ARHGEF12: Rho Guanine Nucleotide Exchange Factor 12
A key regulator of Rho GTPase signaling in cell migration, proliferation, and cancer progression.
Gene Information Card
| Symbol | ARHGEF12 |
|---|---|
| Full Name | Rho guanine nucleotide exchange factor 12 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q23.3 |
| NCBI Gene ID | 23365 ncbi.nlm.nih.gov/gene/23365 |
| Ensembl ID | ENSG00000134352 |
| UniProt ID | Q9NZN5 |
| OMIM ID | 604763 |
| HGNC ID | 681 |
| Aliases | LARG, KIAA0382, MGC131953, PRO2730 |
Description
ARHGEF12 (Rho guanine nucleotide exchange factor 12), also known as LARG (leukemia-associated Rho guanine nucleotide exchange factor), encodes a protein that activates Rho GTPases by catalyzing the exchange of GDP for GTP. It plays a critical role in cytoskeletal reorganization, cell migration, and proliferation. ARHGEF12 is frequently implicated in acute myeloid leukemia (AML) and other cancers through chromosomal rearrangements and aberrant signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute myeloid leukemia (AML) | Chromosomal translocation t(11;15)(q23;q13) fuses ARHGEF12 with MLL, leading to constitutive RhoA activation and leukemogenesis. | PMID: 10911992; COSMIC |
| Breast cancer | Overexpression of ARHGEF12 enhances RhoA activity, promoting invasion and metastasis. | PMID: 22926524; NCBI Gene |
| Colorectal cancer | ARHGEF12 amplification correlates with poor prognosis and increased cell motility. | PMID: 25224220; COSMIC |
| Prostate cancer | ARHGEF12 upregulation drives androgen-independent growth via RhoA/ROCK signaling. | PMID: 24043777; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 6.7 | Low |
| Liver | 4.2 | Low |
| Kidney | 9.1 | Low |
| Testis | 15.8 | Medium |
| Bone marrow | 11.2 | Medium |
| Spleen | 7.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.3 | Embryonic kidney; high expression |
| HeLa | 9.8 | Cervical carcinoma; moderate |
| K562 | 18.2 | Chronic myeloid leukemia; high |
| MCF7 | 6.5 | Breast cancer; low |
| HL-60 | 21.1 | Acute promyelocytic leukemia; very high |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2776C>T (p.Arg926*) | Nonsense | <0.1% (COSMIC) | Truncation; loss of catalytic activity |
| c.1234G>A (p.Glu412Lys) | Missense | 0.2% (COSMIC) | Altered substrate specificity; potential gain-of-function |
| c.3456_3457insA (p.Gln1153Thrfs*5) | Frameshift | <0.1% (ClinVar) | Loss of function; associated with AML |
| c.1987A>G (p.Asn663Asp) | Missense | 0.1% (COSMIC) | Unknown; located in PH domain |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg926*, p.Gln1153Thrfs*5) lead to truncated protein lacking GEF activity, impairing RhoA activation.
Gain of Function (GOF)
Missense mutations (e.g., p.Glu412Lys) may enhance nucleotide exchange activity or alter substrate specificity, contributing to oncogenic signaling.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported in ARHGEF12; however, certain truncations may interfere with wild-type function through dimerization.
View complete mutation data：
Gene Ontology (GO)
| • Rho guanyl-nucleotide exchange factor activity (GO:0005089) | • GTPase activator activity (GO:0005096) |
| • Rho protein signal transduction (GO:0007266) | • Actin cytoskeleton organization (GO:0030036) |
| • Cell migration (GO:0016477) | • Positive regulation of cell proliferation (GO:0008284) |
| • Plasma membrane (GO:0005886) | • Cytoplasm (GO:0005737) |
Pathways
• Rho GTPase cycle (Reactome: R-HSA-194840)
• Signaling by Rho GTPases (Reactome: R-HSA-194315)
• RhoA signaling pathway (KEGG: hsa04810)
• Regulation of actin cytoskeleton (KEGG: hsa04810)
• G protein signaling pathways (BioCarta: h_rhoPathway)
Protein Summary
ARHGEF12 (LARG) is a 1544-amino acid protein containing a Dbl homology (DH) domain responsible for GEF activity, a pleckstrin homology (PH) domain for membrane targeting, and a regulator of G protein signaling (RGS) domain that modulates Gα subunit signaling. It specifically activates RhoA, leading to downstream effects on actin stress fiber formation, focal adhesion assembly, and gene transcription. The protein is widely expressed, with highest levels in brain and hematopoietic tissues. Dysregulation of ARHGEF12 through mutation or translocation is a hallmark of several hematologic and solid malignancies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARHGEF12 Knockout HEK293 Cell Line | EDJ-KQ7993 | Human | 23365 | Details Get a Quote |
| ARHGEF12 Knockout HeLa Cell Line | EDJ-KQ32388 | Human | 23365 | Details Get a Quote |
| ARHGEF12 Knockout A-549 Cell Line | EDJ-KQ33723 | Human | 23365 | Details Get a Quote |
| ARHGEF12 Knockout HCT 116 Cell Line | EDJ-KQ33724 | Human | 23365 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
