GNAZ: Guanine Nucleotide-Binding Protein G(z) Subunit Alpha
A key regulator of signal transduction via G-protein coupled receptors, implicated in neuropsychiatric disorders and cancer.
Gene Information Card
| Symbol | GNAZ |
|---|---|
| Full Name | G protein subunit alpha z |
| Gene Type | protein coding |
| Chromosomal Location | 22q11.22 |
| NCBI Gene ID | 2781 ncbi.nlm.nih.gov/gene/2781 |
| Ensembl ID | ENSG00000128266 |
| UniProt ID | P19086 |
| OMIM ID | 139160 |
| HGNC ID | 4394 |
| Aliases | Gz-alpha, GzA |
Description
GNAZ encodes the alpha subunit of the heterotrimeric G protein G(z), which is a member of the Gi/o family. This subunit is unique in its resistance to pertussis toxin and its ability to inhibit adenylyl cyclase. GNAZ is involved in signal transduction from various G protein-coupled receptors (GPCRs), modulating intracellular cAMP levels and downstream signaling pathways. It is highly expressed in the brain and plays roles in neuronal signaling, platelet activation, and immune regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bipolar disorder | Altered GNAZ expression may disrupt cAMP signaling in prefrontal cortex, affecting mood regulation. | Association studies and postmortem brain analysis (PMID: 19012866) |
| Schizophrenia | Dysregulation of GNAZ in cortical regions linked to impaired GPCR signaling and synaptic plasticity. | Gene expression profiling (PMID: 21533022) |
| Colorectal cancer | GNAZ mutations (e.g., R179C) may alter G-protein signaling, promoting tumorigenesis. | COSMIC database; functional studies (PMID: 23535732) |
| Breast cancer | Overexpression of GNAZ correlates with poor prognosis and may drive metastasis via cAMP-independent pathways. | Expression analysis and clinical data (PMID: 27197191) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Cerebellum | 9.8 | Medium |
| Heart | 3.2 | Low |
| Liver | 1.1 | Not detected |
| Lung | 2.5 | Low |
| Kidney | 4.0 | Low |
| Testis | 6.7 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model; high expression |
| HEK293 (embryonic kidney) | 8.5 | Common overexpression system |
| MCF7 (breast cancer) | 5.3 | Moderate expression; hormone-responsive |
| HCT116 (colorectal cancer) | 7.1 | Mutant R179C reported |
| Jurkat (T-cell leukemia) | 2.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R179C | Missense | <1% (COSMIC) | Alters GTP binding; potential gain-of-function in colorectal cancer |
| R205H | Missense | <0.5% (ClinVar) | Uncertain significance; reported in neurodevelopmental disorders |
| c.118G>A (p.G40S) | Missense | Rare | Reduced GTPase activity; loss-of-function in vitro |
| c.572A>G (p.N191S) | Missense | Rare | Decreased receptor coupling; dominant-negative effect |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair GTP binding or hydrolysis (e.g., G40S) reduce G(z) activity, leading to disrupted cAMP inhibition.
Gain of Function (GOF)
Mutations such as R179C may enhance signaling by stabilizing the active GTP-bound state, promoting oncogenic pathways.
Dominant Negative (DN)
Mutations like N191S that interfere with receptor interaction can act as dominant negatives, blocking wild-type G(z) function.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor signaling pathway (GO:0007186) | • GTPase activity (GO:0003924) |
| • GTP binding (GO:0005525) | • heterotrimeric G-protein complex (GO:0005834) |
| • adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193) | • signal transduction (GO:0007165) |
Pathways
• GPCR downstream signaling (Reactome: R-HSA-388396)
• G alpha (i) signalling events (Reactome: R-HSA-418594)
• cAMP signaling pathway (KEGG: hsa04024)
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
Protein Summary
The GNAZ protein (Gz-alpha) is a 40.9 kDa GTPase that cycles between inactive GDP-bound and active GTP-bound states. It is unique among Gi/o family members in being insensitive to pertussis toxin. Gz-alpha couples to receptors such as dopamine D2-like, alpha2-adrenergic, and serotonin 5-HT1A receptors. It inhibits adenylyl cyclase, reducing cAMP production, and can also activate Src family kinases and MAPK pathways. Its expression is enriched in brain, platelets, and certain cancer cells, where it modulates neurotransmission, platelet aggregation, and cell proliferation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GNAZ Knockout HEK293 Cell Line | EDJ-KQ4732 | Human | 2781 | Details Get a Quote |
| GNAZ Knockout A-549 Cell Line | EDJ-KQ27474 | Human | 2781 | Details Get a Quote |
| GNAZ Knockout HCT 116 Cell Line | EDJ-KQ27475 | Human | 2781 | Details Get a Quote |
| GNAZ Knockout HeLa Cell Line | EDJ-KQ27476 | Human | 2781 | Details Get a Quote |
