CDC42

Summary

CDC42 (cell division cycle 42, HGNC:1736) is a protein-coding gene on chromosome 1p36.12, encoding Cell division control protein 42 homolog (P60953). Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. It is a common-essential gene (DepMap: required in 93.5% of cancer cell lines).

The protein encoded by this gene is a small GTPase of the Rho-subfamily, which regulates signaling pathways that control diverse cellular functions including cell morphology, migration, endocytosis and cell cycle progression. This protein is highly similar to Saccharomyces cerevisiae Cdc 42, and is able to complement the yeast cdc42-1 mutant. The product of oncogene Dbl was reported to specifically catalyze the dissociation of GDP from this protein. This protein could regulate actin polymerization through its direct binding to Neural Wiskott-Aldrich syndrome protein (N-WASP), which subsequently activates Arp2/3 complex. Alternative splicing of this gene results in multiple transcript variants. Pseudogenes of this gene have been identified on chromosomes 3, 4, 5, 7, 8 and 20.

Source: NCBI Gene 998 — RefSeq curated summary.

At a glance

• Gene–disease (curated): macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome (Definitive, ClinGen)
• GWAS associations: 16
• Clinical variants (ClinVar): 162 total — 9 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 84
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 93.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_001791

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1736
Approved symbol	CDC42
Name	cell division cycle 42
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	G25K, CDC42Hs
Ensembl gene	ENSG00000070831
Ensembl biotype	protein_coding
OMIM	116952
Entrez	998

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 33 protein_coding, 4 nonsense_mediated_decay

ENST00000315554, ENST00000344548, ENST00000400259, ENST00000411827, ENST00000498236, ENST00000651171, ENST00000652582, ENST00000656825, ENST00000662562, ENST00000667384, ENST00000695796, ENST00000695797, ENST00000695798, ENST00000695799, ENST00000695800, ENST00000695801, ENST00000695802, ENST00000695857, ENST00000695858, ENST00000695859, ENST00000695860, ENST00000695861, ENST00000695862, ENST00000695863, ENST00000866253, ENST00000866254, ENST00000866255, ENST00000866256, ENST00000866257, ENST00000866258, ENST00000866259, ENST00000932442, ENST00000932443, ENST00000963898, ENST00000963899, ENST00000963900, ENST00000963901

RefSeq mRNA: 3 — MANE Select: NM_001791 NM_001039802, NM_001791, NM_044472

CCDS: CCDS221, CCDS222

Canonical transcript exons

ENST00000656825 — 6 exons

Exon	Start	End
ENSE00001879845	22052709	22052742
ENSE00003836748	22086669	22086866
ENSE00003842433	22081722	22081794
ENSE00003846999	22086439	22086548
ENSE00003849315	22078429	22078583
ENSE00003965058	22091428	22101360

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 211.9120 / max 1626.6213, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1272	187.3164	1826
1271	24.5956	1808
1266	13.0028	1789

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.45	gold quality
monocyte	CL:0000576	99.38	gold quality
mononuclear cell	CL:0000842	99.20	gold quality
leukocyte	CL:0000738	99.19	gold quality
islet of Langerhans	UBERON:0000006	99.15	gold quality
rectum	UBERON:0001052	99.00	gold quality
ganglionic eminence	UBERON:0004023	98.98	gold quality
colonic epithelium	UBERON:0000397	98.87	gold quality
gall bladder	UBERON:0002110	98.87	gold quality
adrenal tissue	UBERON:0018303	98.87	gold quality
smooth muscle tissue	UBERON:0001135	98.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.81	gold quality
granulocyte	CL:0000094	98.65	gold quality
ventricular zone	UBERON:0003053	98.61	gold quality
calcaneal tendon	UBERON:0003701	98.40	gold quality
stromal cell of endometrium	CL:0002255	98.30	gold quality
lymph node	UBERON:0000029	98.29	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.29	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.28	gold quality
endothelial cell	CL:0000115	98.24	gold quality
skin of abdomen	UBERON:0001416	98.23	gold quality
skin of leg	UBERON:0001511	98.14	gold quality
vagina	UBERON:0000996	98.11	gold quality
right lung	UBERON:0002167	98.10	gold quality
left uterine tube	UBERON:0001303	98.08	gold quality
transverse colon	UBERON:0001157	98.06	gold quality
esophagus mucosa	UBERON:0002469	98.06	gold quality
mucosa of transverse colon	UBERON:0004991	98.04	gold quality
upper lobe of left lung	UBERON:0008952	97.97	gold quality
ectocervix	UBERON:0012249	97.97	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-89232	yes	4732.43
E-MTAB-7051	yes	4486.86
E-MTAB-10042	yes	4.07
E-GEOD-70580	no	858.12
E-MTAB-6524	no	214.50
E-HCAD-4	no	78.36
E-HCAD-5	no	47.64
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4, ESR1, JUN, NFKB, PTTG1

miRNA regulators (miRDB)

68 targeting CDC42, 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-3613-3P	100.00	76.36	7965
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-8485	100.00	77.57	4731
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6739-5P	99.80	67.87	2806

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 93.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Mechanistically, miR-998 operates by repressing dCbl, a negative regulator of EGFR signaling. Significantly, dCbl is a critical target of miR-998 since dCbl phenocopies the effects of miR-998 on dE2f1-dependent apoptosis in rbf mutants (PMID:25058496)
• Our findings indicate that different signaling cascades resulting in the activation of ..or Cdc42 can modulate the exocytotic process of neuroendocrine cells. (PMID:11822867)
• Cdc42 is required for capillary lumen formation by vascular endothelial cells in three-dimensional extracellular matrices (PMID:11884513)
• Data show that TGF-beta-induced rearrangements of the actin filament system required the activity of the Rho GTPases Cdc42 and RhoA, because ectopic expression of dominant negative mutant Cdc42 and RhoA abrogated the response. (PMID:11907271)
• signaling to the cytoskeleton involves IQGAP1 as a component (PMID:11948177)
• role for small GTPase CDC42Hs in the generation of skeletal muscle tumors. (PMID:11973651)
• Structural basis for the selective activation of Rho GTPases by Dbl exchange factors (PMID:12006984)
• SopE binds to and locks the switch I and switch II regions of human Cdc42(1-178) in a conformation that promotes guanine nucleotide release. (PMID:12093730)
• Cdc42 play essential role in regulating the formation of dendritic processes by dendritic cell (PMID:12115629)
• Effect of Mg(2+) on the kinetics of guanine nucleotide binding and hydrolysis (PMID:12270144)
• The ability of a Cdc42(D118N) mutant to survive under apoptotic conditions accounts for its superior transforming activity compared to other activated versions of Cdc42. (PMID:12369824)
• Rac1 and Cdc42 are activated independent of RhoG (PMID:12376551)
• Cdc42 is involved in the mediation of intracellular lipid transport. (PMID:12426222)
• Cdc42/Rac1-dependent activation of the p21-activated kinase (PAK) regulates human platelet lamellipodia spreading. (PMID:12453877)
• Rac/Cdc42-dependent activation of MAPK/ERK is a critical event in the immediate phagocytic response of PMNs to microbial challenge. (PMID:12511425)
• Data show that inhibition of endogenous RhoA, Rac1, and Cdc42 by their respective dominant negative mutants inhibits neurotensin-induced interleukin-8 protein production and promoter activity. (PMID:12584113)
• VE-cadherin can serve as a scaffold involved in Cdc42 activation at the endothelial plasma membrane. (PMID:12595527)
• TRE17 coprecipitated specifically with the active forms of Cdc42 and Rac1 in vivo. TRE17 is part of a novel effector complex for Cdc42 and Rac1, potentially contributing to their effects on actin remodeling. (PMID:12612085)
• Upregulation during arachidonic acid mediated HeLa cell adhesion. (PMID:12767056)
• Instead of inducing neurite formation, a constitutively active form of human Cdc42 stimulates the proliferation of rat PC12 cells in the presence of nerve growth factor. (PMID:12824775)
• Cdc42 regulates the activitity of p21-activated protein kinase 5 (PMID:12860998)
• Activated CDC42 at the leading edge of a neutrophil in culture helps orient the cell’s axis in a signaling complex with G beta gamma, PAK1, and PIXalpha. (PMID:12887916)
• Activated CDC42 helps orient the neutrophil’s axis in a signaling complex with Gbeta gamma, PAK1, and PIXalpha. (PMID:12887922)
• Directional sensing requires GNB1-mediated PAK1 and PIX alpha-dependent activation of Cdc42. (PMID:12887923)
• BNIPL-2, a novel homologue of BNIP-2, interacts with Bcl-2 and Cdc42GAP in apoptosis. (PMID:12901880)
• Activation of the small Rho GTPase Cdc42 plays a specific role in the actin reorganization mediated by CD28 in human T cells. (PMID:12928366)
• direct activation of Cdc42 and Rac1 by invasive Salmonella is a prerequisite of Salmonella-mediated death of U937 cells. (PMID:12960245)
• in neutrophils, Rac2 and Cdc42 are involved in FcR- and CR3-induced activation and for properly functioning signal transduction involved in the generation of oxygen radicals. (PMID:12960248)
• The reorganization of actins into podosomes is controlled by CDC42 GTP-binding protein. (PMID:12972601)
• Cdc42 signaling has a role in apoA-I-induced cholesterol efflux (PMID:14563854)
• The delayed activation of Cdc42 represents a negative-feedback mechanism that signals adherens junction reassembly after the increase in endothelial permeability induced by inflammatory mediators such as thrombin. (PMID:14656933)
• Cdc42 synergistically with Rac1 induces lamellipodia and membrane ruffles in EGF-stimulated cells. (PMID:14699061)
• Cdc42 signal transduction to the nucleus requires ACK-1 and ACK-2 (PMID:14733946)
• Cdc42 has a role in mediation of UV-induced p38 activation by G protein betagamma subunits (PMID:14970210)
• novel role for Smad7 in TGF-beta-dependent activation of Cdc42 (PMID:15075243)
• C. parvum invasion of target epithelia results from the organism’s ability to activate a host cell Cdc42 GTPase signaling pathway to induce host cell actin remodeling at the attachment site. (PMID:15102814)
• a specific region in Cdc42 confers the binding specificity to activated Cdc42-associated kinase (PMID:15123659)
• cross-talk between Rac and Cdc42 GTPases regulates generation of reactive oxygen species (PMID:15123662)
• role of frabin, a guanine nucleotide exchange factor specific for Cdc42, in the activation of Cdc42 during Cryptosporidium parvum infection of biliary epithelial cells (PMID:15133042)
• cdc42 has a role in activating c-Jun N-terminal kinase activation with Nck1 (PMID:15187089)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdc42l	ENSDARG00000040158
danio_rerio	cdc42	ENSDARG00000044573
mus_musculus	Cdc42	ENSMUSG00000006699
rattus_norvegicus	Cdc42	ENSRNOG00000013536
rattus_norvegicus		ENSRNOG00000066330
drosophila_melanogaster	Cdc42	FBGN0010341
caenorhabditis_elegans		WBGENE00000390

Paralogs (22): RHOBTB2 (ENSG00000008853), RHOA (ENSG00000067560), RHOBTB1 (ENSG00000072422), RHOV (ENSG00000104140), RND2 (ENSG00000108830), RND3 (ENSG00000115963), RHOU (ENSG00000116574), RHOQ (ENSG00000119729), RHOJ (ENSG00000126785), RHOT1 (ENSG00000126858), RAC2 (ENSG00000128340), RAC1 (ENSG00000136238), RHOF (ENSG00000139725), RHOT2 (ENSG00000140983), RHOB (ENSG00000143878), RHOC (ENSG00000155366), RHOBTB3 (ENSG00000164292), RHOH (ENSG00000168421), RAC3 (ENSG00000169750), RND1 (ENSG00000172602), RHOD (ENSG00000173156), RHOG (ENSG00000177105)

Protein

Protein identifiers

Cell division control protein 42 homolog — P60953 (reviewed: P60953)

Alternative names: G25K GTP-binding protein

All UniProt accessions (9): P60953, A0A3B3IRV0, A0A494BZX6, A0A494C1M1, A0A590UJK8, A0A8Q3SI43, A0A8Q3WKT2, A0A8Q3WLC5, Q5JYX0

UniProt curated annotations — full annotation on UniProt →

Function. Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Regulates cell migration. In neurons, plays a role in the extension and maintenance of the formation of filopodia, thin and actin-rich surface projections. Required for DOCK10-mediated spine formation in Purkinje cells and hippocampal neurons. In podocytes, facilitates filopodia and podosomes formation upon DOCK11-activation. Upon activation by CaMKII, modulates dendritic spine structural plasticity by relaying CaMKII transient activation to synapse-specific, long-term signaling. Also plays a role in phagocytosis through organization of the F-actin cytoskeleton associated with forming phagocytic cups. Upon activation by PLEKHG4B, involved in actin cytoskeletal remodeling during epithelial cell-cell junction formation.

Subunit / interactions. Interacts with CDC42EP1, CDC42EP2, CDC42EP3, CDC42EP4, CDC42EP5, CDC42SE1, CDC42SE2, PARD6A, PARD6B and PARD6G (in a GTP-dependent manner). Interacts with activated CSPG4 and with BAIAP2. Interacts with activated CSPG4 and with BAIAP2. Interacts with DOCK11/Zizimin2; the interaction activates CDC42 by exchanging GDP for GTP. Interacts with DOCK9; the interaction activates CDC42 by exchanging GDP for GTP. Interacts with DOCK8 (via DHR-2 domain); the interaction activates CDC42 by exchanging GDP for GTP. Interacts with IQGAP1. Interacts with NET1 and ARHGAP33/TCGAP. Part of a complex with PARD3, PARD6A or PARD6B and PRKCI or PRKCZ. The GTP-bound form interacts with CCPG1. Interacts with USP6. Interacts with NEK6. Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas. Interacts with ITGB1BP1. Interacts with ARHGDIA; this interaction inactivates and stabilizes CDC42. Interacts with ARHGDIB; this maintains CDC42 in the inactive, GDP-bound form. Interacts (in GTP-bound form) with FNBP1L and ABI1, but only in the presence of FNBP1L. May interact with ARHGEF16; responsible for the activation of CDC42 by the viral protein HPV16 E6. Interacts with MARCKS. Interacts with CD151 and ITGB1. Interacts with TINCR; the interaction promotes CDC42 sumoylation and activation.

Subcellular location. Cell membrane. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle. Midbody. Cell projection. Dendrite.

Post-translational modifications. (Microbial infection) AMPylation at Tyr-32 and Thr-35 are mediated by bacterial enzymes in case of infection by H.somnus and V.parahaemolyticus, respectively. AMPylation occurs in the effector region and leads to inactivation of the GTPase activity by preventing the interaction with downstream effectors, thereby inhibiting actin assembly in infected cells. It is unclear whether some human enzyme mediates AMPylation; FICD has such ability in vitro but additional experiments remain to be done to confirm results in vivo. Phosphorylated by SRC in an EGF-dependent manner, this stimulates the binding of the Rho-GDP dissociation inhibitor RhoGDI. (Microbial infection) Glycosylated at Tyr-32 by Photorhabdus asymbiotica toxin PAU_02230. Mono-O-GlcNAcylation by PAU_02230 inhibits downstream signaling by an impaired interaction with diverse regulator and effector proteins of CDC42 and leads to actin disassembly. (Microbial infection) Glucosylated at Thr-35 by C.difficile toxins TcdA and TcdB in the colonic epithelium. Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption and cell death, resulting in the loss of colonic epithelial barrier function. (Microbial infection) Glycosylated (O-GlcNAcylated) at Thr-35 by C.novyi toxin TcdA. O-GlcNAcylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption. Sumoylated; sumoylation is enhanced by TINCR and promotes CDC42 activation.

Disease relevance. Takenouchi-Kosaki syndrome (TKS) [MIM:616737] An autosomal dominant syndrome characterized by macrothrombocytopenia, lymphedema, intellectual disability, developmental delay, and distinctive facial features. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase.

Similarity. Belongs to the small GTPase superfamily. Rho family. CDC42 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P60953-2	2, Placental	yes
P60953-1	1, Brain

RefSeq proteins (3): NP_001034891, NP_001782, NP_426359 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR003578	Small_GTPase_Rho	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR037874	Cdc42	Family

Pfam: PF00071

Enzyme classification (BRENDA):

• EC 3.6.5.2 — small monomeric GTPase (BRENDA: 49 organisms, 138 substrates, 55 inhibitors, 5 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	—	0

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (46 total): helix 11, strand 9, turn 5, mutagenesis site 4, modified residue 4, glycosylation site 3, binding site 3, splice variant 2, chain 1, propeptide 1, lipid moiety-binding region 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

48 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2NGR	X-RAY DIFFRACTION	1.9
4JS0	X-RAY DIFFRACTION	1.9
6SUP	X-RAY DIFFRACTION	2
3VHL	X-RAY DIFFRACTION	2.08
1GRN	X-RAY DIFFRACTION	2.1
1NF3	X-RAY DIFFRACTION	2.1
2DFK	X-RAY DIFFRACTION	2.15
2WM9	X-RAY DIFFRACTION	2.2
2WMO	X-RAY DIFFRACTION	2.2
1GZS	X-RAY DIFFRACTION	2.3
1KI1	X-RAY DIFFRACTION	2.3
3GCG	X-RAY DIFFRACTION	2.3
4ITR	X-RAY DIFFRACTION	2.3
4DID	X-RAY DIFFRACTION	2.35
2WMN	X-RAY DIFFRACTION	2.39
1KZ7	X-RAY DIFFRACTION	2.4
2ODB	X-RAY DIFFRACTION	2.4
2QRZ	X-RAY DIFFRACTION	2.4
5UPK	X-RAY DIFFRACTION	2.4
6SIU	X-RAY DIFFRACTION	2.49
1A4R	X-RAY DIFFRACTION	2.5
4YC7	X-RAY DIFFRACTION	2.5
6TKY	X-RAY DIFFRACTION	2.55
1DOA	X-RAY DIFFRACTION	2.6
1KZG	X-RAY DIFFRACTION	2.6
5CJP	X-RAY DIFFRACTION	2.6
6TKZ	X-RAY DIFFRACTION	2.64
3QBV	X-RAY DIFFRACTION	2.65
1AM4	X-RAY DIFFRACTION	2.7
7S0Y	X-RAY DIFFRACTION	2.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60953-F1	93.30	0.84

Functional residue map

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

Ligand- & substrate-binding residues (3): 10–17; 57–61; 115–118

Post-translational modifications (5): 188, 32, 35, 64, 188

Glycosylation sites (3): 32, 35, 35

Mutagenesis-validated functional residues (4):

Position	Phenotype
12	constitutively active. interacts with pard6 proteins. does not inhibit filopodia formation. no effect on nr3c2 transcrip
17	constitutively inactive. does not interact with pard6 proteins. inhibits filopodia formation. no effect on nr3c2 transcr
32	abolishes ampylation by haemophilus ibpa.
61	constitutively active. interacts with pard6 proteins.

Function

Pathways and Gene Ontology

Reactome pathways

66 pathways

ID	Pathway
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-182971	EGFR downregulation
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-389359	CD28 dependent Vav1 pathway
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-418885	DCC mediated attractive signaling
R-HSA-428543	Inactivation of CDC42 and RAC1
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-525793	Myogenesis
R-HSA-5625970	RHO GTPases activate KTN1
R-HSA-5626467	RHO GTPases activate IQGAPs
R-HSA-5627123	RHO GTPases activate PAKs
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-5687128	MAPK6/MAPK4 signaling
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-8964616	G beta:gamma signalling through CDC42
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9013420	RHOU GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9013424	RHOV GTPase cycle
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-9958810	SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)
R-HSA-9958825	Activation of STAT3 by cadherin engagement

MSigDB gene sets: 767 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_DENDRITE_DEVELOPMENT, GGGACCA_MIR133A_MIR133B, GCACCTT_MIR18A_MIR18B, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, AAGCAAT_MIR137, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_CELL_MIGRATION_INVOLVED_IN_HEART_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_MONOPOLAR_CELL_POLARITY, GOBP_PINOCYTOSIS, GOBP_LUNG_EPITHELIUM_DEVELOPMENT

GO Biological Process (60): cardiac conduction system development (GO:0003161), cardiac neural crest cell migration involved in outflow tract morphogenesis (GO:0003253), endocytosis (GO:0006897), phagocytosis, engulfment (GO:0006911), actin filament organization (GO:0007015), Golgi organization (GO:0007030), regulation of mitotic nuclear division (GO:0007088), nuclear migration (GO:0007097), establishment or maintenance of cell polarity (GO:0007163), signal transduction (GO:0007165), integrin-mediated signaling pathway (GO:0007229), small GTPase-mediated signal transduction (GO:0007264), intracellular protein localization (GO:0008104), regulation of lamellipodium assembly (GO:0010591), positive regulation of lamellipodium assembly (GO:0010592), substantia nigra development (GO:0021762), establishment of cell polarity (GO:0030010), actin cytoskeleton organization (GO:0030036), macrophage differentiation (GO:0030225), positive regulation of cell growth (GO:0030307), positive regulation of cell migration (GO:0030335), positive regulation of pseudopodium assembly (GO:0031274), negative regulation of protein-containing complex assembly (GO:0031333), positive regulation of cytokinesis (GO:0032467), regulation of actin cytoskeleton organization (GO:0032956), cell junction assembly (GO:0034329), adherens junction organization (GO:0034332), embryonic heart tube development (GO:0035050), dendritic cell migration (GO:0036336), neuropilin signaling pathway (GO:0038189), positive regulation of MAPK cascade (GO:0043410), host-mediated perturbation of viral process (GO:0044788), establishment of epithelial cell apical/basal polarity (GO:0045198), filopodium assembly (GO:0046847), positive regulation of pinocytosis (GO:0048549), neuron fate determination (GO:0048664), regulation of filopodium assembly (GO:0051489), positive regulation of filopodium assembly (GO:0051491), regulation of stress fiber assembly (GO:0051492), positive regulation of stress fiber assembly (GO:0051496)

GO Molecular Function (13): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), protein kinase binding (GO:0019901), GTP-dependent protein binding (GO:0030742), thioesterase binding (GO:0031996), GBD domain binding (GO:0032427), apolipoprotein A-I receptor binding (GO:0034191), identical protein binding (GO:0042802), ubiquitin protein ligase activity (GO:0061630), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (31): Golgi membrane (GO:0000139), storage vacuole (GO:0000322), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), membrane (GO:0016020), COG complex (GO:0017119), filopodium (GO:0030175), dendrite (GO:0030425), midbody (GO:0030496), leading edge membrane (GO:0031256), protein-containing complex (GO:0032991), cytoplasmic ribonucleoprotein granule (GO:0036464), neuron projection (GO:0043005), neuronal cell body (GO:0043025), apical part of cell (GO:0045177), phagocytic vesicle (GO:0045335), spindle midzone (GO:0051233), extracellular exosome (GO:0070062), mitotic spindle (GO:0072686), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), spindle (GO:0005819), cytoskeleton (GO:0005856), cell leading edge (GO:0031252), cell projection (GO:0042995), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
RHO GTPase Effectors	5
RHO GTPase cycle	3
Platelet activation, signaling and aggregation	1
Signaling by EGFR	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Co-stimulation by CD28	1
EPH-Ephrin signaling	1
Netrin-1 signaling	1
Signaling by ROBO receptors	1
Signaling by VEGF	1
Developmental Biology	1
MAPK family signaling cascades	1
Interleukin-12 signaling	1
G-protein beta:gamma signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cellular process	2
lamellipodium assembly	2
protein binding	2
Golgi apparatus	2
cytoplasm	2
cardiac muscle tissue development	1
neural crest cell migration	1
outflow tract morphogenesis	1
cell migration involved in heart development	1
cardiac neural crest cell development involved in outflow tract morphogenesis	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
phagocytosis	1
plasma membrane invagination	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
organelle organization	1
endomembrane system organization	1
regulation of mitotic cell cycle	1
regulation of cell cycle process	1
regulation of nuclear division	1
mitotic nuclear division	1
intracellular transport	1
nucleus localization	1
establishment of organelle localization	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
intracellular signaling cassette	1
macromolecule localization	1
regulation of plasma membrane bounded cell projection assembly	1
regulation of lamellipodium organization	1
regulation of lamellipodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
positive regulation of lamellipodium organization	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

412 interactions, top by confidence:

A	B	Type	Score
CDC24	BEM1	psi-mi:“MI:0914”(association)	0.960
IQGAP1	CDC42	psi-mi:“MI:0914”(association)	0.960
CDC42	IQGAP1	psi-mi:“MI:0403”(colocalization)	0.960
PARD6B	PRKCI	psi-mi:“MI:0914”(association)	0.960
PAK1	CDC42	psi-mi:“MI:0915”(physical association)	0.950
CDC42	WAS	psi-mi:“MI:0915”(physical association)	0.950
PARD6A	PRKCI	psi-mi:“MI:0914”(association)	0.950
CDC42	PAK1	psi-mi:“MI:0915”(physical association)	0.950
PAK1	CDC42	psi-mi:“MI:0914”(association)	0.950
PARD6B	CDC42	psi-mi:“MI:0915”(physical association)	0.900
CDC42	PARD6B	psi-mi:“MI:0915”(physical association)	0.900
CDC42EP1	CDC42	psi-mi:“MI:0915”(physical association)	0.890
CDC42	CDC42EP1	psi-mi:“MI:0915”(physical association)	0.890
PAK2	CDC42	psi-mi:“MI:0915”(physical association)	0.870
CDC42	PAK2	psi-mi:“MI:0915”(physical association)	0.870
CDC42	CDC42EP2	psi-mi:“MI:0915”(physical association)	0.830

BioGRID (2125): PAK2 (Two-hybrid), CDC42EP2 (Two-hybrid), CDC42EP1 (Two-hybrid), PARD6B (Two-hybrid), CDC42 (Reconstituted Complex), TNK2 (Affinity Capture-Western), CDC42 (Affinity Capture-Western), CDC42EP1 (Two-hybrid), CDC42 (Affinity Capture-RNA), AHNAK (Co-fractionation), ARHGDIA (Co-fractionation), ARHGDIG (Co-fractionation), CDC42 (Co-fractionation), CDC42 (Co-fractionation), CDC42 (Co-fractionation)

ESM2 similar proteins: A0A286QZ36, C4YDI6, O88931, P08134, P0CY33, P15153, P19073, P24406, P34144, P34145, P34146, P40792, P40793, P48148, P48554, P60763, P60764, P60766, P60952, P60953, P61585, P61586, P61589, P62998, P62999, P63000, P63001, Q007T2, Q03206, Q05062, Q05144, Q16YG0, Q17031, Q1RMJ6, Q22038, Q29HY3, Q2KJ93, Q4R4R6, Q5RCK9, Q5REY6

Diamond homologs: A0A286QZ36, A5D7J5, C4YDI6, O04369, O76321, O82480, O82481, O88931, O94103, O96390, P01122, P08134, P0CY33, P15153, P17081, P19073, P24406, P34144, P34145, P34146, P34147, P34148, P34149, P34150, P40792, P40793, P48148, P48554, P60763, P60764, P60766, P60952, P60953, P61585, P61586, P61589, P62998, P62999, P63000, P63001

SIGNOR signaling

60 interactions.

A	Effect	B	Mechanism
SRC	up-regulates	CDC42	phosphorylation
CDC42	down-regulates	GSK3B	binding
ITSN1	up-regulates	CDC42	binding
RAP1GDS1	up-regulates	CDC42	binding
CDC42	“up-regulates activity”	MAPK14
BNIP2	“up-regulates activity”	CDC42	binding
DEF6	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”
CDC42	“up-regulates activity”	NFATC1
ARAP1	“down-regulates activity”	CDC42	“gtpase-activating protein”
ARAP2	“down-regulates activity”	CDC42	“gtpase-activating protein”
ARAP3	“down-regulates activity”	CDC42	“gtpase-activating protein”
ARHGAP1	“down-regulates activity”	CDC42	“gtpase-activating protein”
ARHGAP11B	“down-regulates activity”	CDC42	“gtpase-activating protein”
ARHGAP20	“down-regulates activity”	CDC42	“gtpase-activating protein”
ARHGAP22	“down-regulates activity”	CDC42	“gtpase-activating protein”
ARHGAP30	“down-regulates activity”	CDC42	“gtpase-activating protein”
ARHGAP31	“down-regulates activity”	CDC42	“gtpase-activating protein”
ARHGAP39	“down-regulates activity”	CDC42	“gtpase-activating protein”
ARHGAP40	“down-regulates activity”	CDC42	“gtpase-activating protein”
FAM13B	“down-regulates activity”	CDC42	“gtpase-activating protein”
GMIP	“down-regulates activity”	CDC42	“gtpase-activating protein”
MYO9B	“down-regulates activity”	CDC42	“gtpase-activating protein”
SRGAP2	“down-regulates activity”	CDC42	“gtpase-activating protein”
STARD8	“down-regulates activity”	CDC42	“gtpase-activating protein”
ARHGEF4	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”
ARHGEF9	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”
ARHGEF10	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”
ARHGEF15	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”
ARHGEF26	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”
DNMBP	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 124 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
CD209 (DC-SIGN) signaling	6	34.2×	6e-07
RHOV GTPase cycle	10	31.4×	7e-11
FCERI mediated MAPK activation	8	30.4×	2e-08
RHOQ GTPase cycle	13	25.9×	3e-13
Signaling by high-kinase activity BRAF mutants	7	24.4×	6e-07
RHOH GTPase cycle	7	23.7×	6e-07
MAP2K and MAPK activation	7	22.0×	1e-06
Signaling by RAF1 mutants	7	21.4×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
neuron projection extension	5	26.1×	2e-04
regulation of MAPK cascade	5	22.6×	3e-04
Rho protein signal transduction	7	17.2×	4e-05
positive regulation of actin filament polymerization	5	16.4×	9e-04
cellular senescence	5	14.6×	2e-03
Ras protein signal transduction	7	14.2×	1e-04
JNK cascade	5	13.5×	2e-03
regulation of small GTPase mediated signal transduction	7	10.0×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	12
Uncertain significance	48
Likely benign	61
Benign	12

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1203928	NM_001791.4(CDC42):c.563G>A (p.Cys188Tyr)	Pathogenic
1916169	NM_001791.4(CDC42):c.556C>T (p.Arg186Cys)	Pathogenic
208668	NM_001791.4(CDC42):c.196A>G (p.Arg66Gly)	Pathogenic
208731	NM_001791.4(CDC42):c.68A>G (p.Tyr23Cys)	Pathogenic
2664644	NM_001791.4(CDC42):c.191A>C (p.Tyr64Ser)	Pathogenic
450370	NM_001791.4(CDC42):c.203G>A (p.Arg68Gln)	Pathogenic
487652	NM_001791.4(CDC42):c.247T>C (p.Ser83Pro)	Pathogenic
487653	NM_001791.4(CDC42):c.476C>T (p.Ala159Val)	Pathogenic
487654	NM_001791.4(CDC42):c.511G>A (p.Glu171Lys)	Pathogenic
1098376	NM_001791.4(CDC42):c.509A>G (p.Asp170Gly)	Likely pathogenic
1675351	NM_001791.4(CDC42):c.70A>C (p.Thr24Pro)	Likely pathogenic
2584437	NM_001791.4(CDC42):c.552dup (p.Ser185fs)	Likely pathogenic
2672222	NM_001791.4(CDC42):c.227A>T (p.Asp76Val)	Likely pathogenic
3359104	NM_001791.4(CDC42):c.291G>T (p.Trp97Cys)	Likely pathogenic
372848	NM_001791.4(CDC42):c.124G>A (p.Val42Ile)	Likely pathogenic
4075256	NM_001791.4(CDC42):c.67T>C (p.Tyr23His)	Likely pathogenic
422537	NM_001791.4(CDC42):c.62T>C (p.Ile21Thr)	Likely pathogenic
432071	NM_001791.4(CDC42):c.242G>T (p.Cys81Phe)	Likely pathogenic
453192	NM_001791.4(CDC42):c.346C>G (p.Gln116Glu)	Likely pathogenic
666573	NM_001791.4(CDC42):c.137T>C (p.Ile46Thr)	Likely pathogenic
987296	NM_001791.4(CDC42):c.67T>A (p.Tyr23Asn)	Likely pathogenic

SpliceAI

980 predictions. Top by Δscore:

Variant	Effect	Δscore
1:22052739:TGAGG:T	donor_loss	1.0000
1:22052740:GAG:G	donor_gain	1.0000
1:22052743:G:GG	donor_gain	1.0000
1:22052743:GT:G	donor_loss	1.0000
1:22052744:T:A	donor_loss	1.0000
1:22078424:TGCA:T	acceptor_loss	1.0000
1:22078425:GCA:G	acceptor_loss	1.0000
1:22078426:CA:C	acceptor_loss	1.0000
1:22078427:A:AG	acceptor_gain	1.0000
1:22078427:AGG:A	acceptor_loss	1.0000
1:22078428:G:GT	acceptor_gain	1.0000
1:22078579:CGACT:C	donor_gain	1.0000
1:22078580:GACT:G	donor_gain	1.0000
1:22078580:GACTG:G	donor_gain	1.0000
1:22078581:ACT:A	donor_gain	1.0000
1:22078582:CT:C	donor_gain	1.0000
1:22078582:CTG:C	donor_loss	1.0000
1:22078583:TGTA:T	donor_loss	1.0000
1:22078584:G:GG	donor_gain	1.0000
1:22078584:GTAA:G	donor_loss	1.0000
1:22078585:TAAG:T	donor_loss	1.0000
1:22081716:TTTTA:T	acceptor_loss	1.0000
1:22081717:TTTA:T	acceptor_loss	1.0000
1:22081718:TTA:T	acceptor_loss	1.0000
1:22081719:TA:T	acceptor_loss	1.0000
1:22081720:A:AG	acceptor_gain	1.0000
1:22081721:G:GG	acceptor_gain	1.0000
1:22081721:GGT:G	acceptor_gain	1.0000
1:22081721:GGTT:G	acceptor_gain	1.0000
1:22081721:GGTTT:G	acceptor_gain	1.0000

AlphaMissense

1232 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:22078506:G:C	G10R	1.000
1:22078506:G:T	G10C	1.000
1:22078507:G:A	G10D	1.000
1:22078507:G:T	G10V	1.000
1:22078510:A:T	D11V	1.000
1:22078521:G:C	G15R	1.000
1:22078521:G:T	G15C	1.000
1:22078522:G:A	G15D	1.000
1:22078522:G:T	G15V	1.000
1:22078524:A:C	K16Q	1.000
1:22078525:A:T	K16I	1.000
1:22078526:A:C	K16N	1.000
1:22078526:A:T	K16N	1.000
1:22078528:C:T	T17I	1.000
1:22078534:T:C	L19P	1.000
1:22078560:T:C	F28L	1.000
1:22078562:T:A	F28L	1.000
1:22078562:T:G	F28L	1.000
1:22078572:T:C	Y32H	1.000
1:22081725:T:C	F37L	1.000
1:22081727:T:A	F37L	1.000
1:22081727:T:G	F37L	1.000
1:22081729:A:T	D38V	1.000
1:22081780:T:C	L55P	1.000
1:22081782:T:C	F56L	1.000
1:22081784:T:A	F56L	1.000
1:22081784:T:G	F56L	1.000
1:22081785:G:C	D57H	1.000
1:22081785:G:T	D57Y	1.000
1:22081786:A:C	D57A	1.000

dbSNP variants (sampled 300 via entrez): RS1000017529 (1:22097219 C>T), RS1000055276 (1:22098239 CT>C), RS1000068762 (1:22070699 C>T), RS1000130604 (1:22085411 T>C), RS1000164447 (1:22054114 A>G), RS1000174813 (1:22057938 G>A), RS1000203554 (1:22055079 G>A,C,T), RS1000224244 (1:22099395 G>A,C), RS1000276525 (1:22099706 G>T), RS1000276866 (1:22054541 A>T), RS1000277453 (1:22095681 A>G), RS1000361094 (1:22066630 A>T), RS1000386391 (1:22060576 A>C), RS1000448786 (1:22089539 T>C,G), RS1000461804 (1:22089222 T>A)

Disease associations

OMIM: gene MIM:116952 | disease phenotypes: MIM:616737, MIM:267700

GenCC curated gene-disease

Disease	Classification	Inheritance
macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome	Definitive	AD

Mondo (4): macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome (MONDO:0014757), hereditary hemophagocytic lymphohistiocytosis (MONDO:0015541), neurodevelopmental disorder (MONDO:0700092), congenital heart disease (MONDO:0005453)

Orphanet (3): Takenouchi-Kosaki syndrome (Orphanet:487796), Primary hemophagocytic lymphohistiocytosis (Orphanet:158038), Familial hemophagocytic lymphohistiocytosis (Orphanet:540)

HPO phenotypes

84 total (30 of 84 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000119	Abnormality of the genitourinary system
HP:0000122	Unilateral renal agenesis
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000454	Flared nostrils
HP:0000465	Webbed neck
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000577	Exotropia
HP:0000582	Upslanted palpebral fissure
HP:0000648	Optic atrophy

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001532_3	Immune response to smallpox vaccine (IL-6)	2.000000e-07
GCST002919_1	Colorectal cancer	1.000000e-08
GCST003518_28	Daytime sleep phenotypes	3.000000e-06
GCST004899_8	Gestational age at birth (maternal effect)	3.000000e-14
GCST006462_3	Uterine fibroids	5.000000e-14
GCST007044_1	Extremely high intelligence	5.000000e-08
GCST008423_4	Uterine fibroids	2.000000e-24
GCST009158_29	Uterine fibroids	2.000000e-29
GCST009391_536	Metabolite levels	4.000000e-06
GCST009822_5	Gynecologic disease	4.000000e-10
GCST009823_3	Gynecologic disease (multivariate analysis)	7.000000e-11
GCST009824_1	Gynecologic disease	5.000000e-11
GCST009833_1	Uterine fibroids (MTAG)	5.000000e-08
GCST009834_34	Uterine fibroids	1.000000e-12
GCST012227_1389	Hip circumference adjusted for BMI	2.000000e-11
GCST90013406_197	Liver enzyme levels (alkaline phosphatase)	2.000000e-132

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0007828	daytime rest measurement
EFO:0005112	gestational age
EFO:0005939	parental genotype effect measurement
EFO:0004337	intelligence
EFO:0010528	quinolinic acid measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL4106177 (PROTEIN FAMILY), CHEMBL4296113 (PROTEIN COMPLEX), CHEMBL4888458 (PROTEIN-PROTEIN INTERACTION), CHEMBL6088 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 57,177 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL469	KETOROLAC	4	53,920
CHEMBL490129	SANGUINARIUM CHLORIDE	2	3,189
CHEMBL5290216	MBQ-167	1	68

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

Binding affinities (BindingDB)

208 measured of 211 human assays (225 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
cid_11847137	EC50	27 nM
cid_2864686	EC50	29 nM
2-(benzoylcarbamothioylamino)-5,5-dimethyl-4,7-dihydrothieno[2,3-c]pyran-3-carboxylic acid	EC50	92 nM
UNM-0000306121	EC50	148 nM
cid_2857552	EC50	231 nM
1-[2-(2,5-dimethylphenoxy)ethyl]-3-indolecarboxylic acid	EC50	358 nM
KUC103364N	EC50	360 nM
3-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-1-[4-(4-methoxyphenyl)piperazin-1-yl]propan-1-one	EC50	450 nM
2-[2-(4-chlorophenyl)ethylamino]benzoic acid	EC50	885 nM
3-(4-acetylphenyl)-1-(4-nitrophenyl)-2-propyn-1-one	EC50	989 nM
1-[4-(2,5-dimethylphenyl)piperazin-1-yl]-3-[3-(3-methylphenyl)-1,2,4-oxadiazol-5-yl]propan-1-one	EC50	1020 nM
cid_42608817	EC50	1050 nM
1-[4-(2-fluorophenyl)piperazin-1-yl]-3-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]propan-1-one	EC50	1070 nM
UNM-0000306160	EC50	1070 nM
1-[4-(3-fluorophenyl)piperazin-1-yl]-3-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]propan-1-one	EC50	1090 nM
1-[4-(2,3-dimethylphenyl)-1-piperazinyl]-3-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-1-propanone	EC50	1150 nM
3-[3-(2-bromophenyl)-1,2,4-oxadiazol-5-yl]-1-[4-(2,5-dimethylphenyl)-1-piperazinyl]-1-propanone	EC50	1190 nM
KUC103409N	EC50	1190 nM
3-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-1-[4-(4-methylphenyl)piperazin-1-yl]propan-1-one	EC50	1250 nM
UNM-0000306134	EC50	1300 nM
KUC103432N	EC50	1420 nM
KUC103370N	EC50	1430 nM
1-ethyl-6-methyl-3-[(E)-2-phenylethenyl]pyrimido[5,4-e][1,2,4]triazine-5,7-dione	EC50	1440 nM
1-[4-(2,5-dimethylphenyl)piperazin-1-yl]-3-[3-(4-methoxyphenyl)-1,2-oxazol-5-yl]propan-1-one	EC50	1450 nM
4-[5-(3-methoxyphenyl)-3-(4-methoxyphenyl)-3,4-dihydropyrazol-2-yl]benzenesulfonamide	EC50	1460 nM
KUC103401N	EC50	1510 nM
cid_42596906	EC50	1540 nM
UNM-0000306071	EC50	1540 nM
1,3,6-Trimethyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione	EC50	1610 nM
UNM-0000306072	EC50	1620 nM
3-({[1-(1-Cyclopentyl-1H-tetrazol-5-yl)-2-methyl-propyl]-thiophen-2-ylmethyl-amino}-methyl)-8-methyl-1H-quinolin-2-one	EC50	1630 nM
UNM-0000306083	EC50	1660 nM
2-[(5-cyano-4-keto-6-phenyl-1H-pyrimidin-2-yl)thio]-N-phenyl-acetamide	EC50	1660 nM
1-[4-(2,5-dimethylphenyl)piperazin-1-yl]-3-[4-(4-methoxyphenyl)-1,3-oxazol-2-yl]propan-1-one	EC50	1680 nM
cid_42608815	EC50	1690 nM
1,6-dimethyl-3-propyl-pyrimido[5,4-e][1,2,4]triazine-5,7-dione	EC50	1770 nM
KUC103366N	EC50	1840 nM
UNM-0000306082	EC50	1980 nM
1-[4-(2-chlorophenyl)piperazin-1-yl]-3-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]propan-1-one	EC50	2030 nM
UNM-0000306113	EC50	2060 nM
KUC103367N	EC50	2140 nM
UNM-0000306086	EC50	2180 nM
(E)-3-(1-benzyl-3-thiophen-2-ylpyrazol-4-yl)prop-2-enoic acid	EC50	2180 nM
cid_15201821	EC50	2210 nM
1-[4-(2,5-dimethylphenyl)-1-piperazinyl]-3-[3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl]-1-propanone	EC50	2280 nM
UNM-0000306152	EC50	2340 nM
UNM-0000306125	EC50	2340 nM
4-[5-(4-methoxyphenyl)-3-phenylpyrazol-1-yl]benzenesulfonamide	EC50	2430 nM
4-[3,5-bis(4-methoxyphenyl)-3,4-dihydropyrazol-2-yl]benzenesulfonamide	EC50	2510 nM
sodium;(2R)-2-(6-methoxy-2-naphthalenyl)propanoate	EC50	2610 nM

ChEMBL bioactivities

23 potent at pChembl≥5 of 29 total, top 21 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.35	Kd	4.493	nM	CHEMBL5653589
8.35	ED50	4.493	nM	CHEMBL5653589
7.70	EC50	20	nM	CHEMBL1328505
7.27	IC50	54	nM	CHEMBL1082821
7.11	IC50	78	nM	MBQ-167
7.10	IC50	80	nM	MBQ-167
6.48	Kd	332	nM	CHEMBL4303199
6.00	IC50	1000	nM	CHEMBL1619630
5.97	EC50	1070	nM	CHEMBL496240
5.97	EC50	1070	nM	CHEMBL1618254
5.89	IC50	1300	nM	CHEMBL1084892
5.85	EC50	1400	nM	CHEMBL1370630
5.85	IC50	1400	nM	CHEMBL574200
5.77	IC50	1700	nM	CHEMBL1085141
5.70	IC50	2000	nM	KETOROLAC
5.68	EC50	2100	nM	CHEMBL1370630
5.27	IC50	5400	nM	CHEMBL1084890
5.22	IC50	6000	nM	CHEMBL572918
5.19	Kd	6400	nM	CHEMBL4303380
5.16	IC50	7000	nM	SECRAMINE B
5.05	IC50	9000	nM	SECRAMINE A

PubChem BioAssay actives

20 with measured affinity, of 193 total; 17 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148035: Binding affinity to human CDC42 incubated for 45 mins by Kinobead based pull down assay	kd	0.0045	uM
(3S,4R)-N-(7-chloro-1-oxo-2H-isoquinolin-6-yl)-4-(4-chlorophenyl)pyrrolidine-3-carboxamide	483962: Inhibition of CDC42	ic50	0.0540	uM
9-ethyl-3-(5-phenyltriazol-1-yl)carbazole	1974816: Inhibition of Cdc42 P21-binding domain in human MDA-MB-231 cells incubated for 24 hrs by pulldown assay	ic50	0.0780	uM
2-[(6-phenyl-2,3,4,9-tetrahydro-1H-carbazol-1-yl)amino]ethanol	1974810: Binding affinity to fluorescently labeled Cdc42 (unknown origin) assessed as dissociation constant by microscale thermophoresis assay	kd	0.3320	uM
(1R)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid	1435610: Inhibition of RAC1/CDC42 in human ovarian cancer cells	ic50	1.0000	uM
(2R)-2-(6-methoxynaphthalen-2-yl)propanoic acid	1974818: Inhibition of CDC42 in human HeLa cells pretreated for 2 hrs followed by EGF stimulation for 2 mins by flow cytometric analysis	ec50	1.0700	uM
(1S)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid	1920873: Inhibition of Cdc42 in human HeLa cells by Flow cytometric G-trap effector binding assay	ec50	1.0700	uM
N-(7-chloro-1-oxo-2H-isoquinolin-6-yl)-2-(methylamino)-2-phenylacetamide	483716: Inhibition of CDc42	ic50	1.3000	uM
[(2S,3R,4S,5S)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	437566: Inhibition of Cdc42 GTPase activity assessed as incorporation of BODIPY-GTP after 40 mins by nucleotide binding competition assay	ic50	1.4000	uM
4-[3-(4-methoxyphenyl)-5-phenyl-3,4-dihydropyrazol-2-yl]benzenesulfonamide	1974812: Inhibition of GST-tagged wildtype Cdc42 (unknown origin) incubated for 2 hrs in presence of BODIPY FL GDP by flow cytometry	ec50	1.4000	uM
2-amino-N-(7-chloro-1-oxo-2H-isoquinolin-6-yl)-2-phenylacetamide	483716: Inhibition of CDc42	ic50	1.7000	uM
Ketorolac	1435610: Inhibition of RAC1/CDC42 in human ovarian cancer cells	ic50	2.0000	uM
N-(7-chloro-1-oxo-2H-isoquinolin-6-yl)-2-phenylacetamide	483716: Inhibition of CDc42	ic50	5.4000	uM
5,6-dihydroisoquinolino[2,1-b]isoquinolin-7-ium-2,3,9,10-tetrol chloride	437566: Inhibition of Cdc42 GTPase activity assessed as incorporation of BODIPY-GTP after 40 mins by nucleotide binding competition assay	ic50	6.0000	uM
2-(4-bromo-2-chlorophenoxy)-N-[[4-[(4,6-dimethylpyrimidin-2-yl)sulfamoyl]phenyl]carbamothioyl]acetamide	1974807: Binding affinity to Cdc42 (unknown origin) assessed as dissociation constant by fluorescence titration assay	kd	6.4000	uM
[(1R,3S,12R,14E,16R)-9-bromo-8-(cyclopropylmethoxy)-14-methoxyimino-16-[(4-methoxyphenyl)methylsulfanyl]-11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-6,8,10(17)-trien-3-yl]methanol	502930: Inhibition of GEF-independent nucleotide exchange activity of prenylated Cdc42 after 3 mins in presence of 4 mM Mg2+ chelator EDTA	ic50	7.0000	uM
[(1R,3S,12R,14E,16R)-9-bromo-8-(cyclopropylmethoxy)-16-[(4-methoxyphenyl)methylsulfanyl]-14-phenylmethoxyimino-11-oxa-4-azatetracyclo[8.6.1.01,12.06,17]heptadeca-6,8,10(17)-trien-3-yl]methanol	502930: Inhibition of GEF-independent nucleotide exchange activity of prenylated Cdc42 after 3 mins in presence of 4 mM Mg2+ chelator EDTA	ic50	9.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects cotreatment, increases expression, decreases response to substance	4
Guanosine Triphosphate	affects binding, increases reaction, increases abundance, increases expression	3
sodium arsenite	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Arsenic	affects expression, affects methylation	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Lead	affects expression, decreases expression	2
Dronabinol	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression, decreases expression	2
Valproic Acid	affects cotreatment, increases expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	increases methylation	2
bisphenol F	increases expression	1
2-methoxy-5-((3,4,5-trimethosyphenyl)seleninyl)phenol	decreases expression	1
Baizhu	decreases expression	1
Fangfeng	decreases expression	1
palmatine	affects binding	1
tremolite	decreases expression	1
bisphenol A	increases expression	1
methylselenic acid	decreases expression	1
titanium dioxide	decreases methylation	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
scoparone	decreases expression	1
cupric oxide	decreases expression	1
toosendanin	decreases expression	1
epigallocatechin gallate	decreases expression	1
fosbretabulin	decreases expression	1

ChEMBL screening assays

76 unique, capped per target: 76 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4002933	Binding	Inhibition of RAC1/CDC42 in human ovarian cancer cells	1,2,3-Triazolyl ester of Ketorolac: A “Click Chemistry”-based highly potent PAK1-blocking cancer-killer. — Eur J Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2TX	Abcam HEK293T CDC42 KO	Transformed cell line	Female
CVCL_D7MB	Ubigene A-549 CDC42 KO	Cancer cell line	Male
CVCL_SI05	HAP1 CDC42 (-) 1	Cancer cell line	Male
CVCL_SI06	HAP1 CDC42 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05744063	PHASE4	COMPLETED	A Post-authorization Study to Describe the Safety and Efficacy of Emapalumab for the Treatment of pHLH in Treatment Experienced Chinese Patients
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT03312751	PHASE3	COMPLETED	Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00368355	PHASE2	COMPLETED	T Cell Depletion for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)