ArticleAmerican journal of human genetics2009
Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic kidney failure.
Article in American journal of human genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 163 citations in OpenAlex.
- Autosomal dominant tubulointerstitial kidney disease: diagnosis, classification, and management--A KDIGO consensus report.Kidney international · 2015Guideline
- Single-Molecule Real-Time Sequencing for MUC1 Variable Number of Tandem Repeat Variation to Improve Autosomal Dominant Tubulointerstitial Kidney Disease Diagnosis.Journal of the American Society of Nephrology : JASN · 2026Article
- Clinical and Molecular characteristics of kidney and urinary tract congenital anomalies in a cohort of Egyptian patients using whole-exome sequencing.Molecular biology reports · 2026Article
- Autosomal Dominant Tubulointerstitial Kidney Disease-UMOD: Case Report and Disease Update.Diagnostics (Basel, Switzerland) · 2026Article
- Review
- Long-Read Sequencing of thebioRxiv : the preprint server for biology · 2025Article
- Clinical use of the VNtyper-Kestrel pipeline for MUC1 variant detection in autosomal-dominant tubulointerstitial kidney disease.Clinical and experimental nephrology · 2025Article
- Phenotype and genotype of autosomal dominant tubulointerstitial kidney disease in a Japanese cohort.Clinical and experimental nephrology · 2025Article
- Autosomal-dominant tubulointerstitial kidney disease with a novel UMOD mutation, overlapping with Sjogren's syndrome: a case report.CEN case reports · 2025Article
- Case Report: UMOD gene mutation and phenotypic overlap with REN in autosomal dominant tubulointerstitial kidney disease.Frontiers in genetics · 2025Article
- Case-inspired exploration of renin mutations in autosomal dominant tubulointerstitial kidney disease: not all paths lead to the endoplasmic reticulum.Pediatric nephrology (Berlin, Germany) · 2024Article
- A Novel MonoallelicKidney international reports · 2024Article
- Transcriptome Analysis of BAFF/BAFF-R System in Murine Nephrotoxic Serum Nephritis.International journal of molecular sciences · 2024Article
- Genetic Appraisal of RAAS-Associated SNPs: REN (rs16853055), AGT (rs3789678) and ACE (rs4305) in Preeclamptic Women Living with HIV Infection.Current hypertension reports · 2024Review
- Review
- Case Report: A potentially pathogenic new variant of theFrontiers in pediatrics · 2024Article
- Review
- Leader peptide or pro-segment mutants of renin are misrouted to mitochondria in autosomal dominant tubulointerstitial kidney disease.Disease models & mechanisms · 2023Article
- A founderJournal of medical genetics · 2023Article
- Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Through linkage analysis and candidate gene sequencing, we identified three unrelated families with the autosomal-dominant inheritance of early onset anemia, hypouricosuric hyperuricemia, progressive kidney failure, and mutations resulting either in the deletion (p.Leu16del) or the amino acid exchange (p.Leu16Arg) of a single leucine residue in the signal sequence of renin. Both mutations decrease signal sequence hydrophobicity and are predicted by bioinformatic analyses to damage targeting and cotranslational translocation of preprorenin into the endoplasmic reticulum (ER). Transfection and in vitro studies confirmed that both mutations affect ER translocation and processing of nascent preprorenin, resulting either in reduced (p.Leu16del) or abolished (p.Leu16Arg) prorenin and renin biosynthesis and secretion. Expression of renin and other components of the renin-angiotensin system was decreased accordingly in kidney biopsy specimens from affected individuals. Cells stably expressing the p.Leu16del protein showed activated ER stress, unfolded protein response, and reduced growth rate. It is likely that expression of the mutant proteins has a dominant toxic effect gradually reducing the viability of renin-expressing cells. This alters the intrarenal renin-angiotensin system and the juxtaglomerular apparatus functionality and leads to nephron dropout and progressive kidney failure. Our findings provide insight into the functionality of renin-angiotensin system and stress the importance of renin analysis in families and individuals with early onset hyperuricemia, anemia, and progressive kidney failure.
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