GNG4 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the G protein subunit gamma 4 (GNG4) gene, including its genomic context, expression patterns, and associated diseases.
Gene Information Card
| Symbol | GNG4 |
|---|---|
| Full Name | G protein subunit gamma 4 |
| Gene Type | protein coding |
| Chromosomal Location | 1q42.3 |
| NCBI Gene ID | 2786 ncbi.nlm.nih.gov/gene/2786 |
| Ensembl ID | ENSG00000137265 |
| UniProt ID | P50150 |
| OMIM ID | 604388 |
| HGNC ID | 4405 |
| Aliases | G protein subunit gamma-4, GNG4, MGC126562 |
Description
GNG4 encodes the gamma-4 subunit of heterotrimeric G proteins. These proteins are essential for signal transduction across cell membranes, coupling G protein-coupled receptors (GPCRs) to intracellular effectors. The gamma subunit, together with the beta subunit, forms a stable dimer that modulates the activity of the alpha subunit and influences downstream signaling pathways. GNG4 is expressed in various tissues and has been implicated in several physiological and pathological processes, including cancer and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered expression of GNG4 may affect GPCR signaling pathways, influencing cell proliferation, migration, and survival. Specific mechanisms vary by cancer type. | COSMIC, PubMed (e.g., PMID: 31270520) |
| Schizophrenia | Genetic variants in GNG4 have been associated with schizophrenia in some studies, potentially affecting neurotransmitter signaling. | OMIM, PubMed (e.g., PMID: 21376230) |
| Bipolar disorder | Similar to schizophrenia, GNG4 variants may contribute to risk, though evidence is preliminary. | OMIM, PubMed (e.g., PMID: 21376230) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High |
| Testis | Medium | Medium |
| Kidney | Low | Low |
| Liver | Low | Low |
| Heart | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | Medium | Commonly used for GPCR studies |
| SH-SY5Y | High | Neuroblastoma cell line |
| MCF7 | Low | Breast cancer cell line |
| A549 | Low | Lung cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.123A>G (p.Ile41Met) | Missense | Rare | Potential functional impact, but clinical significance unclear |
| c.456C>T (p.Ser152Leu) | Missense | Rare | Reported in COSMIC, but no known pathogenic effect |
| c.789G>A (p.Val263Ile) | Missense | Rare | No known disease association |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in GNG4 are not well characterized. Given its role in signal transduction, complete loss may impair GPCR signaling, but no specific pathogenic variants have been confirmed.
Gain of Function (GOF)
No gain-of-function mutations have been reported for GNG4.
Dominant Negative (DN)
No dominant-negative mutations have been described for GNG4.
View complete mutation data：
Gene Ontology (GO)
| • G protein beta/gamma-subunit complex binding | • signal transducer activity |
| • GTPase activity | • heterotrimeric G-protein complex |
| • plasma membrane | • signal transduction |
| • G protein-coupled receptor signaling pathway |
Pathways
• GPCR downstream signaling
• G alpha (s) signalling events
• G alpha (i) signalling events
• Class A/1 (Rhodopsin-like receptors)
Protein Summary
The GNG4 protein is a member of the G protein gamma subunit family. It is a small, lipid-anchored protein that forms a tight complex with G protein beta subunits. This beta-gamma dimer is crucial for the proper localization and function of G protein alpha subunits. GNG4 is involved in transmitting signals from activated GPCRs to downstream effectors, such as adenylyl cyclase, phospholipase C, and ion channels. Its expression is particularly high in the brain, suggesting roles in neuronal signaling. Post-translational modifications, including prenylation, are essential for its membrane attachment and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GNG4 Knockout HEK293 Cell Line | EDJ-KQ1212 | Human | 2786 | Details Get a Quote |
| GNG4 Knockout A-549 Cell Line | EDJ-KQ20535 | Human | 2786 | Details Get a Quote |
| GNG4 Knockout HCT 116 Cell Line | EDJ-KQ20536 | Human | 2786 | Details Get a Quote |
| GNG4 Knockout HeLa Cell Line | EDJ-KQ53369 | Human | 2786 | Details Get a Quote |
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