ARHGEF2 (Rho Guanine Nucleotide Exchange Factor 2)
A key regulator of Rho GTPase signaling, implicated in cancer metastasis, neurodevelopment, and cellular mechanics.
Gene Information Card
| Symbol | ARHGEF2 |
|---|---|
| Full Name | Rho/Rac guanine nucleotide exchange factor 2 |
| Gene Type | protein coding |
| Chromosomal Location | 1q22 |
| NCBI Gene ID | 9181 ncbi.nlm.nih.gov/gene/9181 |
| Ensembl ID | ENSG00000116584 |
| UniProt ID | Q92974 |
| OMIM ID | 608136 |
| HGNC ID | 682 |
| Aliases | GEF-H1, LFP40, P40, RhoGEF2 |
Description
ARHGEF2 encodes a guanine nucleotide exchange factor (GEF) that activates Rho GTPases, particularly RhoA, by catalyzing the exchange of GDP for GTP. It is involved in various cellular processes including cytoskeletal dynamics, cell migration, proliferation, and microtubule-dependent signaling. ARHGEF2 is implicated in cancer progression, metastasis, and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Overexpression or activation promotes RhoA signaling, enhancing cell motility, invasion, and metastasis. | COSMIC: mutations and expression changes in multiple cancer types; PubMed studies. |
| Neurodevelopmental disorders (e.g., intellectual disability) | Mutations may disrupt neuronal migration and dendritic spine formation. | ClinVar: reported variants; OMIM: phenotype association. |
| Infectious diseases (e.g., HIV, bacterial infections) | ARHGEF2 is involved in pathogen-induced cytoskeletal rearrangements. | PubMed: mechanistic studies. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | nTPM ~ 50-100 (Human Protein Atlas) |
| Lung | Medium | nTPM ~ 20-50 |
| Kidney | Medium | nTPM ~ 20-40 |
| Liver | Low | nTPM < 10 |
| Heart | Low | nTPM < 10 |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | High | Cervical cancer cell line; strong expression |
| A549 | Medium | Lung carcinoma; moderate expression |
| MCF7 | Medium | Breast cancer; moderate expression |
| HEK293 | High | Embryonic kidney; strong expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.118G>A (p.Ala40Thr) | Missense | Rare | Potential loss of function; associated with neurodevelopmental phenotype (ClinVar). |
| c.155C>T (p.Pro52Leu) | Missense | Rare | Uncertain significance; possibly damaging. |
| c.220A>G (p.Thr74Ala) | Missense | Rare | Uncertain significance. |
| c.331C>T (p.Arg111Trp) | Missense | Rare | Reported in cancer (COSMIC); potential gain of function. |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants may impair GEF activity, leading to defective RhoA signaling and neuronal migration defects.
Gain of Function (GOF)
Amplification or overexpression in tumors enhances RhoA activation, promoting invasion and metastasis.
Dominant Negative (DN)
Not well characterized; some mutations may interfere with dimerization or regulatory interactions.
View complete mutation data：
Gene Ontology (GO)
| • Rho guanyl-nucleotide exchange factor activity | • GTPase activator activity |
| • Microtubule binding | • Protein binding |
| • Cytoplasm | • Cytoskeleton |
| • Cell junction | • Nucleus |
Pathways
• Rho GTPase cycle
• Signaling by Rho GTPases
• Axon guidance
• Regulation of actin cytoskeleton
• Tight junction signaling
Protein Summary
ARHGEF2 (GEF-H1) is a 985-amino acid protein containing a Dbl homology (DH) domain and a pleckstrin homology (PH) domain, which are characteristic of Rho GEFs. It is sequestered on microtubules in an inactive state and released upon microtubule depolymerization or phosphorylation, allowing it to activate RhoA at specific cellular locations. It plays critical roles in cell division, migration, and barrier function. Its dysregulation is linked to cancer and neurological disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARHGEF2 Knockout HEK293 Cell Line | EDJ-KQ2886 | Human | 9181 | Details Get a Quote |
| ARHGEF25 Knockout HEK293 Cell Line | EDJ-KQ7523 | Human | 115557 | Details Get a Quote |
| ARHGEF26 Knockout HEK293 Cell Line | EDJ-KQ8391 | Human | 26084 | Details Get a Quote |
| ARHGEF28 Knockout HEK293 Cell Line | EDJ-KQ12415 | Human | 64283 | Details Get a Quote |
| ARHGEF2 Knockout A-549 Cell Line | EDJ-KQ23954 | Human | 9181 | Details Get a Quote |
| ARHGEF2 Knockout HCT 116 Cell Line | EDJ-KQ23955 | Human | 9181 | Details Get a Quote |
| ARHGEF2 Knockout HeLa Cell Line | EDJ-KQ23956 | Human | 9181 | Details Get a Quote |
| ARHGEF26 Knockout HeLa Cell Line | EDJ-KQ33122 | Human | 26084 | Details Get a Quote |
| ARHGEF28 Knockout A-549 Cell Line | EDJ-KQ40032 | Human | 64283 | Details Get a Quote |
| ARHGEF28 Knockout HCT 116 Cell Line | EDJ-KQ41321 | Human | 64283 | Details Get a Quote |
| ARHGEF28 Knockout HeLa Cell Line | EDJ-KQ41322 | Human | 64283 | Details Get a Quote |
| ARHGEF25 Knockout A-549 Cell Line | EDJ-KQ32800 | Human | 115557 | Details Get a Quote |
| ARHGEF25 Knockout HCT 116 Cell Line | EDJ-KQ32801 | Human | 115557 | Details Get a Quote |
| ARHGEF25 Knockout HeLa Cell Line | EDJ-KQ32802 | Human | 115557 | Details Get a Quote |
| ARHGEF26 Knockout A-549 Cell Line | EDJ-KQ34455 | Human | 26084 | Details Get a Quote |
