GNAO1
G Protein Subunit Alpha O1
Gene Information Card
| Symbol | GNAO1 |
|---|---|
| Full Name | G protein subunit alpha O1 |
| Gene Type | protein coding |
| Chromosomal Location | 16q13 |
| NCBI Gene ID | 2775 ncbi.nlm.nih.gov/gene/2775 |
| Ensembl ID | ENSG00000187288 |
| UniProt ID | P09471 |
| OMIM ID | 139311 |
| HGNC ID | 4389 |
| Aliases | GNAO, G-ALPHA-O |
Description
GNAO1 encodes the alpha subunit of the heterotrimeric G protein Go, which is highly expressed in the brain and involved in modulating signal transduction pathways, including adenylate cyclase inhibition and ion channel regulation. Mutations in GNAO1 are associated with neurodevelopmental disorders, epileptic encephalopathies, and movement disorders. Somatic mutations have also been identified in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Early infantile epileptic encephalopathy 66 (EIEE66) | De novo missense mutations impair GTPase activity or alter G protein signaling, leading to neuronal hyperexcitability. | ClinVar, OMIM |
| Neurodevelopmental disorder with involuntary movements (NEDIM) | Gain-of-function mutations disrupt normal G protein cycling, causing abnormal motor control. | ClinVar, OMIM |
| Developmental and epileptic encephalopathy (DEE) | Loss-of-function or dominant-negative mutations reduce Go-mediated signaling, contributing to seizure susceptibility. | ClinVar |
| Breast cancer | Somatic mutations (e.g., p.Gln205Leu) may activate oncogenic signaling pathways. | COSMIC |
| Colorectal cancer | Recurrent somatic mutations in GNAO1 are implicated in tumorigenesis. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebral cortex | 28.5 | High |
| Cerebellum | 22.3 | High |
| Hippocampus | 26.1 | High |
| Heart | 1.2 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.7 | High expression |
| U-87 MG (glioblastoma) | 12.4 | Moderate expression |
| HEK293 (embryonic kidney) | 0.8 | Low expression |
| MCF7 (breast cancer) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.118G>A (p.Gly40Arg) | Missense | De novo | Gain-of-function; associated with movement disorder |
| c.626A>G (p.Gln209Arg) | Missense | De novo | Gain-of-function; linked to epileptic encephalopathy |
| c.709G>A (p.Glu237Lys) | Missense | De novo | Loss-of-function; associated with developmental delay |
| c.614A>T (p.Gln205Leu) | Missense | Somatic | Putative oncogenic; found in breast cancer |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair GTP hydrolysis or reduce protein stability, leading to decreased Go signaling (e.g., p.Glu237Lys).
Gain of Function (GOF)
Mutations that impair GTPase activity or enhance downstream signaling, causing constitutive activation (e.g., p.Gly40Arg, p.Gln209Arg).
Dominant Negative (DN)
Mutations that interfere with wild-type G protein function, often by sequestering Gβγ subunits or disrupting receptor coupling.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor signaling pathway | • GTPase activity |
| • GTP binding | • signal transduction |
| • adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | • regulation of ion transmembrane transport |
Pathways
• G alpha (o) signaling events
• GPCR downstream signaling
• cAMP signaling pathway
• Neurotransmitter receptor binding and downstream transmission
Protein Summary
GNAO1 encodes the alpha subunit of the heterotrimeric G protein Go, a member of the Gi/o family. The protein is 354 amino acids long and functions as a molecular switch that cycles between GDP-bound (inactive) and GTP-bound (active) states. It is predominantly expressed in the central nervous system, where it modulates synaptic transmission, neuronal excitability, and ion channel activity. Mutations in GNAO1 disrupt these processes, leading to a spectrum of neurological disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GNAO1 Knockout HEK293 Cell Line | EDJ-KQ750 | Human | 2775 | Details Get a Quote |
| GNAO1 Knockout HeLa Cell Line | EDJ-KQ20751 | Human | 2775 | Details Get a Quote |
| GNAO1 Knockout A-549 Cell Line | EDJ-KQ61842 | Human | 2775 | Details Get a Quote |
| GNAO1 Knockout HCT 116 Cell Line | EDJ-KQ70327 | Human | 2775 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
