CDC14B

Summary

CDC14B (cell division cycle 14B, HGNC:1719) is a protein-coding gene on chromosome 9q22.32-q22.33, encoding Dual specificity protein phosphatase CDC14B (O60729). Dual-specificity phosphatase involved in DNA damage response.

The protein encoded by this gene is a member of the dual specificity protein tyrosine phosphatase family. This protein is highly similar to Saccharomyces cerevisiae Cdc14, a protein tyrosine phosphatase involved in the exit of cell mitosis and initiation of DNA replication, which suggests the role in cell cycle control. This protein has been shown to interact with and dephosphorylates tumor suppressor protein p53, and is thought to regulate the function of p53. Alternative splice of this gene results in 3 transcript variants encoding distinct isoforms.

Source: NCBI Gene 8555 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 83 total — 2 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_033331

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1719
Approved symbol	CDC14B
Name	cell division cycle 14B
Location	9q22.32-q22.33
Locus type	gene with protein product
Status	Approved
Aliases	Cdc14B1, Cdc14B2, CDC14B3, hCDC14B
Ensembl gene	ENSG00000081377
Ensembl biotype	protein_coding
OMIM	603505
Entrez	8555

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 13 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000375240, ENST00000375241, ENST00000375242, ENST00000412285, ENST00000415608, ENST00000452280, ENST00000463547, ENST00000463569, ENST00000474602, ENST00000480920, ENST00000481149, ENST00000484948, ENST00000496750, ENST00000856416, ENST00000856417, ENST00000856418, ENST00000937053, ENST00000937054, ENST00000937055

RefSeq mRNA: 7 — MANE Select: NM_033331 NM_001077181, NM_001351567, NM_001351568, NM_001351569, NM_001351570, NM_003671, NM_033331

CCDS: CCDS43853, CCDS6721, CCDS6722, CCDS87662

Canonical transcript exons

ENST00000375241 — 14 exons

Exon	Start	End
ENSE00000983160	96534455	96534542
ENSE00001608556	96523261	96523420
ENSE00001732055	96523587	96523725
ENSE00002208091	96533927	96534157
ENSE00003459293	96541826	96541892
ENSE00003479558	96551796	96551872
ENSE00003521261	96522506	96522603
ENSE00003527078	96539078	96539140
ENSE00003529616	96565393	96565483
ENSE00003534150	96564777	96564852
ENSE00003537373	96562693	96562785
ENSE00003560833	96509673	96509789
ENSE00003574533	96500113	96503789
ENSE00003893691	96619219	96619843

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 95.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.7391 / max 83.0202, expressed in 1503 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101602	3.3128	1148
101601	2.7914	1114
101599	1.2929	553
101600	0.3167	163
101598	0.0252	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	95.33	gold quality
tendon of biceps brachii	UBERON:0008188	93.47	gold quality
medial globus pallidus	UBERON:0002477	93.39	gold quality
blood vessel layer	UBERON:0004797	92.96	gold quality
cranial nerve II	UBERON:0000941	92.41	gold quality
pigmented layer of retina	UBERON:0001782	91.73	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.70	gold quality
globus pallidus	UBERON:0001875	91.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.61	gold quality
spinal cord	UBERON:0002240	90.61	gold quality
inferior vagus X ganglion	UBERON:0005363	90.56	gold quality
bronchial epithelial cell	CL:0002328	90.15	gold quality
seminal vesicle	UBERON:0000998	90.04	gold quality
sperm	CL:0000019	89.93	gold quality
jejunal mucosa	UBERON:0000399	89.85	gold quality
tendon	UBERON:0000043	89.74	gold quality
inferior olivary complex	UBERON:0002127	89.43	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.82	gold quality
calcaneal tendon	UBERON:0003701	88.62	gold quality
liver	UBERON:0002107	88.48	gold quality
male germ cell	CL:0000015	88.10	gold quality
right lobe of liver	UBERON:0001114	87.95	gold quality
caput epididymis	UBERON:0004358	87.86	gold quality
pylorus	UBERON:0001166	87.77	gold quality
epithelium of bronchus	UBERON:0002031	87.71	gold quality
bronchus	UBERON:0002185	87.62	gold quality
amygdala	UBERON:0001876	87.53	gold quality
germinal epithelium of ovary	UBERON:0001304	87.22	gold quality
urinary bladder	UBERON:0001255	86.93	gold quality
saphenous vein	UBERON:0007318	86.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

153 targeting CDC14B, 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-4533	100.00	69.48	2758
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-507	99.97	70.11	1915

Literature-anchored findings (GeneRIF, showing 19)

• Cdc14B is critical for the maintenance of proper nuclear structure. (PMID:15362113)
• CDC14B is a novel microtubule-bundling and -stabilizing protein, whose regulated subcellular localization may help modulate spindle and microtubule dynamics in mitosis. (PMID:15899858)
• hCdc14A and hCdc14B have functional homology to S. pombe Cdc25 and flp1 (PMID:15911625)
• Our findings reveal substantial divergence in mitotic regulation between yeast and mammalian cells, as the latter possess efficient mechanisms for completing late M-phase events in the absence of a nucleolar Cdc14-related phosphatase. (PMID:18418058)
• Results suggest a potential function for Cdc14B phosphatase in maintaining the fidelity of centrosome duplication cycle. (PMID:18458157)
• In response to genotoxic stress in G2, the phosphatase Cdc14B translocates from the nucleolus to the nucleoplasm and induces the activation of the ubiquitin ligase APC/C(Cdh1), with the consequent degradation of Plk1, a prominent mitotic kinase. (PMID:18662541)
• human HCT116, and human telomerase reverse transcription-immortalized retinal pigment epithelial cells deleted for Cdc14B are DNA damage checkpoint proficient and arrest efficiently in G2 in response to irradiation. (PMID:20479464)
• studies have revealed a novel interplay between Chk1 kinase and Cdc14B phosphatase involving radiation-induced nucleolar shuttling to facilitate error-free cell cycle progression and prevent genomic instability (PMID:21301228)
• Cdc14B-dependent modulation of Cdc25 phosphatase and Cdk1/cyclin B activity is linked to correct chromosome segregation and bipolar spindle formation, processes that are required for proper progression through mitosis and maintenance of genomic stability. (PMID:21379580)
• CDC (cell division cycle) 14A/B phosphatases associate with KIBRA, and CDK1-non-phosphorylatable KIBRA has greatly reduced interaction with CDC14B. (PMID:22784093)
• CDC14B expression is downregulated in clear cell renal carinoma, suggesting its role in renal carcinogenesis (PMID:24619757)
• hCdc14B promotes reactivation of rDNA transcription by dephosphorylating TAFI110. SIRT1 becomes transiently enriched in nucleoli at the onset of mitosis. SIRT1 deacetylates TAFI68 destabilizing SL1 binding to the rDNA promoter (PMID:26023773)
• The authors found a significant association between the localization of RET mutations and the expression of three genes: NNAT (suggested to be a tumour suppressor gene), CDC14B (involved in cell cycle control) and NTRK3 (tyrosine receptor kinase that undergoes rearrangement in papillary thyroid cancer) in patients with medullary thyroid cancer. (PMID:28181547)
• miR-1225 targets CDC14B 3’-UTR and recovery of CDC14B expression counteracted the suppressive influence of miR-1225 on laryngeal cancer cells (PMID:30138106)
• MiR-1247-5p Functions as a Tumor Suppressor in Human Astroglioma Cells by Targeting CDC14B. (PMID:32366555)
• Human cells lacking CDC14A and CDC14B show differences in ciliogenesis but not in mitotic progression. (PMID:33328327)
• Downregulation of CDC14B in 5218 breast cancer patients: A novel prognosticator for triple-negative breast cancer. (PMID:33378938)
• CDC14B is a favorable biomarker for recurrence and prognosis of GBM. (PMID:36898299)
• The diverging role of CDC14B: from mitotic exit in yeast to cell fate control in humans. (PMID:37493185)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdc14b	ENSDARG00000021483
mus_musculus	Cdc14b	ENSMUSG00000033102
rattus_norvegicus	Cdc14b	ENSRNOG00000018999

Paralogs (8): CDC14A (ENSG00000079335), CDKN3 (ENSG00000100526), PALD1 (ENSG00000107719), PTP4A1 (ENSG00000112245), PTPDC1 (ENSG00000158079), PTP4A2 (ENSG00000184007), PTP4A3 (ENSG00000184489), CDC14C (ENSG00000218305)

Protein

Protein identifiers

Dual specificity protein phosphatase CDC14B — O60729 (reviewed: O60729)

Alternative names: CDC14 cell division cycle 14 homolog B

All UniProt accessions (5): O60729, A0A9L9PY50, H0Y577, H7C3U8, Q5JU07

UniProt curated annotations — full annotation on UniProt →

Function. Dual-specificity phosphatase involved in DNA damage response. Essential regulator of the G2 DNA damage checkpoint: following DNA damage, translocates to the nucleus and dephosphorylates FZR1/CDH1, a key activator of the anaphase promoting complex/cyclosome (APC/C). Dephosphorylates SIRT2 around early anaphase. Dephosphorylation of FZR1/CDH1 activates the APC/C, leading to the ubiquitination of PLK1, preventing entry into mitosis. Preferentially dephosphorylates proteins modified by proline-directed kinases.

Subunit / interactions. Interacts with FZR1/CDH1.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm.

Domain organisation. Composed of two structurally equivalent A and B domains that adopt a dual specificity protein phosphatase (DSP) fold.

Similarity. Belongs to the protein-tyrosine phosphatase family. Non-receptor class CDC14 subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
O60729-1	2, CDC14B2	yes
O60729-2	1, CDC14B1
O60729-3	3, CDC14B3
O60729-4	4
O60729-5	5

RefSeq proteins (7): NP_001070649, NP_001338496, NP_001338497, NP_001338498, NP_001338499, NP_003662, NP_201588* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR016130	Tyr_Pase_AS	Active_site
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR029260	DSPn	Domain
IPR044506	CDC14_C	Domain
IPR050561	PTP	Family

Pfam: PF14671, PF22785

Catalyzed reactions (Rhea), 3 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)
• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (50 total): helix 14, strand 13, region of interest 5, compositionally biased region 4, splice variant 4, turn 4, sequence variant 2, chain 1, domain 1, active site 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1OHE	X-RAY DIFFRACTION	2.2
1OHC	X-RAY DIFFRACTION	2.5
1OHD	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60729-F1	81.04	0.64

Functional residue map

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

Catalytic / active sites (1): 314 (phosphocysteine intermediate)

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5687128	MAPK6/MAPK4 signaling
R-HSA-162582	Signal Transduction
R-HSA-5683057	MAPK family signaling cascades

MSigDB gene sets: 292 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, CMYB_01, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_REGULATION_OF_EXIT_FROM_MITOSIS, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, CREB_Q4, GTGCCTT_MIR506, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_ORGANELLE_FISSION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS

GO Biological Process (10): microtubule cytoskeleton organization (GO:0000226), DNA repair (GO:0006281), protein dephosphorylation (GO:0006470), mitotic G2 DNA damage checkpoint signaling (GO:0007095), regulation of exit from mitosis (GO:0007096), positive regulation of cytokinesis (GO:0032467), cilium assembly (GO:0060271), positive regulation of ubiquitin protein ligase activity (GO:1904668), DNA damage response (GO:0006974), dephosphorylation (GO:0016311)

GO Molecular Function (5): protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), cell junction (GO:0030054), mitotic spindle (GO:0072686), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
MAPK family signaling cascades	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
phosphoprotein phosphatase activity	2
spindle	2
nuclear lumen	2
cytoskeleton organization	1
microtubule-based process	1
DNA metabolic process	1
DNA damage response	1
dephosphorylation	1
protein modification process	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
exit from mitosis	1
regulation of mitotic cell cycle phase transition	1
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
positive regulation of ubiquitin-protein transferase activity	1
ubiquitin protein ligase activity	1
regulation of ubiquitin protein ligase activity	1
cellular response to stress	1
phosphate-containing compound metabolic process	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1160 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC14B	GMCL2	Q8NEA9	448
CDC14B	C11orf24	Q96F05	396
CDC14B	ESPL1	Q14674	357
CDC14B	ME2	P23368	349
CDC14B	PIP5K1A	Q99755	349
CDC14B	ZNF616	Q08AN1	348
CDC14B	PTS	Q03393	329
CDC14B	MLC1	Q15049	323
CDC14B	KRCC1	Q9NPI7	323
CDC14B	KIF4B	Q2VIQ3	314
CDC14B	NACA2	Q9H009	305
CDC14B	DUSP19	Q8WTR2	303
CDC14B	ADARB1	P78555	298
CDC14B	MOB1A	Q9H8S9	294
CDC14B	CEP15	Q9HBI5	290

IntAct

34 interactions, top by confidence:

A	B	Type	Score
CDC14B	SPANXN2	psi-mi:“MI:0915”(physical association)	0.560
PRKAB2	CDC14B	psi-mi:“MI:0915”(physical association)	0.560
CDC14B	ZNF696	psi-mi:“MI:0915”(physical association)	0.560
CDC14B	MFAP1	psi-mi:“MI:0915”(physical association)	0.560
CDC14B	PSMB1	psi-mi:“MI:0915”(physical association)	0.560
CDC14B	SIRT2	psi-mi:“MI:0915”(physical association)	0.520
CDC14B	MSH2	psi-mi:“MI:0915”(physical association)	0.520
FZR1	CDC14B	psi-mi:“MI:0915”(physical association)	0.400
CDC14B	GRHPR	psi-mi:“MI:0915”(physical association)	0.400
CDC14B	RPL36	psi-mi:“MI:0915”(physical association)	0.400
BCL10	CDC14B	psi-mi:“MI:0915”(physical association)	0.370
BUB1	CDC14B	psi-mi:“MI:0915”(physical association)	0.370
CCND1	CDC14B	psi-mi:“MI:0915”(physical association)	0.370
CDKN2A	CDC14B	psi-mi:“MI:0915”(physical association)	0.370
CDC14B	DLC1	psi-mi:“MI:0915”(physical association)	0.370
CDC14B	MCC	psi-mi:“MI:0915”(physical association)	0.370
MLH3	CDC14B	psi-mi:“MI:0915”(physical association)	0.370
SMAD4	CDC14B	psi-mi:“MI:0915”(physical association)	0.370
CDC14B	STK11	psi-mi:“MI:0915”(physical association)	0.370
CDC14B	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
	CDC14B	psi-mi:“MI:0914”(association)	0.350
CDC14B	PES1	psi-mi:“MI:2364”(proximity)	0.270
SPANXN2	CDC14B	psi-mi:“MI:0915”(physical association)	0.000
PRKAB2	CDC14B	psi-mi:“MI:0915”(physical association)	0.000
ZNF696	CDC14B	psi-mi:“MI:0915”(physical association)	0.000
MFAP1	CDC14B	psi-mi:“MI:0915”(physical association)	0.000
PSMB1	CDC14B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (161): RPL36 (Affinity Capture-MS), CCDC86 (Proximity Label-MS), CENPC (Proximity Label-MS), DNMT1 (Proximity Label-MS), NUSAP1 (Proximity Label-MS), RNF169 (Proximity Label-MS), USP36 (Proximity Label-MS), WHSC1L1 (Proximity Label-MS), XRCC1 (Proximity Label-MS), ZKSCAN4 (Proximity Label-MS), ZNF174 (Proximity Label-MS), ZNF280C (Proximity Label-MS), CBX8 (Proximity Label-MS), ZNF512 (Proximity Label-MS), ZNF362 (Proximity Label-MS)

ESM2 similar proteins: A0A0R4IVA4, A1Z7A6, A4D256, A6N3Q4, A8XQD5, B3M301, B3P8A3, B4G437, B4HGG6, B4JII0, B4K799, B4M0H8, B4NBP4, B4PL32, B4QSF0, B7WN72, G5EFD2, O02626, O43078, O43166, O60729, P24583, P34400, P34680, P43125, P50527, P81299, Q00684, Q07292, Q19469, Q19857, Q298L4, Q59NH8, Q5B323, Q61UC4, Q6GQT0, Q6NRL1, Q6PFY9, Q8BXK8, Q8I0P1

Diamond homologs: A0A0R4IVA4, A1L1R5, A2VDT1, A4D256, A6N3Q4, O60729, O61722, O70274, O75365, P81299, Q00684, Q12974, Q1LWL2, Q59NH8, Q5B323, Q5R7J8, Q63739, Q6GQT0, Q6NZK8, Q6P9X4, Q6PFY9, Q78EG7, Q86BN8, Q93096, Q9D658, Q9JLY7, Q9P7H1, Q9TSM6, Q9UNH5, Q9ZQP1, A2A3K4, A7E379, P35821, Q196Z3, Q4CUJ8, Q6NT99, Q86IL4, Q9BVJ7, Q6NKR2, Q54DU9

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
CDC14B	down-regulates	MAPK6	dephosphorylation
CDC14B	up-regulates	APC	dephosphorylation
CDC14B	up-regulates	CDCA3	dephosphorylation
CDC14B	up-regulates	GSK3B/Axin/APC	dephosphorylation
CDC14B	“down-regulates activity”	TP53	dephosphorylation
CDC14B	“down-regulates quantity by destabilization”	SKP2	dephosphorylation
CDC14B	“down-regulates quantity by destabilization”	MAPK6	dephosphorylation
CDC14B	unknown	SIRT2	dephosphorylation
CDC14B	“down-regulates quantity by destabilization”	KMT5A	dephosphorylation
CDC14B	“up-regulates activity”	CDH1	dephosphorylation
CDC14B	“up-regulates activity”	TAF1C	dephosphorylation
CDC14B	“down-regulates quantity by destabilization”	USP9X	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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
Cell Cycle, Mitotic	5	12.7×	4e-03
Cell Cycle	6	11.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	62
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
59904	GRCh38/hg38 9q22.32-22.33(chr9:96094968-96620662)x3	Pathogenic
688061	GRCh37/hg19 9q22.32-22.33(chr9:98156960-99345624)x1	Pathogenic

SpliceAI

3251 predictions. Top by Δscore:

Variant	Effect	Δscore
9:96509667:TCTCA:T	donor_loss	1.0000
9:96509668:CTCAC:C	donor_loss	1.0000
9:96509669:TCA:T	donor_loss	1.0000
9:96509670:CA:C	donor_loss	1.0000
9:96509671:A:C	donor_loss	1.0000
9:96509785:TTACT:T	acceptor_gain	1.0000
9:96509786:TACT:T	acceptor_gain	1.0000
9:96509788:CT:C	acceptor_gain	1.0000
9:96509790:C:CC	acceptor_gain	1.0000
9:96509800:T:C	acceptor_gain	1.0000
9:96509800:T:TC	acceptor_gain	1.0000
9:96515647:A:AC	donor_gain	1.0000
9:96515648:C:CC	donor_gain	1.0000
9:96515648:CAG:C	donor_gain	1.0000
9:96522504:A:AC	donor_gain	1.0000
9:96522505:C:CT	donor_gain	1.0000
9:96522599:CTGTA:C	acceptor_gain	1.0000
9:96522600:TGTA:T	acceptor_gain	1.0000
9:96522601:GTA:G	acceptor_gain	1.0000
9:96522601:GTACT:G	acceptor_loss	1.0000
9:96522602:TA:T	acceptor_gain	1.0000
9:96522604:C:CC	acceptor_gain	1.0000
9:96522606:G:C	acceptor_gain	1.0000
9:96522606:G:GC	acceptor_gain	1.0000
9:96523584:TACA:T	donor_loss	1.0000
9:96523585:A:AC	donor_gain	1.0000
9:96523585:A:C	donor_loss	1.0000
9:96523585:ACAT:A	donor_gain	1.0000
9:96523586:C:CA	donor_gain	1.0000
9:96523586:CAT:C	donor_gain	1.0000

AlphaMissense

3311 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:96523629:C:G	R348T	1.000
9:96523714:G:T	R320S	1.000
9:96523719:A:G	L318P	1.000
9:96523722:C:T	G317D	1.000
9:96533931:G:C	C314W	1.000
9:96562719:C:G	A132P	1.000
9:96564835:C:T	G90E	1.000
9:96564837:A:C	F89L	1.000
9:96564837:A:T	F89L	1.000
9:96564839:A:G	F89L	1.000
9:96523604:C:A	Q356H	0.999
9:96523604:C:G	Q356H	0.999
9:96523623:C:T	G350D	0.999
9:96523628:T:A	R348S	0.999
9:96523628:T:G	R348S	0.999
9:96523629:C:A	R348I	0.999
9:96523630:T:C	R348G	0.999
9:96523637:C:A	R345S	0.999
9:96523637:C:G	R345S	0.999
9:96523638:C:A	R345M	0.999
9:96523638:C:G	R345T	0.999
9:96523645:A:G	W343R	0.999
9:96523645:A:T	W343R	0.999
9:96523713:C:G	R320P	0.999
9:96523714:G:C	R320G	0.999
9:96523716:C:A	G319V	0.999
9:96523716:C:T	G319D	0.999
9:96523717:C:G	G319R	0.999
9:96523719:A:T	L318H	0.999
9:96523722:C:A	G317V	0.999

dbSNP variants (sampled 300 via entrez): RS1000000019 (9:96534105 A>G), RS1000010586 (9:96577353 G>A), RS1000039706 (9:96528280 G>A), RS1000043827 (9:96555170 G>A), RS1000050285 (9:96494117 A>T), RS1000079485 (9:96583337 C>G), RS1000106559 (9:96491192 C>T), RS1000166690 (9:96591739 G>C), RS1000175873 (9:96495940 G>A), RS1000201766 (9:96502418 C>G), RS1000244641 (9:96547221 C>G), RS1000257282 (9:96502692 C>T), RS1000266440 (9:96607130 G>A), RS1000269197 (9:96546066 G>A), RS1000271998 (9:96541225 G>C)

Disease associations

OMIM: gene MIM:603505 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST005141_66	Cognitive ability (MTAG)	4.000000e-09
GCST005142_20	Cognitive ability	2.000000e-06
GCST005316_62	Intelligence (MTAG)	2.000000e-09
GCST008514_14	Peginterferon alfa-2a treatment response in chronic hepatitis B infection	5.000000e-06
GCST008839_304	Height	4.000000e-14
GCST009523_53	Household income	3.000000e-08
GCST010796_5123	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST012226_95	Waist circumference adjusted for body mass index	6.000000e-12
GCST012227_440	Hip circumference adjusted for BMI	1.000000e-13

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0010103	response to peginterferon alfa-2a
EFO:0009695	household income
EFO:0004327	electrocardiography
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066204 (SINGLE PROTEIN)

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

ChEMBL bioactivities

8 potent at pChembl≥5 of 10 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.05	Ki	90	nM	CHEMBL5567968
5.66	IC50	2170	nM	CHEMBL5568076
5.42	IC50	3760	nM	CHEMBL5563039
5.42	IC50	3770	nM	CHEMBL5565218
5.38	IC50	4190	nM	CHEMBL5560702
5.28	IC50	5210	nM	CHEMBL5568214
5.23	IC50	5850	nM	CHEMBL5556755
5.14	Ki	7300	nM	CHEMBL5561438

PubChem BioAssay actives

8 with measured affinity, of 10 total; 8 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
[difluoro-[4-(1-phenylethenyl)dibenzofuran-1-yl]methyl]phosphonic acid	2076964: Reversible competitive inhibition of human CDC14B using DiFMUP as substrate incubated for 10 mins by fluorescence based assay	ki	0.0900	uM
[difluoro-(4-phenyldibenzofuran-1-yl)methyl]phosphonic acid	2076950: Inhibition of human CDC14B using DiFMUP as substrate incubated for 10 mins by fluorescence based assay	ic50	2.1700	uM
[difluoro-[4-[2-fluoro-4-(trifluoromethyl)phenyl]dibenzofuran-1-yl]methyl]phosphonic acid	2076950: Inhibition of human CDC14B using DiFMUP as substrate incubated for 10 mins by fluorescence based assay	ic50	3.7600	uM
[difluoro-[4-(2-phenylethynyl)dibenzofuran-1-yl]methyl]phosphonic acid	2076950: Inhibition of human CDC14B using DiFMUP as substrate incubated for 10 mins by fluorescence based assay	ic50	3.7700	uM
[difluoro-[4-[(E)-2-phenylethenyl]dibenzofuran-1-yl]methyl]phosphonic acid	2076950: Inhibition of human CDC14B using DiFMUP as substrate incubated for 10 mins by fluorescence based assay	ic50	4.1900	uM
[difluoro-[4-(4-hydroxyphenyl)dibenzofuran-1-yl]methyl]phosphonic acid	2076950: Inhibition of human CDC14B using DiFMUP as substrate incubated for 10 mins by fluorescence based assay	ic50	5.2100	uM
[[4-(5-chlorothiophen-2-yl)dibenzofuran-1-yl]-difluoromethyl]phosphonic acid	2076950: Inhibition of human CDC14B using DiFMUP as substrate incubated for 10 mins by fluorescence based assay	ic50	5.8500	uM
[dibenzofuran-1-yl(difluoro)methyl]phosphonic acid	2076949: Competitive inhibition of human CDC14B using DiFMUP as substrate incubated for 10 mins by fluorescence based assay	ki	7.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	4
Tetrachlorodibenzodioxin	affects expression, increases expression	4
Valproic Acid	affects expression, increases expression	3
Estradiol	affects cotreatment, increases expression	2
Progesterone	affects cotreatment, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
methylselenic acid	affects expression	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
perfluorooctanoic acid	increases expression	1
mercuric bromide	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
GW 3965	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	increases expression, decreases reaction	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	increases methylation	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression	1
Air Pollutants, Occupational	affects expression	1
Arsenic	affects methylation	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5516367	Binding	Competitive inhibition of human CDC14B using DiFMUP as substrate incubated for 10 mins by fluorescence based assay	Development of Novel Phosphonodifluoromethyl-Containing Phosphotyrosine Mimetics and a First-In-Class, Potent, Selective, and Bioavailable Inhibitor of Human CDC14 Phosphatases. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2TV	Abcam HEK293T CDC14B KO	Transformed cell line	Female

Clinical trials (associated diseases)

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