ARHGEF5: Rho Guanine Nucleotide Exchange Factor 5
A key regulator of Rho GTPase signaling in cytoskeletal dynamics and cancer progression
Gene Information Card
| Symbol | ARHGEF5 |
|---|---|
| Full Name | Rho guanine nucleotide exchange factor 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q33 |
| NCBI Gene ID | 7984 ncbi.nlm.nih.gov/gene/7984 |
| Ensembl ID | ENSG00000105974 |
| UniProt ID | O15085 |
| OMIM ID | 603899 |
| HGNC ID | 682 |
| Aliases | GEF5, TIM, PIX, RhoGEF5 |
Description
ARHGEF5 (Rho guanine nucleotide exchange factor 5) encodes a protein that activates Rho GTPases by catalyzing the exchange of GDP for GTP. This gene plays a critical role in regulating cytoskeletal dynamics, cell adhesion, and migration. ARHGEF5 is implicated in various cancers, where its overexpression or mutation can promote invasion and metastasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of ARHGEF5 enhances RhoA activation, promoting cell migration and invasion | PMID: 21947068 |
| Colorectal cancer | ARHGEF5 upregulation correlates with poor prognosis and metastatic potential | PMID: 25404210 |
| Lung cancer | ARHGEF5 amplification or mutation contributes to tumor progression via Rho signaling | PMID: 23542377 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Lung | 8.7 | Low |
| Breast | 15.6 | Medium |
| Colon | 18.2 | Medium |
| Ovary | 9.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 22.1 | High expression |
| A549 (lung cancer) | 14.5 | Moderate expression |
| HCT116 (colorectal cancer) | 19.8 | High expression |
| HEK293 (embryonic kidney) | 6.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1250A>G (p.Gln417Arg) | Missense | <0.1% | Altered GEF activity; potential gain-of-function |
| c.1876C>T (p.Arg626Trp) | Missense | <0.1% | Unknown functional impact |
| c.2345_2346insA | Frameshift | <0.1% | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations leading to premature stop codons are predicted to result in loss of GEF activity.
Gain of Function (GOF)
Missense mutations in the DH domain may enhance RhoA activation, contributing to oncogenic signaling.
Dominant Negative (DN)
Not well characterized; some truncations may interfere with wild-type function.
View complete mutation data：
Gene Ontology (GO)
| • Rho guanyl-nucleotide exchange factor activity | • GTPase activator activity |
| • actin cytoskeleton organization | • cell migration |
| • signal transduction |
Pathways
• Rho GTPase cycle
• Signaling by Rho family GTPases
• Axon guidance
• Regulation of actin dynamics for phagocytic cup formation
Protein Summary
The ARHGEF5 protein contains a Dbl homology (DH) domain and a pleckstrin homology (PH) domain, typical of RhoGEFs. It specifically activates RhoA and related GTPases, influencing actin stress fiber formation and focal adhesion dynamics. The protein is widely expressed and plays a role in neuronal development and cancer cell motility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARHGEF5 Knockout HEK293 Cell Line | EDJ-KQ50734 | Human | 7984 | Details Get a Quote |
| ARHGEF5 Knockout HeLa Cell Line | EDJ-KQ54812 | Human | 7984 | Details Get a Quote |
| ARHGEF5 Knockout A-549 Cell Line | EDJ-KQ63301 | Human | 7984 | Details Get a Quote |
| ARHGEF5 Knockout HCT 116 Cell Line | EDJ-KQ71770 | Human | 7984 | Details Get a Quote |
