RAC1
Rac family small GTPase 1, the group of Receptor ligands|Rho family GTPases
Basic information
Region (hg38): 7:6374526-6403967
Links
Phenotypes
GenCC
Source:
- intellectual disability, autosomal dominant 48 (Strong), mode of inheritance: AD
- intellectual disability, autosomal dominant 48 (Supportive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Intellectual developmental disorder, autosomal dominant 48 | 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; Neurologic | 28886345 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (31 variants)
- Intellectual disability, autosomal dominant 48 (24 variants)
- not specified (3 variants)
- Inborn genetic diseases (2 variants)
- RAC1-related condition (1 variants)
- Global developmental delay (1 variants)
- Developmental disorder (1 variants)
- Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (1 variants)
- Neurodevelopmental delay (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 RAC1 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 | 8 | |||||
| missense | 10 | 14 | 31 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| splice region ? | 0 | |||||
| non coding ? | 5 | |||||
| Total | 6 | 11 | 20 | 7 | 5 |
Variants in RAC1
This is a list of pathogenic ClinVar variants found in the RAC1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 7-6374747-C-G | not specified | Uncertain significance (Mar 11, 2024) | ||
| 7-6374755-T-TGGTGGTGGGAGACGGGTGAGTGCGC | not specified | Uncertain significance (Mar 30, 2020) | ||
| 7-6374772-T-G | not specified | Uncertain significance (Sep 28, 2022) | ||
| 7-6387216-G-A | Uncertain significance (Apr 22, 2023) | |||
| 7-6387226-C-G | Inborn genetic diseases | Uncertain significance (Jun 13, 2019) | ||
| 7-6387229-G-A | Intellectual disability, autosomal dominant 48 | Pathogenic (Nov 11, 2023) | ||
| 7-6387245-C-T | not specified | Likely benign (Dec 15, 2023) | ||
| 7-6387249-A-T | Uncertain significance (May 27, 2022) | |||
| 7-6387251-C-G | RAC1-related disorder | Benign/Likely benign (Oct 01, 2022) | ||
| 7-6387253-A-G | Inborn genetic diseases | Conflicting classifications of pathogenicity (Apr 27, 2022) | ||
| 7-6387257-A-G | Likely benign (Apr 01, 2021) | |||
| 7-6387261-C-A | Squamous cell carcinoma of the head and neck • Malignant melanoma of skin • Malignant neoplasm of body of uterus • Squamous cell carcinoma of the skin | Likely pathogenic (May 31, 2016) | ||
| 7-6387261-C-T | Malignant neoplasm of body of uterus • Squamous cell carcinoma of the head and neck • Melanoma • Malignant melanoma of skin • Squamous cell carcinoma of the skin | Likely pathogenic (May 31, 2016) | ||
| 7-6387262-C-T | Malignant neoplasm of body of uterus • Squamous cell carcinoma of the skin • Squamous cell carcinoma of the head and neck • Malignant melanoma of skin | Likely pathogenic (May 31, 2016) | ||
| 7-6387268-A-T | Uncertain significance (Sep 16, 2022) | |||
| 7-6387310-C-T | Intellectual disability, autosomal dominant 48 | Benign (Nov 07, 2021) | ||
| 7-6391932-A-G | Intellectual disability, autosomal dominant 48 • Global developmental delay • Neurodevelopmental delay | Pathogenic/Likely pathogenic (Jul 24, 2023) | ||
| 7-6391938-CT-AC | Likely pathogenic (Apr 26, 2018) | |||
| 7-6391945-T-A | Intellectual disability, autosomal dominant 48 | Likely pathogenic (Feb 22, 2024) | ||
| 7-6391956-A-G | Uncertain significance (Dec 15, 2022) | |||
| 7-6391967-G-A | Intellectual disability, autosomal dominant 48 | Pathogenic (Nov 21, 2018) | ||
| 7-6391967-G-C | Intellectual disability, autosomal dominant 48 • Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies | Likely pathogenic (Mar 09, 2023) | ||
| 7-6391983-G-T | Uncertain significance (Jul 29, 2022) | |||
| 7-6391984-G-C | Intellectual disability, autosomal dominant 48 | Likely pathogenic (Feb 27, 2023) | ||
| 7-6391986-A-C | Intellectual disability, autosomal dominant 48 | Uncertain significance (Dec 02, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RAC1 | protein_coding | protein_coding | ENST00000356142 | 7 | 29455 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.762 | 0.237 | 125557 | 0 | 15 | 125572 | 0.0000597 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.13 | 24 | 121 | 0.198 | 0.00000718 | 1349 |
| Missense in Polyphen | 5 | 38.374 | 0.1303 | 489 | ||
| Synonymous | 0.956 | 42 | 50.7 | 0.829 | 0.00000334 | 419 |
| Loss of Function | 2.90 | 2 | 13.5 | 0.148 | 8.36e-7 | 149 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000181 | 0.000181 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000707 | 0.0000705 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000327 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. Required for atypical chemokine receptor ACKR2-induced LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3. {ECO:0000250|UniProtKB:P63001, ECO:0000269|PubMed:1643658, ECO:0000269|PubMed:28886345, ECO:0000269|PubMed:9121475}.;
- Disease
- DISEASE: Mental retardation, autosomal dominant 48 (MRD48) [MIM:617751]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD48 patients manifest global developmental delay and moderate to severe intellectual disability. {ECO:0000269|PubMed:28886345}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Focal adhesion - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - 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);Choline metabolism in cancer - 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);Viral myocarditis - Homo sapiens (human);Tight junction - Homo sapiens (human);Phagosome - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - 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);Toll-like receptor signaling pathway - 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);Pancreatic secretion - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Shigellosis - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Bisphosphonate Pathway, Pharmacodynamics;Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics;Fc Epsilon Receptor I Signaling in Mast Cells;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Thioguanine Action Pathway;Mercaptopurine Metabolism Pathway;EGF-Core;JAK-STAT-Core;Androgen receptor signaling pathway;Nucleotide-binding Oligomerization Domain (NOD) pathway;Regulation of toll-like receptor signaling pathway;Target Of Rapamycin (TOR) Signaling;Physiological and Pathological Hypertrophy of the Heart;MicroRNAs in cardiomyocyte hypertrophy;Angiogenesis overview;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Integrin-mediated Cell Adhesion;Leptin signaling pathway;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;Prolactin Signaling Pathway;Regulation of Microtubule Cytoskeleton;RalA downstream regulated genes;B Cell Receptor Signaling Pathway;TNF alpha Signaling Pathway;AGE-RAGE pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Spinal Cord Injury;Alpha 6 Beta 4 signaling pathway;Amyotrophic lateral sclerosis (ALS);Integrated Lung Cancer Pathway;JAK-STAT;Cardiac Hypertrophic Response;Focal Adhesion;Rac1-Pak1-p38-MMP-2 pathway;Wnt Signaling Pathway;IL-6 signaling pathway;Hepatitis C and Hepatocellular Carcinoma;TGF-beta Signaling Pathway;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;Microglia Pathogen Phagocytosis Pathway;Robo4 and VEGF Signaling Pathways Crosstalk;p38 MAPK Signaling Pathway;PI3K-Akt Signaling Pathway;Ebola Virus Pathway on Host;MET in type 1 papillary renal cell carcinoma;Chromosomal and microsatellite instability in colorectal cancer;Ebola Virus Pathway on Host;Ras Signaling;Wnt Signaling Pathway;EGF-EGFR Signaling Pathway;Insulin Signaling;Regulation of Actin Cytoskeleton;G13 Signaling Pathway;Interferon type I signaling pathways;DNA Damage Response (only ATM dependent);Toll-like Receptor Signaling Pathway;Developmental Biology;Signaling by PTK6;Signaling by GPCR;TWEAK;Neutrophil degranulation;Disease;Signaling by WNT;Signal Transduction;DAP12 signaling;DAP12 interactions;DSCAM interactions;links between pyk2 and map kinases;role of pi3k subunit p85 in regulation of actin organization and cell migration;influence of ras and rho proteins on g1 to s transition;tumor suppressor arf inhibits ribosomal biogenesis;ucalpain and friends in cell spread;p38 mapk signaling pathway;angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling;ras signaling pathway;phospholipids as signalling intermediaries;how does salmonella hijack a cell;mcalpain and friends in cell motility;VEGFA-VEGFR2 Pathway;ras-independent pathway in nk cell-mediated cytotoxicity;phosphoinositides and their downstream targets;t cell receptor signaling pathway;y branching of actin filaments;bcr signaling pathway;rac1 cell motility signaling pathway;mapkinase signaling pathway;map kinase inactivation of smrt corepressor;Alpha6Beta4Integrin;RHO GTPases activate KTN1;Host Interactions of HIV factors;HIV Infection;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;HGF;EPH-Ephrin signaling;FCERI mediated MAPK activation;Fc epsilon receptor (FCERI) signaling;Infectious disease;Innate Immune System;Immune System;EPHB-mediated forward signaling;RHO GTPases Activate WASPs and WAVEs;Ephrin signaling;EPH-ephrin mediated repulsion of cells;Adaptive Immune System;RHO GTPases Activate Formins;Activation of RAC1;Rho GTPase cycle;Inactivation of CDC42 and RAC1;RHO GTPases activate PAKs;GPVI-mediated activation cascade;RHO GTPases activate PKNs;RHO GTPases activate CIT;RHO GTPases activate IQGAPs;Platelet activation, signaling and aggregation;RHO GTPases Activate NADPH Oxidases;RHO GTPase Effectors;Signaling by Rho GTPases;DCC mediated attractive signaling;Integrin;PCP/CE pathway;Activated NTRK2 signals through CDK5;Signaling by NTRK2 (TRKB);Signaling by NTRKs;Sema4D mediated inhibition of cell attachment and migration;Nef and signal transduction;EGFR1;agrin in postsynaptic differentiation;Sema4D in semaphorin signaling;Regulation of RAC1 activity;role of mal in rho-mediated activation of srf;Beta-catenin independent WNT signaling;SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion;CXCR4-mediated signaling events;ErbB1 downstream signaling;Sema3A PAK dependent Axon repulsion;fmlp induced chemokine gene expression in hmc-1 cells;Hemostasis;NRAGE signals death through JNK;MAPK family signaling cascades;BCR signaling pathway;Semaphorin interactions;Thromboxane A2 receptor signaling;The role of Nef in HIV-1 replication and disease pathogenesis;Regulation of actin dynamics for phagocytic cup formation;Noncanonical Wnt signaling pathway;E-cadherin signaling in keratinocytes;PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases;Signaling by Non-Receptor Tyrosine Kinases;Posttranslational regulation of adherens junction stability and dissassembly;Netrin-1 signaling;Death Receptor Signalling;Arf1 pathway;Signaling events regulated by Ret tyrosine kinase;a6b1 and a6b4 Integrin signaling;p75 NTR receptor-mediated signalling;Signal transduction by L1;Ephrin B reverse signaling;Signaling by ROBO receptors;Class I PI3K signaling events;Signaling by VEGF;L1CAM interactions;Angiopoietin receptor Tie2-mediated signaling;Axon guidance;G alpha (12/13) signalling events;Signaling by SCF-KIT;IL6;Wnt;Integrin-linked kinase signaling;Signaling by Receptor Tyrosine Kinases;GPCR downstream signalling;ErbB2/ErbB3 signaling events;Osteopontin-mediated events;RAC1 signaling pathway;Nectin adhesion pathway;Alpha9 beta1 integrin signaling events;Neurotrophic factor-mediated Trk receptor signaling;LPA receptor mediated events;CDC42 signaling events;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Netrin-mediated signaling events;N-cadherin signaling events;S1P1 pathway;Signaling events mediated by focal adhesion kinase;IL2 signaling events mediated by PI3K;S1P3 pathway;Regulation of p38-alpha and p38-beta;p75(NTR)-mediated signaling;EPHB forward signaling;Cell death signalling via NRAGE, NRIF and NADE;p38 MAPK signaling pathway;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling;Nongenotropic Androgen signaling;Arf6 downstream pathway;Alpha4 beta1 integrin signaling events;PDGFR-beta signaling pathway;EPHA2 forward signaling;Lissencephaly gene (LIS1) in neuronal migration and development;Syndecan-4-mediated signaling events;IL6-mediated signaling events;Endothelins;Nephrin/Neph1 signaling in the kidney podocyte;Integrins in angiogenesis;E-cadherin signaling in the nascent adherens junction;Signaling events mediated by PRL;S1P2 pathway;CD4 T cell receptor signaling-JNK cascade;VEGFR2 mediated vascular permeability;CD4 T cell receptor signaling
(Consensus)
Recessive Scores
- pRec
- 0.479
Intolerance Scores
- loftool
- 0.220
- rvis_EVS
- -0.16
- rvis_percentile_EVS
- 41.25
Haploinsufficiency Scores
- pHI
- 0.988
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.562
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rac1
- 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; immune system phenotype; embryo phenotype; 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); 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); hematopoietic system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; pigmentation phenotype; muscle phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism 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);
Zebrafish Information Network
- Gene name
- rac1b
- Affected structure
- pronephros
- Phenotype tag
- abnormal
- Phenotype quality
- cystic
Gene ontology
- Biological process
- neuron migration;positive regulation of protein phosphorylation;mast cell chemotaxis;protein phosphorylation;inflammatory response;cell adhesion;cell-matrix adhesion;Rho protein signal transduction;blood coagulation;motor neuron axon guidance;cell population proliferation;regulation of cell size;response to wounding;anatomical structure morphogenesis;regulation of hydrogen peroxide metabolic process;regulation of lamellipodium assembly;positive regulation of lamellipodium assembly;positive regulation of cell-substrate adhesion;cell migration;Rac protein signal transduction;cell projection assembly;lamellipodium assembly;actin cytoskeleton organization;actin filament polymerization;regulation of cell migration;positive regulation of microtubule polymerization;T cell costimulation;ruffle organization;negative regulation of interleukin-23 production;substrate adhesion-dependent cell spreading;positive regulation of Rho protein signal transduction;intracellular signal transduction;Fc-epsilon receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;neutrophil degranulation;regulation of nitric oxide biosynthetic process;bone resorption;positive regulation of DNA replication;phosphatidylinositol phosphorylation;vascular endothelial growth factor receptor signaling pathway;hepatocyte growth factor receptor signaling pathway;ephrin receptor signaling pathway;negative regulation of receptor-mediated endocytosis;cell motility;regulation of defense response to virus by virus;regulation of small GTPase mediated signal transduction;regulation of stress fiber assembly;positive regulation of stress fiber assembly;localization within membrane;positive regulation of focal adhesion assembly;positive regulation of protein kinase B signaling;Wnt signaling pathway, planar cell polarity pathway;regulation of respiratory burst;cellular response to mechanical stimulus;semaphorin-plexin signaling pathway;positive regulation of neutrophil chemotaxis;ruffle assembly;positive regulation of substrate adhesion-dependent cell spreading;regulation of neutrophil migration
- Cellular component
- Golgi membrane;cytoplasm;endoplasmic reticulum membrane;trans-Golgi network;cytosol;actin filament;plasma membrane;focal adhesion;membrane;lamellipodium;secretory granule membrane;cytoplasmic vesicle;ruffle membrane;cytoplasmic ribonucleoprotein granule;melanosome;cell projection;dendritic spine;recycling endosome membrane;extracellular exosome;postsynapse;glutamatergic synapse;ficolin-1-rich granule membrane
- Molecular function
- GTPase activity;protein serine/threonine kinase activity;protein binding;GTP binding;Rab GTPase binding;enzyme binding;protein kinase binding;thioesterase binding;histone deacetylase binding;protein-containing complex binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity;Rho GDP-dissociation inhibitor binding;ATPase binding