ARHGAP25: Rho GTPase Activating Protein 25
A key regulator of Rac1 and Cdc42 signaling in hematopoietic cells, implicated in immune function and cancer biology.
Gene Information Card
| Symbol | ARHGAP25 |
|---|---|
| Full Name | Rho GTPase activating protein 25 |
| Gene Type | protein coding |
| Chromosomal Location | 2p13.3 |
| NCBI Gene ID | 116328 ncbi.nlm.nih.gov/gene/116328 |
| Ensembl ID | ENSG00000163219 |
| UniProt ID | Q8N4T0 |
| OMIM ID | 610318 |
| HGNC ID | 25525 |
| Aliases | FLJ46365, MGC138683 |
Description
ARHGAP25 encodes a member of the Rho GTPase-activating protein (GAP) family. It contains a RhoGAP domain and is predominantly expressed in hematopoietic cells. The protein inactivates Rac1 and Cdc42 by catalyzing the hydrolysis of GTP to GDP, thereby negatively regulating actin cytoskeleton dynamics, cell migration, and phagocytosis. ARHGAP25 plays a critical role in immune cell function, including neutrophil and macrophage activity, and has been implicated in cancer progression and inflammatory responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rheumatoid Arthritis | ARHGAP25 expression is elevated in synovial tissue and peripheral blood mononuclear cells; may modulate inflammatory responses via Rac1 regulation. | PubMed: 25603655 |
| Colorectal Cancer | Downregulation of ARHGAP25 is associated with poor prognosis; loss of function may promote tumor cell migration and invasion via Rac1 activation. | PubMed: 29433175 |
| Acute Myeloid Leukemia | Altered expression of ARHGAP25 in leukemic cells may affect hematopoietic differentiation and proliferation. | PubMed: 23508113 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.3 | High |
| Spleen | 9.8 | Medium |
| Lymph Node | 8.5 | Medium |
| Blood | 7.2 | Medium |
| Lung | 2.1 | Low |
| Brain | 0.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | 15.4 | High expression; used as model for macrophage differentiation |
| HL-60 (promyelocytic leukemia) | 12.1 | High expression; neutrophil-like differentiation |
| K-562 (chronic myelogenous leukemia) | 8.3 | Moderate expression |
| HeLa (cervical carcinoma) | 1.2 | Low expression; non-hematopoietic |
| A549 (lung carcinoma) | 0.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1045C>T (p.Arg349Trp) | Missense | 0.01% (gnomAD) | May affect GAP activity; not well characterized |
| c.1567G>A (p.Val523Met) | Missense | 0.02% (gnomAD) | Potential impact on protein stability; clinical significance unknown |
| c.210delC (p.Leu71CysfsTer26) | Frameshift | Rare | Predicted loss-of-function; may lead to haploinsufficiency |
Mutation functional classification
Loss of Function (LOF)
Frameshift and truncating mutations are predicted to cause loss of GAP activity, leading to sustained Rac1/Cdc42 activation and altered cell motility.
Gain of Function (GOF)
No gain-of-function mutations have been reported; overexpression of wild-type ARHGAP25 may act as a tumor suppressor in some contexts.
Dominant Negative (DN)
No dominant-negative mutations have been described; however, missense variants in the GAP domain could potentially exert dominant-negative effects by competing with wild-type protein.
View complete mutation data：
Gene Ontology (GO)
| • Rho GTPase activator activity | • GTPase activator activity |
| • Protein binding | • Cytoplasm |
| • Cytosol | • Plasma membrane |
| • Regulation of cell migration | • Regulation of actin cytoskeleton organization |
| • Signal transduction |
Pathways
• Rho GTPase cycle
• Rac1 signaling
• Cdc42 signaling
• Fc gamma receptor-mediated phagocytosis
• Chemokine signaling
Protein Summary
ARHGAP25 is a 75 kDa protein consisting of 648 amino acids. It contains a RhoGAP domain that specifically accelerates GTP hydrolysis of Rac1 and Cdc42. The protein is localized in the cytoplasm and at the plasma membrane, where it regulates actin dynamics. It is highly expressed in hematopoietic tissues, particularly in myeloid cells. ARHGAP25 modulates phagocytosis by controlling Rac1 activity during Fc receptor-mediated engulfment. Its expression is regulated during immune responses, and dysregulation is linked to inflammatory diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARHGAP25 Knockout HEK293 Cell Line | EDJ-KQ6830 | Human | 9938 | Details Get a Quote |
| ARHGAP25 Knockout HeLa Cell Line | EDJ-KQ55280 | Human | 9938 | Details Get a Quote |
| ARHGAP25 Knockout A-549 Cell Line | EDJ-KQ63762 | Human | 9938 | Details Get a Quote |
| ARHGAP25 Knockout HCT 116 Cell Line | EDJ-KQ72222 | Human | 9938 | Details Get a Quote |
