GNB4 Gene - G Protein Subunit Beta 4
A key component of heterotrimeric G-protein signaling, implicated in Charcot-Marie-Tooth disease and cancer.
Gene Information Card
| Symbol | GNB4 |
|---|---|
| Full Name | G Protein Subunit Beta 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q26.33 |
| NCBI Gene ID | 59345 ncbi.nlm.nih.gov/gene/59345 |
| Ensembl ID | ENSG00000114450 |
| UniProt ID | Q9HAV0 |
| OMIM ID | 610442 |
| HGNC ID | 4397 |
| Aliases | Gbeta4, MGC131962 |
Description
The GNB4 gene encodes the beta-4 subunit of heterotrimeric guanine nucleotide-binding proteins (G proteins). G protein beta subunits are essential for modulating G protein-coupled receptor (GPCR) signaling by forming a beta-gamma dimer that regulates downstream effectors such as ion channels and enzymes. GNB4 is widely expressed and plays a role in signal transduction, cell migration, and neuronal function. Mutations in GNB4 are associated with Charcot-Marie-Tooth disease type 2 (CMT2) and have been implicated in certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease type 2 (CMT2) | Missense mutations in GNB4 disrupt G protein signaling in peripheral neurons, leading to axonal degeneration. | ClinVar, OMIM |
| Hereditary motor and sensory neuropathy | Dominant-negative or loss-of-function mutations impair beta-gamma dimer formation and downstream signaling. | OMIM, PubMed |
| Cancer (various) | Altered GNB4 expression or mutations may contribute to aberrant GPCR signaling and tumor progression. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Lung | 7.4 | Low |
| Testis | 15.2 | Medium |
| Skeletal Muscle | 5.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Moderate expression |
| HeLa | 8.5 | Low expression |
| K562 | 6.3 | Low expression |
| SH-SY5Y | 14.7 | High expression (neuronal) |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.244G>A (p.Asp82Asn) | Missense | Rare | Dominant-negative; associated with CMT2 |
| c.458C>T (p.Thr153Ile) | Missense | Rare | Likely pathogenic; disrupts protein folding |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of function; predicted to abolish translation |
Mutation functional classification
Loss of Function (LOF)
Start loss mutations (e.g., p.Met1Val) lead to absent or truncated protein.
Gain of Function (GOF)
Not well documented for GNB4; most pathogenic mutations are dominant-negative.
Dominant Negative (DN)
Missense mutations (e.g., p.Asp82Asn) impair beta-gamma dimer function, interfering with wild-type signaling.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor signaling pathway | • signal transduction |
| • GTPase activity | • protein heterodimerization activity |
| • plasma membrane | • cytoplasm |
Pathways
• GPCR downstream signaling
• G alpha (i) signaling events
• G beta:gamma signaling through PI3Kgamma
• Charcot-Marie-Tooth disease pathway
Protein Summary
The GNB4 protein (UniProt Q9HAV0) is a 340-amino acid beta subunit of heterotrimeric G proteins. It contains seven WD40 repeats that form a beta-propeller structure, enabling interaction with G gamma subunits and downstream effectors. GNB4 is critical for modulating GPCR signals, including those involved in neuronal development and function. Mutations in GNB4 cause Charcot-Marie-Tooth disease type 2 by disrupting the beta-gamma dimer, leading to impaired axonal transport and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GNB4 Knockout HEK293 Cell Line | EDJ-KQ256 | Human | 59345 | Details Get a Quote |
| GNB4 Knockout HeLa Cell Line | EDJ-KQ18355 | Human | 59345 | Details Get a Quote |
| GNB4 Knockout A-549 Cell Line | EDJ-KQ19529 | Human | 59345 | Details Get a Quote |
| GNB4 Knockout HCT 116 Cell Line | EDJ-KQ73910 | Human | 59345 | Details Get a Quote |
