ARHGAP15
Rho GTPase Activating Protein 15
Gene Information Card
| Symbol | ARHGAP15 |
|---|---|
| Full Name | Rho GTPase Activating Protein 15 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q22.2 |
| NCBI Gene ID | 55843 ncbi.nlm.nih.gov/gene/55843 |
| Ensembl ID | ENSG00000115970 |
| UniProt ID | Q53QZ3 |
| OMIM ID | 610576 |
| HGNC ID | 25530 |
| Aliases | RACGAP1L, GRAF2, RICH2 |
Description
ARHGAP15 encodes a member of the Rho GTPase-activating protein (GAP) family. The protein specifically inactivates Rac1 and Cdc42 by catalyzing the hydrolysis of GTP to GDP, thereby negatively regulating actin cytoskeleton remodeling, cell migration, and immune cell function. It is highly expressed in hematopoietic tissues and plays a role in B-cell development and neutrophil chemotaxis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic lymphocytic leukemia (CLL) | Loss of ARHGAP15 expression leads to increased Rac1 activity, promoting B-cell survival and proliferation. | PMID: 25349174; COSMIC |
| Diffuse large B-cell lymphoma (DLBCL) | Somatic mutations and reduced expression correlate with aberrant Rac1 signaling and tumor progression. | PMID: 25349174; COSMIC |
| Primary immunodeficiency (e.g., neutropenia) | Biallelic loss-of-function variants impair neutrophil migration and respiratory burst. | ClinVar; PMID: 31073040 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 28.5 | High |
| Lymph node | 22.1 | High |
| Bone marrow | 18.3 | High |
| Whole blood | 12.7 | Medium |
| Lung | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.8 | Moderate expression |
| HL-60 (promyeloblast) | 20.1 | High expression |
| HeLa (cervical) | 2.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.106C>T (p.Arg36*) | Nonsense | <1% (COSMIC) | Loss of function; truncated protein |
| c.497G>A (p.Arg166Gln) | Missense | <0.5% (ClinVar) | Reduced GAP activity toward Rac1 |
| c.1120_1121insA (p.Thr374Asnfs*12) | Frameshift | <0.1% (COSMIC) | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg36*, p.Thr374Asnfs*12) result in truncated or unstable protein, leading to loss of GAP activity and constitutive Rac1 activation.
Gain of Function (GOF)
No gain-of-function mutations reported in ARHGAP15.
Dominant Negative (DN)
No dominant-negative mutations reported; loss-of-function is recessive in immunodeficiency contexts.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Rac1 signaling pathway (Reactome: R-HSA-9013408)
• Regulation of actin dynamics for phagocytic cup formation (Reactome: R-HSA-2029480)
• Rho GTPase cycle (Reactome: R-HSA-194840)
Protein Summary
ARHGAP15 is a 596-amino acid protein containing an N-terminal BAR domain and a C-terminal RhoGAP domain. It localizes to the cytoplasm and plasma membrane, where it negatively regulates Rac1 and Cdc42. The protein is critical for hematopoietic cell homeostasis, and its loss is associated with lymphoid malignancies and immune defects.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARHGAP15 Knockout HEK293 Cell Line | EDJ-KQ12406 | Human | 55843 | Details Get a Quote |
| ARHGAP15 Knockout HeLa Cell Line | EDJ-KQ56643 | Human | 55843 | Details Get a Quote |
| ARHGAP15 Knockout A-549 Cell Line | EDJ-KQ65148 | Human | 55843 | Details Get a Quote |
| ARHGAP15 Knockout HCT 116 Cell Line | EDJ-KQ73584 | Human | 55843 | Details Get a Quote |
