GNAI2
G Protein Subunit Alpha i2
Gene Information Card
| Symbol | GNAI2 |
|---|---|
| Full Name | G Protein Subunit Alpha i2 |
| Gene Type | protein-coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 2771 ncbi.nlm.nih.gov/gene/2771 |
| Ensembl ID | ENSG00000114353 |
| UniProt ID | P04899 |
| OMIM ID | 139320 |
| HGNC ID | 4385 |
| Aliases | GNAI2, GIP, GNAI2B, H_LUCA15.1, G protein alpha i2 |
Description
GNAI2 encodes the alpha subunit of the heterotrimeric G protein Gi2, which inhibits adenylyl cyclase and modulates intracellular cAMP levels. It plays a critical role in signal transduction from G protein-coupled receptors (GPCRs) and is involved in cell proliferation, migration, and differentiation. Mutations and altered expression of GNAI2 are implicated in various cancers and endocrine disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pituitary adenoma (McCune-Albright syndrome-like) | Activating mutations in GNAI2 lead to constitutive cAMP signaling, promoting hormone secretion and cell proliferation. | OMIM #139320; PMID: 2549426 |
| Ovarian cancer | GNAI2 overexpression or gain-of-function mutations enhance oncogenic signaling via MAPK and PI3K pathways. | COSMIC; PMID: 21552269 |
| Breast cancer | Altered GNAI2 expression correlates with poor prognosis and metastasis through modulation of cAMP and Rho pathways. | PMID: 23542345 |
| Colorectal cancer | GNAI2 mutations (e.g., R179C) are recurrent and associated with Wnt/β-catenin pathway activation. | COSMIC; PMID: 23542345 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Medium |
| Lung | 10.1 | Medium |
| Liver | 6.7 | Low |
| Kidney | 9.4 | Medium |
| Ovary | 11.2 | Medium |
| Breast | 7.8 | Medium |
| Colon | 9.9 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 12.8 | High expression |
| MCF7 | 10.5 | Medium expression |
| A549 | 9.1 | Medium expression |
| HCT116 | 11.7 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R179C | Missense | <1% (cancer) | Gain-of-function; reduces GTPase activity, leading to constitutive activation. |
| R179H | Missense | <1% (cancer) | Gain-of-function; similar to R179C, found in pituitary adenomas. |
| Q205L | Missense | <1% (cancer) | Gain-of-function; impairs GTP hydrolysis, persistent signaling. |
| G203R | Missense | <1% (cancer) | Gain-of-function; associated with uveal melanoma. |
Mutation functional classification
Loss of Function (LOF)
Rare; reported in some developmental disorders but not well characterized.
Gain of Function (GOF)
Common in cancer; mutations at codons 179, 205, and 203 impair GTPase activity, leading to constitutive GPCR signaling.
Dominant Negative (DN)
Not well documented for GNAI2.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor signaling pathway (GO:0007186) | • adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193) |
| • GTPase activity (GO:0003924) | • GTP binding (GO:0005525) |
| • signal transduction (GO:0007165) | • cell proliferation (GO:0008283) |
Pathways
• GPCR downstream signaling (Reactome: R-HSA-388396)
• cAMP signaling pathway (KEGG: hsa04024)
• MAPK signaling pathway (KEGG: hsa04010)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
Protein Summary
GNAI2 encodes the alpha i2 subunit of heterotrimeric G proteins. The protein binds GTP and hydrolyzes it to GDP, acting as a molecular switch that inhibits adenylyl cyclase and reduces cAMP levels. It is ubiquitously expressed and mediates signals from numerous GPCRs. Gain-of-function mutations are oncogenic, particularly in pituitary, ovarian, and colorectal cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GNAI2 Knockout HEK293 Cell Line | EDJ-KQ1318 | Human | 2771 | Details Get a Quote |
| GNAI2 Knockout A-549 Cell Line | EDJ-KQ20747 | Human | 2771 | Details Get a Quote |
| GNAI2 Knockout HCT 116 Cell Line | EDJ-KQ20748 | Human | 2771 | Details Get a Quote |
| GNAI2 Knockout HeLa Cell Line | EDJ-KQ20749 | Human | 2771 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
