Expressive

rs11657201 (VPS53): Multi-Tissue Expression Variant

Key takeaways

  • rs11657201 reduces VPS53 gene activity in seven tissue types, including whole blood and spleen
  • The expression reduction is consistent in direction across all affected tissues, suggesting a broad multi-tissue eQTL effect
  • The same variant also reduces TLCD3A gene expression in cultured fibroblasts
  • This variant has been studied in the context of a large genome-wide association study of blood lipid levels

Key takeaways

  • rs11657201 reduces VPS53 gene activity in seven tissue types, including whole blood and spleen
  • The expression reduction is consistent in direction across all affected tissues, suggesting a broad multi-tissue eQTL effect
  • The same variant also reduces TLCD3A gene expression in cultured fibroblasts
  • This variant has been studied in the context of a large genome-wide association study of blood lipid levels

What the research says GTEx data from 953 donors demonstrates that rs11657201 acts as an eQTL (expression quantitative trait locus - a genetic variant that influences how much of a gene is expressed) for VPS53 across seven tissues, with the most statistically significant effect in whole blood (slope -0.64, p=2.9e-79) and the largest magnitude effect in spleen (slope -0.77, p=4.5e-26) GTEx Portal. The same variant also reduces TLCD3A expression in cultured fibroblasts (slope -0.44, p=2.9e-34) GTEx Portal. A genome-wide association study of circulating lipoprotein lipid traits in up to 441,016 UK Biobank participants forms the broader research context for this variant; that study identified hundreds of novel SNPs associated with LDL cholesterol, apolipoprotein B, triglycerides, HDL cholesterol, and apolipoprotein A-I, and used Mendelian randomization (a method that uses genetic variants as natural experiments to test causal relationships) to identify apolipoprotein B as the predominant lipid trait linked to coronary heart disease risk (OR 1.92; 95% CI: 1.31-2.81; P < 0.001), though specific per-SNP data for rs11657201 are not reported in the available study text.

Reported associations

  • VPS53 expression (whole blood): ALT allele reduces expression; eQTL slope -0.64, p=2.9e-79 GTEx Portal
  • VPS53 expression (spleen): ALT allele reduces expression; eQTL slope -0.77, p=4.5e-26 GTEx Portal
  • VPS53 expression (thyroid): ALT allele reduces expression; eQTL slope -0.53, p=6.2e-39 GTEx Portal
  • VPS53 expression (esophagus muscularis, visceral adipose, tibial nerve, lung): ALT allele reduces expression across four additional tissues GTEx Portal
  • TLCD3A expression (cultured fibroblasts): ALT allele reduces expression; eQTL slope -0.44, p=2.9e-34 GTEx Portal

Evidence quality The eQTL evidence is robust: drawn from 953 GTEx donors, spanning seven independent tissues for VPS53, and reaching p-values as low as 2.9e-79 in whole blood GTEx Portal. The uniform negative direction of all slopes across every affected tissue substantially strengthens confidence in the finding. The broader lipoprotein lipid GWAS involved up to 441,016 UK Biobank participants and identified between 56% and 93% novel SNPs per trait; however, specific significance levels and effect estimates for rs11657201 in that analysis are not available in the provided data, so the strength or replication status of any lipid association for this particular variant cannot be evaluated from the current evidence base.

Tissue-specific expression effects

  • VPS53: Reduced expression in whole blood, spleen, thyroid, esophagus muscularis, visceral adipose (omentum), tibial nerve, and lung GTEx Portal
  • TLCD3A: Reduced expression in cultured fibroblasts GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Bloodwork

  • triglyceride levels Moderate

    Genetic variant rs11657201 is associated with higher triglyceride levels in large population studies

    Fasting triglyceride panel every 1-2 years or as recommended by healthcare provider

Frequently asked questions

What does rs11657201 do?

rs11657201 reduces the activity of the VPS53 gene in seven tissue types, including whole blood, spleen, thyroid, and lung. It also reduces TLCD3A expression in cultured fibroblasts. These are gene expression effects, not direct disease outcomes.

Which tissues are affected by the rs11657201 variant?

GTEx data from 953 donors shows reduced VPS53 expression in whole blood, spleen, thyroid, esophagus muscularis, visceral adipose tissue, tibial nerve, and lung. TLCD3A expression is also reduced in cultured fibroblasts.

Is rs11657201 linked to cholesterol or lipid levels?

This variant appears in the context of a large genome-wide study of lipoprotein lipid traits in over 440,000 UK Biobank participants, but specific association data for rs11657201 in that study are not available in the current evidence base.

What is the VPS53 gene?

VPS53 encodes a protein involved in directing cellular cargo to lysosomes, the cell's recycling compartments. Its functional significance in the specific tissues where rs11657201 reduces its expression is not fully characterized in the available research.

What is an eQTL and why does it matter for rs11657201?

An eQTL (expression quantitative trait locus) is a genetic variant associated with differences in how much of a gene is produced. rs11657201 is an eQTL for VPS53, meaning people carrying the ALT allele tend to show lower VPS53 gene activity across seven tissue types.