CDC42EP2

Summary

CDC42EP2 (CDC42 effector protein 2, HGNC:16263) is a protein-coding gene on chromosome 11q13.1, encoding Cdc42 effector protein 2 (O14613). Probably involved in the organization of the actin cytoskeleton.

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 family of CDC42 effector proteins. Borg family proteins contain a CRIB (Cdc42/Rac interactive-binding) domain. They bind to, and negatively regulate the function of CDC42. Coexpression of this protein with CDC42 suggested a role of this protein in actin filament assembly and cell shape control.

Source: NCBI Gene 10435 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_006779

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16263
Approved symbol	CDC42EP2
Name	CDC42 effector protein 2
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	CEP2, BORG1
Ensembl gene	ENSG00000149798
Ensembl biotype	protein_coding
OMIM	606132
Entrez	10435

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000279249, ENST00000533419, ENST00000905621, ENST00000905622, ENST00000905623, ENST00000911954, ENST00000911955, ENST00000911956

RefSeq mRNA: 1 — MANE Select: NM_006779 NM_006779

CCDS: CCDS8099

Canonical transcript exons

ENST00000279249 — 2 exons

Exon	Start	End
ENSE00000992560	65320544	65322417
ENSE00001063655	65314866	65314954

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 92.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.7550 / max 325.6449, expressed in 1715 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115066	30.2366	1663
115065	8.5184	1620

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	92.01	gold quality
omental fat pad	UBERON:0010414	90.42	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.39	gold quality
lower esophagus	UBERON:0013473	90.28	gold quality
mucosa of stomach	UBERON:0001199	89.40	gold quality
blood	UBERON:0000178	88.70	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.57	gold quality
adipose tissue	UBERON:0001013	87.88	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.41	gold quality
stromal cell of endometrium	CL:0002255	86.44	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.74	gold quality
left uterine tube	UBERON:0001303	85.53	gold quality
gall bladder	UBERON:0002110	84.83	gold quality
upper lobe of left lung	UBERON:0008952	84.80	gold quality
heart left ventricle	UBERON:0002084	83.29	gold quality
granulocyte	CL:0000094	82.69	gold quality
placenta	UBERON:0001987	82.66	gold quality
left lobe of thyroid gland	UBERON:0001120	82.61	gold quality
spleen	UBERON:0002106	82.53	gold quality
thyroid gland	UBERON:0002046	82.50	gold quality
myometrium	UBERON:0001296	82.29	gold quality
metanephros cortex	UBERON:0010533	82.11	gold quality
urinary bladder	UBERON:0001255	81.88	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.87	gold quality
thoracic mammary gland	UBERON:0005200	81.85	gold quality
right lobe of thyroid gland	UBERON:0001119	81.79	gold quality
body of uterus	UBERON:0009853	81.64	gold quality
fundus of stomach	UBERON:0001160	81.56	gold quality
esophagus	UBERON:0001043	81.43	gold quality
substantia nigra	UBERON:0002038	81.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting CDC42EP2, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-5187-3P	97.28	67.10	1037
HSA-MIR-3649	96.85	64.10	340
HSA-MIR-1226-5P	96.50	65.28	643
HSA-MIR-4435	95.90	65.47	1201
HSA-MIR-6874-5P	95.73	64.94	545

Literature-anchored findings (GeneRIF, showing 3)

• activations of Rac1 and Cdc42 are involved in the hypoxia-induced production of angiogenesis-promoting factors and tumor suppressors, and suggest that the Rho family GTPases Rac1 and Cdc42 may contribute to the hypoxia-mediated angiogenesis. (PMID:16395716)
• CDC42EP2 is upregulated in human PDLCs subjected to tensile stress related to mechano-induced cell cycle arrest. (PMID:20934684)
• 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

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdc42ep2	ENSDARG00000053959
mus_musculus	Cdc42ep2	ENSMUSG00000045664
rattus_norvegicus	Cdc42ep2	ENSRNOG00000020904

Paralogs (5): CDC42EP1 (ENSG00000128283), CDC42EP3 (ENSG00000163171), CDC42EP5 (ENSG00000167617), CDC42EP4 (ENSG00000179604), C15orf62 (ENSG00000188277)

Protein

Protein identifiers

Cdc42 effector protein 2 — O14613 (reviewed: O14613)

Alternative names: Binder of Rho GTPases 1

All UniProt accessions (1): O14613

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 in a CDC42-dependent manner.

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

Subcellular location. Endomembrane system. Cytoplasm. Cytoskeleton.

Tissue specificity. Highly expressed in the heart. Weakly expressed in the pancreas and liver.

Domain organisation. The CRIB domain mediates interaction with CDC42.

Similarity. Belongs to the BORG/CEP family.

RefSeq proteins (1): NP_006770* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000095	CRIB_dom	Domain
IPR017363	Cdc42_effector_prot_2	Family
IPR029273	Cdc42_effect-like	Domain
IPR051296	Cdc42_Effector_BORG/CEP	Family

Pfam: PF00786, PF14957

UniProt features (12 total): modified residue 4, sequence variant 2, initiator methionine 1, chain 1, mutagenesis site 1, sequence conflict 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14613-F1	62.22	0.03

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 (4): 2, 31, 101, 141

Mutagenesis-validated functional residues (1):

Position	Phenotype
39–42	no binding with cdc42; no induced pseudopodia formation.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5687128	MAPK6/MAPK4 signaling
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013406	RHOQ 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: 190 (showing top): GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_PEPTIDE, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOMF_GTPASE_BINDING, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, chr11q13, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, BROWNE_HCMV_INFECTION_48HR_DN

GO Biological Process (8): actin filament organization (GO:0007015), Rho protein signal transduction (GO:0007266), regulation of cell shape (GO:0008360), actin cytoskeleton organization (GO:0030036), positive regulation of actin filament polymerization (GO:0030838), positive regulation of pseudopodium assembly (GO:0031274), positive regulation of protein-containing complex assembly (GO:0031334), cellular response to type II interferon (GO:0071346)

GO Molecular Function (4): opioid peptide activity (GO:0001515), GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (8): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), endomembrane system (GO:0012505), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), phagocytic vesicle (GO:0045335)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RHO GTPase cycle	2
Signal Transduction	2
MAPK family signaling cascades	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
actin cytoskeleton organization	1
supramolecular fiber organization	1
small GTPase-mediated signal transduction	1
regulation of cell morphogenesis	1
regulation of biological quality	1
cytoskeleton organization	1
actin filament-based process	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
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
response to type II interferon	1
cellular response to cytokine stimulus	1
receptor ligand activity	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
GTPase binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1
cytoskeleton	1
endocytic vesicle	1

Protein interactions and networks

STRING

540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC42EP2	CDC42EP5	Q6NZY7	962
CDC42EP2	RHOQ	P17081	887
CDC42EP2	CDC42	P21181	762
CDC42EP2	SLC25A45	Q8N413	534
CDC42EP2	GOSR1	O95249	529
CDC42EP2	ACY1	Q03154	513
CDC42EP2	FAM89B	Q8N5H3	492
CDC42EP2	UNC50	Q53HI1	478
CDC42EP2	SEPTIN2	Q15019	460
CDC42EP2	H3BQ15	H3BQ15	457
CDC42EP2	SEPTIN6	Q14141	456
CDC42EP2	AMDHD2	Q9Y303	453
CDC42EP2	TIGD3	Q6B0B8	447
CDC42EP2	ZNRD2	O60232	437
CDC42EP2	DPF2	Q92785	423

IntAct

38 interactions, top by confidence:

A	B	Type	Score
CDC42	CDC42EP2	psi-mi:“MI:0915”(physical association)	0.830
CDC42EP2	CDC42	psi-mi:“MI:0915”(physical association)	0.830
NME7	CDC42EP2	psi-mi:“MI:0915”(physical association)	0.720
CDC42EP2	NME7	psi-mi:“MI:0915”(physical association)	0.720
CDC42EP2	CASS4	psi-mi:“MI:0915”(physical association)	0.670
CDC42EP2	ARHGAP26	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP26	CDC42EP2	psi-mi:“MI:0915”(physical association)	0.560
CDC42EP2	COX5B	psi-mi:“MI:0915”(physical association)	0.560
CDC42EP2	PICK1	psi-mi:“MI:0915”(physical association)	0.560
CDC42EP2	NEDD9	psi-mi:“MI:0915”(physical association)	0.560
PCNA	CDC42EP2	psi-mi:“MI:0915”(physical association)	0.370
KCNK3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
CASS4	CDC42EP2	psi-mi:“MI:0915”(physical association)	0.000
CDC42	CDC42EP2	psi-mi:“MI:0915”(physical association)	0.000
NME7	CDC42EP2	psi-mi:“MI:0915”(physical association)	0.000
COX5B	CDC42EP2	psi-mi:“MI:0915”(physical association)	0.000
PICK1	CDC42EP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): CDC42EP2 (Two-hybrid), ARHGAP26 (Two-hybrid), NME7 (Two-hybrid), ARHGAP26 (Two-hybrid), CDC42EP2 (Two-hybrid), CDC42EP2 (Proximity Label-MS), CDC42EP2 (Affinity Capture-RNA), CDC42EP2 (Two-hybrid), CDC42EP2 (Two-hybrid), CDC42EP2 (Two-hybrid), CDC42EP2 (Two-hybrid), CDC42EP2 (Two-hybrid), CDC42EP2 (Two-hybrid), SEPT7 (Reconstituted Complex), SEPT6 (Reconstituted Complex)

ESM2 similar proteins: A0FGR0, A0JMD2, A1L253, A3KP40, A7LKB2, A8K5M9, B1AXH1, B1AZP2, B5X7E4, B5XBI1, E2QSX5, F1QPR4, F1QR98, F1RDM5, O14490, O14613, O35413, O54834, O94875, O95886, P0CAX8, P28290, P97836, P97837, P97838, P97839, Q2HJ75, Q3UTJ2, Q3ZBS1, Q5REU9, Q5SYE7, Q60592, Q62417, Q6P0Q8, Q6PD31, Q6PFD5, Q7ZYZ6, Q80Y24, Q8BJ42, Q8BLN6

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MAPK1	unknown	CDC42EP2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

393 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65314951:CACGG:C	donor_loss	0.9900
11:65314952:ACGGT:A	donor_loss	0.9900
11:65314953:CGG:C	donor_loss	0.9900
11:65314954:GGTG:G	donor_loss	0.9900
11:65314955:G:GC	donor_loss	0.9900
11:65314955:G:GG	donor_gain	0.9900
11:65314956:T:A	donor_loss	0.9900
11:65320542:A:AG	acceptor_gain	0.9900
11:65320543:G:GA	acceptor_gain	0.9900
11:65314957:GAG:G	donor_loss	0.9800
11:65320537:GTTTC:G	acceptor_loss	0.9800
11:65320538:TTTCA:T	acceptor_loss	0.9800
11:65320540:TCA:T	acceptor_loss	0.9800
11:65320542:A:G	acceptor_loss	0.9800
11:65320543:GCTC:G	acceptor_gain	0.9800
11:65320543:GC:G	acceptor_gain	0.9700
11:65320543:GCT:G	acceptor_gain	0.9700
11:65314953:CG:C	donor_gain	0.9600
11:65314954:GG:G	donor_gain	0.9600
11:65314952:ACG:A	donor_gain	0.9500
11:65314950:TCACG:T	donor_gain	0.9300
11:65320540:TCAG:T	acceptor_gain	0.9200
11:65320541:CAGC:C	acceptor_gain	0.9200
11:65320542:AG:A	acceptor_gain	0.9100
11:65320534:T:A	acceptor_loss	0.9000
11:65320543:G:T	acceptor_gain	0.9000
11:65320543:GCTCC:G	acceptor_gain	0.8900
11:65320728:G:A	acceptor_gain	0.8800
11:65314951:CACG:C	donor_gain	0.8700
11:65320539:TTCAG:T	acceptor_gain	0.8700

AlphaMissense

1364 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65320987:T:A	I30N	0.999
11:65320987:T:C	I30T	0.999
11:65320987:T:G	I30S	0.999
11:65320989:A:C	S31R	0.999
11:65320991:C:A	S31R	0.999
11:65320991:C:G	S31R	0.999
11:65321022:C:G	H42D	0.998
11:65321052:T:C	F52L	0.998
11:65321054:T:A	F52L	0.998
11:65321054:T:G	F52L	0.998
11:65321067:T:C	F57L	0.998
11:65321069:C:A	F57L	0.998
11:65321069:C:G	F57L	0.998
11:65321008:T:C	F37S	0.997
11:65321013:C:G	H39D	0.997
11:65321014:A:G	H39R	0.997
11:65321056:G:A	G53D	0.997
11:65321056:G:T	G53V	0.997
11:65321460:G:A	G188R	0.997
11:65321460:G:C	G188R	0.997
11:65320972:T:A	L25Q	0.996
11:65321011:G:C	R38P	0.996
11:65321015:C:A	H39Q	0.996
11:65321015:C:G	H39Q	0.996
11:65321024:T:A	H42Q	0.996
11:65321024:T:G	H42Q	0.996
11:65321461:G:A	G188E	0.996
11:65321053:T:G	F52C	0.995
11:65321055:G:C	G53R	0.995
11:65321458:T:C	L187P	0.995

dbSNP variants (sampled 300 via entrez): RS1000521534 (11:65315855 G>C), RS1001415894 (11:65316553 A>G), RS1001760828 (11:65317023 C>A,G,T), RS1001803013 (11:65322003 G>A), RS1002460934 (11:65317393 C>T), RS1003058552 (11:65318952 C>A), RS1003609063 (11:65313866 C>A), RS1003699671 (11:65318347 C>G,T), RS1003907466 (11:65322397 G>C), RS1003920890 (11:65315553 A>G), RS1004530797 (11:65322027 C>T), RS1004581221 (11:65319152 G>A,T), RS1006042145 (11:65317280 C>A), RS1006205755 (11:65322177 A>C), RS1006984881 (11:65314931 G>A,C)

Disease associations

OMIM: gene MIM:606132 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002481_8	Acne (severe)	3.000000e-11
GCST004602_196	Mean corpuscular volume	4.000000e-09
GCST90002390_32	Mean corpuscular hemoglobin	5.000000e-19
GCST90002392_348	Mean corpuscular volume	9.000000e-22

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	3
Estradiol	affects cotreatment, increases expression	3
bisphenol A	increases methylation, affects expression, affects cotreatment	2
Dexamethasone	increases expression, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases abundance, increases expression	1
butyraldehyde	increases expression	1
ferrous chloride	decreases expression	1
muconaldehyde	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
licochalcone B	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Cadmium	increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, decreases expression	1
N-Nitrosopyrrolidine	increases expression	1

Clinical trials (associated diseases)

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