ARHGEF15
Rho Guanine Nucleotide Exchange Factor 15
Gene Information Card
| Symbol | ARHGEF15 |
|---|---|
| Full Name | Rho Guanine Nucleotide Exchange Factor 15 |
| Gene Type | Protein coding |
| Chromosomal Location | 17p13.1 |
| NCBI Gene ID | 22899 ncbi.nlm.nih.gov/gene/22899 |
| Ensembl ID | ENSG00000108349 |
| UniProt ID | O94989 |
| OMIM ID | 609476 |
| HGNC ID | 14509 |
| Aliases | Ephexin5, Vsm-RhoGEF, KIAA0911 |
Description
ARHGEF15 (Rho Guanine Nucleotide Exchange Factor 15) encodes a protein that activates Rho GTPases by exchanging GDP for GTP. It is involved in vascular development, angiogenesis, and neuronal signaling. The protein contains a Dbl homology (DH) domain and a pleckstrin homology (PH) domain, characteristic of RhoGEFs. ARHGEF15 is primarily expressed in the brain and vascular endothelium.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cerebral Cavernous Malformations | Loss-of-function mutations in ARHGEF15 impair endothelial cell junction integrity, leading to vascular malformations. | ClinVar, OMIM |
| Intracranial Hemorrhage | Disruption of ARHGEF15-mediated RhoA signaling increases vascular permeability and hemorrhage risk. | ClinVar, OMIM |
| Cancer (angiogenesis-related) | Altered ARHGEF15 expression may influence tumor vascularization and metastasis. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Heart | 5.1 | Low |
| Lung | 4.8 | Low |
| Liver | 2.0 | Not detected |
| Kidney | 3.5 | Low |
| Endothelium | 15.0 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (umbilical vein endothelial) | 18.2 | High expression |
| HEK293 | 6.7 | Moderate |
| SH-SY5Y (neuroblastoma) | 9.1 | Moderate |
| A549 (lung carcinoma) | 4.3 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Loss of function; associated with cerebral cavernous malformations |
| c.567G>A (p.Trp189*) | Nonsense | <0.01% | Loss of function; vascular defects |
| c.890A>G (p.Tyr297Cys) | Missense | <0.01% | Unknown significance; reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Arg412*, p.Trp189*) lead to truncated protein and loss of GEF activity, impairing endothelial barrier function.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Not established for ARHGEF15.
View complete mutation data：
Gene Ontology (GO)
| • Rho guanyl-nucleotide exchange factor activity | • GTPase activator activity |
| • Signal transduction | • Angiogenesis |
| • Cell adhesion | • Actin cytoskeleton organization |
Pathways
• Rho GTPase signaling
• Vascular endothelial growth factor (VEGF) signaling
• Regulation of actin cytoskeleton
Protein Summary
ARHGEF15 (Ephexin5) is a 927-amino acid protein containing a DH-PH domain tandem. It specifically activates RhoA and RhoC GTPases, regulating actin dynamics and endothelial cell-cell junctions. The protein is highly expressed in the brain and vascular endothelium, where it stabilizes adherens junctions. Mutations in ARHGEF15 are linked to cerebral cavernous malformations and intracranial hemorrhage.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARHGEF15 Knockout HEK293 Cell Line | EDJ-KQ7726 | Human | 22899 | Details Get a Quote |
| ARHGEF15 Knockout HeLa Cell Line | EDJ-KQ55653 | Human | 22899 | Details Get a Quote |
| ARHGEF15 Knockout A-549 Cell Line | EDJ-KQ64151 | Human | 22899 | Details Get a Quote |
| ARHGEF15 Knockout HCT 116 Cell Line | EDJ-KQ72599 | Human | 22899 | Details Get a Quote |
