Expressive

rs116350475 (ATP1A4): Athlete Metabolomics Variant

Key takeaways

  • This variant appears in a metabolic GWAS of 490 elite athletes that profiled 751 serum metabolites.
  • The alternative allele reduces CASQ1 expression in brain frontal cortex and IGSF8 expression in thyroid.
  • The alternative allele increases NCSTN and COPA expression in whole blood.
  • Evidence is limited to tissue-specific expression (eQTL) data; no direct phenotypic effect sizes for this variant are available from the provided sources.

Key takeaways

  • This variant appears in a metabolic genome-wide association study (GWAS) of 490 elite athletes that profiled 751 serum metabolites.
  • The alternative allele is associated with reduced expression of CASQ1 in brain frontal cortex and reduced IGSF8 expression in thyroid.
  • The alternative allele is associated with increased NCSTN and COPA expression in whole blood.
  • Evidence is limited to tissue-specific expression (eQTL) data; no direct phenotypic effect sizes for this variant are available from the provided sources.

What the research says A metabolic GWAS was conducted in 490 elite athletes across varied sport disciplines, using 275,016 quality-controlled SNPs alongside high-resolution profiling of 751 serum metabolites; identified mQTLs (metabolite-linked genetic variants) in athletes were compared against those previously reported in non-elite populations to highlight athlete-specific genetic influences. Tissue-specific expression data from GTEx v11 (953 donors, cis-window analysis, FDR < 0.05) shows that the alternative allele of this variant is associated with altered expression of four genes across three tissues: CASQ1 (calsequestrin-1, a calcium-binding storage protein), IGSF8 (an immunoglobulin superfamily membrane protein), NCSTN (nicastrin, a component of the gamma-secretase cell-signaling complex), and COPA (a coatomer protein subunit involved in intracellular vesicle transport). GTEx Portal

Reported associations

  • Athletic performance metabolomics context: This variant was examined in a study designed to identify genetic variants linked to metabolites that differentiate elite from non-elite athletes (n=490, 751 serum metabolites profiled); the specific metabolite association for this variant is not detailed in the available study excerpt.
  • CASQ1 expression, brain frontal cortex: The alternative allele is linked to reduced CASQ1 expression in the frontal cortex (BA9 region). GTEx Portal
  • IGSF8 expression, thyroid: The alternative allele is linked to reduced IGSF8 expression in thyroid tissue. GTEx Portal
  • NCSTN expression, whole blood: The alternative allele is linked to increased NCSTN expression in whole blood. GTEx Portal
  • COPA expression, whole blood: The alternative allele is linked to increased COPA expression in whole blood. GTEx Portal

Evidence quality The metabolic GWAS covered 490 elite athletes assessed with 275,016 SNPs and 751 serum metabolites; the source study does not carry a PMID in its provided metadata, so study-level claims appear here without a direct citation link. The GTEx eQTL findings are based on 953 donors (GTEx v11, cis-window, FDR < 0.05), with p-values for the four gene-tissue pairs ranging from 5.9e-6 (CASQ1, brain) to 1.1e-4 (COPA, whole blood). GTEx Portal No replication studies or conflicting findings are present in the provided data, and no direct phenotypic effect sizes for this variant are available. The evidence is therefore preliminary and limited to expression-level associations.

Tissue-specific expression effects

  • CASQ1: Reduced expression in brain frontal cortex (BA9 region); CASQ1 encodes calsequestrin-1, a calcium-binding protein primarily associated with calcium storage in muscle cells. GTEx Portal
  • IGSF8: Reduced expression in thyroid tissue; IGSF8 encodes a membrane protein belonging to the immunoglobulin superfamily. GTEx Portal
  • NCSTN: Increased expression in whole blood; NCSTN encodes nicastrin, a structural component of the gamma-secretase complex involved in cell signaling. GTEx Portal
  • COPA: Increased expression in whole blood; COPA encodes a subunit of the coatomer protein complex, which directs vesicle-mediated protein transport between cellular compartments. GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs116350475?

rs116350475 is a single-letter DNA variant (SNP) located near the ATP1A4 gene. It has been examined in genetic research on elite athletic performance and appears in tissue-specific gene expression databases.

What is ATP1A4 and why is this variant linked to it?

ATP1A4 is the gene associated with rs116350475 in this research context. The variant was identified in a metabolic GWAS comparing genetic influences on serum metabolites in 490 elite athletes versus non-elite populations.

Which tissues does rs116350475 affect gene expression in?

According to GTEx v11 data from 953 donors, the alternative allele is linked to reduced CASQ1 expression in brain frontal cortex, reduced IGSF8 expression in thyroid, and increased NCSTN and COPA expression in whole blood.

Is rs116350475 directly associated with a specific athletic performance trait?

This variant appears in the context of a metabolic GWAS of 490 elite athletes, but the specific metabolite or performance trait directly attributed to it is not detailed in the available study excerpt. Current evidence is preliminary and limited to expression-level data.

What does CASQ1 do and why is the brain finding notable?

CASQ1 (calsequestrin-1) encodes a calcium-binding protein associated with calcium storage, typically studied in muscle tissue. GTEx data shows this variant reduces CASQ1 expression specifically in brain frontal cortex, which is a less typical tissue context for this gene.