GNB2

Chr 7

G protein subunit beta 2

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

NCBI Gene: 2783ENSG00000172354UniProt: P62879

Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. This gene contains a trinucleotide (CCG) repeat length polymorphism in its 5' UTR. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with hypotonia and dysmorphic facies
UniProtSick sinus syndrome 4
107
ClinVar variants
33
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
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
33 Pathogenic / Likely Pathogenic· 62 VUS of 107 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.02–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.39 (0.33–0.47)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.33
0≤1.21.6
LoF obs/exp: 1 / 17.9Missense obs/exp: 87 / 221.7Syn Z: -2.58

ClinVar Variant Classifications

107 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic7
VUS62
Likely Benign10
Benign2
26
Pathogenic
7
Likely Pathogenic
62
VUS
10
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
7
19
0
26
Likely Pathogenic
0
5
2
0
7
VUS
1
52
9
0
62
Likely Benign
0
2
3
5
10
Benign
0
1
0
1
2
Total167336107

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.

Gene2Phenotype Curations

GNB2-related developmental disorder

definitive
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ZDHHC11-mediated palmitoylation alleviates chondrocyte senescence and serves as a therapeutic target for osteoarthritis.
Wang K et al.·Nat Aging
2025
Recurrent de novo missense variants in GNB2 can cause syndromic intellectual disability.
Tan NB et al.·J Med Genet
2022Case report
Exome reports A de novo GNB2 variant associated with global developmental delay, intellectual disability, and dysmorphic features.
Fukuda T et al.·Eur J Med Genet
2020Case report
Molecular pathogenesis of disease progression in MLL-rearranged AML.
Kotani S et al.·Leukemia
2019
GNB2 promotes breast cancer progression by up-regulating HSPA5/GPX4 and inhibiting ferroptosis.
Wang Y et al.·Mol Cell Biochem
2026
Second patient with GNB2-related neurodevelopmental disease: Further evidence for a gene-disease association.
Lansdon LA et al.·Eur J Med Genet
2021Case report
A Mutation in the G-Protein Gene GNB2 Causes Familial Sinus Node and Atrioventricular Conduction Dysfunction.
Stallmeyer B et al.·Circ Res
2017
A novel somatic mutation in GNB2 provides new insights to the pathogenesis of Sturge-Weber syndrome.
Fjær R et al.·Hum Mol Genet
2021
Familial Sinus Node Disease Caused by a Gain of GIRK (G-Protein Activated Inwardly Rectifying K(+) Channel) Channel Function.
Kuß J et al.·Circ Genom Precis Med
2019
Suppression subtractive hybridization identified differentially expressed genes in colorectal cancer: microRNA-451a as a novel colorectal cancer-related gene.
Xu K et al.·Tumour Biol
2017
Top 10 resultsSearch 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
2026🔓 Open Access
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
2025🔓 Open 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
2024🔓 Open 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 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools