RAC3
Rac family small GTPase 3, the group of Receptor ligands|Rho family GTPases
Basic information
Region (hg38): 17:82031678-82034204
Links
Phenotypes
GenCC
Source:
- neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (Limited), mode of inheritance: AD
- neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (Strong), mode of inheritance: AD
- neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| 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
- not_provided (19 variants)
- Inborn_genetic_diseases (18 variants)
- Neurodevelopmental_disorder_with_structural_brain_anomalies_and_dysmorphic_facies (15 variants)
- RAC3-related_disorder (9 variants)
- Intellectual_disability (2 variants)
- Abnormal_brain_morphology (2 variants)
- See_cases (2 variants)
- Distal_shortening_of_limbs (1 variants)
- not_specified (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. These statistics are base on transcript: NM_000005052.3. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 10 | 11 | ||||
| missense | 27 | 40 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 3 | 8 | 28 | 12 | 0 |
Highest pathogenic variant AF is 6.8460423e-7
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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