RHOA
ras homolog family member A, the group of Rho family GTPases
Basic information
Region (hg38): 3:49359138-49412998
Previous symbols: [ "ARH12", "ARHA" ]
Links
Phenotypes
GenCC
Source:
- ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies (Limited), mode of inheritance: Unknown
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies | 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; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic | 31570889 |
| Causative variants have been postzygotic mosaic (and not detected via blood-based testing) |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (4 variants)
- Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies (2 variants)
- Hemihypertrophy (1 variants)
- Inborn genetic diseases (1 variants)
- neuro-ectodermal phenotype (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RHOA 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 | |||||
| missense | 5 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 1 | 1 | 3 | 0 | 1 |
Variants in RHOA
This is a list of pathogenic ClinVar variants found in the RHOA region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-49360377-C-T | RHOA-related disorder | Likely benign (Feb 23, 2022) | ||
| 3-49368494-G-A | Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies | Pathogenic (Jan 29, 2020) | ||
| 3-49368497-T-C | Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies | Likely pathogenic (-) | ||
| 3-49368502-C-T | Uncertain significance (Jul 31, 2023) | |||
| 3-49368509-A-G | Inborn genetic diseases | Uncertain significance (Oct 06, 2016) | ||
| 3-49368524-C-T | Uncertain significance (Jun 26, 2021) | |||
| 3-49375451-C-T | neuro-ectodermal phenotype • Hemihypertrophy • Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies | Pathogenic (Oct 05, 2023) | ||
| 3-49375465-T-A | Gastric adenocarcinoma • Non-Hodgkin lymphoma • Squamous cell carcinoma of the head and neck | Likely pathogenic (May 31, 2016) | ||
| 3-49375465-T-C | Squamous cell carcinoma of the head and neck • Gastric adenocarcinoma • Non-Hodgkin lymphoma | Likely pathogenic (May 31, 2016) | ||
| 3-49375465-T-G | Non-Hodgkin lymphoma • Gastric adenocarcinoma • Squamous cell carcinoma of the head and neck | Likely pathogenic (May 31, 2016) | ||
| 3-49375472-C-G | Breast neoplasm • Lung adenocarcinoma • Gastric adenocarcinoma • Squamous cell carcinoma of the head and neck | Likely pathogenic (May 31, 2016) | ||
| 3-49375472-C-T | Lung adenocarcinoma • Gastric adenocarcinoma • Breast neoplasm • Squamous cell carcinoma of the head and neck | Likely pathogenic (May 31, 2016) | ||
| 3-49375563-C-T | Benign (Jul 06, 2018) | |||
| 3-49375576-C-A | Non-Hodgkin lymphoma • Carcinoma of esophagus • Neoplasm of the large intestine • Breast neoplasm • Gastric adenocarcinoma | Likely pathogenic (May 31, 2016) | ||
| 3-49375576-C-T | Breast neoplasm • Gastric adenocarcinoma • Carcinoma of esophagus • Non-Hodgkin lymphoma • Neoplasm of the large intestine | Likely pathogenic (May 31, 2016) | ||
| 3-49375577-G-A | Carcinoma of esophagus • Non-Hodgkin lymphoma • Gastric adenocarcinoma • Breast neoplasm • Neoplasm of the large intestine | Likely pathogenic (May 31, 2016) | ||
| 3-49412460-G-A | not specified | Uncertain significance (Jan 19, 2024) | ||
| 3-49412551-T-C | not specified | Uncertain significance (Oct 25, 2023) | ||
| 3-49412633-C-A | not specified | Uncertain significance (Nov 15, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RHOA | protein_coding | protein_coding | ENST00000418115 | 4 | 53854 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.604 | 0.388 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.36 | 13 | 114 | 0.114 | 0.00000622 | 1274 |
| Missense in Polyphen | 0 | 32.164 | 0 | 418 | ||
| Synonymous | -0.431 | 46 | 42.4 | 1.08 | 0.00000239 | 369 |
| Loss of Function | 2.13 | 1 | 7.14 | 0.140 | 2.98e-7 | 100 |
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) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. Stimulates PKN2 kinase activity. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (By similarity). Regulates KCNA2 potassium channel activity by reducing its location at the cell surface in response to CHRM1 activation; promotes KCNA2 endocytosis (PubMed:9635436, PubMed:19403695). {ECO:0000250, ECO:0000269|PubMed:12900402, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:19934221, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:20974804, ECO:0000269|PubMed:8910519, ECO:0000269|PubMed:9121475, ECO:0000269|PubMed:9635436}.; FUNCTION: (Microbial infection) Serves as a target for the yopT cysteine peptidase from Yersinia pseudotuberculosis, which causes gastrointestinal disorders. {ECO:0000269|PubMed:12062101, ECO:0000269|PubMed:12538863}.;
- Pathway
- Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);TGF-beta signaling pathway - Homo sapiens (human);Pertussis - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Adherens junction - Homo sapiens (human);Endocytosis - Homo sapiens (human);Tight junction - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Axon guidance - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Bisphosphonate Pathway, Pharmacodynamics;Androgen receptor signaling pathway;Physiological and Pathological Hypertrophy of the Heart;MicroRNAs in cardiomyocyte hypertrophy;Leptin signaling pathway;Pathogenic Escherichia coli infection;AGE-RAGE pathway;Corticotropin-releasing hormone signaling pathway;Spinal Cord Injury;Alpha 6 Beta 4 signaling pathway;JAK-STAT;Focal Adhesion;G Protein Signaling Pathways;Wnt Signaling Pathway;Hypothetical Craniofacial Development Pathway;TGF-beta Signaling Pathway;Association Between Physico-Chemical Features and Toxicity Associated Pathways;VEGFA-VEGFR2 Signaling Pathway;Wnt Signaling Pathway and Pluripotency;Fibrin Complement Receptor 3 Signaling Pathway;Wnt Signaling in Kidney Disease;Ebola Virus Pathway on Host;Chromosomal and microsatellite instability in colorectal cancer;Ebola Virus Pathway on Host;Ras Signaling;Wnt Signaling Pathway;Regulation of Actin Cytoskeleton;G13 Signaling Pathway;DNA Damage Response (only ATM dependent);Serotonin HTR1 Group and FOS Pathway;Developmental Biology;Signaling by PTK6;Signaling by GPCR;RAGE;Neutrophil degranulation;Signaling by WNT;Signal Transduction;erk and pi-3 kinase are necessary for collagen binding in corneal epithelia;role of pi3k subunit p85 in regulation of actin organization and cell migration;influence of ras and rho proteins on g1 to s transition;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;trefoil factors initiate mucosal healing;ucalpain and friends in cell spread;integrin signaling pathway;ras signaling pathway;ccr3 signaling in eosinophils;VEGFA-VEGFR2 Pathway;rho cell motility signaling pathway;rho-selective guanine exchange factor akap13 mediates stress fiber formation;thrombin signaling and protease-activated receptors;protein kinase a at the centrosome;Alpha6Beta4Integrin;RHO GTPases activate KTN1;Post-translational protein modification;Metabolism of proteins;SLIT2:ROBO1 increases RHOA activity;EPH-Ephrin signaling;EPHA-mediated growth cone collapse;Innate Immune System;Immune System;EPHB-mediated forward signaling;RHO GTPases Activate Rhotekin and Rhophilins;RHO GTPases Activate Formins;Rho GTPase cycle;RHO GTPases Activate ROCKs;GPVI-mediated activation cascade;RHO GTPases activate PKNs;RHO GTPases activate CIT;Platelet activation, signaling and aggregation;RHO GTPase Effectors;Signaling by Rho GTPases;Signaling by NTRK1 (TRKA);Integrin;TGF_beta_Receptor;PCP/CE pathway;S1P5 pathway;Signaling by NTRKs;Sema4D mediated inhibition of cell attachment and migration;EGFR1;SHP2 signaling;Sema4D induced cell migration and growth-cone collapse;Sema4D in semaphorin signaling;d4gdi signaling pathway;role of mal in rho-mediated activation of srf;Beta-catenin independent WNT signaling;CXCR4-mediated signaling events;Hemostasis;PI3K/AKT activation;Semaphorin interactions;Thromboxane A2 receptor signaling;Ovarian tumor domain proteases;Noncanonical Wnt signaling pathway;E-cadherin signaling in keratinocytes;PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases;Signaling by Non-Receptor Tyrosine Kinases;Deubiquitination;Death Receptor Signalling;Signaling events regulated by Ret tyrosine kinase;Axonal growth stimulation;Axonal growth inhibition (RHOA activation);p75NTR regulates axonogenesis;p75 NTR receptor-mediated signalling;IL2-mediated signaling events;Signaling by ROBO receptors;Class I PI3K signaling events;Signaling by VEGF;Axon guidance;G alpha (12/13) signalling events;Signaling by ERBB2;ERBB2 Regulates Cell Motility;Wnt;Signaling by Receptor Tyrosine Kinases;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;Osteopontin-mediated events;Stabilization and expansion of the E-cadherin adherens junction;a4b7 Integrin signaling;PAR4-mediated thrombin signaling events;PAR1-mediated thrombin signaling events;Neurotrophic factor-mediated Trk receptor signaling;Aurora B signaling;LPA receptor mediated events;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Netrin-mediated signaling events;N-cadherin signaling events;S1P1 pathway;Endogenous TLR signaling;Signaling events mediated by focal adhesion kinase;PLK1 signaling events;S1P3 pathway;amb2 Integrin signaling;S1P4 pathway;p75(NTR)-mediated signaling;Plasma membrane estrogen receptor signaling;Arf6 downstream pathway;PDGFR-beta signaling pathway;Signaling events mediated by PTP1B;EPHA2 forward signaling;Lissencephaly gene (LIS1) in neuronal migration and development;Syndecan-4-mediated signaling events;Endothelins;Signaling events mediated by VEGFR1 and VEGFR2;TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition);Integrins in angiogenesis;E-cadherin signaling in the nascent adherens junction;EPHA forward signaling;Syndecan-2-mediated signaling events;RhoA signaling pathway;Regulation of RhoA activity;Signaling events mediated by PRL;S1P2 pathway
(Consensus)
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- loftool
- rvis_EVS
- -0.01
- rvis_percentile_EVS
- 52.85
Haploinsufficiency Scores
- pHI
- 0.874
- hipred
- Y
- hipred_score
- 0.752
- ghis
- 0.667
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.982
Mouse Genome Informatics
- Gene name
- Rhoa
- Phenotype
- cellular phenotype; embryo 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); normal 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); hematopoietic system phenotype;
Zebrafish Information Network
- Gene name
- rhoab
- Affected structure
- somite border
- Phenotype tag
- abnormal
- Phenotype quality
- hypoplastic
Gene ontology
- Biological process
- response to hypoxia;angiotensin-mediated vasoconstriction involved in regulation of systemic arterial blood pressure;alpha-beta T cell lineage commitment;regulation of systemic arterial blood pressure by endothelin;regulation of transcription by RNA polymerase II;actin filament organization;cell-matrix adhesion;transforming growth factor beta receptor signaling pathway;G protein-coupled receptor signaling pathway;Rho protein signal transduction;skeletal muscle tissue development;regulation of cell shape;response to mechanical stimulus;response to glucose;negative regulation of cell-substrate adhesion;viral process;cell migration;protein deubiquitination;substantia nigra development;cerebral cortex cell migration;forebrain radial glial cell differentiation;actin cytoskeleton organization;positive regulation of cell growth;regulation of cell migration;androgen receptor signaling pathway;positive regulation of actin filament polymerization;establishment or maintenance of actin cytoskeleton polarity;stress-activated protein kinase signaling cascade;actin cytoskeleton reorganization;positive regulation of cytokinesis;regulation of actin cytoskeleton organization;negative regulation of intracellular steroid hormone receptor signaling pathway;regulation of osteoblast proliferation;cell junction assembly;Roundabout signaling pathway;cleavage furrow formation;apolipoprotein A-I-mediated signaling pathway;odontogenesis;positive regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of I-kappaB kinase/NF-kappaB signaling;stress fiber assembly;response to amino acid;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;apical junction assembly;neutrophil degranulation;beta selection;negative regulation of neuron apoptotic process;positive regulation of neuron apoptotic process;endothelial cell migration;ossification involved in bone maturation;wound healing, spreading of cells;establishment of epithelial cell apical/basal polarity;response to ethanol;positive regulation of neuron differentiation;positive regulation of translation;negative regulation of cell size;GTP metabolic process;positive regulation of alpha-beta T cell differentiation;vascular endothelial growth factor receptor signaling pathway;ephrin receptor signaling pathway;phosphatidylinositol-mediated signaling;neuron projection morphogenesis;negative regulation of axonogenesis;positive regulation of axonogenesis;regulation of dendrite development;negative chemotaxis;actin filament bundle assembly;regulation of small GTPase mediated signal transduction;response to glucocorticoid;positive regulation of stress fiber assembly;regulation of focal adhesion assembly;regulation of calcium ion transport;Wnt signaling pathway, planar cell polarity pathway;positive regulation of lipase activity;trabecula morphogenesis;regulation of microtubule cytoskeleton organization;cellular response to lipopolysaccharide;cellular response to cytokine stimulus;positive regulation of podosome assembly;positive regulation of protein serine/threonine kinase activity;negative regulation of cell migration involved in sprouting angiogenesis;mitotic spindle assembly;negative regulation of oxidative phosphorylation;endothelial tube lumen extension;positive regulation of NIK/NF-kappaB signaling;skeletal muscle satellite cell migration;negative regulation of reactive oxygen species biosynthetic process;mitotic cleavage furrow formation;positive regulation of vascular smooth muscle contraction;positive regulation of leukocyte adhesion to vascular endothelial cell;regulation of modification of postsynaptic actin cytoskeleton;cellular response to chemokine;regulation of cell motility;regulation of neural precursor cell proliferation;positive regulation of T cell migration
- Cellular component
- nucleus;cytoplasm;endosome;endoplasmic reticulum membrane;cytosol;cytoskeleton;plasma membrane;focal adhesion;cell cortex;lamellipodium;cell junction;axon;midbody;secretory granule membrane;extrinsic component of cytoplasmic side of plasma membrane;vesicle;cell division site;cleavage furrow;ruffle membrane;dendritic spine;intracellular membrane-bounded organelle;apical junction complex;extracellular exosome;cell periphery;postsynapse;glutamatergic synapse;ficolin-1-rich granule membrane
- Molecular function
- GTPase activity;protein binding;GTP binding;myosin binding;GDP binding;protein kinase binding;protein domain specific binding;Rho GDP-dissociation inhibitor binding