RHOA Gene: Structure, Function, and Clinical Significance
A comprehensive guide to the RHOA gene, its protein product, associated diseases, and mutation landscape.
Gene Information Card
| Symbol | RHOA |
|---|---|
| Full Name | ras homolog family member A |
| Gene Type | protein coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 387 ncbi.nlm.nih.gov/gene/387 |
| Ensembl ID | ENSG00000067560 |
| UniProt ID | P61586 |
| OMIM ID | 165390 |
| HGNC ID | 667 |
| Aliases | ARHA, ARH12, RHO12, RHOH12 |
Description
RHOA (ras homolog family member A) is a small GTPase protein that belongs to the Rho family of GTPases. It acts as a molecular switch, cycling between an active GTP-bound state and an inactive GDP-bound state. RHOA regulates a wide range of cellular processes including actin cytoskeleton organization, cell migration, proliferation, and gene expression. Dysregulation of RHOA signaling is implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Activating mutations (e.g., G17V) or overexpression lead to increased cell proliferation, migration, and invasion. | COSMIC, ClinVar, literature |
| Developmental disorders | Germline mutations can cause syndromic conditions, though specific phenotypes are still being characterized. | OMIM, literature |
| Cardiovascular disease | RHOA signaling contributes to vascular smooth muscle contraction and endothelial barrier function; dysregulation is linked to hypertension and atherosclerosis. | Literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High |
| Heart | Medium | Medium |
| Lung | Medium | Medium |
| Liver | Medium | Medium |
| Kidney | Medium | Medium |
| Testis | High | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | High | Cervical cancer cell line |
| A549 | High | Lung carcinoma cell line |
| MCF7 | Medium | Breast cancer cell line |
| HepG2 | Medium | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| G17V | Missense | ~5-10% in angioimmunoblastic T-cell lymphoma (AITL) | Gain-of-function; impairs GTP hydrolysis, leading to constitutive activation |
| Y42C | Missense | Rare | Gain-of-function; alters GTP binding affinity |
| L57V | Missense | Rare | Gain-of-function; disrupts interaction with regulators |
| R5Q | Missense | Rare | Loss-of-function; reduces GTP binding |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair GTP binding or hydrolysis, reducing RHOA activity. These are less common and may act as tumor suppressors in some contexts.
Gain of Function (GOF)
Mutations that lock RHOA in the active GTP-bound state, leading to constitutive signaling. These are oncogenic and promote cell proliferation and migration.
Dominant Negative (DN)
Mutations that produce a protein that binds GDP but cannot exchange to GTP, thereby sequestering upstream activators and blocking signaling from wild-type RHOA.
View complete mutation data：
Gene Ontology (GO)
| • GTP binding | • GTPase activity |
| • Protein binding | • Signal transduction |
| • Actin cytoskeleton organization | • Cell migration |
| • Cell proliferation | • Apoptosis |
Pathways
• RhoA signaling pathway
• Actin cytoskeleton regulation
• Cell cycle
• MAPK signaling
• Cytokine-cytokine receptor interaction
Protein Summary
RHOA is a 22 kDa protein consisting of 193 amino acids. It contains conserved G-domains for GTP/GDP binding and a C-terminal CAAX motif for membrane anchoring. RHOA cycles between active (GTP-bound) and inactive (GDP-bound) states, regulated by GEFs, GAPs, and GDIs. Active RHOA interacts with effectors such as ROCK, mDia, and PKN to modulate actin dynamics and gene transcription. Post-translational modifications, including prenylation and phosphorylation, regulate its localization and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RHOA Knockout HEK293 Cell Line | EDJ-KQ50130 | Human | 387 | Details Get a Quote |
| RHOA Knockout HeLa Cell Line | EDJ-KQ52654 | Human | 387 | Details Get a Quote |
| RHOA Knockout A-549 Cell Line | EDJ-KQ61128 | Human | 387 | Details Get a Quote |
| RHOA Knockout HCT 116 Cell Line | EDJ-KQ69615 | Human | 387 | Details Get a Quote |
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