rs5442

This is a variant in the GNB3 gene that changes a glycine to an serine.

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GWAS Catalog Trait Associations (9)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

refractive error

Han X et al. “Association of Myopia and Intraocular Pressure With Retinal Detachment in European Descent Participants of the UK Biobank Cohort: A Mendelian Randomization Study.” Jama Ophthalmology 138(6):671-678 (2020)
Allele G
OR 0.29
p 8.0e-40
N 95,827
Major Consortium StudyLarge GWAS
European
Guggenheim JA et al. “Whole exome sequence analysis in 51 624 participants identifies novel genes and variants associated with refractive error and myopia.” Human Molecular Genetics 31(11):1909-1919 (2022)
Allele G
OR 0.10
p 4.0e-16
N 51,624
Large GWAS
European

retinal layer thickness

Jackson VE et al. “Multi-omic spatial effects on high-resolution AI-derived retinal thickness.” Nature Communications 16(1):1317 (2025)
Allele A
OR 0.58
p 3.0e-29
N 43,148
Large GWAS
multi-ancestry
Currant H et al. “Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images.” Plos Genetics 17(5):e1009497 (2021)
Allele A
OR 0.69
p 2.0e-13
N 31,434
Major Consortium StudyLarge GWAS
European

retinal vasculature measurement

Zekavat SM et al. “Deep Learning of the Retina Enables Phenome- and Genome-Wide Analyses of the Microvasculature.” Circulation 145(2):134-150 (2022)
Allele A
OR 0.13
p 1.0e-21
N 38,932
Large GWAS
European
Jiang X et al. “GWAS on retinal vasculometry phenotypes.” Plos Genetics 19(2):e1010583 (2023)
Allele A
OR 0.74
p 2.0e-17
N 52,798
Large GWAS
European
Jensen RA et al. “Novel Genetic Loci Associated With Retinal Microvascular Diameter.” Circulation. Cardiovascular Genetics 9(1):45-54 (2016)
Allele A
OR 0.11
p 7.0e-10
N 24,275
Large GWAS
multi-ancestry

Myopia

Xue Z et al. “Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK Biobank.” Ebiomedicine 82:104161 (2022)
Allele A
OR 0.19
p 6.0e-19
N 64,268
Meta-analysisMajor Consortium StudyLarge GWAS
European
Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.08
p 8.0e-12
N 398,816
Major Consortium StudyLarge GWAS
European

refractive error, age at onset, Myopia

Tedja MS et al. “Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error.” Nature Genetics 50(6):834-848 (2018)
Allele A
OR 7.82
p 5.0e-15
N 170,420
Meta-analysisLarge GWAS
multi-ancestry

open-angle glaucoma

Han X et al. “Large-scale multitrait genome-wide association analyses identify hundreds of glaucoma risk loci.” Nature Genetics 55(7):1116-1125 (2023)
Allele A
OR 0.13
p 5.0e-14
N 432,017
Large GWAS
multi-ancestry
Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele A
OR 0.08
p 4.0e-11
N 434,033
Major Consortium StudyLarge GWAS
European

ganglion thickness

Currant H et al. “Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images.” Plos Genetics 17(5):e1009497 (2021)
Allele A
OR 0.69
p 2.0e-13
N 31,434
Major Consortium StudyLarge GWAS
European

age at onset, Myopia

Tedja MS et al. “Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error.” Nature Genetics 50(6):834-848 (2018)
Allele A
OR 0.10
p 9.0e-13
N 104,293
Meta-analysisLarge GWAS
European

Hypermetropia

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele G
OR 0.08
p 3.0e-12
N 394,687
Major Consortium StudyLarge GWAS
European
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ClinVar annotation

Benign★★★☆
3 submitters2 publications
View on ClinVar →
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Research that mentions this SNP (2)

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Influence of neurexin 1 (NRXN1) polymorphisms in clozapine response
ReviewRenan P. Souza et al.(2010)· Human Psychopharmacology: Clinical and Experimental

This systematic review of 98 studies examined biological predictors of clozapine response in treatment-resistant schizophrenia patients. Of 379 different gene variants investigated across 70 genetic studies, only three variants (DRD3 Ser9Gly rs6280, HTR2A His452Tyr, and GNB3 C825T) achieved independent replication. Non-genetic predictors included higher prefrontal cortical volumes and lower HVA:5-HIAA ratio in cerebrospinal fluid.

Traits studied:Clozapine responseSchizophreniaTreatment-resistant schizophrenia
PubMedDOIMetascience Observatory
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Lack of association of GPX1 and MnSOD genes with symptom severity and response to clozapine treatment in schizophrenia subjects
ReviewRenan P. Souza et al.(2009)· Human Psychopharmacology: Clinical and Experimental

A systematic review of 98 studies investigating biological predictors of clozapine response in treatment-resistant schizophrenia. Of 70 genetic studies examining 379 variants, only three genetic variants have independently replicated findings: DRD3 Ser9Gly (rs6280), HTR2A His452Tyr, and GNB3 C825T (rs5442/rs5443). Non-genetic predictors include higher prefrontal cortical structural integrity and activity, and lower HVA:5-HIAA ratio in cerebrospinal fluid.

Traits studied:Clozapine responseSchizophreniaTreatment-resistant schizophrenia
PubMedDOIMetascience Observatory

About GNB3

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 which belongs to the WD repeat G protein beta family. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. A single-nucleotide polymorphism (C825T) in this gene is associated with essential hypertension and obesity. This polymorphism is also associated with the occurrence of the splice variant GNB3-s, which appears to have increased activity. GNB3-s is an example of alternative splicing caused by a nucleotide change outside of the splice donor and acceptor sites. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Jul 2014]

View all GNB3 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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