CDC42

cell division cycle 42, the group of Rho family GTPases

Basic information

Region (hg38): 1:22052626-22101360

Links

ENSG00000070831 ∙ NCBI:998 ∙ OMIM:116952 ∙ HGNC:1736 ∙ Uniprot:P60953 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome (Strong), mode of inheritance: AD
• macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome (Strong), mode of inheritance: AD
• macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Takenouchi-Kosaki syndrome	AD	Cardiovascular	Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management	Cardiovascular; Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Renal	26386261; 26708094; 29394990

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDC42 gene.

• not provided (66 variants)
• Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome (15 variants)
• Inborn genetic diseases (4 variants)
• Abnormal facial shape;Abnormality of blood and blood-forming tissues;Abnormality of the immune system;Neurodevelopmental abnormality;Postnatal growth retardation (2 variants)
• Postnatal growth retardation;Abnormal facial shape;Neurodevelopmental abnormality;Abnormality of blood and blood-forming tissues;Abnormality of the immune system (2 variants)
• CDC42-related condition (2 variants)
• Noonan-like syndrome (1 variants)
• Postnatal growth retardation;Abnormality of blood and blood-forming tissues;Abnormal facial shape;Abnormality of the immune system;Neurodevelopmental abnormality (1 variants)
• CDC42-related disorders (1 variants)
• Neurodevelopmental disorder (1 variants)
• Abnormality of blood and blood-forming tissues;Neurodevelopmental abnormality;Postnatal growth retardation;Abnormality of the immune system;Abnormal facial shape (1 variants)
• See cases (1 variants)
• Neurodevelopmental abnormality;Postnatal growth retardation;Abnormality of the immune system;Abnormality of blood and blood-forming tissues;Abnormal facial shape (1 variants)
• Neurodevelopmental abnormality;Abnormality of the immune system;Abnormality of blood and blood-forming tissues;Abnormal facial shape;Postnatal growth retardation (1 variants)
• Abnormal facial shape;Abnormality of blood and blood-forming tissues;Abnormality of the immune system;Postnatal growth retardation;Neurodevelopmental abnormality (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDC42 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	19	3	23
missense	7	11	9			27
nonsense						0
start loss						0
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	6	2	10
non coding			1	8	4	13
Total	7	12	12	27	7

Variants in CDC42

This is a list of pathogenic ClinVar variants found in the CDC42 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-22078484-G-A			Likely benign (Dec 12, 2022)
1-22078508-C-T			Likely benign (Dec 18, 2023)
1-22078529-A-G			Likely benign (Aug 30, 2023)
1-22078538-G-C			Likely benign (Oct 05, 2023)
1-22078540-T-C		Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome • Postnatal growth retardation;Abnormal facial shape;Neurodevelopmental abnormality;Abnormality of blood and blood-forming tissues;Abnormality of the immune system	Likely pathogenic (Oct 27, 2016)
1-22078545-T-A			Likely pathogenic (Oct 23, 2020)
1-22078546-A-G		Inborn genetic diseases • Neurodevelopmental abnormality;Postnatal growth retardation;Abnormality of the immune system;Abnormality of blood and blood-forming tissues;Abnormal facial shape • Neurodevelopmental disorder • Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome	Pathogenic (Dec 15, 2022)
1-22078548-A-C			Likely pathogenic (Jan 01, 2022)
1-22078579-C-A		Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome • CDC42-related disorder	Conflicting classifications of pathogenicity (Jun 26, 2023)
1-22078579-C-T			Uncertain significance (Jul 31, 2019)
1-22078580-G-A			Likely benign (Jul 21, 2022)
1-22078590-A-G			Likely benign (Sep 25, 2023)
1-22078598-T-C			Likely benign (Oct 17, 2023)
1-22078709-T-A			Benign (Jul 01, 2023)
1-22078812-C-G			Benign (May 01, 2022)
1-22081613-G-A			Benign (May 10, 2021)
1-22081702-T-A			Likely benign (Apr 25, 2023)
1-22081706-A-AT		CDC42-related disorder	Benign/Likely benign (Jan 31, 2024)
1-22081707-T-A			Likely benign (Dec 21, 2023)
1-22081719-T-C			Benign (Jan 29, 2024)
1-22081740-G-A			Likely pathogenic (Aug 01, 2020)
1-22081753-T-C		Macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome	Likely pathogenic (Jun 12, 2018)
1-22081802-C-T			Likely benign (Oct 03, 2023)
1-22081972-C-T			Benign (May 10, 2021)
1-22086434-T-C			Likely benign (Oct 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDC42	protein_coding	protein_coding	ENST00000344548	5	40318

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.787	0.211	125677	0	2	125679	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.04	17	104	0.163	0.00000544	1229
Missense in Polyphen		1	29.982	0.033353		378
Synonymous	-0.608	45	40.1	1.12	0.00000222	388
Loss of Function	2.55	1	9.47	0.106	4.99e-7	115

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000889	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration. Required for DOCK10-mediated spine formation in Purkinje cells and hippocampal neurons. Facilitates filopodia formation upon DOCK11-activation (By similarity). Also plays a role in phagocytosis through organization of the F-actin cytoskeleton associated with forming phagocytic cups. {ECO:0000250|UniProtKB:P60766, ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:17038317, ECO:0000269|PubMed:26465210}.
• Disease: DISEASE: Takenouchi-Kosaki syndrome (TKS) [MIM:616737]: A syndrome characterized by macrothrombocytopenia, lymphedema, mental retardation, developmental delay, and distinctive facial features. {ECO:0000269|PubMed:26386261, ECO:0000269|PubMed:26708094}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Focal adhesion - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Salmonella infection - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Adherens junction - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Endocytosis - Homo sapiens (human);Tight junction - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Axon guidance - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Shigellosis - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Bisphosphonate Pathway, Pharmacodynamics;Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;EGF-Core;IGF-Core;Androgen receptor signaling pathway;Target Of Rapamycin (TOR) Signaling;Integrated Breast Cancer Pathway;Angiogenesis overview;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Integrin-mediated Cell Adhesion;Leptin signaling pathway;Regulation of Microtubule Cytoskeleton;Metastatic brain tumor;Pathogenic Escherichia coli infection;RalA downstream regulated genes;B Cell Receptor Signaling Pathway;AGE-RAGE pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Spinal Cord Injury;JAK-STAT;Focal Adhesion;TGF-beta Signaling Pathway;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;Oxidative Damage;p38 MAPK Signaling Pathway;Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;Ebola Virus Pathway on Host;MET in type 1 papillary renal cell carcinoma;Ebola Virus Pathway on Host;Ras Signaling;EGF-EGFR Signaling Pathway;Regulation of Actin Cytoskeleton;G13 Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;DNA Damage Response (only ATM dependent);Developmental Biology;Signaling by GPCR;Signal Transduction;role of pi3k subunit p85 in regulation of actin organization and cell migration;p38 mapk signaling pathway;ras signaling pathway;how does salmonella hijack a cell;VEGFA-VEGFR2 Pathway;y branching of actin filaments;RHO GTPases activate KTN1;MAPK6/MAPK4 signaling;Factors involved in megakaryocyte development and platelet production;CD28 dependent Vav1 pathway;CD28 co-stimulation;Costimulation by the CD28 family;Fcgamma receptor (FCGR) dependent phagocytosis;EPH-Ephrin signaling;Innate Immune System;Immune System;EPHB-mediated forward signaling;RHO GTPases Activate WASPs and WAVEs;Adaptive Immune System;RHO GTPases Activate Formins;Rho GTPase cycle;Inactivation of CDC42 and RAC1;RHO GTPases activate PAKs;GPVI-mediated activation cascade;EGFR downregulation;Signaling by EGFR;RHO GTPases activate IQGAPs;Platelet activation, signaling and aggregation;CDO in myogenesis;Myogenesis;RHO GTPase Effectors;Signaling by Rho GTPases;DCC mediated attractive signaling;Integrin;EGFR1;agrin in postsynaptic differentiation;role of mal in rho-mediated activation of srf;CXCR4-mediated signaling events;ErbB1 downstream signaling;Hemostasis;MAPK family signaling cascades;PDGF;Regulation of actin dynamics for phagocytic cup formation;Noncanonical Wnt signaling pathway;Posttranslational regulation of adherens junction stability and dissassembly;Netrin-1 signaling;Signaling by ROBO receptors;Signaling by VEGF;Axon guidance;G alpha (12/13) signalling events;Integrin-linked kinase signaling;Signaling by Receptor Tyrosine Kinases;GPCR downstream signalling;ErbB2/ErbB3 signaling events;Osteopontin-mediated events;Regulation of CDC42 activity;Nectin adhesion pathway;Neurotrophic factor-mediated Trk receptor signaling;CDC42 signaling events;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Internalization of ErbB1;Netrin-mediated signaling events;N-cadherin signaling events;Regulation of p38-alpha and p38-beta;S1P4 pathway;EPHB forward signaling;Nongenotropic Androgen signaling;Lissencephaly gene (LIS1) in neuronal migration and development;Endothelins;Signaling events mediated by VEGFR1 and VEGFR2;TCR signaling in naïve CD4+ T cells;E-cadherin signaling in the nascent adherens junction;RhoA signaling pathway (Consensus)

Recessive Scores

• pRec: 0.914

Intolerance Scores

• loftool: 0.282
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.783
• ghis: 0.646

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.926

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cdc42
• Phenotype: hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; renal/urinary system phenotype; skeleton phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; craniofacial phenotype; vision/eye phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: cdc42
• Affected structure: photoreceptor cell
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: sprouting angiogenesis;protein phosphorylation;endocytosis;phagocytosis, engulfment;actin filament organization;Golgi organization;establishment or maintenance of cell polarity;integrin-mediated signaling pathway;Rho protein signal transduction;blood coagulation;regulation of cell shape;regulation of lamellipodium assembly;positive regulation of lamellipodium assembly;protein ubiquitination;substantia nigra development;cell projection assembly;actin cytoskeleton organization;macrophage differentiation;positive regulation of cell growth;positive regulation of pseudopodium assembly;T cell costimulation;negative regulation of protein complex assembly;positive regulation of cytokinesis;Cdc42 protein signal transduction;regulation of actin cytoskeleton organization;cell junction assembly;interleukin-12-mediated signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;neuropilin signaling pathway;viral RNA genome replication;negative regulation of epidermal growth factor receptor signaling pathway;positive regulation of catalytic activity;positive regulation of neuron apoptotic process;establishment of epithelial cell apical/basal polarity;positive regulation of DNA replication;positive regulation of JNK cascade;vascular endothelial growth factor receptor signaling pathway;ephrin receptor signaling pathway;regulation of small GTPase mediated signal transduction;positive regulation of muscle cell differentiation;regulation of filopodium assembly;positive regulation of filopodium assembly;regulation of stress fiber assembly;positive regulation of stress fiber assembly;establishment of Golgi localization;positive regulation of synapse structural plasticity;regulation of attachment of spindle microtubules to kinetochore;Wnt signaling pathway, planar cell polarity pathway;submandibular salivary gland formation;dendritic spine morphogenesis;organelle transport along microtubule;actin filament branching;positive regulation of intracellular protein transport;regulation of modification of postsynaptic structure;modification of synaptic structure;positive regulation of substrate adhesion-dependent cell spreading;positive regulation of actin cytoskeleton reorganization
• Cellular component: Golgi membrane;cytoplasm;endoplasmic reticulum membrane;centrosome;cytosol;plasma membrane;focal adhesion;cell cortex;membrane;Golgi transport complex;secretory granule;filopodium;midbody;protein-containing complex;cytoplasmic ribonucleoprotein granule;cell projection;neuron projection;neuronal cell body;dendritic spine;spindle midzone;extracellular exosome;mitotic spindle;Schaffer collateral - CA1 synapse
• Molecular function: GTPase activity;protein serine/threonine kinase activity;protein binding;GTP binding;protein kinase binding;mitogen-activated protein kinase kinase kinase binding;thioesterase binding;GBD domain binding;apolipoprotein A-I receptor binding;identical protein binding;ubiquitin protein ligase activity