ArticleNature genetics2012
KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron.
Article in Nature genetics, 2012. 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 167 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
167 citing papers in PubMed, 1 synthesis or guideline pooled it, 331 citations in OpenAlex.
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- Trial
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- Proteome-wide prediction of interactions between structured domains and peptide motifs reveals functionally coherent subnetworks.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The genetics of hypertension.Nature reviews. Nephrology · 2026Review
- KLHL13 functional defects cause neurodevelopmental disorder in humans that can be rescued via inhibition of AURKB in cellular and animal models.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- The functional study of novel KLHL3 missense mutations associated with pseudohypoaldosteronism type II.Endocrine · 2025Article
- Adrenal causes of endocrine hypertension in childhood or adolescence.Journal of endocrinological investigation · 2025Review
- Genes Encoding Heat Shock Proteins Are Associated with Risk and Clinical Course of Severe COVID-19: A Pilot Study.International journal of molecular sciences · 2025Article
- Article
- Hyperkalaemic acidosis: blood pressure is the diagnostic clue.Pediatric nephrology (Berlin, Germany) · 2025Article
- The evolving concepts of KS-WNK1 effect on NCC activity.American journal of physiology. Renal physiology · 2025Review
- Peroxiredoxin 5 Acts as a Negative Regulator of the Sodium-Chloride Cotransporter Involved in Alleviating Angiotensin II-Induced Hypertension.Antioxidants (Basel, Switzerland) · 2025Article
- Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024Review
- Article
- Distal convoluted tubule-specific disruption of the COP9 signalosome but not its regulatory target cullin 3 causes tubular injury.American journal of physiology. Renal physiology · 2024Article
- Deletion of KS-WNK1 promotes NCC activation by increasing WNK1/4 abundance.American journal of physiology. Renal physiology · 2024Article
- Role of calcineurin in regulating renal potassium (KActa physiologica (Oxford, England) · 2024Review
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Arginine vasopressin regulates the renal NaAmerican journal of physiology. Renal physiology · 2024Article
107 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
39 authors at 16 institutions in 7 countries.
Funding
Abstract
Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron. Using combined linkage analysis and whole-exome sequencing in two families, we identified KLHL3 as a third gene responsible for FHHt. Direct sequencing of 43 other affected individuals revealed 11 additional missense mutations that were associated with heterogeneous phenotypes and diverse modes of inheritance. Polymorphisms at KLHL3 were not associated with blood pressure. The KLHL3 protein belongs to the BTB-BACK-kelch family of actin-binding proteins that recruit substrates for Cullin3-based ubiquitin ligase complexes. KLHL3 is coexpressed with NCC and downregulates NCC expression at the cell surface. Our study establishes a role for KLHL3 as a new member of the complex signaling pathway regulating ion homeostasis in the distal nephron and indirectly blood pressure.
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Registered trials
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.