GNAI3 (G Protein Subunit Alpha I3)
A key heterotrimeric G-protein alpha subunit involved in signal transduction, with emerging roles in development and disease.
Gene Information Card
| Symbol | GNAI3 |
|---|---|
| Full Name | G protein subunit alpha i3 |
| Gene Type | protein coding |
| Chromosomal Location | 1p13.3 |
| NCBI Gene ID | 2773 ncbi.nlm.nih.gov/gene/2773 |
| Ensembl ID | ENSG00000165136 |
| UniProt ID | P08754 |
| OMIM ID | 139370 |
| HGNC ID | 4388 |
| Aliases | GNAI3, Gi alpha 3, 87U6, HG1I |
Description
GNAI3 encodes the alpha subunit of the heterotrimeric G protein Gi3. This protein is a member of the G alpha i family, which mediates signal transduction from G protein-coupled receptors (GPCRs) to downstream effectors, including inhibition of adenylyl cyclase and modulation of ion channels. GNAI3 is involved in various cellular processes such as cell proliferation, differentiation, and cytoskeletal organization. Mutations in GNAI3 have been associated with auriculocondylar syndrome and other developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Auriculocondylar syndrome | Missense mutations in GNAI3 disrupt G protein signaling, affecting neural crest cell development and craniofacial morphogenesis. | ClinVar, OMIM |
| Questionable association with certain cancers | Altered GNAI3 expression or mutations may contribute to tumorigenesis through dysregulated GPCR signaling, but evidence is limited. | COSMIC, PubMed (via NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High expression in multiple brain regions |
| Heart | Medium | Moderate expression in cardiac tissue |
| Liver | Medium | Moderate expression in liver |
| Kidney | Medium | Moderate expression in kidney |
| Lung | Medium | Moderate expression in lung |
| Testis | High | High expression in testis |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | High | Cervical cancer cell line |
| A549 | Medium | Lung carcinoma cell line |
| MCF7 | Medium | Breast cancer cell line |
| HEK293 | High | Embryonic kidney cell line |
| K562 | Medium | Chronic myeloid leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Asp176His | Missense | Rare | Associated with auriculocondylar syndrome; disrupts G protein function. |
| p.Gly40Ser | Missense | Rare | Reported in COSMIC; potential oncogenic role in some cancers. |
| p.Arg179Cys | Missense | Rare | Found in ClinVar; likely pathogenic for auriculocondylar syndrome. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in GNAI3 impair G protein signaling, leading to developmental defects such as auriculocondylar syndrome.
Gain of Function (GOF)
Gain-of-function mutations are not well characterized; some somatic mutations in cancer may lead to constitutive activation, but evidence is limited.
Dominant Negative (DN)
Dominant-negative effects have been suggested for certain missense mutations that interfere with normal G protein function.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor signaling pathway | • GTPase activity |
| • Signal transduction | • Heterotrimeric G-protein complex |
| • Adenylate cyclase inhibition | • Cell proliferation |
| • Neural crest cell development |
Pathways
• GPCR downstream signaling
• G alpha i signaling events
• Adenylate cyclase inhibitory pathway
• Development and morphogenesis
Protein Summary
GNAI3 encodes the alpha subunit of the inhibitory G protein Gi3. The protein is a GTPase that cycles between active GTP-bound and inactive GDP-bound states. Upon GPCR activation, GNAI3 dissociates from the beta/gamma subunits and inhibits adenylyl cyclase, reducing cAMP levels. It also regulates ion channels and other effectors. GNAI3 is widely expressed and plays critical roles in embryonic development, particularly in craniofacial formation. Mutations in GNAI3 are linked to auriculocondylar syndrome, and altered expression is observed in some cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GNAI3 Knockout HEK293 Cell Line | EDJ-KQ1317 | Human | 2773 | Details Get a Quote |
| GNAI3 Knockout A-549 Cell Line | EDJ-KQ20744 | Human | 2773 | Details Get a Quote |
| GNAI3 Knockout HCT 116 Cell Line | EDJ-KQ20745 | Human | 2773 | Details Get a Quote |
| GNAI3 Knockout HeLa Cell Line | EDJ-KQ20746 | Human | 2773 | Details Get a Quote |
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