ARHGEF18: Rho Guanine Nucleotide Exchange Factor 18
A key regulator of RhoA signaling in cell adhesion, polarity, and barrier function
Gene Information Card
| Symbol | ARHGEF18 |
|---|---|
| Full Name | Rho guanine nucleotide exchange factor 18 |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.2 |
| NCBI Gene ID | 23370 ncbi.nlm.nih.gov/gene/23370 |
| Ensembl ID | ENSG00000104872 |
| UniProt ID | Q6ZSZ5 |
| OMIM ID | 616405 |
| HGNC ID | 17090 |
| Aliases | p114-RhoGEF, RhoGEF18, KIAA0521 |
Description
ARHGEF18 encodes a Rho guanine nucleotide exchange factor (RhoGEF) that specifically activates RhoA by catalyzing the exchange of GDP for GTP. The protein localizes to tight junctions and regulates actin cytoskeleton dynamics, cell polarity, and paracellular permeability. Mutations in ARHGEF18 are associated with hereditary spastic paraplegia and microvillus inclusion disease-like enteropathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spastic paraplegia (SPG78) | Loss-of-function mutations impair RhoA activation at tight junctions, disrupting neuronal polarity and axonal transport | OMIM #616405; PMID: 28111017 |
| Microvillus inclusion disease-like enteropathy | Biallelic truncating mutations disrupt epithelial barrier function and microvillar assembly | PMID: 28111017; ClinVar |
| Congenital tufting enteropathy-like phenotype | ARHGEF18 deficiency leads to defective tight junction formation and intestinal epithelial integrity | PMID: 28111017 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Colon | 18.7 | Medium |
| Small intestine | 22.1 | High |
| Kidney | 8.5 | Low |
| Lung | 6.2 | Low |
| Liver | 4.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 | 25.4 | Intestinal epithelial model |
| HeLa | 9.8 | Cervical carcinoma |
| HEK 293 | 7.3 | Embryonic kidney |
| SH-SY5Y | 14.6 | Neuroblastoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2071C>T (p.Arg691*) | Nonsense | Rare | Loss of function; truncation of C-terminal PH domain |
| c.1336C>T (p.Arg446*) | Nonsense | Rare | Loss of function; premature stop in DH domain |
| c.1756G>A (p.Gly586Arg) | Missense | Rare | Likely loss of function; disrupts catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein lacking functional DH/PH domains; associated with hereditary spastic paraplegia and enteropathy
Gain of Function (GOF)
Not reported
Dominant Negative (DN)
Not reported
View complete mutation data：
Gene Ontology (GO)
| • Rho guanyl-nucleotide exchange factor activity (GO:0005089) | • regulation of Rho protein signal transduction (GO:0035023) |
| • actin cytoskeleton organization (GO:0030036) | • bicellular tight junction (GO:0005923) |
| • actin filament bundle assembly (GO:0051015) | • small GTPase mediated signal transduction (GO:0007264) |
Pathways
• RhoA signaling pathway (Reactome: R-HSA-194315)
• Tight junction organization (Reactome: R-HSA-420029)
• Regulation of actin dynamics for phagocytic cup formation (Reactome: R-HSA-2029482)
Protein Summary
ARHGEF18 (p114-RhoGEF) is a 1042-amino acid protein containing a Dbl homology (DH) domain and a pleckstrin homology (PH) domain. It specifically activates RhoA, not Rac1 or Cdc42. The protein localizes to tight junctions via interaction with ZO-1 and cingulin, and is essential for junctional actin assembly and barrier maintenance. In neurons, it regulates axonal growth cone dynamics and polarity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARHGEF18 Knockout HEK293 Cell Line | EDJ-KQ3725 | Human | 23370 | Details Get a Quote |
| ARHGEF18 Knockout HCT 116 Cell Line | EDJ-KQ24401 | Human | 23370 | Details Get a Quote |
| ARHGEF18 Knockout A-549 Cell Line | EDJ-KQ25769 | Human | 23370 | Details Get a Quote |
| ARHGEF18 Knockout HeLa Cell Line | EDJ-KQ25771 | Human | 23370 | Details Get a Quote |
