ArticleNature genetics2021
Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.
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Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
8.1field-weighted citation impact, top 2% of its field
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Identification of risk loci for primary aldosteronism in genome-wide association studies.Nature communications · 2022Pooled it
- Evaluation of Aldosterone Suppression by Cinnarizine, a Putative Cav1.3 Inhibitor.The Journal of clinical endocrinology and metabolism · 2025Trial
- [Nature medicine · 2023Trial
- Inter- and intratumoral heterogeneity of aldosterone-producing adenomas: recent advances and clinical implications.Endocrine journal · 2026Review
- Primary aldosteronism.Nature reviews. Disease primers · 2026Review
- Increased Frequency and Distinct Genotypic Patterns of Somatic Aldosterone-Driver Mutations in Aldosterone-Producing Micronodules from Primary Aldosteronism Patients.Endocrine pathology · 2026Article
- Rho/ROCK signaling and α-catenin mediate β-catenin-driven hyperplasia in the adrenal cortex via adherens junctions.The Journal of clinical investigation · 2026Article
- Adrenal histologic and genetic characteristics of primary aldosteronism in late adulthood.European journal of endocrinology · 2026Article
- The genetics of hypertension.Nature reviews. Nephrology · 2026Review
- Molecular investigation of primary aldosteronism: exploring genetic heterogeneity in understudied populations.Archives of endocrinology and metabolism · 2025Article
- Somatic Mutations inHypertension (Dallas, Tex. : 1979) · 2025Article
- Adrenocortical stem cells in health and disease.Nature reviews. Endocrinology · 2025Review
- Review
- Intratumoural aldosterone and CYP11B2 expression levels among different genotypes of aldosterone producing tumours.Endocrine connections · 2025Article
- Sexual dimorphism in benign adrenocortical tumours.European journal of endocrinology · 2025Review
- The adrenal gland and primary aldosteronism: anatomy, steroidogenesis, regulation, and genetic insights.Frontiers in endocrinology · 2025Review
- Histopathological spectrum of common aldosterone-driver gene mutations in aldosterone-producing adenomas.Frontiers in medicine · 2025Article
- Editorial: Advances in diagnostics and management of adrenal tumors.Frontiers in endocrinology · 2025Article
- SomaticHypertension (Dallas, Tex. : 1979) · 2024Article
- GNAQ/GNA11-Related Benign and Malignant Entities-A Common Histoembriologic Origin or a Tissue-Dependent Coincidence.Cancers · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
44 authors at 14 institutions in 7 countries.
Junhua Zhou *Endocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0002-8593-8393
Elena A B Azizan *Endocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK. elena.azizan@ukm.edu.my.ORCID http://orcid.org/0000-0002-5549-4242
Claudia P Cabrera *NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Fabio L Fernandes-Rosa *Université de Paris, PARCC, Inserm, Paris, France.ORCID http://orcid.org/0000-0002-0162-0792
Sheerazed Boulkroun *Université de Paris, PARCC, Inserm, Paris, France.ORCID http://orcid.org/0000-0002-8796-7534
Giulia ArgentesiEndocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
Emily CottrellCentre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0001-6773-6547
Laurence AmarUniversité de Paris, PARCC, Inserm, Paris, France.
Xilin WuEndocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
Sam O'TooleEndocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0002-8943-8556
Emily GoodchildEndocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.
Alison MarkerDepartment of Histopathology, Addenbrooke's Hospital, Cambridge, UK.
Russell SenanayakeMetabolic Research Laboratories, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Sumedha GargEndocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0002-4375-8968
Tobias ÅkerströmDepartment of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Samuel BackmanDepartment of Surgical Sciences, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0002-4208-9395
Suzanne JordanCellular Pathology Department, Royal London Hospital, London, UK.
Satyamaanasa PolubothuGenetics and Genomic Medicine, University College London Great Ormond Street Institute of Child Health, London, UK.
Daniel M BerneyCentre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.
Anna GluckAcademic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Kate E LinesAcademic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-0764-8681
Rajesh V ThakkerAcademic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-1438-3220
Antoinette TuthillDepartment of Endocrinology and Diabetes, Cork University Hospital, Cork, Ireland.ORCID http://orcid.org/0000-0002-1460-517X
Caroline JoyceClinical Biochemistry, Cork University Hospital, Cork, Ireland.
Juan Pablo KaskiCentre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital and University College London Institute of Cardiovascular Science, London, UK.ORCID http://orcid.org/0000-0002-0014-9927
Fiona E Karet FranklCambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Lou A MetherellCentre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0002-0530-3524
Ada E D TeoDept of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.ORCID http://orcid.org/0000-0002-8832-0409
Mark GurnellMetabolic Research Laboratories, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0001-5745-6832
Laila ParvantaDepartment of Surgery, St Bartholomew's Hospital, London, UK.
William M DrakeDepartment of Endocrinology, St Bartholomew's Hospital, London, UK.
Eva WozniakBarts and London Genome Centre, School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK.
David KlinzingCardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Jyn Ling KuanCardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Zenia TiangCardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.ORCID http://orcid.org/0000-0003-1182-0023
Celso E Gomez SanchezG.V. (Sonny) Montgomery VA Medical Center and Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Per HellmanDepartment of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Roger S Y FooCardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.ORCID http://orcid.org/0000-0002-8079-4618
Charles A MeinBarts and London Genome Centre, School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK.
Veronica A KinslerCellular Pathology Department, Royal London Hospital, London, UK.
Peyman BjörklundDepartment of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Helen L StorrCentre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0002-9963-1931
Maria-Christina ZennaroUniversité de Paris, PARCC, Inserm, Paris, France. maria-christina.zennaro@inserm.fr.ORCID http://orcid.org/0000-0001-5449-9191
Morris J BrownEndocrine Hypertension, Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK. morris.brown@qmul.ac.uk.ORCID http://orcid.org/0000-0001-8409-1082
Queen Mary University of London · GBInserm · FRNational University of Singapore · SGUppsala University · SEUniversity of Oxford · GBCork University Hospital · IEGreat Ormond Street Hospital · GBRoyal London Hospital · GBSt Bartholomew's Hospital · GBWellcome/MRC Institute of Metabolic Science · GBAddenbrooke's Hospital · GBAgency for Science, Technology and Research · SGUniversity of Cambridge · GBUniversity of Mississippi Medical Center · US
Funding
Adrenal cell ATP1A1 mutations and mechanisms of aldosterone biosynthesisR01HL144847 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI GOMEZ-SANCHEZ, CELSO ENRIQUE · 2019 to 2022
$1.3MBLRD VA I01 BX004681British Heart Foundation FS/11/35/28871British Heart Foundation FS/14/12/30540British Heart Foundation FS/14/75/31134British Heart Foundation FS/19/50/34566British Heart Foundation PG/07/085/23349British Heart Foundation PG/16/40/32137British Heart Foundation SP/08/002/24118Medical Research Council G0801265Medical Research Council MR/K020455/1Medical Research Council MR/K501050/1Medical Research Council MR/S006869/1NHLBI NIH HHS R01 HL144847Wellcome TrustWellcome Trust 106995/Z/15/Z
Abstract
Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1.
Indexed as
AdolescentAdrenal Cortex NeoplasmsAdrenocortical AdenomaAdultAldosteronebeta CateninFemaleGTP-Binding Protein alpha SubunitsGTP-Binding Protein alpha Subunits, Gq-G11HumansHyperaldosteronismMaleMenopauseMiddle AgedPregnancyPubertyAldosteronebeta CateninCTNNB1 protein, humanGNA11 protein, humanGNAQ protein, humanGTP-Binding Protein alpha SubunitsGTP-Binding Protein alpha Subunits, Gq-G11
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