RHOA (ras homolog family member A)
RHOA, a member of the Rho GTPase family within the small GTPase superfamily, functions as a critical molecular switch that orchestrates cytoskeletal reorganization, cell migration, proliferation, and gene expression regulation by cycling between active GTP-bound and inactive GDP-bound states. Upon activation, RHOA engages downstream effectors such as Rho-associated kinase (ROCK) and mammalian Diaphanous-related proteins (mDia) to drive the formation of actin stress fibers, modulate cell adhesion, and generate contractile forces, primarily operating at the plasma membrane and in the cytoplasm where it cooperates with other Rho family members like RAC1 and CDC42 to establish cellular polarity. The gene encodes a protein that integrates growth factor and adhesion signals through shared guanine nucleotide exchange factor (GEF) and GTPase-activating protein (GAP) regulatory systems, and its dysregulation is linked to a spectrum of pathologies; gain-of-function mutations such as G17V and L57V can constitutively activate signaling to promote tumor invasion and metastasis in cancers including gastric and breast carcinoma, while loss-of-function variants may impair cardiovascular development, potentially leading to conditions like patent ductus arteriosus. Notably, RHOA is intimately associated with diffuse large B-cell lymphoma (DLBCL), where the p.D120N mutation is present in approximately 20% of cases, and its aberrant expression can either enhance migratory capacity while suppressing cell cycle progression—contributing to fibrosis and metastasis—or disrupt cell-cell junctions and hinder epithelial-mesenchymal transition, thereby affecting embryonic processes such as neural crest cell migration. Beyond classical cytoskeletal roles, RHOA plays a pivotal part in immune regulation by modulating T-cell receptor signaling, where its imbalance may contribute to autoimmune disorders, and recent evidence highlights its central function in mechanotransduction, sensing extracellular matrix stiffness to regulate the YAP/TAZ pathway. Therapeutically, the RHOA-ROCK axis is a significant target, with inhibitors such as fasudil already utilized in the management of cerebral vasospasm and pulmonary arterial hypertension.
Gene Ontology
Subcellular localization of RHOA (and its protein):
- plasma membrane
- cytoplasm
- extracellular
- golgi
- vesicle
- cytoskeleton
- endoplasmic reticulum
- nucleus
- endosome
- lysosome
- mitochondrion
Gene Ontology (GO) terms for RHOA:
| Interacting Gene | Interaction | Source/Score |
| Name |
|---|
| 4014 Ras signaling pathway [PATH:hsa04014] |
| 4015 Rap1 signaling pathway [PATH:hsa04015] |
| 4310 Wnt signaling pathway [PATH:hsa04310] |
| 4350 TGF-beta signaling pathway [PATH:hsa04350] |
| 4071 Sphingolipid signaling pathway [PATH:hsa04071] |
| 4024 cAMP signaling pathway [PATH:hsa04024] |
| 4022 cGMP - PKG signaling pathway [PATH:hsa04022] |
| 4144 Endocytosis [PATH:hsa04144] |
| 4810 Regulation of actin cytoskeleton [PATH:hsa04810] |
| 4510 Focal adhesion [PATH:hsa04510] |
| 4520 Adherens junction [PATH:hsa04520] |
| 4530 Tight junction [PATH:hsa04530] |
| 4611 Platelet activation [PATH:hsa04611] |
| 4660 T cell receptor signaling pathway [PATH:hsa04660] |
| 4670 Leukocyte transendothelial migration [PATH:hsa04670] |
| 4062 Chemokine signaling pathway [PATH:hsa04062] |
| 4921 Oxytocin signaling pathway [PATH:hsa04921] |
| 4270 Vascular smooth muscle contraction [PATH:hsa04270] |
| 4972 Pancreatic secretion [PATH:hsa04972] |
| 4722 Neurotrophin signaling pathway [PATH:hsa04722] |
| 4360 Axon guidance [PATH:hsa04360] |
| 5200 Pathways in cancer [PATH:hsa05200] |
| 5206 MicroRNAs in cancer [PATH:hsa05206] |
| 5205 Proteoglycans in cancer [PATH:hsa05205] |
| 5203 Viral carcinogenesis [PATH:hsa05203] |
| 5210 Colorectal cancer [PATH:hsa05210] |
| 5130 Pathogenic Escherichia coli infection [PATH:hsa05130] |
| 5133 Pertussis [PATH:hsa05133] |
| 5152 Tuberculosis [PATH:hsa05152] |
| 5100 Bacterial invasion of epithelial cells [PATH:hsa05100] |
| Name |
|---|
| Axon guidance |
| Axonal growth inhibition (RHOA activation) |
| Axonal growth stimulation |
| beta-catenin independent WNT signaling |
| Developmental Biology |
| EPH-Ephrin signaling |
| EPHA-mediated growth cone collapse |
| EPHB-mediated forward signaling |
| G alpha (12/13) signalling events |
| G beta:gamma signalling through PI3Kgamma |
| G-protein beta:gamma signalling |
| GPCR downstream signaling |
| GPVI-mediated activation cascade |
| Hemostasis |
| NGF signalling via TRKA from the plasma membrane |
| p75 NTR receptor-mediated signalling |
| p75NTR regulates axonogenesis |
| PCP/CE pathway |
| PI3K/AKT activation |
| Platelet activation, signaling and aggregation |
| Rho GTPase cycle |
| RHO GTPase Effectors |
| RHO GTPases activate CIT |
| RHO GTPases Activate Formins |
| RHO GTPases activate KTN1 |
| RHO GTPases activate PKNs |
| RHO GTPases Activate Rhotekin and Rhophilins |
| RHO GTPases Activate ROCKs |
| Sema4D in semaphorin signaling |
| Sema4D induced cell migration and growth-cone collapse |
| Sema4D mediated inhibition of cell attachment and migration |
| Semaphorin interactions |
| Signaling by GPCR |
| Signaling by Rho GTPases |
| Signaling by TGF-beta Receptor Complex |
| Signaling by VEGF |
| Signaling by Wnt |
| Signalling by NGF |
| TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) |
| VEGFA-VEGFR2 Pathway |
| Disease | Score | NofPmids | NofSnps | Source |
| Stomach Neoplasms | 0.1254487 | 4 | 0 | CTD_human_LHGDN |
| IGA Glomerulonephritis | 0.12272435 | 2 | 0 | CTD_human_LHGDN |
| Angioimmunoblastic Lymphadenopathy | 0.121357209 | 5 | 3 | BeFree_CTD_human |
| Peripheral T-Cell Lymphoma | 0.120814326 | 4 | 3 | BeFree_CTD_human |
| T-Cell Lymphoma | 0.120271442 | 1 | 0 | BeFree_CTD_human |
| Neoplasm Invasiveness | 0.12 | 1 | 0 | CTD_human |
| Lymphoma, T-Cell, Cutaneous | 0.12 | 1 | 0 | CTD_human |
| Proteinuria | 0.12 | 1 | 0 | CTD_human |
| Bladder Neoplasm | 0.12 | 1 | 0 | CTD_human |
| Fibrosis | 0.08272435 | 2 | 0 | LHGDN_RGD |
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