CDC42EP5

Summary

CDC42EP5 (CDC42 effector protein 5, HGNC:17408) is a protein-coding gene on chromosome 19q13.42, encoding Cdc42 effector protein 5 (Q6NZY7). Probably involved in the organization of the actin cytoskeleton.

Cell division control protein 42 (CDC42), a small Rho GTPase, regulates the formation of F-actin-containing structures through its interaction with the downstream effector proteins. The protein encoded by this gene is a member of the Borg (binder of Rho GTPases) family of CDC42 effector proteins. Borg family proteins contain a CRIB (Cdc42/Rac interactive-binding) domain. They bind to CDC42 and regulate its function negatively. The encoded protein may inhibit c-Jun N-terminal kinase (JNK) independently of CDC42 binding. The protein may also play a role in septin organization and inducing pseudopodia formation in fibroblasts

Source: NCBI Gene 148170 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_145057

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17408
Approved symbol	CDC42EP5
Name	CDC42 effector protein 5
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	CEP5, Borg3
Ensembl gene	ENSG00000167617
Ensembl biotype	protein_coding
OMIM	609171
Entrez	148170

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000301200, ENST00000472703, ENST00000870796, ENST00000912085, ENST00000969460

RefSeq mRNA: 1 — MANE Select: NM_145057 NM_145057

CCDS: CCDS12896

Canonical transcript exons

ENST00000301200 — 3 exons

Exon	Start	End
ENSE00001114997	54465026	54465547
ENSE00001180924	54471545	54471685
ENSE00001180929	54473064	54473296

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.3699 / max 182.6689, expressed in 1165 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182660	13.4064	1158
182658	0.7942	381
182659	0.1522	70
182661	0.0171	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.88	gold quality
duodenum	UBERON:0002114	97.23	gold quality
transverse colon	UBERON:0001157	94.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.40	gold quality
prostate gland	UBERON:0002367	94.27	gold quality
small intestine	UBERON:0002108	93.32	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.10	gold quality
rectum	UBERON:0001052	92.66	gold quality
ascending aorta	UBERON:0001496	92.63	gold quality
thoracic aorta	UBERON:0001515	92.46	gold quality
tibial nerve	UBERON:0001323	92.11	gold quality
descending thoracic aorta	UBERON:0002345	91.84	gold quality
endocervix	UBERON:0000458	91.73	gold quality
intestine	UBERON:0000160	91.36	gold quality
colon	UBERON:0001155	91.22	gold quality
calcaneal tendon	UBERON:0003701	90.67	gold quality
minor salivary gland	UBERON:0001830	89.75	gold quality
saliva-secreting gland	UBERON:0001044	89.71	gold quality
ectocervix	UBERON:0012249	89.37	gold quality
omental fat pad	UBERON:0010414	88.76	gold quality
adipose tissue	UBERON:0001013	87.91	gold quality
urinary bladder	UBERON:0001255	87.81	gold quality
right lung	UBERON:0002167	87.69	gold quality
uterine cervix	UBERON:0000002	87.68	gold quality
mucosa of stomach	UBERON:0001199	87.47	gold quality
left coronary artery	UBERON:0001626	87.40	gold quality
vagina	UBERON:0000996	87.33	gold quality
thoracic mammary gland	UBERON:0005200	87.29	gold quality
colonic epithelium	UBERON:0000397	87.23	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.19	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	55.65
E-GEOD-125970	yes	17.85
E-ANND-3	yes	13.62

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Studies indicate some of the functional and mechanistic roles of the binder of Rho GTPases Borg1-5 proteins (Cdc42EP1-5), including cytoskeletal remodelling and signalling. (PMID:27913681)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdc42ep5	ENSDARG00000062390
mus_musculus	Cdc42ep5	ENSMUSG00000063838

Paralogs (5): CDC42EP1 (ENSG00000128283), CDC42EP2 (ENSG00000149798), CDC42EP3 (ENSG00000163171), CDC42EP4 (ENSG00000179604), C15orf62 (ENSG00000188277)

Protein

Protein identifiers

Cdc42 effector protein 5 — Q6NZY7 (reviewed: Q6NZY7)

Alternative names: Binder of Rho GTPases 3

All UniProt accessions (1): Q6NZY7

UniProt curated annotations — full annotation on UniProt →

Function. Probably involved in the organization of the actin cytoskeleton. May act downstream of CDC42 to induce actin filament assembly leading to cell shape changes. Induces pseudopodia formation in fibroblasts. Inhibits MAPK8 independently of CDC42 binding. Controls septin organization and this effect is negatively regulated by CDC42.

Subunit / interactions. Interacts with CDC42, in a GTP-dependent manner, and with SEPT7.

Subcellular location. Endomembrane system. Cytoplasm. Cytoskeleton.

Domain organisation. The CRIB domain mediates interaction with CDC42.

Similarity. Belongs to the BORG/CEP family.

RefSeq proteins (1): NP_659494* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000095	CRIB_dom	Domain
IPR029273	Cdc42_effect-like	Domain
IPR051296	Cdc42_Effector_BORG/CEP	Family

Pfam: PF00786, PF14957

UniProt features (8 total): region of interest 2, compositionally biased region 2, chain 1, domain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NZY7-F1	65.09	0.08

Functional residue map

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

Post-translational modifications (1): 38

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-5687128	MAPK6/MAPK4 signaling
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-5683057	MAPK family signaling cascades
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 113 (showing top): GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOMF_GTPASE_BINDING, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_JNK_CASCADE, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_ACTIN_FILAMENT_POLYMERIZATION

GO Biological Process (5): JNK cascade (GO:0007254), Rho protein signal transduction (GO:0007266), regulation of cell shape (GO:0008360), positive regulation of actin filament polymerization (GO:0030838), positive regulation of pseudopodium assembly (GO:0031274)

GO Molecular Function (1): small GTPase binding (GO:0031267)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signal Transduction	2
MAPK family signaling cascades	1
RHO GTPase cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
MAPK cascade	1
small GTPase-mediated signal transduction	1
regulation of cell morphogenesis	1
regulation of biological quality	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
pseudopodium assembly	1
regulation of pseudopodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
GTPase binding	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC42EP5	CDC42EP2	O14613	962
CDC42EP5	CDC42EP3	Q9UKI2	955
CDC42EP5	CDC42	P21181	922
CDC42EP5	SEPTIN6	Q14141	893
CDC42EP5	RHOQ	P17081	843
CDC42EP5	SEPTIN7	Q16181	749
CDC42EP5	LENG8	Q96PV6	666
CDC42EP5	LENG9	Q96B70	636
CDC42EP5	TTYH1	Q9H313	617
CDC42EP5	TTC13	Q8NBP0	519
CDC42EP5	LAIR1	Q6GTX8	515
CDC42EP5	SEPTIN11	Q9NVA2	507
CDC42EP5	SEPTIN12	Q8IYM1	494
CDC42EP5	SEPTIN9	Q9UHD8	488
CDC42EP5	SHISA2	Q6UWI4	449

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): CDC42EP5 (Synthetic Growth Defect), Sept7 (Reconstituted Complex), Sept2 (Reconstituted Complex), Sept6 (Reconstituted Complex), CDC42EP5 (Affinity Capture-MS), CDC42EP5 (Reconstituted Complex), CDC42 (Two-hybrid), CDC42 (Reconstituted Complex)

ESM2 similar proteins: A0A286YDK6, A0A286YF18, A5PKK9, A8WFF7, F5HGI9, O08664, O10331, O12165, P03407, P05856, P06499, P12479, P17473, P27114, P28925, P46695, P52511, P52512, P89457, Q00336, Q14493, Q17QW1, Q32LJ5, Q5STR5, Q66619, Q6NZY7, Q6S6U0, Q6VUC0, Q75009, Q7YR42, Q82855, Q84240, Q86YL5, Q89448, Q8BGN9, Q8BRE0, Q8C1R3, Q8N4L4, Q8N5W9, Q8QVL8

Diamond homologs: A1A5P0, Q00587, Q08DN6, Q17QW1, Q5PQP4, Q6NZY7, Q8JZX9, Q91W92, Q9CQC5, Q9H3Q1, Q9I7F7, Q9JM96, Q9UKI2, Q9Z0X0, O14613

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

439 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54466619:ACAGT:A	donor_gain	1.0000
19:54466620:CAGTC:C	donor_gain	1.0000
19:54466623:T:TA	donor_gain	0.9900
19:54473065:TGC:T	donor_gain	0.9800
19:54466616:A:C	donor_gain	0.9700
19:54473058:CTTTA:C	donor_loss	0.9600
19:54473059:TTTA:T	donor_loss	0.9600
19:54473060:TTA:T	donor_loss	0.9600
19:54473061:TA:T	donor_loss	0.9600
19:54473063:C:A	donor_loss	0.9600
19:54473063:CCT:C	donor_gain	0.9600
19:54466591:G:A	donor_gain	0.9500
19:54466680:C:CC	acceptor_gain	0.9500
19:54471683:CACCT:C	acceptor_loss	0.9500
19:54471686:C:CG	acceptor_loss	0.9500
19:54471687:T:G	acceptor_loss	0.9500
19:54473064:CTG:C	donor_gain	0.9500
19:54471539:CCTTA:C	donor_loss	0.9400
19:54471540:CTTA:C	donor_loss	0.9400
19:54471541:TTA:T	donor_loss	0.9400
19:54471542:TA:T	donor_loss	0.9400
19:54471543:A:AT	donor_loss	0.9400
19:54466491:AGGCT:A	donor_gain	0.9300
19:54466545:G:A	donor_gain	0.9200
19:54466621:A:C	donor_gain	0.9200
19:54471683:CAC:C	acceptor_gain	0.9100
19:54465544:GCATC:G	acceptor_loss	0.8900
19:54465546:ATCT:A	acceptor_loss	0.8900
19:54465547:TC:T	acceptor_loss	0.8900
19:54465548:CTG:C	acceptor_loss	0.8900

AlphaMissense

931 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:54465404:G:C	F48L	0.996
19:54465404:G:T	F48L	0.996
19:54465406:A:G	F48L	0.996
19:54465458:G:C	F30L	0.995
19:54465458:G:T	F30L	0.995
19:54465459:A:G	F30S	0.995
19:54465460:A:G	F30L	0.995
19:54465419:G:C	F43L	0.994
19:54465419:G:T	F43L	0.994
19:54465421:A:G	F43L	0.994
19:54465459:A:C	F30C	0.991
19:54465417:C:T	G44E	0.990
19:54465405:A:C	F48C	0.989
19:54465462:T:A	D29V	0.989
19:54465445:G:C	H35D	0.987
19:54465480:A:G	I23T	0.987
19:54465417:C:A	G44V	0.986
19:54465420:A:C	F43C	0.986
19:54465405:A:G	F48S	0.985
19:54465462:T:C	D29G	0.984
19:54465262:C:G	G96R	0.983
19:54465262:C:T	G96R	0.983
19:54465452:G:C	H32Q	0.983
19:54465452:G:T	H32Q	0.983
19:54465454:G:C	H32D	0.983
19:54465463:C:G	D29H	0.983
19:54465480:A:T	I23N	0.983
19:54465462:T:G	D29A	0.982
19:54465418:C:A	G44W	0.981
19:54465453:T:C	H32R	0.980

dbSNP variants (sampled 300 via entrez): RS1000015318 (19:54465694 G>A), RS1000023329 (19:54469598 T>G), RS1000027697 (19:54474270 G>A,T), RS1000246736 (19:54471323 G>A), RS1000564431 (19:54474955 G>C), RS1000998781 (19:54475265 C>T), RS1001596536 (19:54470286 C>A), RS10017 (19:54465172 C>A,T), RS1001818651 (19:54472442 T>C,G), RS1001847567 (19:54473406 A>T), RS1001957642 (19:54469125 G>A), RS1002635406 (19:54473013 C>T), RS1002993963 (19:54469124 A>C), RS1003119682 (19:54464556 C>CG), RS1003350814 (19:54469421 C>A)

Disease associations

OMIM: gene MIM:609171 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
bisphenol A	affects cotreatment, increases methylation	1
terbufos	increases methylation	1
sodium arsenite	increases expression	1
muconaldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	affects expression	1
Copper	affects binding, increases expression	1
Cytarabine	decreases expression	1
Disulfiram	affects binding, increases expression	1
Fonofos	increases methylation	1
Lipopolysaccharides	increases expression, decreases reaction	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery