GNB5 Gene - G Protein Subunit Beta 5
A key regulator of G protein signaling, associated with neurodevelopmental and cardiac disorders.
Gene Information Card
| Symbol | GNB5 |
|---|---|
| Full Name | G Protein Subunit Beta 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 15q21.2 |
| NCBI Gene ID | 10627 ncbi.nlm.nih.gov/gene/10627 |
| Ensembl ID | ENSG00000137822 |
| UniProt ID | O14775 |
| OMIM ID | 604447 |
| HGNC ID | 4401 |
| Aliases | GB5, Gbeta5 |
Description
The GNB5 gene encodes the beta-5 subunit of guanine nucleotide-binding proteins (G proteins). This subunit is unique among Gbeta isoforms due to its preferential interaction with regulator of G protein signaling (RGS) proteins, particularly RGS6, RGS7, RGS9, and RGS11. GNB5 modulates G protein-coupled receptor (GPCR) signaling kinetics and is essential for normal neuronal and cardiac function. Loss-of-function mutations cause a spectrum of neurodevelopmental and cardiac phenotypes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| LADCI (Language delay, ADHD, and cognitive impairment) | Loss-of-function mutations in GNB5 disrupt RGS protein complex formation, impairing GPCR signaling in the brain, leading to neurodevelopmental deficits. | ClinVar, OMIM #617718 |
| IDDCA (Intellectual developmental disorder with cardiac arrhythmia) | Biallelic GNB5 mutations cause severe neurodevelopmental delay, seizures, and cardiac arrhythmias (e.g., sinus bradycardia, long QT) due to disrupted G protein signaling in both neurons and cardiomyocytes. | ClinVar, OMIM #617173 |
| Cardiac arrhythmia | GNB5 variants alter RGS-mediated regulation of GIRK channels in the heart, predisposing to bradycardia and conduction defects. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 15.2 | Medium |
| Heart (left ventricle) | 8.7 | Low |
| Testis | 6.3 | Low |
| Adipose tissue | 4.1 | Not detected |
| Liver | 2.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 12.1 | Neuronal model |
| HEK293 (embryonic kidney) | 9.8 | Common expression |
| K562 (leukemia) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.113G>A (p.Arg38Gln) | Missense | Rare | Loss of function; disrupts RGS binding |
| c.367C>T (p.Arg123*) | Nonsense | Rare | Loss of function; premature truncation |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein produced |
| c.433_434del (p.Leu145Glufs*12) | Frameshift | Rare | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Most reported GNB5 mutations are loss-of-function, leading to haploinsufficiency or complete loss of protein function, causing neurodevelopmental and cardiac phenotypes.
Gain of Function (GOF)
No gain-of-function mutations have been reported for GNB5.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for GNB5.
View complete mutation data：
Gene Ontology (GO)
| • signal transducer activity (GO:0004871) | • G protein-coupled receptor signaling pathway (GO:0007186) |
| • heterotrimeric G-protein complex (GO:0005834) | • G-protein beta/gamma-subunit complex (GO:0031683) |
| • metal ion binding (GO:0046872) |
Pathways
• GPCR downstream signaling (Reactome: R-HSA-388396)
• G alpha (i) signaling events (Reactome: R-HSA-418594)
• RGS regulation of G protein signaling (Reactome: R-HSA-8851805)
Protein Summary
The GNB5 protein (UniProt O14775) is a 395-amino-acid G protein beta subunit that forms dimers with Ggamma subunits and interacts specifically with RGS proteins. Unlike other Gbeta isoforms, GNB5 does not bind Galpha subunits directly but modulates GPCR signaling by accelerating GTP hydrolysis via RGS proteins. It is highly expressed in the brain and heart, where it regulates synaptic transmission and cardiac pacemaking. Structural studies show a seven-bladed beta-propeller fold typical of Gbeta subunits, with unique surface residues for RGS binding.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GNB5 Knockout HEK293 Cell Line | EDJ-KQ801 | Human | 10681 | Details Get a Quote |
| GNB5 Knockout A-549 Cell Line | EDJ-KQ19531 | Human | 10681 | Details Get a Quote |
| GNB5 Knockout HCT 116 Cell Line | EDJ-KQ19532 | Human | 10681 | Details Get a Quote |
| GNB5 Knockout HeLa Cell Line | EDJ-KQ19533 | Human | 10681 | Details Get a Quote |
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