
CyclinB/CDK1	up-regulates	CDC25A	phosphorylation
SCF-betaTRCP	up-regulates	CDC25A	ubiquitination
SMAD3	“down-regulates quantity by repression”	CDC25A	“transcriptional regulation”
CDC25A	“up-regulates activity”	CDK2	dephosphorylation
CDC25A	“up-regulates activity”	CyclinE/CDK2	dephosphorylation
CDC25A	“up-regulates activity”	CyclinD/CDK4	dephosphorylation
MYC	“up-regulates quantity by expression”	CDC25A	“transcriptional regulation”
E2F1	“up-regulates quantity by expression”	CDC25A	“transcriptional regulation”
CDC25A	“up-regulates activity”	CDK1	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	125.0×	2e-13
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	93.7×	5e-09
Activation of BAD and translocation to mitochondria	5	88.5×	2e-07
Activation of BH3-only proteins	5	57.7×	1e-06
RHO GTPases activate PKNs	5	36.9×	1e-05
Intrinsic Pathway for Apoptosis	5	34.0×	2e-05
G2/M DNA damage checkpoint	9	25.2×	9e-09
SARS-CoV-1-host interactions	6	24.5×	9e-06

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein localization	8	16.1×	2e-05
MAPK cascade	5	14.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	44
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1255549	NM_001789.3(CDC25A):c.263C>T (p.Ser88Phe)	Likely pathogenic

SpliceAI

1768 predictions. Top by Δscore:

Variant	Effect	Δscore
3:48159081:TAAGA:T	acceptor_gain	1.0000
3:48159082:AAGA:A	acceptor_gain	1.0000
3:48159083:AGA:A	acceptor_gain	1.0000
3:48159084:GA:G	acceptor_gain	1.0000
3:48159085:AC:A	acceptor_loss	1.0000
3:48159086:C:CC	acceptor_gain	1.0000
3:48159086:CTGA:C	acceptor_loss	1.0000
3:48159087:T:G	acceptor_loss	1.0000
3:48159338:TCTTA:T	donor_loss	1.0000
3:48159339:CTTAC:C	donor_loss	1.0000
3:48159340:TTACC:T	donor_loss	1.0000
3:48159341:TACC:T	donor_loss	1.0000
3:48159343:C:CT	donor_loss	1.0000
3:48159453:CAC:C	acceptor_gain	1.0000
3:48159454:ACCTA:A	acceptor_loss	1.0000
3:48159455:CCTA:C	acceptor_loss	1.0000
3:48159456:C:A	acceptor_loss	1.0000
3:48159457:T:A	acceptor_loss	1.0000
3:48159461:C:CT	acceptor_gain	1.0000
3:48159462:A:T	acceptor_gain	1.0000
3:48164305:A:AC	donor_gain	1.0000
3:48164306:C:CC	donor_gain	1.0000
3:48164306:CATG:C	donor_gain	1.0000
3:48164434:CACC:C	acceptor_gain	1.0000
3:48164436:CC:C	acceptor_gain	1.0000
3:48164437:CC:C	acceptor_gain	1.0000
3:48164437:CCTG:C	acceptor_loss	1.0000
3:48164438:C:CC	acceptor_gain	1.0000
3:48164438:C:CG	acceptor_loss	1.0000
3:48164439:T:A	acceptor_loss	1.0000

AlphaMissense

3463 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:48159015:C:G	R502P	1.000
3:48159027:A:G	L498P	1.000
3:48159038:A:C	F494L	1.000
3:48159038:A:T	F494L	1.000
3:48159040:A:G	F494L	1.000
3:48159053:C:A	M489I	1.000
3:48159053:C:G	M489I	1.000
3:48159053:C:T	M489I	1.000
3:48159054:A:G	M489T	1.000
3:48159372:C:A	G469V	1.000
3:48159372:C:T	G469E	1.000
3:48159381:A:G	L466P	1.000
3:48159400:A:C	Y460D	1.000
3:48159405:A:G	L458P	1.000
3:48159415:A:G	Y455H	1.000
3:48159429:C:G	R450P	1.000
3:48159430:G:T	R450S	1.000
3:48159440:T:A	R446S	1.000
3:48159440:T:G	R446S	1.000
3:48159441:C:A	R446I	1.000
3:48159441:C:G	R446T	1.000
3:48164316:C:T	G438D	1.000
3:48164318:T:A	R437S	1.000
3:48164318:T:G	R437S	1.000
3:48164319:C:A	R437I	1.000
3:48164319:C:G	R437T	1.000
3:48164330:A:C	F433L	1.000
3:48164330:A:T	F433L	1.000
3:48164331:A:G	F433S	1.000
3:48164332:A:G	F433L	1.000

dbSNP variants (sampled 300 via entrez): RS1000072837 (3:48157711 TA>T), RS1000190056 (3:48185230 T>C), RS1000252284 (3:48164882 C>A,T), RS1000392875 (3:48171113 T>G), RS1000428241 (3:48172471 A>C), RS1000527377 (3:48183543 G>A), RS1000559914 (3:48184033 A>C), RS1000586274 (3:48166642 T>C), RS1000718804 (3:48169660 G>A), RS1000812026 (3:48178564 T>A,C), RS1000818330 (3:48158163 T>C), RS1001010588 (3:48186119 A>C), RS1001468933 (3:48187236 G>A,C), RS1001483048 (3:48164142 G>A,T), RS1001526961 (3:48185814 G>C)

Disease associations

OMIM: gene MIM:116947 | disease phenotypes: MIM:174050

GenCC curated gene-disease

Mondo (1): autosomal dominant polycystic liver disease (MONDO:0000447)

Orphanet (1): Isolated polycystic liver disease (Orphanet:2924)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0006557	Polycystic liver disease

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST003773_13	Loneliness (multivariate analysis)	4.000000e-06
GCST005195_100	Coronary artery disease	3.000000e-11
GCST005196_104	Coronary artery disease	2.000000e-11
GCST006021_20	Systolic blood pressure	6.000000e-08
GCST007094_202	Diastolic blood pressure	4.000000e-17
GCST007095_30	Systolic blood pressure	5.000000e-07
GCST007096_132	Pulse pressure	3.000000e-06
GCST007098_41	Diastolic blood pressure	5.000000e-06
GCST007099_260	Systolic blood pressure	3.000000e-16
GCST007927_5	Medication use (beta blocking agents)	6.000000e-09
GCST007928_44	Medication use (diuretics)	5.000000e-08
GCST007930_35	Medication use (agents acting on the renin-angiotensin system)	3.000000e-13
GCST009524_104	Household income (MTAG)	2.000000e-08
GCST010242_209	HDL cholesterol levels	6.000000e-09
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST010989_217	Body size at age 10	7.000000e-14
GCST90020024_1142	A body shape index	4.000000e-10
GCST90020029_1170	Waist circumference adjusted for body mass index	3.000000e-11

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0007865	loneliness measurement
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0009929	Beta blocking agent use measurement
EFO:0009928	Diuretic use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009695	household income
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004346	neuroimaging measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3775 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 63,448 (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
CHEMBL125	MILTEFOSINE	4	24,203
CHEMBL590	MENADIONE	4	21,034
CHEMBL15245	YOHIMBINE	3	11,917
CHEMBL85943	SODIUM TUNGSTATE	2
CHEMBL295316	PLUMBAGIN	1	6,294

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

Binding affinities (BindingDB)

1 measured of 19 human assays (19 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
NSC-95397	IC50	12700 nM

ChEMBL bioactivities

230 potent at pChembl≥5 of 378 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.66	IC50	22	nM	CHEMBL429095
7.64	IC50	23	nM	CHEMBL5271462
7.64	IC50	23	nM	CHEMBL5288122
7.54	Ki	29	nM	CHEMBL337173
7.30	IC50	50	nM	CHEMBL189010
7.26	IC50	55	nM	CHEMBL429095
7.16	Ki	70	nM	CHEMBL1481974
7.14	Ki	72	nM	CHEMBL2000194
6.96	IC50	110	nM	CHEMBL2000194
6.82	IC50	150	nM	CHEMBL5423941
6.66	IC50	220	nM	SHIKONIN
6.62	IC50	240	nM	CHEMBL1481974
6.60	IC50	250	nM	CHEMBL1765351
6.48	IC50	330	nM	CHEMBL1481974
6.36	IC50	440	nM	CHEMBL109990
6.36	IC50	440	nM	CHEMBL1765356
6.32	IC50	480	nM	CHEMBL111717
6.28	IC50	530	nM	CHEMBL4521092
6.27	IC50	540	nM	CHEMBL4566962
6.22	Ki	600	nM	CHEMBL4570006
6.22	Ki	600	nM	CHEMBL4442406
6.19	IC50	650	nM	CHEMBL1967787
6.16	IC50	700	nM	CHEMBL182645
6.16	IC50	700	nM	PLUMBAGIN
6.16	IC50	700	nM	CHEMBL354794
6.10	IC50	790	nM	CHEMBL337173
6.10	IC50	800	nM	CHEMBL1765355
6.10	IC50	800	nM	CHEMBL459929
6.09	IC50	820	nM	CHEMBL459929
6.07	IC50	860	nM	CHEMBL109588
6.05	IC50	900	nM	CHEMBL179992
6.05	IC50	890	nM	CHEMBL432780
6.05	IC50	890	nM	CHEMBL110952
6.05	IC50	900	nM	CHEMBL354215
6.00	IC50	1000	nM	CHEMBL87763
6.00	IC50	1000	nM	CHEMBL87872
6.00	IC50	1000	nM	CHEMBL1165659
5.96	IC50	1100	nM	CHEMBL169020
5.92	IC50	1200	nM	CHEMBL4066424
5.92	IC50	1200	nM	CHEMBL4466461
5.91	IC50	1240	nM	CHEMBL337173
5.88	IC50	1330	nM	CHEMBL200117
5.85	IC50	1400	nM	CHEMBL429095
5.82	IC50	1500	nM	CHEMBL4093222
5.82	IC50	1500	nM	CHEMBL100206
5.80	IC50	1600	nM	CHEMBL521835
5.79	IC50	1610	nM	CHEMBL4097725
5.78	IC50	1680	nM	CHEMBL5278031
5.77	Ki	1700	nM	CHEMBL2057662
5.77	IC50	1700	nM	CHEMBL493800

PubChem BioAssay actives

209 with measured affinity, of 574 total; 50 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
2,3-bis(2-hydroxyethylsulfanyl)naphthalene-1,4-dione	593355: Inhibition of human Cdc25A	ic50	0.0220	uM
5-[2-(dimethylamino)ethylamino]-2-methyl-1,3-benzothiazole-4,7-dione	1942248: Inhibition of recombinant CDC25A (unknown origin)	ic50	0.0230	uM
2-(2,5-difluorophenyl)-6-[2-(dimethylamino)ethylamino]-1,3-benzoxazole-4,7-dione	1942248: Inhibition of recombinant CDC25A (unknown origin)	ic50	0.0230	uM
6-chloro-7-(2-morpholin-4-ylethylamino)quinoline-5,8-dione	593355: Inhibition of human Cdc25A	ki	0.0290	uM
2-(1,4-dioxonaphthalen-2-yl)sulfanylacetic acid	1517763: Inhibition of recombinant Cdc25A (unknown origin) using OMFP as substrate measured every 30 sec for 10 mins by fluorometric assay	ic50	0.0500	uM
3-(3,4,5-trihydroxy-6-oxoxanthen-9-yl)propanoic acid	673294: Inhibition of recombinant phosphatase activity of Cdc25A catalytic domain expressed in Escherichia coli BL21(DE3) using OMFP as substrate by Lineweaver-Burk plot analysis	ki	0.0700	uM
6-chloro-7-[1-[1-[4-(hydroxymethyl)phenyl]triazol-4-yl]ethylamino]quinoline-5,8-dione	2009521: Inhibition of full-length recombinant human CDC25A using OMFP as substrate incubated for 5 to 8 mins by fluorescence based assay	ic50	0.1500	uM
5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione	1517763: Inhibition of recombinant Cdc25A (unknown origin) using OMFP as substrate measured every 30 sec for 10 mins by fluorometric assay	ic50	0.2200	uM
5-[2-(dimethylamino)ethylamino]-2,6-dimethyl-1,3-benzothiazole-4,7-dione	593355: Inhibition of human Cdc25A	ic50	0.2500	uM
3-[(1S)-2-[(1R,4S,7aR)-4,7a-dimethyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-yl]-1-hydroxyethyl]-2-hydroxy-2H-furan-5-one	51858: Concentration required to inhibit human Cell division cycle 25A activity	ic50	0.4400	uM
3-[(1S)-2-[(1R,3aS,4S,7aR)-4,7a-dimethyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-yl]-1-hydroxyethyl]-2-hydroxy-2H-furan-5-one	593355: Inhibition of human Cdc25A	ic50	0.4400	uM
3-[(1R)-2-[(1R,4R,7aR)-4,7a-dimethyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-yl]-1-hydroxyethyl]-2-hydroxy-2H-furan-5-one	51858: Concentration required to inhibit human Cell division cycle 25A activity	ic50	0.4800	uM
6-chloro-7-[[1-[(4-methylphenyl)methyl]triazol-4-yl]methylamino]quinoline-5,8-dione	1517349: Inhibition of recombinant human Cdc25A using OMFP as substrate preincubated for 5 to 8 mins and measured every 5 mins 60 mins by fluorescence based assay	ic50	0.5300	uM
3-[[4-[[(6-chloro-5,8-dioxoquinolin-7-yl)amino]methyl]triazol-1-yl]methyl]benzonitrile	1517349: Inhibition of recombinant human Cdc25A using OMFP as substrate preincubated for 5 to 8 mins and measured every 5 mins 60 mins by fluorescence based assay	ic50	0.5400	uM
ethyl 2-(naphthalen-1-ylamino)benzoate	1516498: Inhibition of N-terminal His6-tagged human CDC25A (336 to 508 residues) expressed in Escherichia coli BL21(DE3) cells using OMFP as substrate by double reciprocal Lineweaver-Burk plot analysis	ki	0.6000	uM
3-[(5-aminonaphthalen-1-yl)amino]benzoic acid	1516498: Inhibition of N-terminal His6-tagged human CDC25A (336 to 508 residues) expressed in Escherichia coli BL21(DE3) cells using OMFP as substrate by double reciprocal Lineweaver-Burk plot analysis	ki	0.6000	uM
2-(3-hydroxy-6-oxoxanthen-9-yl)cyclohexane-1-carboxylic acid	1942242: Inhibition of CDC25A (unknown origin)	ic50	0.6500	uM
5-hydroxy-2-methylnaphthalene-1,4-dione	1517763: Inhibition of recombinant Cdc25A (unknown origin) using OMFP as substrate measured every 30 sec for 10 mins by fluorometric assay	ic50	0.7000	uM
2-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]acetic acid	51863: Inhibitory activity tested against cell division cycle 25A (assay using fluorescein diphosphate (FDP) as substrate)	ic50	0.7000	uM
[(1R,4S,7aR)-4,7a-dimethyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-yl]methyl dihydrogen phosphate	241804: Inhibitory concentration against dual-specificity phosphatase Cell division cycle (Cdc) 25A	ic50	0.7000	uM
2-[[4-(4-chlorophenyl)-5-(4-methylphenyl)-1,2,4-triazol-3-yl]sulfanyl]-1-(3,4-dihydroxyphenyl)ethanone	593355: Inhibition of human Cdc25A	ic50	0.8000	uM
(2R)-3-[2-[(1R,2R,5S,8aS)-1,2,5-trimethyl-5-(4-methylpent-4-enyl)-2,3,6,7,8,8a-hexahydronaphthalen-1-yl]acetyl]-2-hydroxy-2H-furan-5-one	593355: Inhibition of human Cdc25A	ic50	0.8000	uM
3-[(1R)-2-[(1R,4S,7aR)-4,7a-dimethyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-yl]-1-hydroxyethyl]-2-hydroxy-2H-furan-5-one	51858: Concentration required to inhibit human Cell division cycle 25A activity	ic50	0.8600	uM
(1S,3Z)-3-[(2E)-2-[(1R,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexan-1-ol	51859: Concentration required to inhibit human Cell division cycle 25A activity; Value ranges from 0.44 uM to 0.89 uM	ic50	0.8900	uM
3-[(1S)-2-[(1R,4R,7aR)-4,7a-dimethyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-yl]-1-hydroxyethyl]-2-hydroxy-2H-furan-5-one	51858: Concentration required to inhibit human Cell division cycle 25A activity	ic50	0.8900	uM
2-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxycarbothioylsulfanyl]acetic acid	51863: Inhibitory activity tested against cell division cycle 25A (assay using fluorescein diphosphate (FDP) as substrate)	ic50	0.9000	uM
[(1R,4R,7aR)-4,7a-dimethyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-yl]methyl dihydrogen phosphate	241804: Inhibitory concentration against dual-specificity phosphatase Cell division cycle (Cdc) 25A	ic50	0.9000	uM
3,4-bis(2-hydroxyethylsulfanyl)-1-(4-phenylphenyl)pyrrole-2,5-dione	593355: Inhibition of human Cdc25A	ic50	1.0000	uM
2,5-dihydroxy-3-[7-[(2-methylphenyl)methyl]-1H-indol-3-yl]cyclohexa-2,5-diene-1,4-dione	51860: Eight point inhibitory concentration against Cell division cycle 25A was determined	ic50	1.0000	uM
3-[7-[(2E)-3,7-dimethylocta-2,6-dienyl]-1H-indol-3-yl]-2,5-dihydroxycyclohexa-2,5-diene-1,4-dione	51860: Eight point inhibitory concentration against Cell division cycle 25A was determined	ic50	1.0000	uM
[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxymethanedithioic acid	51863: Inhibitory activity tested against cell division cycle 25A (assay using fluorescein diphosphate (FDP) as substrate)	ic50	1.1000	uM
8-(diethylamino)naphtho[1,2-c]chromene-1,4,5-trione	1452403: Inhibition of recombinant human full length GST-tagged CDC25A expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	1.2000	uM
2-[[4-[[(6-chloro-5,8-dioxoquinolin-7-yl)amino]methyl]triazol-1-yl]methyl]benzonitrile	1517349: Inhibition of recombinant human Cdc25A using OMFP as substrate preincubated for 5 to 8 mins and measured every 5 mins 60 mins by fluorescence based assay	ic50	1.2000	uM
2-[4-[7-(4-tetradecylbenzoyl)cyclopenta[d]oxazin-4-yl]phenoxy]acetic acid	259931: Inhibitory activity against cdc25A phosphatase	ic50	1.3300	uM
12-oxapentacyclo[12.8.0.02,11.05,10.015,20]docosa-1(14),2(11),3,5,7,9,15(20),17,21-nonaene-13,16,19-trione	1452403: Inhibition of recombinant human full length GST-tagged CDC25A expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	1.5000	uM
3-(1,4-dioxonaphthalen-2-yl)sulfanylpropanoic acid	1517763: Inhibition of recombinant Cdc25A (unknown origin) using OMFP as substrate measured every 30 sec for 10 mins by fluorometric assay	ic50	1.5000	uM
(2Z)-2-(1-hexadecyl-2-oxoindol-3-ylidene)acetic acid	404251: Inhibition of human Cdc25A phosphatase activity	ic50	1.6000	uM
8-chloronaphtho[1,2-c]chromene-1,4,5-trione	1452403: Inhibition of recombinant human full length GST-tagged CDC25A expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	1.6100	uM
7-(furan-2-yl)-5-propan-2-ylindeno[1,2-b]indole-6,9,10-trione	1942242: Inhibition of CDC25A (unknown origin)	ic50	1.6800	uM
(2Z)-2-(2-oxo-1-tetradecylindol-3-ylidene)acetic acid	404251: Inhibition of human Cdc25A phosphatase activity	ic50	1.7000	uM
2-[(1R,3aS,4R,5R,7aR)-5-(6-cyanohexan-2-yl)-7a-methyl-1-(6-methylheptan-2-yl)-1,2,3,3a,4,5,6,7-octahydroinden-4-yl]acetic acid	51863: Inhibitory activity tested against cell division cycle 25A (assay using fluorescein diphosphate (FDP) as substrate)	ic50	1.9000	uM
(2E)-2-(1-hexadecyl-2-oxoindol-3-ylidene)acetic acid	404251: Inhibition of human Cdc25A phosphatase activity	ic50	1.9000	uM
8-methyl-5-propan-2-ylindeno[1,2-b]indole-6,9,10-trione	1942242: Inhibition of CDC25A (unknown origin)	ic50	2.0000	uM
(2R,3R)-2,3-dibromo-3-methyl-1,1-dioxo-2H-thiochromen-4-one	593355: Inhibition of human Cdc25A	ic50	2.0000	uM
7-phenyl-5-propan-2-ylindeno[1,2-b]indole-6,9,10-trione	1942242: Inhibition of CDC25A (unknown origin)	ic50	2.0100	uM
O-[[(3S,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]] N-phenylcarbamothioate	51863: Inhibitory activity tested against cell division cycle 25A (assay using fluorescein diphosphate (FDP) as substrate)	ic50	2.1000	uM
N-(1-benzylpyrrolo[3,2-b]quinoxalin-2-yl)benzenesulfonamide	432342: Inhibition of Cdc25A	ic50	2.1000	uM
8-fluoronaphtho[1,2-c]chromene-1,4,5-trione	1452403: Inhibition of recombinant human full length GST-tagged CDC25A expressed in Escherichia coli BL21-DE3 pLysS using 3-O-methylfluorescein phosphate as substrate after 2 hrs by fluorimetric analysis	ic50	2.1900	uM
2-[(1R,3aS,4R,5S,7aR)-5-(6-cyanohex-1-en-2-yl)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-1,2,3,3a,4,5,6,7-octahydroinden-4-yl]acetic acid	42951: Compound was evaluated for the inhibition of Cdc25A phosphatase by using fluorescein diphosphate as substrate	ic50	2.2000	uM
3-(7-benzyl-1H-indol-3-yl)-2,5-dihydroxycyclohexa-2,5-diene-1,4-dione	51860: Eight point inhibitory concentration against Cell division cycle 25A was determined	ic50	2.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, decreases reaction, increases expression, affects binding, increases reaction (+2 more)	8
Estradiol	decreases reaction, increases expression, decreases phosphorylation	5
(+)-JQ1 compound	affects cotreatment, decreases expression, increases expression	4
Valproic Acid	decreases expression	4
Cyclosporine	decreases expression	4
bisphenol A	affects cotreatment, increases expression, decreases expression	3
Arsenic Trioxide	increases expression	3
Benzo(a)pyrene	decreases methylation, decreases phosphorylation, increases expression, increases methylation, affects reaction	3
Cisplatin	decreases expression, increases expression, affects cotreatment	3
Tobacco Smoke Pollution	decreases expression, increases expression	3
Tretinoin	affects expression, decreases expression	3
lasiocarpine	increases expression, decreases expression, increases metabolic processing	2
methylselenic acid	affects expression, decreases expression	2
ochratoxin A	decreases expression, affects cotreatment	2
chromium hexavalent ion	increases expression, decreases expression, increases abundance	2
Arsenic	increases abundance, increases expression, affects cotreatment	2
Copper	affects binding, increases expression, decreases expression	2
Hydrogen Peroxide	decreases expression, affects expression	2
Nickel	increases expression	2
Silicon Dioxide	increases expression	2
Tetrachlorodibenzodioxin	decreases expression, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
ON123300	increases expression	1
gamabufotalin	decreases expression	1
TAK-243	increases sumoylation	1

ChEMBL screening assays

111 unique, capped per target: 111 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003156	Binding	Inhibition of Cdc25A (336-523) expressed in Escherichia coli at 50 uM	Discovery of novel Cdc25 phosphatase inhibitors with micromolar activity based on the structure-based virtual screening. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KZ69	PathHunter NCI-H460 CDC25A Degradation	Cancer cell line	Male
CVCL_KZ99	PathHunter U2OS CDC25A Degradation	Cancer cell line	Female
CVCL_SI01	HAP1 CDC25A (-) 1	Cancer cell line	Male
CVCL_XM64	HAP1 CDC25A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01157858	PHASE2	COMPLETED	Everolimus and LongActing Octreotide Trial in Polycystic Livers
NCT01670110	PHASE2	COMPLETED	Pasireotide LAR in Severe Polycystic Liver Disease
NCT02021110	PHASE2	COMPLETED	Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease
NCT05478083	PHASE2	RECRUITING	A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease
NCT00426153	PHASE2/PHASE3	COMPLETED	Octreotide in Severe Polycystic Liver Disease
NCT00565097	PHASE2/PHASE3	COMPLETED	Lanreotide as Treatment of Polycystic Livers
NCT00771888	PHASE2/PHASE3	UNKNOWN	Open-Label Extension of LOCKCYST Trial
NCT01315795	PHASE2/PHASE3	COMPLETED	Lanreotide Autogel in the Treatment of Symptomatic Polycystic Liver Disease
NCT05281328	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Assess the Efficacy and Safety of Octreotide Subcutaneous Depot in Patients With PLD
NCT00934791	Not specified	TERMINATED	Polycystic Liver Disease in Kidney Transplant
NCT01354405	Not specified	COMPLETED	Somatostatin Analogues as a Volume Reducing Treatment of Polycystic Livers (RESOLVE)
NCT02173080	Not specified	COMPLETED	Development and Assessment of The Polycystic Liver Disease Questionnaire (PLD-Q).
NCT03960710	Not specified	UNKNOWN	Automatic Segmentation of Polycystic Liver
NCT04111692	Not specified	RECRUITING	A Prospective Observational Study of Foam Sclerotherapy .
NCT04645251	Not specified	RECRUITING	Polycystic Liver Disease Registry (UK)
NCT05215964	Not specified	UNKNOWN	The Association Between Skeletal Muscle Mass and Severity of Polycystic Liver Disease and Polycystic Kidney Disease
NCT05500157	Not specified	UNKNOWN	Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts