ARHGAP12
Rho GTPase Activating Protein 12
Gene Information Card
| Symbol | ARHGAP12 |
|---|---|
| Full Name | Rho GTPase Activating Protein 12 |
| Gene Type | protein-coding |
| Chromosomal Location | 10p11.22 |
| NCBI Gene ID | 94134 ncbi.nlm.nih.gov/gene/94134 |
| Ensembl ID | ENSG00000148773 |
| UniProt ID | Q8N2W9 |
| OMIM ID | 610578 |
| HGNC ID | 24065 |
| Aliases | GRAF2, KIAA1428 |
Description
ARHGAP12 encodes a member of the Rho GTPase-activating protein (GAP) family. The protein contains an N-terminal SEC14 domain, a pleckstrin homology (PH) domain, and a C-terminal RhoGAP domain. It functions as a GTPase activator for RhoA, Rac1, and Cdc42, converting them to the inactive GDP-bound state, thereby regulating cytoskeletal dynamics, cell adhesion, and migration. ARHGAP12 is implicated in cancer progression and metastasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | ARHGAP12 overexpression correlates with increased invasiveness and poor prognosis; modulates Rho/ROCK signaling | PMID: 25605247 |
| Colorectal cancer | Downregulation of ARHGAP12 promotes cell migration and invasion via Rac1 activation | PMID: 29367600 |
| Gastric cancer | ARHGAP12 loss enhances tumor growth and metastasis through Cdc42 deregulation | PMID: 31076543 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Breast | 6.7 | Low |
| Colon | 5.2 | Low |
| Kidney | 9.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 8.5 | Moderate expression |
| A549 (lung cancer) | 6.2 | Low expression |
| HCT116 (colorectal cancer) | 4.8 | Low expression |
| HEK293 (embryonic kidney) | 10.1 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | <0.01% (gnomAD) | Unknown functional effect |
| c.1456G>A (p.Glu486Lys) | Missense | <0.01% (gnomAD) | Unknown functional effect |
| c.1870_1871insA (p.Thr624Asnfs*2) | Frameshift | <0.01% (COSMIC) | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., p.Thr624Asnfs*2) likely truncate the RhoGAP domain, impairing GTPase activation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations characterized.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • Rho GTPase binding |
| • cytosol | • plasma membrane |
| • cell projection | • regulation of cell migration |
| • actin cytoskeleton organization |
Pathways
• Rho GTPase cycle (R-HSA-194840)
• Signaling by Rho GTPases (R-HSA-194315)
• RAC1 GTPase cycle (R-HSA-9012999)
Protein Summary
ARHGAP12 is a 729-amino acid protein with a molecular weight of approximately 82 kDa. It contains an N-terminal SEC14 domain (lipid binding), a PH domain (membrane targeting), and a C-terminal RhoGAP domain (catalytic). The protein localizes to the cytoplasm and plasma membrane, and regulates RhoA, Rac1, and Cdc42 activity. It is involved in cell morphology, adhesion, and migration. Altered expression is linked to cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARHGAP12 Knockout HEK293 Cell Line | EDJ-KQ11294 | Human | 94134 | Details Get a Quote |
| ARHGAP12 Knockout HCT 116 Cell Line | EDJ-KQ38092 | Human | 94134 | Details Get a Quote |
| ARHGAP12 Knockout A-549 Cell Line | EDJ-KQ39413 | Human | 94134 | Details Get a Quote |
| ARHGAP12 Knockout HeLa Cell Line | EDJ-KQ39415 | Human | 94134 | Details Get a Quote |
