rs10179584 (KCNS3/RDH14): Kidney Function Variant

Key takeaways

• rs10179584 sits near KCNS3, a potassium channel gene, and RDH14, a vitamin A metabolism gene
• This variant has been studied in the context of kidney filtration rate (eGFR) in a transethnic GWAS of over 280,000 veterans
• The study identifying this class of kidney function variants replicated findings in over 765,000 additional participants
• Individual eGFR-associated variants typically explain only a small fraction of variation in kidney filtration rate

What the research says The rs10179584 variant is located near two genes, KCNS3 (potassium voltage-gated channel, modifier subfamily S, member 3, a subunit of voltage-gated potassium channels) and RDH14 (retinol dehydrogenase 14, an enzyme involved in vitamin A metabolism), which together define the locus. A transethnic genome-wide association study (GWAS, a method that scans millions of genetic variants across a large population to find statistical associations with a trait) of estimated glomerular filtration rate (eGFR, an estimate of how many milliliters of blood the kidneys filter per minute per 1.73 m2 of body surface area) was conducted in 280,722 participants of the Million Veteran Program (MVP), with replication in 765,289 participants from the Chronic Kidney Disease Genetics (CKDGen) Consortium; the study identified 82 previously unreported eGFR-associated variants, confirmed 54 known loci, and mapped gene expression patterns to specific kidney cell types. A second study developed and applied an improved GWAS algorithm called Quickdraws to 405,088 UK Biobank participants across 79 quantitative and 50 binary traits, identifying 4.97% more quantitative-trait associations and 3.25% more binary-trait associations than the REGENIE method.

Reported associations

• Estimated glomerular filtration rate (eGFR): The locus was evaluated in a transethnic GWAS of eGFR in 280,722 MVP participants (replicated in 765,289 CKDGen participants); the overall study identified 82 previously unreported eGFR-associated variants, though specific effect size data for rs10179584 at this locus were not available in the provided study excerpts
• Chronic kidney disease (CKD) stages, complications, and kidney stones: A phenome-wide association study (PheWAS, a scan of clinical records for traits linked to a genetic score) using a weighted eGFR genetic risk score in 192,868 MVP participants detected associations with CKD stages, CKD complications, and kidney stones, indicating that eGFR-associated variants as a class have broad kidney-related clinical associations

Evidence quality The primary evidence base comes from a transethnic GWAS with 280,722 discovery participants and 765,289 replication participants, one of the most statistically powered kidney function genetic studies reported at its time of publication. The transethnic design, combining participants of different ancestral backgrounds, strengthens confidence that identified associations reflect true biological signals rather than population-specific noise. A second study using an improved GWAS methodology in 405,088 UK Biobank participants provides additional context for identifying variant associations at this scale. Specific p-values, effect sizes, and minor allele frequencies for rs10179584 are not reported in the available study excerpts, so the magnitude of this variant's individual contribution to eGFR variation cannot be precisely characterized from these sources. No conflicting findings were noted between the two provided studies.

Lifestyle considerations No lifestyle considerations on file for this variant.