ArticleJournal of the American Society of Nephrology : JASN2016
The Uromodulin Gene Locus Shows Evidence of Pathogen Adaptation through Human Evolution.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.Nature communications · 2019Pooled it
- Is uromodulin a reliable biomarker in pediatric vesicoureteral reflux? An exploratory pilot study.International urology and nephrology · 2026Article
- Exploring promising biomarkers based on pathogenic mechanisms in interstitial cystitis/bladder pain syndrome.Nature reviews. Urology · 2026Review
- Recent advances in the clinical significance and physiological functions of uromodulin: a narrative review.BMC nephrology · 2026Review
- Endocrine regulation of uromodulin in aging.Frontiers in endocrinology · 2026Review
- Structure of human glycoprotein 2 reveals mechanisms underlying filament formation and adaption to proteolytic environment in the digestive tract.PLoS biology · 2025Article
- Article
- Article
- Advances in uromodulin biology and potential clinical applications.Nature reviews. Nephrology · 2024Review
- Uropathogen and host responses in pyelonephritis.Nature reviews. Nephrology · 2023Review
- Unveiling the Hidden Power of Uromodulin: A Promising Potential Biomarker for Kidney Diseases.Diagnostics (Basel, Switzerland) · 2023Review
- Review
- Comparative physiological anthropogeny: exploring molecular underpinnings of distinctly human phenotypes.Physiological reviews · 2023Review
- Uromodulin and Vesico-Ureteral Reflux: A Genetic Study.Biomedicines · 2023Article
- UMOD and the architecture of kidney disease.Pflugers Archiv : European journal of physiology · 2022Review
- Phenome-Wide Association Study ofKidney international reports · 2022Article
- New genetic insights into kidney physiology and disease.Nature reviews. Nephrology · 2021Review
- The cryo-EM structure of the human uromodulin filament core reveals a unique assembly mechanism.eLife · 2020Article
- Uromodulin (Tamm-Horsfall protein): guardian of urinary and systemic homeostasis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2020Review
- Uromodulin in mineral metabolism.Current opinion in nephrology and hypertension · 2019Review
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
Common variants in the UMOD gene encoding uromodulin, associated with risk of hypertension and CKD in the general population, increase UMOD expression and urinary excretion of uromodulin, causing salt-sensitive hypertension and renal lesions. To determine the effect of selective pressure on variant frequency, we investigated the allelic frequency of the lead UMOD variant rs4293393 in 156 human populations, in eight ancient human genomes, and in primate genomes. The T allele of rs4293393, associated with CKD risk, has high frequency in most modern populations and was the one detected in primate genomes. In contrast, we identified only the derived, C allele in Denisovan and Neanderthal genomes. The distribution of the UMOD ancestral allele did not follow the ancestral susceptibility model observed for variants associated with salt-sensitive hypertension. Instead, the global frequencies of the UMOD alleles significantly correlated with pathogen diversity (bacteria, helminths) and prevalence of antibiotic-resistant urinary tract infections (UTIs). The inverse correlation found between urinary levels of uromodulin and markers of UTIs in the general population substantiates the link between UMOD variants and protection against UTIs. These data strongly suggest that the UMOD ancestral allele, driving higher urinary excretion of uromodulin, has been kept at a high frequency because of its protective effect against UTIs.
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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.