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): 85 total — 2 pathogenic
• GTEx eGene: eQTL in 21 tissues, sQTL in 18 (q < 0.05)
• Constraint (gnomAD): pLI 0.96 (loss-of-function intolerant), LOEUF 0.53 (moderately constrained)
• MANE Select transcript: NM_033331
• Notable: 85 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 37 — 19 protein_coding, 14 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

MANE Select: ENST00000375241

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 1, TSL 3: 4, TSL 4: 1, TSL 5: 3

ENST00000375241, ENST00000375240, ENST00000375242, ENST00000412285, ENST00000415608, ENST00000452280, ENST00000463547, ENST00000463569, ENST00000474602, ENST00000480920, ENST00000481149, ENST00000484948, ENST00000496750, ENST00000856416, ENST00000856417, ENST00000856418, ENST00000937053, ENST00000937054, ENST00000937055, ENST00000974365, ENST00000974366, ENST00000974367, ENST00000974368, ENST00000974369, ENST00000974370, ENST00000974371, ENST00000974372, ENST00001081062, ENST00001106847, ENST00001106848, ENST00001117640, ENST00001117641, ENST00001117642, ENST00001117643, ENST00001117644, ENST00001129301, ENST00001139025

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.

Highest expression (Bgee): corpus callosum, tendon of biceps brachii, medial globus pallidus, blood vessel layer, cranial nerve II.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CDC14B is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 21 tissues and its splicing (sQTL) in 18 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 39 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	8.8e-55	+1.41	9:96497462:C:T
Cells Cultured fibroblasts	sqtl	7.4e-22	-0.75	9:96498292:A:G
Esophagus Mucosa	eqtl	9.6e-15	+0.98	9:96611350:G:A
Nerve Tibial	sqtl	3.8e-13	-0.63	9:96498292:A:G
Thyroid	sqtl	9.9e-11	-0.57	9:96497580:T:C
Artery Tibial	sqtl	1.2e-10	-0.49	9:96519987:G:C
Cells EBV-transformed lymphocytes	eqtl	9.0e-10	+0.49	9:96492158:A:G
Brain Caudate basal ganglia	eqtl	1.0e-07	-0.25	9:96500890:G:GCGAGCACACTGGCCT
Artery Aorta	sqtl	1.5e-07	-0.46	9:96497462:C:T
Adipose Subcutaneous	sqtl	3.4e-06	-0.46	9:96497580:T:C
Brain Putamen basal ganglia	eqtl	4.7e-06	-0.32	9:96497462:C:T
Brain Nucleus accumbens basal ganglia	eqtl	2.6e-05	-0.26	9:96498292:A:G
Colon Transverse	sqtl	5.0e-05	-0.47	9:96517226:C:T
Artery Coronary	sqtl	6.0e-05	-0.55	9:96497580:T:C
Stomach	sqtl	9.8e-05	-0.46	9:96495862:T:C
Colon Sigmoid	sqtl	1.8e-04	-0.56	9:96496969:C:T
Esophagus Muscularis	sqtl	3.7e-04	-0.44	9:96506139:A:C
Ovary	eqtl	5.3e-04	+1.43	9:96570032:A:G
Thyroid	eqtl	1.2e-03	-0.46	9:96486391:A:G
Lung	eqtl	1.2e-03	-0.15	9:96551611:C:T

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

showing 100 of 294 tissues 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
Ammon’s horn	UBERON:0001954	86.78	gold quality
nephron tubule	UBERON:0001231	86.77	gold quality
caudate nucleus	UBERON:0001873	86.69	gold quality
substantia nigra	UBERON:0002038	86.67	gold quality
tibia	UBERON:0000979	86.66	gold quality
popliteal artery	UBERON:0002250	86.65	gold quality
tibial artery	UBERON:0007610	86.64	gold quality
tibial nerve	UBERON:0001323	86.45	gold quality
midbrain	UBERON:0001891	86.41	gold quality
CA1 field of hippocampus	UBERON:0003881	86.37	gold quality
putamen	UBERON:0001874	86.31	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.18	gold quality
parietal pleura	UBERON:0002400	86.17	gold quality
aorta	UBERON:0000947	86.07	gold quality
nipple	UBERON:0002030	85.82	gold quality
buccal mucosa cell	CL:0002336	85.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.69	gold quality
medulla oblongata	UBERON:0001896	85.65	gold quality
nucleus accumbens	UBERON:0001882	85.62	gold quality
descending thoracic aorta	UBERON:0002345	85.58	gold quality
choroid plexus epithelium	UBERON:0003911	85.56	gold quality
renal medulla	UBERON:0000362	85.52	gold quality
right coronary artery	UBERON:0001625	85.47	gold quality
monocyte	CL:0000576	85.41	gold quality
adipose tissue	UBERON:0001013	85.36	gold quality
corpus epididymis	UBERON:0004359	85.36	gold quality
thoracic aorta	UBERON:0001515	85.34	gold quality
ascending aorta	UBERON:0001496	85.29	gold quality
temporal lobe	UBERON:0001871	85.28	gold quality
connective tissue	UBERON:0002384	85.13	gold quality
duodenum	UBERON:0002114	85.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.08	gold quality
ventral tegmental area	UBERON:0002691	85.06	gold quality
pleura	UBERON:0000977	85.01	gold quality
hypothalamus	UBERON:0001898	84.91	gold quality
pancreatic ductal cell	CL:0002079	84.79	silver quality
coronary artery	UBERON:0001621	84.78	gold quality
left coronary artery	UBERON:0001626	84.76	gold quality
subthalamic nucleus	UBERON:0001906	84.76	gold quality
gall bladder	UBERON:0002110	84.69	gold quality
mononuclear cell	CL:0000842	84.68	gold quality
trachea	UBERON:0003126	84.68	gold quality
islet of Langerhans	UBERON:0000006	84.61	gold quality
stomach	UBERON:0000945	84.53	gold quality
mucosa of stomach	UBERON:0001199	84.45	gold quality
nasal cavity mucosa	UBERON:0001826	84.44	gold quality
substantia nigra pars reticulata	UBERON:0001966	84.31	gold quality
primary visual cortex	UBERON:0002436	84.30	gold quality
right testis	UBERON:0004534	84.29	gold quality
palpebral conjunctiva	UBERON:0001812	84.18	gold quality
testis	UBERON:0000473	84.07	gold quality
body of stomach	UBERON:0001161	84.07	gold quality
right frontal lobe	UBERON:0002810	84.07	gold quality
body of pancreas	UBERON:0001150	84.06	gold quality
occipital lobe	UBERON:0002021	84.05	gold quality
leukocyte	CL:0000738	84.03	gold quality
left testis	UBERON:0004533	84.03	gold quality
renal glomerulus	UBERON:0000074	84.00	gold quality
thyroid gland	UBERON:0002046	83.96	gold quality
telencephalon	UBERON:0001893	83.90	gold quality
superior vestibular nucleus	UBERON:0007227	83.90	gold quality
pancreas	UBERON:0001264	83.88	gold quality
forebrain	UBERON:0001890	83.84	gold quality
fundus of stomach	UBERON:0001160	83.78	gold quality
Brodmann (1909) area 46	UBERON:0006483	83.76	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	83.67	gold quality
cauda epididymis	UBERON:0004360	83.54	gold quality
urethra	UBERON:0000057	83.45	gold quality
cortex of kidney	UBERON:0001225	83.41	gold quality
cardia of stomach	UBERON:0001162	83.40	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 61 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Basal ganglia	tissue	59.7
Medulla oblongata	tissue	51.8
Midbrain	tissue	50.1
Pons	tissue	49.5
Amygdala	tissue	45.6
Thalamus	tissue	45.5
Cerebral cortex	tissue	45.4
Spinal cord	tissue	43.9
Hypothalamus	tissue	37.8
Cerebellum	tissue	36.4
Substantia nigra	tissue	34.6
Hippocampal formation	tissue	33.2
Nucleus accumbens	tissue	32.1
Locus coeruleus	tissue	29.0
Putamen	tissue	27.9
Retrosplenial cortex	tissue	26.4
Hippocampus	tissue	26.1
Occipital cortex	tissue	25.1
Postcentral gyrus	tissue	20.2
Choroid plexus	tissue	17.4
Liver	tissue	11.8
Testis	tissue	9.4
Thyroid gland	tissue	8.6
Parathyroid gland	tissue	6.9
Stomach 1	tissue	6.8
Kidney	tissue	5.9
Adipose tissue	tissue	5.3
Pancreas	tissue	5.2
Heart muscle	tissue	4.9
Urinary bladder	tissue	4.6
Seminal vesicle	tissue	4.5
Fallopian tube	tissue	4.4
Small intestine	tissue	4.2
Prostate	tissue	3.8
Gallbladder	tissue	3.6
Breast	tissue	3.4
Rectum	tissue	3.4
Colon	tissue	3.3
Lung	tissue	3.3
Duodenum	tissue	3.2
Bone marrow	tissue	3.2
Cervix	tissue	3.0
Adrenal gland	tissue	2.9
Thymus	tissue	2.9
Ovary	tissue	2.8
Epididymis	tissue	2.6
Placenta	tissue	2.4
Retina	tissue	2.2
Salivary gland	tissue	2.1
Smooth muscle	tissue	2.1
Tongue	tissue	1.8
Endometrium 1	tissue	1.7
Esophagus	tissue	1.6
Appendix	tissue	1.3
Tonsil	tissue	1.2
Lymph node	tissue	1.0
Pituitary gland	tissue	0.9
Spleen	tissue	0.9
Skin 1	tissue	0.8
Vagina	tissue	0.7

Brain sub-regions (HPA Brain Atlas): detected in 185; highest nTPM — Parieto-temporal junction (white matter) (91.5), White matter (91.5), Temporal white matter (85.7), Angular gyrus (white matter) (84.2), Corpus callosum, genu (white matter) (76.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CDC14B by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 153 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.959, LOEUF 0.526, missense Z 0.808 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000375241 — one region, missense o/e 0.79.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2441808) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 14 distinct phenotype terms.

Mouse phenotype (MP)	Records
kyphosis	1
abnormal lens morphology	1
cataract	1
abnormal cornea morphology	1
cornea opacity	1
reduced fertility	1
reduced male fertility	1
reduced female fertility	1
decreased litter size	1
premature aging	1
early cellular replicative senescence	1
impaired contextual conditioning behavior	1
increased cornea thickness	1
impaired DNA repair	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q9TSM6	100.0%	Diamond
Pongo abelii	Q5R7J8	98.8%	Diamond
Symphalangus syndactylus	A6N3Q4	94.0%	Diamond
Arabidopsis thaliana	Q6NKR2	66.1%	Diamond
Drosophila melanogaster	O61722	58.3%	Diamond
Saccharomyces cerevisiae S288C	Q00684	55.2%	Diamond
Candida albicans SC5314	Q59NH8	55.2%	Diamond
Schizosaccharomyces pombe 972h-	Q9P7H1	53.1%	Diamond
Trypanosoma cruzi strain CL Brener	Q4CUJ8	53.0%	Diamond
Dictyostelium discoideum	Q54DU9	51.8%	Diamond
Aspergillus nidulans FGSC A4	Q5B323	50.7%	Diamond
Caenorhabditis elegans	P81299	48.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SLC35D2	protein-coding	11046
SLC35D2-HSD17B3	ncRNA	127748585
ZNF367	protein-coding	195828
HABP4	protein-coding	22927
HSD17B3	protein-coding	3293
PRXL2C	protein-coding	195827
HSD17B3-AS1	ncRNA	105376162
ZNF510	protein-coding	22869
ZNF782	protein-coding	158431

Protein

Protein identifiers

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

Alternative names: CDC14 cell division cycle 14 homolog B

All UniProt accessions (5): A0A9L9PY50, O60729, 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)

• 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 (54 total): helix 18, 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 by resolution:

PDB	Title	Method	Resolution (Å)
1OHE	Structure of cdc14b phosphatase with a peptide ligand	X-RAY DIFFRACTION	2.2
1OHC	Structure of the proline directed phosphatase cdc14	X-RAY DIFFRACTION	2.5
1OHD	structure of cdc14 in complex with tungstate	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted membrane proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cell junctions; cytosol

Antibody reliability (HPA): IF supported

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)

Position	Role
314	phosphocysteine intermediate

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

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

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 (6): spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitotic spindle (GO:0072686)

Reactome top-level categories

2 top-level categories:

Category	Pathways
MAPK family signaling cascades	1
Signal Transduction	1

GO top-level categories

39 GO namespaces:

Category	Terms
cellular anatomical structure	3
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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
mitotic G2 DNA damage checkpoint signaling	BP	direct assay
positive regulation of ubiquitin protein ligase activity	BP	mutant phenotype
protein dephosphorylation	BP	mutant phenotype
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
protein serine/threonine phosphatase activity	MF	direct assay
protein tyrosine phosphatase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 810 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC14B	EXOC1	Q9NV70	364
CDC14B	GMCL2	Q8NEA9	359
CDC14B	AHSP	Q9NZD4	357
CDC14B	FBXO16	Q8IX29	356
CDC14B	FZR1	Q9UM11	341
CDC14B	HINT1	P49773	327
CDC14B	SKP2	Q13309	308
CDC14B	PPP1R7	Q15435	294
CDC14B	PPP1R8	Q12972	289
CDC14B	AZIN1	O14977	289
CDC14B	TBRG1	Q3YBR2	271
CDC14B	CDC25B	P30305	269
CDC14B	CDC23	Q9UJX2	267
CDC14B	C11orf24	Q96F05	260
CDC14B	NACA2	Q9H009	260

IntAct

Human interaction partners of CDC14B in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

21 partners by confidence:

Partner	Interaction type	MIscore	Records
MFAP1	physical association	0.560	3
PRKAB2	physical association	0.560	3
PSMB1	physical association	0.560	3
SPANXN2	physical association	0.560	3
ZNF696	physical association	0.560	3
SIRT2	physical association	0.520	2
MSH2	physical association	0.520	1
FZR1	physical association	0.400	1
GRHPR	physical association	0.400	1
RPL36	physical association	0.400	1
BCL10	physical association	0.370	1
BUB1	physical association	0.370	1
CCND1	physical association	0.370	1
CDKN2A	physical association	0.370	1
DLC1	physical association	0.370	1
MCC	physical association	0.370	1
MLH3	physical association	0.370	1
SMAD4	physical association	0.370	1
STK11	physical association	0.370	1
PPP1R12A	association	0.350	1
PES1	proximity	0.270	1

BioGRID (162 interactions; top human partners by supporting records): CHEK1 (Affinity Capture-Western; 2 records), MSH2 (Proximity Label-MS; 2 records), SKP2 (Affinity Capture-Western; 2 records), TP53 (Affinity Capture-Western; 2 records), AATF (Proximity Label-MS), AHCYL2 (Affinity Capture-MS), ANKRD28 (Affinity Capture-MS), ANKRD44 (Affinity Capture-MS), ANKRD50 (Affinity Capture-MS), ANKRD52 (Affinity Capture-MS), ATAD5 (Proximity Label-MS), AURKB (Proximity Label-MS), BCL10 (Two-hybrid), BMS1 (Proximity Label-MS), BRCA2 (Positive Genetic)

SIGNOR signaling

showing 12 of 18 signaling 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

Genetic variants

Variant evidence for CDC14B: 85 ClinVar records (2 pathogenic / likely pathogenic); 9 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	64
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
59904	GRCh38/hg38 9q22.32-22.33(chr9:96094968-96620662)x3	Pathogenic	criteria provided, single submitter	1
688061	GRCh37/hg19 9q22.32-22.33(chr9:98156960-99345624)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CDC14B’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 1,731):

Position(s)	Effect	Δscore	Sites
9:96509671–96509672	donor_loss	1.0000	5
9:96509800	acceptor_gain	1.0000
9:96522604–96522605	acceptor_loss	1.0000	4
9:96522606	acceptor_gain	1.0000
9:96523585–96523586	donor_loss	1.0000	5
9:96523726–96523727	acceptor_loss	1.0000	3
9:96533925–96533926	donor_loss	1.0000	3
9:96534453–96534454	donor_loss	1.0000	5
9:96534543–96534544	acceptor_loss	1.0000	5
9:96541824–96541825	donor_loss	1.0000	5

AlphaMissense

1,223 missense substitutions predicted likely pathogenic (of 3,311 scored), across 285 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D88	8	0.998	0.999
D167	8	0.997	0.999
D287	8	0.997	0.999
H313	8	0.994	0.998
D215	8	0.991	0.997
F85	8	0.975	0.999
F89	8	0.971	1.000
F273	8	0.971	0.999
F299	8	0.965	0.998
F252	8	0.963	0.997
F285	8	0.962	0.996
F227	8	0.958	0.993
F74	8	0.952	0.998
D77	8	0.949	0.995
H280	8	0.948	0.996
F165	8	0.947	0.999
F200	8	0.944	0.995
N264	8	0.943	0.997
F58	8	0.942	0.998
D429	8	0.930	0.979

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.92e-09
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.00018

Disease associations

OMIM: gene MIM:603505 | disease phenotypes:

GWAS associations

9 associations:

Study	Trait	p-value
GCST008839_512	Height	4e-14
GCST012227_1086	Hip circumference adjusted for BMI	1e-13
GCST012226_583	Waist circumference adjusted for body mass index	6e-12
GCST005316_362	Intelligence (MTAG)	2e-9
GCST005141_41	Cognitive ability (MTAG)	4e-9
GCST009523_53	Household income	3e-8
GCST010796_3048	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-8
GCST005142_36	Cognitive ability	2e-6
GCST008514_14	Peginterferon alfa-2a treatment response in chronic hepatitis B infection	5e-6

EFO canonical traits (from GWAS)

7 canonical traits:

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 (CPIC guideline: no)

Binding affinities (BindingDB)

7 measured of 7 human assays (9 total across all organisms); most potent 7 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5568076	IC50	1920 nM
CHEMBL5560702	IC50	2000 nM
CHEMBL5568214	IC50	2170 nM
CHEMBL5565218	IC50	2740 nM
CHEMBL5563039	IC50	2780 nM
CHEMBL5556755	IC50	3210 nM
CHEMBL5542122	IC50	9410 nM

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	increases expression, affects 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	increases expression, affects cotreatment	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	decreases reaction, increases expression	1
dorsomorphin	affects cotreatment, increases expression	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CDC14B across ~30M SureChEMBL compounds — explore on Sugi Predict.