RAC3

Rac family small GTPase 3, the group of Receptor ligands|Rho family GTPases

Basic information

Region (hg38): 17:82031678-82034204

Links

ENSG00000169750 ∙ NCBI:5881 ∙ OMIM:602050 ∙ HGNC:9803 ∙ Uniprot:P60763 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (Strong), mode of inheritance: AD
• neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dental; Musculoskeletal; Neurologic	29276006; 30293988; 35851598

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAC3 gene.

• Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (1 variants)
• not provided (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAC3 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				7	1	8
missense	1	6	8	1		16
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				1		1
Total	1	6	9	9	1

Variants in RAC3

This is a list of pathogenic ClinVar variants found in the RAC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-82031773-C-T			Likely benign (Feb 01, 2024)
17-82031795-G-C		Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	Likely pathogenic (Nov 06, 2019)
17-82032423-G-A		RAC3-related disorder	Likely benign (Dec 01, 2023)
17-82032437-C-G		Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	Likely pathogenic (Jun 13, 2023)
17-82032437-C-T		Abnormal brain morphology;Intellectual disability • Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	Pathogenic; association (Nov 08, 2022)
17-82032445-T-C		RAC3-related disorder	Uncertain significance (Jun 23, 2023)
17-82032736-ATGG-A		Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	Uncertain significance (May 22, 2022)
17-82032767-T-A			Uncertain significance (Oct 06, 2023)
17-82032779-C-G		Distal shortening of limbs • Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	Conflicting classifications of pathogenicity (Mar 25, 2024)
17-82032782-G-A		Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	Uncertain significance (Oct 19, 2020)
17-82032784-CAGG-C		Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	Pathogenic (Nov 08, 2022)
17-82032785-A-T		Abnormal brain morphology;Intellectual disability • Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	Pathogenic; association (Aug 03, 2021)
17-82032787-G-A		Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies • See cases	Pathogenic (Apr 26, 2021)
17-82032790-G-A		Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	Likely pathogenic (Feb 01, 2020)
17-82032794-A-G		Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	Likely pathogenic (Jul 29, 2021)
17-82032796-G-A		RAC3-related disorder	Likely pathogenic (Jul 12, 2024)
17-82032806-G-A			Uncertain significance (Jan 07, 2022)
17-82032806-G-C		Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	Uncertain significance (Apr 05, 2022)
17-82032956-C-T		RAC3-related disorder	Likely benign (Jun 20, 2019)
17-82032997-T-A		Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	Likely pathogenic (Dec 13, 2022)
17-82032998-G-A		Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies	Conflicting classifications of pathogenicity (Feb 01, 2024)
17-82033443-T-C		Inborn genetic diseases	Uncertain significance (Nov 14, 2023)
17-82033457-G-A		RAC3-related disorder	Likely benign (Apr 05, 2019)
17-82033499-G-C		RAC3-related disorder	Likely pathogenic (-)
17-82033510-G-A		See cases	Uncertain significance (Jul 19, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAC3	protein_coding	protein_coding	ENST00000306897	6	2581

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00261	0.803	125576	0	7	125583	0.0000279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.46	78	124	0.630	0.00000841	1227
Missense in Polyphen		13	43.173	0.30111		469
Synonymous	-4.09	96	56.8	1.69	0.00000411	404
Loss of Function	1.06	5	8.28	0.604	3.51e-7	107

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000218
Finnish	0.00	0.00
European (Non-Finnish)	0.0000268	0.0000264
Middle Eastern	0.000218	0.000218
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as cell spreading and the formation of actin-based protusions including lamellipodia and membrane ruffles. Promotes cell adhesion and spreading on fibrinogen in a CIB1 and alpha-IIb/beta3 integrin-mediated manner. {ECO:0000269|PubMed:11756406, ECO:0000269|PubMed:11956649}.
• Pathway: Focal adhesion - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Adherens junction - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Axon guidance - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Bisphosphonate Pathway, Pharmacodynamics;Integrin-mediated Cell Adhesion;RalA downstream regulated genes;Focal Adhesion;MAPK Signaling Pathway;Microglia Pathogen Phagocytosis Pathway;Chromosomal and microsatellite instability in colorectal cancer;Ras Signaling;Regulation of Actin Cytoskeleton;DNA Damage Response (only ATM dependent);Signaling by WNT;Signal Transduction;HGF;Rho GTPase cycle;AndrogenReceptor;Signaling by Rho GTPases;PCP/CE pathway;Beta-catenin independent WNT signaling;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.194

Intolerance Scores

• loftool: 0.263
• rvis_EVS: -0.05
• rvis_percentile_EVS: 49.76

Haploinsufficiency Scores

• pHI: 0.925
• hipred: Y
• hipred_score: 0.595
• ghis: 0.550

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.813

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rac3
• 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); neoplasm; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: cell morphogenesis;actin filament organization;Rho protein signal transduction;regulation of neuron maturation;cell migration;cerebral cortex GABAergic interneuron development;cell projection assembly;actin cytoskeleton organization;positive regulation of actin filament polymerization;neuron projection development;actin cytoskeleton reorganization;positive regulation of cell adhesion mediated by integrin;intracellular signal transduction;engulfment of apoptotic cell;homeostasis of number of cells within a tissue;neuromuscular process controlling balance;regulation of small GTPase mediated signal transduction;synaptic transmission, GABAergic;positive regulation of substrate adhesion-dependent cell spreading
• Cellular component: cytoplasm;cytosol;cytoskeleton;plasma membrane;endomembrane system;lamellipodium;growth cone;filamentous actin;cell projection;neuron projection;neuronal cell body;perinuclear region of cytoplasm;extracellular exosome;cell periphery
• Molecular function: GTPase activity;protein binding;GTP binding;protein kinase binding;calcium-dependent protein binding