ArticleAmerican journal of human genetics2016
GNB5 Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability.
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Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
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41citing papers in PubMed
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41 citing papers in PubMed, 81 citations in OpenAlex.
- The p.Arg52Leu variant in GNB2 causes a gain-of-function due to an increase of IBMC cardiovascular disorders · 2026Article
- Identification of Gβ5 Interactome Associated with Neuronal Development in Neuro-2a Cells through miniTurbo Proximity Labeling.ACS omega · 2026Article
- Early pacing in a child with Lodder-Merla syndrome and progressive sinus node dysfunction: a case report.European heart journal. Case reports · 2026Article
- Successful cryoablation for typical atrial flutter in a toddler with sinus node dysfunction: the youngest case report.European heart journal. Case reports · 2026Article
- Integrative gene-metabolite network analysis of GLP-1 receptor agonists and related incretin pathways in cardiometabolic health.NPJ systems biology and applications · 2025Article
- Lodder-Merla Syndrome, a Multisystemic Disorder: Perioperative Anesthetic Management of an Infant.Acta medica academica · 2025Article
- Mixed Segmental Uniparental Disomy of Chromosome 15q11-q1 Coexists with Homozygous Variant inGenes · 2025Article
- Gnb5 is a negative regulator of the BACE1-mediated Aβ generation and ameliorates cognitive deficits in a mouse model of Alzheimer's disease.PLoS biology · 2025Article
- Disease-causing mutations in the G protein β5 β-propeller disrupt its chaperonin-mediated folding trajectory.bioRxiv : the preprint server for biology · 2025Article
- Identification of GBN5 as a molecular biomarker of pan-cancer species by integrated multi-omics analysis.Discover oncology · 2025Article
- Cardiac L-type calcium channel regulation by Leucine-Rich Repeat-Containing Protein 10.Channels (Austin, Tex.) · 2024Review
- The association of GNB5 with Alzheimer disease revealed by genomic analysis restricted to variants impacting gene function.American journal of human genetics · 2024Article
- Prioritizing cardiovascular disease-associated variants altering NKX2-5 and TBX5 binding through an integrative computational approach.The Journal of biological chemistry · 2023Article
- Visualizing the chaperone-mediated folding trajectory of the G protein β5 β-propeller.Molecular cell · 2023Article
- How genomic insights into the evolutionary history of clouded leopards inform their conservation.Science advances · 2023Article
- Genetics of sinoatrial node function and heart rate disorders.Disease models & mechanisms · 2023Review
- Zebrafish as a Model of Cardiac Pathology and Toxicity: Spotlight on Uremic Toxins.International journal of molecular sciences · 2023Review
- Sinus node dysfunction: current understanding and future directions.American journal of physiology. Heart and circulatory physiology · 2023Review
- Gene mutations in comorbidity of epilepsy and arrhythmia.Journal of neurology · 2023Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
33 authors at 15 institutions in 6 countries.
Elisabeth M LodderDepartment of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
Pasquelena De NittisCenter for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland; Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, viale Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy.
Charlotte D KoopmanDepartment of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Hubrecht Institute- Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht, 3584 CT Utrecht, the Netherlands.
Wojciech WiszniewskiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Carolina Fischinger Moura de SouzaMedical Genetics Service, Hospital de Clinicas de Porto Alegre, 2350 Porto Alegre, Brazil.
Najim LahrouchiDepartment of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
Nicolas GuexCenter for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
Valerio NapolioniDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Federico TessadoriHubrecht Institute- Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht, 3584 CT Utrecht, the Netherlands.
Leander BeekmanDepartment of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
Eline A NannenbergDepartment of Clinical Genetics, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
Lamiae BouallaCentre de Génomique Humaine, Faculté de Médecine et Pharmacie, Mohammed V University of Rabat, 8007, Rabat, Morocco.
Nico A BlomDepartment of Pediatric Cardiology, Emma Children's Hospital, Academic Medical Centre, 1105 AZ Amsterdam, the Netherlands.
Wim de GraaffRetinal Signal Processing Lab, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands.
Maarten KamermansRetinal Signal Processing Lab, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands; Department of Genome Analysis, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
Dario CocciadiferroMedical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, viale Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy; PhD Program in Experimental and Regenerative Medicine, Faculty of Medicine, University of Foggia, 71121 Foggia, Italy.
Natascia MalerbaMedical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, viale Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy; PhD Program in Experimental and Regenerative Medicine, Faculty of Medicine, University of Foggia, 71121 Foggia, Italy.
Barbara MandrianiMedical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, viale Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy; PhD Program in Molecular Genetics Applied to Medical Sciences, Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy.
Zeynep Hande Coban AkdemirDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Richard J FishDepartment of Genetic Medicine and Development, University Medical Centre (CMU), 1211 Geneva, Switzerland.
Mohammad K EldomeryDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Ilham RatbiCentre de Génomique Humaine, Faculté de Médecine et Pharmacie, Mohammed V University of Rabat, 8007, Rabat, Morocco.
Arthur A M WildeDepartment of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
Teun de BoerDepartment of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands.
William F SimondsMetabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892-2560, USA.
Marguerite Neerman-ArbezDepartment of Genetic Medicine and Development, University Medical Centre (CMU), 1211 Geneva, Switzerland.
V Reid SuttonDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA.
Fernando KokChild Neurology Division, Department of Neurology, School of Medicine, University of Sao Paulo, 01246903 Sao Paulo, Brazil.
James R LupskiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Alexandre ReymondCenter for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
Connie R BezzinaDepartment of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
Jeroen BakkersDepartment of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Hubrecht Institute- Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Centre Utrecht, 3584 CT Utrecht, the Netherlands. Electronic address: j.bakkers@hubrecht.eu.
Giuseppe MerlaMedical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, viale Cappuccini, 71013 San Giovanni Rotondo, Foggia, Italy. Electronic address: g.merla@operapadrepio.it.
Amsterdam UMC Location University of Amsterdam · NLBaylor College of Medicine · USCasa Sollievo della Sofferenza · ITRoyal Netherlands Academy of Arts and Sciences · NLMohammed V University · MANetherlands Institute for Neuroscience · NLUniversity of Foggia · ITEmma Kinderziekenhuis · NLHospital de Clínicas de Porto Alegre · BRNational Institute of Diabetes and Digestive and Kidney Diseases · USSIB Swiss Institute of Bioinformatics · CHStanford University · USUniversidade de São Paulo · BRUniversity Medical Center Utrecht · NLUniversity of Lausanne · CH
Funding
Genome analysis to elucidate molecular mechanisms for peripheral neuropathiesK23NS078056 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI WISZNIEWSKI, WOJCIECH KRZYSZTOF · 2012 to 2016
$783kNINDS NIH HHS K23 NS078056
Abstract
GNB5 encodes the G protein β subunit 5 and is involved in inhibitory G protein signaling. Here, we report mutations in GNB5 that are associated with heart-rate disturbance, eye disease, intellectual disability, gastric problems, hypotonia, and seizures in nine individuals from six families. We observed an association between the nature of the variants and clinical severity; individuals with loss-of-function alleles had more severe symptoms, including substantial developmental delay, speech defects, severe hypotonia, pathological gastro-esophageal reflux, retinal disease, and sinus-node dysfunction, whereas related heterozygotes harboring missense variants presented with a clinically milder phenotype. Zebrafish gnb5 knockouts recapitulated the phenotypic spectrum of affected individuals, including cardiac, neurological, and ophthalmological abnormalities, supporting a direct role of GNB5 in the control of heart rate, hypotonia, and vision.
Indexed as
AdolescentAnimalsBradycardiaChildDevelopmental DisabilitiesFemaleGastroesophageal RefluxGene DeletionGenes, RecessiveGTP-Binding Protein beta SubunitsHeart RateHeterozygoteHumansMaleMuscle HypotoniaMutationgnb5b protein, zebrafishGNB5 protein, humanGTP-Binding Protein beta SubunitsZebrafish ProteinsG-protein signalingheart ratehypotoniaintellectual disabilityparasympathetic systemwhole-exome sequencing
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.