Kidney Week

Abstract: TH-PO0039

Analysis of Common SLC26A1 Variants as Potential Determinants of Sulfate Metabolism

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Basic Research
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

• Penter, Tiberius Carl Friedrich, Mayo Clinic Minnesota, Rochester, United States

Tiberius Carl Friedrich Penter

• Pitzken, Felix, Mayo Clinic Minnesota, Rochester, United States

Felix Pitzken

• Bizer, Benjamin, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Benjamin Bizer, MD

• Song, Esther Gawon, Mayo Clinic Minnesota, Rochester, United States

Esther Gawon Song

• Chang, Minhwang, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Minhwang Chang, MS, PhD

• Olson, Rory, Mayo Clinic Research Rochester, Rochester, Minnesota, United States

Rory Olson

• Olson, Janet Elaine, Mayo Clinic Research Rochester, Rochester, Minnesota, United States

Janet Elaine Olson, PhD, MPH

• Romero, Michael F., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Michael F. Romero, PhD

• Aronson, Peter S., Yale School of Medicine, New Haven, Connecticut, United States

Peter S. Aronson, MD, FASN

• Knauf, Felix, Mayo Clinic Minnesota, Rochester, United States

Felix Knauf, MD

Background

Sulfate is the fourth most abundant anion in humans and is primarily eliminated in the urine. SLC26A1 is a renal anion exchanger that plays a critical role in sulfate homeostasis. Putatively damaging SLC26A1 variants have been associated with hyposulfatemia and musculoskeletal disease. However, systematic population-level analyses assessing the functional impact of SLC26A1 variants remain limited.

Methods

Using whole-exome sequencing data from the Mayo Clinic Biobank (52.863 individuals), we selected the 10% most prevalent putatively damaging SLC26A1 missense variants for functional characterization. Variants were expressed in Xenopus laevis oocytes, with sulfate uptake serving as the functional readout. All variants were mapped onto an AlphaFold-based structural dimer model of SLC26A1 to evaluate structure-function relationships.

Results

We identified six previously unreported SLC26A1 missense variants that exhibited >50% reduction in sulfate transport. Together with three previously reported damaging variants, these showed a high prevalence of ~1% in our study population. Variants in transmembrane spans were most often associated with functional impairment, whereas variants in loops and the STAS domain were more frequently functionally tolerated.

Conclusion

We identified a subset of functionally impaired SLC26A1 missense variants with substantial prevalence in a large population-based cohort. These results provide the basis for future studies examining the impact of these variants on plasma sulfate concentration and disease outcomes. Moreover, the relationship between transmembrane localization and functional impairment may provide a strategy to improve functional prediction of rare SLC26A1 variants.

SLC26A1 sulfate transport: Variants with <50% activity cluster in transmembrane spans (colored), loop/STAS variants are more tolerated (black).

Funding

• Private Foundation Support