ArticlePloS one2012
A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- X-Linked Hypophosphatemia Management in Adults: An International Working Group Clinical Practice Guideline.The Journal of clinical endocrinology and metabolism · 2025Guideline
- X-Linked Hypophosphatemia Management in Children: An International Working Group Clinical Practice Guideline.The Journal of clinical endocrinology and metabolism · 2025Guideline
- The molecular sociology of NHERF1 PDZ proteins controlling renal hormone-regulated phosphate transport.Bioscience reports · 2024Article
- Hypomagnesaemia with varying degrees of extrarenal symptoms as a consequence of heterozygous CNNM2 variants.Scientific reports · 2024Article
- Review of childhood genetic nephrolithiasis and nephrocalcinosis.Frontiers in genetics · 2024Review
- Mutations in an unrecognized internal NPT2A PDZ motif disrupt phosphate transport and cause congenital hypophosphatemia.The Biochemical journal · 2023Article
- Article
- Overlapping Phenotypes Associated WithFrontiers in endocrinology · 2021Article
- Renal phosphate handling and inherited disorders of phosphate reabsorption: an update.Pediatric nephrology (Berlin, Germany) · 2019Review
- Parathyroid hormone initiates dynamic NHERF1 phosphorylation cycling and conformational changes that regulate NPT2A-dependent phosphate transport.The Journal of biological chemistry · 2019Article
- Analysis of opossum kidney NaPi-IIc sodium-dependent phosphate transporter to understand Pi handling in human kidney.Clinical and experimental nephrology · 2019Article
- Inherited proximal tubular disorders and nephrolithiasis.Urolithiasis · 2019Review
- NaPi-IIa interacting partners and their (un)known functional roles.Pflugers Archiv : European journal of physiology · 2019Review
- Review
- Genetics of Refractory Rickets: Identification of NovelJournal of pediatric genetics · 2018Review
- Evidence for a role of PDZ domain-containing proteins to mediate hypophosphatemia in calcium stone formers.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2018Article
- Genetic Causes of Rickets.Journal of clinical research in pediatric endocrinology · 2017Review
- Origins of PDZ Binding Specificity. A Computational and Experimental Study Using NHERF1 and the Parathyroid Hormone Receptor.Biochemistry · 2017Article
- Dynamic NHERF interaction with TRPC4/5 proteins is required for channel gating by diacylglycerol.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Effects of phospho- and calciotropic hormones on electrolyte transport in the proximal tubule.F1000Research · 2017Review
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe sodium-hydrogen exchanger regulatory factor 1 (NHERF1) binds to the main renal phosphate transporter NPT2a and to the parathyroid hormone (PTH) receptor. We have recently identified mutations in NHERF1 that decrease renal phosphate reabsorption by increasing PTH-induced cAMP production in the renal proximal tubule.
methodsWe compared relevant parameters of phosphate homeostasis in a patient with a previously undescribed mutation in NHERF1 and in control subjects. We expressed the mutant NHERF1 protein in Xenopus Oocytes and in cultured cells to study its effects on phosphate transport and PTH-induced cAMP production.
resultsWe identified in a patient with inappropriate renal phosphate reabsorption a previously unidentified mutation (E68A) located in the PDZ1 domain of NHERF1.We report the consequences of this mutation on NHERF1 function. E68A mutation did not modify cAMP production in the patient. PTH-induced cAMP synthesis and PKC activity were not altered by E68A mutation in renal cells in culture. In contrast to wild-type NHERF1, expression of the E68A mutant in Xenopus oocytes and in human cells failed to increase phosphate transport. Pull down experiments showed that E68A mutant did not interact with NPT2a, which robustly interacted with wild type NHERF1 and previously identified mutants. Biotinylation studies revealed that E68A mutant was unable to increase cell surface expression of NPT2a.
conclusionsOur results indicate that the PDZ1 domain is critical for NHERF1-NPT2a interaction in humans and for the control of NPT2a expression at the plasma membrane. Thus we have identified a new mechanism of renal phosphate loss and shown that different mutations in NHERF1 can alter renal phosphate reabsorption via distinct mechanisms.
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