CDC14C

Summary

CDC14C (cell division cycle 14C, HGNC:22427) is a protein-coding gene on chromosome 7p12.3, encoding Dual specificity protein phosphatase CDC14C (A4D256). Dual-specificity phosphatase.

This gene represents a retrogene of cell division cycle 14B (CDC14B), which is located on chromosome 9. The introns in the coding sequence have been processed out relative to the CDC14B locus, but there is an intact open reading frame that is missing only some sequence at the N-terminus, including the nuclear localiztion signal, relative to proteins encoded by the CDC14B gene. There is a difference in the subcellular localization of the protein encoded by this gene, relative to its parental gene product. While the parental gene product displays microtubular localization, GFP chimeras of the protein encoded by this gene localize to the endoplasmic reticulum, indicating a possible new functional role for this gene.

Source: NCBI Gene 168448 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_152627

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22427
Approved symbol	CDC14C
Name	cell division cycle 14C
Location	7p12.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC26484, CDC14B2, CDC14Bretro, CDC14CP
Ensembl gene	ENSG00000218305
Ensembl biotype	protein_coding
Entrez	168448

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000650262

RefSeq mRNA: 1 — MANE Select: NM_152627 NM_152627

CCDS: CCDS94101

Canonical transcript exons

ENST00000650262 — 1 exons

Exon	Start	End
ENSE00003835562	48924547	48927454

Expression profiles

Bgee: expression breadth broad, 14 present calls, max score 75.30.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0148 / max 15.3369, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78603	0.0109	3
204435	0.0039	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.30	gold quality
sperm	CL:0000019	66.99	silver quality
left testis	UBERON:0004533	66.09	gold quality
right testis	UBERON:0004534	65.61	gold quality
testis	UBERON:0000473	65.09	gold quality
lower lobe of lung	UBERON:0008949	54.99	silver quality
ventricular zone	UBERON:0003053	43.81	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
sural nerve	UBERON:0015488	41.55	gold quality
upper leg skin	UBERON:0004262	41.50	silver quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
oviduct epithelium	UBERON:0004804	40.03	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.56

Regulation

Is transcription factor: no

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), CDC14B (ENSG00000081377), CDKN3 (ENSG00000100526), PALD1 (ENSG00000107719), PTP4A1 (ENSG00000112245), PTPDC1 (ENSG00000158079), PTP4A2 (ENSG00000184007), PTP4A3 (ENSG00000184489)

Protein

Protein identifiers

Dual specificity protein phosphatase CDC14C — A4D256 (reviewed: A4D256)

Alternative names: CDC14 cell division cycle 14 homolog C

All UniProt accessions (1): A4D256

UniProt curated annotations — full annotation on UniProt →

Function. Dual-specificity phosphatase. Preferentially dephosphorylates proteins modified by proline-directed kinases.

Subcellular location. Endoplasmic reticulum membrane.

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

Miscellaneous. May act as an autosomal functional substitute.

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

RefSeq proteins (1): NP_689840* (*=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 (13 total): sequence conflict 4, region of interest 3, sequence variant 2, chain 1, transmembrane region 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A4D256-F1	85.91	0.70

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): 284 (phosphocysteine intermediate)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 53 (showing top): GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_REGULATION_OF_EXIT_FROM_MITOSIS, GOBP_ORGANELLE_FISSION, GOBP_CYTOKINESIS, GOBP_POSITIVE_REGULATION_OF_CELL_DIVISION, GOBP_EXIT_FROM_MITOSIS, GOBP_CILIUM_ORGANIZATION, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_MITOTIC_NUCLEAR_DIVISION, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_REGULATION_OF_CYTOKINESIS, GOBP_POSITIVE_REGULATION_OF_CYTOKINESIS, GOBP_REGULATION_OF_CELL_DIVISION, GOBP_ORGANELLE_ASSEMBLY, GOBP_MITOTIC_CELL_CYCLE

GO Biological Process (6): microtubule cytoskeleton organization (GO:0000226), regulation of exit from mitosis (GO:0007096), positive regulation of cytokinesis (GO:0032467), cilium assembly (GO:0060271), protein dephosphorylation (GO:0006470), dephosphorylation (GO:0016311)

GO Molecular Function (4): protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), phosphoprotein phosphatase activity (GO:0004721), hydrolase activity (GO:0016787)

GO Cellular Component (7): spindle pole (GO:0000922), nucleolus (GO:0005730), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), mitotic spindle (GO:0072686), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
phosphoprotein phosphatase activity	2
spindle	2
cytoskeleton organization	1
microtubule-based process	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
dephosphorylation	1
protein modification process	1
phosphate-containing compound metabolic process	1
phosphatase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1164 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC14C	GMCL2	Q8NEA9	434
CDC14C	NT5DC4	Q86YG4	373
CDC14C	UTP14C	Q5TAP6	371
CDC14C	ESPL1	Q14674	367
CDC14C	FAM153A	Q9UHL3	324
CDC14C	OR12D2	P58182	320
CDC14C	OR5V1	Q9UGF6	313
CDC14C	POM121L12	Q8N7R1	311
CDC14C	MOB1A	Q9H8S9	310
CDC14C	NT5DC1	Q5TFE4	305
CDC14C	TMCC3	Q9ULS5	298
CDC14C	KIF4B	Q2VIQ3	292
CDC14C	MNMIP1	A4FU49	290
CDC14C	ARMC12	Q5T9G4	289
CDC14C	SLC35G5	Q96KT7	289
CDC14C	PPM1M	Q96MI6	289

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PRDM9	CDC14C	psi-mi:“MI:0914”(association)	0.350

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, Q54DU9, Q6NKR2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2984 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:48924994:T:C	C108R	0.977
7:48924976:G:C	A102P	0.976
7:48925609:T:A	W313R	0.968
7:48925609:T:C	W313R	0.968
7:48924980:C:A	A103D	0.959
7:48925477:T:C	F269L	0.953
7:48925479:T:A	F269L	0.953
7:48925479:T:G	F269L	0.953
7:48924754:T:C	F28L	0.952
7:48924756:T:A	F28L	0.952
7:48924756:T:G	F28L	0.952
7:48924755:T:C	F28S	0.950
7:48924757:G:C	A29P	0.950
7:48925075:T:C	F135L	0.948
7:48925077:C:A	F135L	0.948
7:48925077:C:G	F135L	0.948
7:48924992:G:A	G107E	0.947
7:48924996:C:G	C108W	0.947
7:48924802:T:C	F44L	0.946
7:48924804:C:A	F44L	0.946
7:48924804:C:G	F44L	0.946
7:48924847:T:C	F59L	0.945
7:48924849:T:A	F59L	0.945
7:48924849:T:G	F59L	0.945
7:48924943:T:C	F91L	0.943
7:48924945:T:A	F91L	0.943
7:48924945:T:G	F91L	0.943
7:48925128:T:G	C152W	0.943
7:48924991:G:A	G107R	0.940
7:48924991:G:C	G107R	0.940

dbSNP variants (sampled 300 via entrez): RS1001536141 (7:48926894 A>G), RS1001649221 (7:48926663 G>A,T), RS1001871702 (7:48927785 G>A,C,T), RS1001986438 (7:48927599 T>C), RS1002828872 (7:48924571 G>A,C,T), RS1002908130 (7:48923808 T>A,C,G), RS1003939160 (7:48924488 C>T), RS1004334713 (7:48927511 G>A), RS1004394410 (7:48923584 C>T), RS1004730972 (7:48924478 C>A,G,T), RS1004843726 (7:48924411 C>A,G,T), RS1006435939 (7:48924756 T>C), RS1006741626 (7:48926382 G>T), RS1006775852 (7:48926169 G>C), RS1008304977 (7:48922617 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001859_17	Thiazide-induced adverse metabolic effects in hypertensive patients	7.000000e-07
GCST004642_4	QT interval (ambient particulate matter interaction)	2.000000e-06
GCST004747_20	Lung cancer in never smokers	4.000000e-06
GCST004904_76	Body mass index	5.000000e-10
GCST008514_14	Peginterferon alfa-2a treatment response in chronic hepatitis B infection	5.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0008255	particulate matter air pollution measurement
EFO:0004340	body mass index
EFO:0010103	response to peginterferon alfa-2a

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
MT19c compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases expression	1
Estradiol	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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