GNB1

Chr 1

G protein subunit beta 1

Also known as: HG2A, MDS, MRD42

NCBI Gene: 2782ENSG00000078369UniProt: P62873

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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal dominant 42
545
ClinVar variants
194
Pathogenic / LP
1.00
pLI score· haploinsufficient
3
Active trials
Clinical Summary— GNB1
🧬
Gene-Disease Validity (ClinGen)
intellectual disability, autosomal dominant 42 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
194 Pathogenic / Likely Pathogenic· 145 VUS of 545 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
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.
0.14LOEUF
pLI 0.999
Z-score 4.21
OE 0.00 (0.00–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
3.83Z-score
OE missense 0.28 (0.23–0.35)
64 obs / 226.2 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.0.00 (0.00–0.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.28 (0.23–0.35)
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.0.96
0≤1.21.6
LoF obs/exp: 0 / 20.6Missense obs/exp: 64 / 226.2Syn Z: 0.33

ClinVar Variant Classifications

545 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic155
Likely Pathogenic39
VUS145
Likely Benign171
Benign22
Conflicting13
155
Pathogenic
39
Likely Pathogenic
145
VUS
171
Likely Benign
22
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
14
132
0
155
Likely Pathogenic
5
25
9
0
39
VUS
5
93
46
1
145
Likely Benign
1
9
57
104
171
Benign
0
7
13
2
22
Conflicting
—13
Total20148257107545

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

View in ClinVar →

Protein Context — Lollipop Plot

GNB1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

GNB1-related severe neurodevelopmental disability, hypotonia, and seizures

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — GNB1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
GNB1 promotes hepatocellular carcinoma progression by targeting BAG2 to activate P38/MAPK signaling.
Zhang X et al.·Cancer Sci
2023
GNB1 Encephalopathy: Clinical Case Report and Literature Review.
Nasvytis M et al.·Medicina (Kaunas)
2024Review
Refining the phenotype associated with GNB1 mutations: Clinical data on 18 newly identified patients and review of the literature.
Hemati P et al.·Am J Med Genet A
2018Review
Identification of fusions with potential clinical significance in melanoma.
Moran JMT et al.·Mod Pathol
2022
GNB1 and obesity: Evidence for a correlation between haploinsufficiency and syndromic obesity.
Kleinendorst L et al.·Clin Obes
2024Case report
Genetic Diversity and Expanded Phenotypes in Dystonia: Insights From Large-Scale Exome Sequencing.
Thomsen M et al.·Ann Clin Transl Neurol
2025
KCNJ15 inhibits chemical-induced lung carcinogenesis and progression through GNB1 mediated Hippo pathway.
Chen HQ et al.·Toxicology
2025
Rod-cone dystrophy in an adult with GNB1-related disorder: An expansion of the phenotype and natural history.
Yang XR et al.·Am J Med Genet C Semin Med Genet
2023Case report
Novel GNB1 de novo mutation in a patient with neurodevelopmental disorder and cutaneous mastocytosis: Clinical report and literature review.
Szczałuba K et al.·Eur J Med Genet
2018Review
Genetic Dystonias: Update on Classification and New Genetic Discoveries.
Keller Sarmiento IJ et al.·Curr Neurol Neurosci Rep
2021Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07
Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING
NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19
Usual Care GroupControlled exercise with telerehabilitation

External Resources

Links to major genomics databases and tools