ARHGDIA (Rho GDP Dissociation Inhibitor Alpha) Gene
A key regulator of Rho GTPase signaling, implicated in nephrotic syndrome and cancer
Gene Information Card
| Symbol | ARHGDIA |
|---|---|
| Full Name | Rho GDP dissociation inhibitor alpha |
| Gene Type | protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 396 ncbi.nlm.nih.gov/gene/396 |
| Ensembl ID | ENSG00000134245 |
| UniProt ID | P52565 |
| OMIM ID | 601925 |
| HGNC ID | 678 |
| Aliases | RhoGDI1, GDIA1, RHOGDI, HEL-S-44e |
Description
ARHGDIA encodes Rho GDP dissociation inhibitor alpha, a key regulator of Rho GTPases. It inhibits the dissociation of GDP from Rho proteins, maintaining them in an inactive state and controlling their subcellular localization. This gene plays a critical role in cell motility, proliferation, and differentiation. Mutations in ARHGDIA are associated with nephrotic syndrome type 8, and altered expression is observed in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nephrotic syndrome type 8 | Loss-of-function mutations impair Rho GTPase regulation, leading to podocyte dysfunction and proteinuria. | ClinVar, OMIM |
| Focal segmental glomerulosclerosis | ARHGDIA mutations disrupt actin cytoskeleton in podocytes, contributing to glomerular scarring. | ClinVar, OMIM |
| Cancer (various types) | Altered expression (often reduced) affects Rho GTPase activity, promoting tumor invasion and metastasis. | COSMIC, PubMed (via NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | High (e.g., 100+ nTPM) | Strong expression in renal tubules and glomeruli. |
| Brain | Moderate (e.g., 50-100 nTPM) | Widespread expression in neurons and glia. |
| Lung | Moderate (e.g., 30-50 nTPM) | Present in epithelial and stromal cells. |
| Liver | Low (e.g., <10 nTPM) | Minimal expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | High (e.g., 80 nTPM) | Embryonic kidney cells; used in functional studies. |
| HeLa | Moderate (e.g., 40 nTPM) | Cervical cancer cell line. |
| A549 | Low (e.g., 15 nTPM) | Lung carcinoma cell line. |
| MCF7 | Moderate (e.g., 35 nTPM) | Breast cancer cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.263C>T (p.Ala88Val) | Missense | Rare (found in familial nephrotic syndrome) | Impairs RhoGDI activity, leading to podocyte damage. |
| c.364G>A (p.Gly122Arg) | Missense | Rare (found in sporadic cases) | Disrupts protein stability and function. |
| c.518delA (p.Lys173Argfs*3) | Frameshift | Very rare | Truncated protein, loss of function. |
| c.70G>A (p.Gly24Ser) | Missense | Reported in cancer (COSMIC) | Potential gain-of-function or altered regulation. |
Mutation functional classification
Loss of Function (LOF)
Most nephrotic syndrome-associated mutations are loss-of-function, reducing RhoGDI activity and leading to unregulated Rho GTPase signaling.
Gain of Function (GOF)
Rare somatic mutations in cancer may lead to increased stability or altered binding, but evidence is limited.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner, interfering with wild-type protein function, though not well characterized.
View complete mutation data：
Gene Ontology (GO)
| • Rho GDP-dissociation inhibitor activity | • GTPase binding |
| • Protein stabilization | • Negative regulation of cell migration |
| • Regulation of actin cytoskeleton organization | • Cytoplasm |
| • Cytosol | • Membrane |
Pathways
• Rho GTPase cycle
• Axon guidance
• Regulation of actin dynamics
• Podocyte differentiation
Protein Summary
The ARHGDIA protein (RhoGDI alpha) is a 204-amino acid protein that binds to Rho GTPases (RhoA, Rac1, Cdc42) and regulates their GDP/GTP exchange. It inhibits nucleotide dissociation and sequesters Rho proteins in the cytosol, preventing their membrane localization and activation. This protein is essential for maintaining cell shape, motility, and adhesion. Mutations cause nephrotic syndrome, and dysregulation is linked to cancer metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARHGDIA Knockout HEK293 Cell Line | EDJ-KQ3796 | Human | 396 | Details Get a Quote |
| ARHGDIA Knockout HeLa Cell Line | EDJ-KQ24551 | Human | 396 | Details Get a Quote |
| ARHGDIA Knockout A-549 Cell Line | EDJ-KQ25907 | Human | 396 | Details Get a Quote |
| ARHGDIA Knockout HCT 116 Cell Line | EDJ-KQ25908 | Human | 396 | Details Get a Quote |
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