GNB2

Chr 7AD

G protein subunit beta 2

Also known as: HG2C1, NEDHYDF, SSS4, SSS4; NEDHYDF

NCBI Gene: 2783ENSG00000172354UniProt: P62879OMIM: 139390

The GNB2 protein functions as the beta subunit of heterotrimeric G proteins, regulating alpha subunit activity and mediating signal transduction between cell surface receptors and intracellular effector proteins. Mutations cause autosomal dominant neurodevelopmental disorder with hypotonia and dysmorphic facies, and potentially sick sinus syndrome, affecting both the nervous system and cardiac conduction. The gene is highly constrained against loss-of-function variants (pLI = 0.99), indicating that such mutations are likely to have severe consequences.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.272 OMIM phenotypes
Clinical Summary— GNB2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 63 VUS of 133 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.27LOEUF
pLI 0.989
Z-score 3.71
OE 0.06 (0.02–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.21Z-score
OE missense 0.39 (0.33–0.47)
87 obs / 221.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.06 (0.02–0.27)
0≤0.351.4
Missense OE0.39 (0.33–0.47)
0≤0.61.4
Synonymous OE1.33
0≤1.21.6
LoF obs/exp: 1 / 17.9Missense obs/exp: 87 / 221.7Syn Z: -2.58
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGNB2-related developmental disorderOTHERAD
DN
0.3296th %ile
GOF
0.3491th %ile
LOF
0.78top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.27
GOF1 literature citation

Literature Evidence

GOFA GNB2 gene mutation is associated with familial SND+AVB and leads to a sustained activation of cardiac GIRK channels, which is likely to hyperpolarize the myocellular membrane potential and thus reduces their spontaneous activity.PMID:28219978

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

133 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic7
VUS63
Likely Benign12
Benign2
27
Pathogenic
7
Likely Pathogenic
63
VUS
12
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
7
20
0
27
Likely Pathogenic
0
5
2
0
7
VUS
2
56
5
0
63
Likely Benign
0
2
3
7
12
Benign
0
1
0
1
2
Total271308111

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GNB2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SNHG5 enhances colorectal cancer metastasis through RNA-protein interaction with GNB2 and activation of canonical Wnt signaling.
Chen X et al.·Noncoding RNA Res
2026Open Access
GNB2 promotes breast cancer progression by up-regulating HSPA5/GPX4 and inhibiting ferroptosis.
Wang Y et al.·Mol Cell Biochem
2026
RETRACTION: LncRNA CCAT2 Promotes the Proliferation and Metastasis of Colorectal Cancer Through Activation of the ERK and Wnt Signaling Pathways by Regulating GNB2 Expression.
·Cancer Med
2025Open Access
LncRNA CCAT2 promotes the proliferation and metastasis of colorectal cancer through activation of the ERK and Wnt signaling pathways by regulating GNB2 expression.
Tian J et al.·Cancer Med
2024Open Access
Generation of a patient-specific hiPS cell line with heterozygous GNB2 mutation (UKMi003-A) causative for human sinus node dysfunction and a corresponding CRISPR/Cas9-corrected isogenic control (UKMi004-A).
Kayser A et al.·Stem Cell Res
2024
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients