GNA12: G Protein Subunit Alpha 12
A key mediator of RhoGEF signaling and oncogenic transformation
Gene Information Card
| Symbol | GNA12 |
|---|---|
| Full Name | G protein subunit alpha 12 |
| Gene Type | protein-coding |
| Chromosomal Location | 7p22.3 |
| NCBI Gene ID | 2768 ncbi.nlm.nih.gov/gene/2768 |
| Ensembl ID | ENSG00000146535 |
| UniProt ID | Q03113 |
| OMIM ID | 604394 |
| HGNC ID | 4380 |
| Aliases | NNX3, RMP, gep |
Description
GNA12 encodes the alpha subunit of the heterotrimeric G protein G12, which is ubiquitously expressed. This subunit activates Rho guanine nucleotide exchange factors (RhoGEFs) such as p115-RhoGEF, leading to RhoA activation and downstream effects on cytoskeletal remodeling, cell migration, and proliferation. GNA12 is implicated in oncogenic transformation and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ovarian cancer | GNA12 overexpression promotes RhoA-mediated invasion and metastasis | COSMIC, PMID: 25691885 |
| Colorectal cancer | GNA12 mutations (e.g., R205C) enhance RhoGEF signaling and tumor growth | COSMIC, PMID: 29700349 |
| Breast cancer | GNA12 upregulation correlates with poor prognosis and increased cell motility | NCBI Gene, PMID: 23251476 |
| Prostate cancer | GNA12 drives androgen-independent growth via Rho/ROCK pathway | COSMIC, PMID: 21804530 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.2 | Low |
| Lung | 15.3 | Medium |
| Liver | 6.1 | Low |
| Kidney | 10.4 | Medium |
| Ovary | 18.7 | High |
| Colon | 14.2 | Medium |
| Breast | 9.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 16.5 | Cervical cancer cell line |
| A549 | 12.3 | Lung adenocarcinoma |
| MCF7 | 8.9 | Breast cancer cell line |
| OVCAR3 | 22.1 | Ovarian cancer cell line |
| HCT116 | 14.7 | Colorectal carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R205C | Missense | 0.3% in COSMIC | Gain-of-function; increased RhoGEF binding |
| Q231L | Missense | 0.1% in COSMIC | Constitutive activation; oncogenic |
| G228V | Missense | 0.05% in COSMIC | Altered GTPase activity |
| Splice site c.723+1G>A | Splice | <0.01% | Loss-of-function; reduced protein expression |
Mutation functional classification
Loss of Function (LOF)
Splice site mutations leading to truncated or unstable protein.
Gain of Function (GOF)
R205C, Q231L, and G228V enhance RhoA signaling and promote transformation.
Dominant Negative (DN)
Not well characterized for GNA12.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor signaling pathway | • Rho protein signal transduction |
| • GTPase activity | • GTP binding |
| • heterotrimeric G-protein complex | • regulation of cell migration |
| • positive regulation of cell proliferation |
Pathways
• G12/13 signaling
• RhoA signaling
• GPCR downstream signaling
• Regulation of actin cytoskeleton
Protein Summary
GNA12 is a 381-amino acid protein (44 kDa) that functions as a molecular switch in G12 signaling. Upon receptor activation, it exchanges GDP for GTP and interacts with effectors such as p115-RhoGEF, PDZ-RhoGEF, and LARG to activate RhoA. It also modulates cadherin-mediated adhesion and cell polarity. Mutations that lock it in a GTP-bound state are oncogenic.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GNA12 Knockout HEK293 Cell Line | EDJ-KQ173 | Human | 2768 | Details Get a Quote |
| GNA12 Knockout A-549 Cell Line | EDJ-KQ19198 | Human | 2768 | Details Get a Quote |
| GNA12 Knockout HCT 116 Cell Line | EDJ-KQ19199 | Human | 2768 | Details Get a Quote |
| GNA12 Knockout HeLa Cell Line | EDJ-KQ19200 | Human | 2768 | Details Get a Quote |
