Expressive

rs111806580 (SLC22A10): Transporter Gene Variant

Key takeaways

  • rs111806580 sits in SLC22A10, a member of a gene family that transports organic acids and small molecules across cell membranes
  • The ALT allele is associated with notably increased SLC22A9 expression in pancreatic tissue
  • The same allele shows a smaller but significant increase in ATL3 expression in skeletal muscle
  • This variant falls within the scope of a large UK Biobank study of 35 blood and urine biomarkers across 363,228 individuals
  • Current evidence is preliminary and based primarily on tissue expression data

Key takeaways

  • rs111806580 sits in SLC22A10, a member of the solute carrier family 22 (SLC22), which encodes transporter proteins that move organic acids and other small molecules across cell membranes
  • The ALT allele is associated with notably increased expression of the neighboring gene SLC22A9 (organic anion transporter 4) in pancreatic tissue
  • The same allele shows a smaller but significant increase in ATL3 expression in skeletal muscle
  • This variant falls within the scope of a large UK Biobank study of 35 blood and urine biomarkers across 363,228 individuals
  • Current evidence is preliminary and based primarily on tissue-level expression data

What the research says A genome-wide study of 35 blood and urine biomarkers in the UK Biobank (n=363,228 across multiple ancestry groups) identified 1,857 loci associated with at least one clinical measurement, with 3,374 fine-mapped associations reported. Tissue-level expression data from GTEx v11 (953 donors, FDR<0.05) shows the ALT allele of rs111806580 is linked to increased SLC22A9 expression in pancreatic tissue (slope +0.63, p=2.0e-6) GTEx Portal. The same allele shows a more modest increase in ATL3 (atlastin GTPase 3) expression in skeletal muscle (slope +0.16, p=1.1e-5) GTEx Portal.

Reported associations

  • SLC22A9 expression in pancreas: The ALT allele is linked to increased expression of SLC22A9, an organic anion transporter gene, in pancreatic tissue, with a log2-normalized effect size of +0.63 (p=2.0e-6) GTEx Portal
  • ATL3 expression in skeletal muscle: The ALT allele is linked to increased expression of ATL3 (atlastin GTPase 3, a protein involved in membrane dynamics) in skeletal muscle, with a log2-normalized effect size of +0.16 (p=1.1e-5) GTEx Portal

Evidence quality The GTEx eQTL associations for rs111806580 come from a well-powered expression dataset of 953 donors with FDR-controlled significance thresholds. The pancreatic SLC22A9 signal (slope +0.63, p=2.0e-6) is notably larger in magnitude than the skeletal muscle ATL3 signal (slope +0.16, p=1.1e-5). The UK Biobank biomarker GWAS used a large, multi-ancestry discovery sample of 363,228 individuals including 318,953 White British, 23,582 non-British White, 6,019 African, 7,338 South Asian, and 1,082 East Asian individuals, with stringent fine-mapping and Bonferroni-corrected thresholds of p<5e-9. Specific effect sizes and replication data for rs111806580 as an individual association signal in that biomarker study are not detailed in the available study excerpt, so the evidence for this variant should be considered preliminary overall.

Tissue-specific expression effects

  • SLC22A9: The ALT allele is associated with increased expression in pancreas, a relatively strong eQTL effect among tissues surveyed (slope +0.63, p=2.0e-6) GTEx Portal
  • ATL3: The ALT allele is associated with modestly increased expression in skeletal muscle (slope +0.16, p=1.1e-5) GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is SLC22A10?

SLC22A10 is a member of solute carrier family 22, a group of genes encoding transporter proteins that move organic compounds such as acids, drugs, and metabolites across cell membranes. It sits close to the related transporter gene SLC22A9 in the genome.

What does rs111806580 affect?

Based on tissue-specific expression data from GTEx v11, the ALT allele of rs111806580 is associated with increased activity of SLC22A9 in pancreatic tissue and ATL3 in skeletal muscle. These are gene expression effects and do not directly indicate a disease outcome.

What is SLC22A9?

SLC22A9 encodes organic anion transporter 4 (OAT4), a protein that moves organic acids across cell membranes and is involved in handling metabolites, hormones, and certain drugs. It is a genomic neighbor of SLC22A10 and shows the strongest expression response to this variant in pancreatic tissue.

Is rs111806580 linked to any diseases?

The provided evidence does not establish a direct disease link for rs111806580. The variant appears in the context of a large UK Biobank study cataloguing genetics of 35 blood and urine biomarkers, but specific disease associations are not detailed in the available data.

What does eQTL mean?

eQTL stands for expression quantitative trait locus, meaning a genetic variant statistically associated with differences in how much a nearby gene is expressed in a given tissue. An eQTL association describes a regulatory effect on gene activity but does not on its own establish a disease risk.