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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GNG3
G protein subunit gamma 3
Chromosome 11 · 11q12.3
NCBI Gene: 2785Ensembl: ENSG00000162188.8HGNC: HGNC:4405UniProt: P63215
31PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingheterotrimeric G-protein complexG-protein beta-subunit bindingG protein-coupled receptor signaling pathwayneurodegenerative diseasebreast carcinomaReduced delayed hypersensitivitySymphalangism affecting the proximal phalanx of the 4th finger
✦AI Summary

GNG3 (G protein subunit gamma 3) is a component of heterotrimeric G-protein complexes that functions as a modulator in transmembrane signaling systems. As part of the G-protein beta-gamma dimer, GNG3 is required for GTPase activity, GDP-GTP exchange, and G-protein effector interactions, enabling G protein-coupled receptor signaling 1. Mechanistically, GNG3 protein stability is regulated through acetylation. CREBBP-mediated acetylation of GNG3 enhances its stability and promotes NF-κB pathway activation 1. GNG3 participates in G protein-coupled receptor signaling pathways and associates with other components in regulating cellular responses 2. GNG3 shows disease relevance across multiple conditions. In allergic rhinitis, elevated GNG3 expression exacerbates airway inflammation through NF-κB activation, and GNG3 knockdown significantly reduces inflammatory responses 1. In neurological diseases, GNG3 is identified as a hub gene associated with brain aging in the prefrontal cortex 3 and represents a potential biomarker for Alzheimer's disease pathogenesis 4. Additionally, GNG3 appears as a key gene in glioblastoma 5, epilepsy-glioma comorbidity 6, and colorectal cancer 7, though its specific functional roles in these contexts require further investigation. Clinically, GNG3 may serve as a diagnostic/prognostic marker and therapeutic target in inflammatory and neoplastic diseases, particularly where NF-κB pathway modulation is relevant.

Sources cited
1
CREBBP stabilizes GNG3 through acetylation, activating NF-κB pathway and exacerbating airway inflammation in allergic rhinitis; GNG3 knockdown reduces inflammatory responses
PMID: 40616825
2
GNG3 identified as hub gene with high connectivity in brain aging, particularly in prefrontal cortex aging module
PMID: 30210331
3
GNG3 is a hub gene significantly correlated with Alzheimer's disease and identified as potential AD biomarker
PMID: 34024830
4
GNG3 identified as key hub gene in glioblastoma multiforme with relevance to disease pathogenesis
PMID: 32467990
5
GNG3 included as core feature gene in both glioma prognosis model and epilepsy diagnosis model with high predictive accuracy
PMID: 37192718
6
GNG3 identified as Top10 hub gene in colorectal cancer ceRNA network, downregulated in CRC tissues
PMID: 35545337
7
GNG3 identified as core gene enriched in G protein-coupled receptor signaling pathway in keloid formation
PMID: 34600545
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.37Weak
breast carcinomaOpen Targets
0.33Weak
Reduced delayed hypersensitivityOpen Targets
0.33Weak
Symphalangism affecting the proximal phalanx of the 4th fingerOpen Targets
0.33Weak
Autosomal dominant spastic paraplegia type 17Open Targets
0.31Weak
congenital generalized lipodystrophy type 2Open Targets
0.31Weak
hereditary spastic paraplegia 17Open Targets
0.31Weak
genetic disorderOpen Targets
0.27Weak
neuronopathy, distal hereditary motor, type 5COpen Targets
0.15Weak
severe neurodegenerative syndrome with lipodystrophyOpen Targets
0.15Weak
Generalized epilepsy with febrile seizures-plusOpen Targets
0.05Suggestive
glioblastoma multiformeOpen Targets
0.05Suggestive
generalised epilepsyOpen Targets
0.04Suggestive
epilepsy, early-onset, 3, with or without developmental delayOpen Targets
0.04Suggestive
autosomal dominant epilepsy with auditory featuresOpen Targets
0.04Suggestive
developmental and epileptic encephalopathy 108Open Targets
0.04Suggestive
generalized epilepsy with febrile seizures plus, type 2Open Targets
0.04Suggestive
benign familial infantile epilepsyOpen Targets
0.03Suggestive
developmental and epileptic encephalopathy, 9Open Targets
0.03Suggestive
X-linked intellectual disability - epilepsyOpen Targets
0.03Suggestive
Pathogenic Variants1
NM_012202.5(GNG3):c.12_13dup (p.Thr5fs)Likely pathogenic
Inborn genetic diseases
★☆☆☆2018→ Residue 5
View on ClinVar ↗
Related Genes
ADCY2Protein interaction100%APLNRProtein interaction100%CACNA1BProtein interaction100%CNR1Protein interaction100%GNALProtein interaction100%GNAO1Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
1%
Liver
1%
Ovary
0%
Lung
0%
Heart
0%
Gene Interaction Network
Click a node to explore
GNG3ADCY2APLNRCACNA1BCNR1GNALGNAO1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P63215
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.49LoF Tolerant
pLIⓘ
0.22Tolerant
Observed/Expected LoF0.50 [0.20–1.49]
RankingsWhere GNG3 stands among ~20K protein-coding genes
  • #11,719of 20,598
    Most Researched31
  • #5,254of 5,498
    Most Pathogenic Variants1
  • #15,083of 17,882
    Most Constrained (LOEUF)1.49
Genes detectedGNG3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Gene Expression Analysis Reveals Novel Gene Signatures Between Young and Old Adults in Human Prefrontal Cortex.
PMID: 30210331
Front Aging Neurosci · 2018
1.00
2
Insight on the hub gene associated signatures and potential therapeutic agents in epilepsy and glioma.
PMID: 37192718
Brain Res Bull · 2023
0.90
3
Genome-Wide Study of Diabetes Mellitus (Type 2)-Associated Genes in Homo sapiens (Human).
PMID: 40462586
J Gene Med · 2025
0.80
4
CREBBP stabilizes GNG3 protein through acetylation, thereby activating the NF-κB pathway and exacerbating airway inflammation in allergic rhinitis.
PMID: 40616825
Inhal Toxicol · 2025
0.70
5
Construction of Long Noncoding RNA-Associated ceRNA Networks Reveals Potential Biomarkers in Alzheimer's Disease.
PMID: 34024830
J Alzheimers Dis · 2021
0.60