Expressive

rs114058530 (PRKCD-TKT): Multi-Tissue Expression Variant

Key takeaways

  • The alternative allele of rs114058530 strongly reduces STIMATE expression in skeletal muscle, among the larger expression effects documented in GTEx.
  • The same allele increases TKT gene expression in esophageal mucosa and thyroid tissue.
  • Additional effects on GLT8D1 and ITIH4 expression (both reduced) and PBRM1 expression (increased) are documented across muscle and fibroblast tissue.
  • This locus was examined in a UK Biobank biomarker study covering 363,228 individuals and a metabolomics study of 490 elite athletes.
  • All documented associations are from gene expression studies; no clinical endpoint associations are confirmed in the provided research.

Key takeaways

  • The alternative allele of rs114058530 strongly reduces STIMATE expression in skeletal muscle, among the larger per-allele expression effects documented in GTEx.
  • The same allele increases TKT gene expression in esophageal mucosa and thyroid tissue.
  • Additional effects on GLT8D1 and ITIH4 expression (both reduced) and PBRM1 expression (increased) are documented across muscle and fibroblast tissue.
  • This locus falls within a chromosomal region examined by a UK Biobank biomarker GWAS covering 363,228 individuals and a metabolomics GWAS of 490 elite athletes.
  • All documented associations are from gene expression studies; no clinical endpoint associations are confirmed in the provided research.

What the research says A large-scale genome-wide association study (GWAS) of 35 blood and urine biomarkers in the UK Biobank analyzed 363,228 individuals and identified 1,857 genetic loci associated with at least one clinical laboratory measurement, establishing a broad map of common variant effects on biomarkers relevant to kidney function, liver function, lipid metabolism, and glycemic status PMID 33462484. A separate metabolomics GWAS of 490 elite athletes identified novel metabolic quantitative trait loci (mQTLs - variants that influence measurable metabolite concentrations) linked to endurance performance, including previously unreported loci in FOLH1 and VNN1 PMID 32317750. At the gene expression level, cis-eQTL analysis (which measures how a variant influences the expression of genes in its immediate chromosomal neighborhood) in the GTEx v11 dataset (953 donors, FDR < 0.05) identifies this locus as influencing the expression of five nearby genes across several tissue types GTEx Portal.

Reported associations

  • STIMATE expression, skeletal muscle: The alternative allele is associated with reduced STIMATE expression in skeletal muscle (slope -0.46 per allele on the log2-normalized scale, p=6.4e-14) GTEx Portal
  • GLT8D1 expression, cultured fibroblasts: Reduced GLT8D1 expression in cultured fibroblasts (slope -0.32, p=8.3e-14) GTEx Portal
  • TKT expression, esophagus mucosa: Increased TKT expression in esophageal mucosa (slope +0.21, p=5.3e-6) GTEx Portal
  • TKT expression, thyroid: Increased TKT expression in thyroid tissue (slope +0.19, p=5.9e-5) GTEx Portal
  • ITIH4 expression, skeletal muscle: Reduced ITIH4 expression in skeletal muscle (slope -0.21, p=1.6e-4) GTEx Portal
  • PBRM1 expression, cultured fibroblasts: Increased PBRM1 expression in cultured fibroblasts (slope +0.14, p=6.1e-4) GTEx Portal

Evidence quality Expression associations for this variant come from GTEx v11 (953 donors, FDR < 0.05), with the strongest signals at STIMATE in skeletal muscle and GLT8D1 in fibroblasts (both p < 1e-13), meeting a very high statistical threshold; the associations with ITIH4 (p=1.6e-4) and PBRM1 (p=6.1e-4) are weaker and should be treated as preliminary GTEx Portal. The UK Biobank biomarker GWAS (n=363,228) and the elite athlete metabolomics GWAS (n=490) represent the large-scale human studies in which this chromosomal region has been examined, though neither provided study excerpt explicitly reports a trait-level association for this specific variant PMID 33462484 PMID 32317750. All evidence currently on file is from gene expression studies rather than clinical outcome studies, and the health relevance of the documented expression changes has not been established in the provided research.

Tissue-specific expression effects

  • STIMATE: Reduced expression in skeletal muscle GTEx Portal
  • GLT8D1: Reduced expression in cultured fibroblasts GTEx Portal
  • TKT: Increased expression in esophageal mucosa and thyroid GTEx Portal
  • ITIH4: Reduced expression in skeletal muscle GTEx Portal
  • PBRM1: Increased 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.

Lifestyle

  • Lifestyle modifications to lower uric acid Moderate

    This SNP is associated with elevated serum uric acid, a risk factor for gout and cardiovascular disease

    Maintain healthy weight; limit purine-rich foods and alcohol; stay well-hydrated

    • GWAS_CATALOG:33462484

Screening

  • Serum uric acid levels Moderate

    This SNP is associated with higher uric acid levels, increasing risk for gout, cardiovascular disease, and metabolic syndrome

    Check serum urate annually; discuss with doctor if elevated or to assess screening frequency

    • GWAS_CATALOG:33462484

Frequently asked questions

What is rs114058530?

rs114058530 is a common genetic variant in the chromosomal region containing the PRKCD and TKT genes. Based on population-level gene expression data from nearly 1,000 donors, it influences the activity of five nearby genes across several tissue types including skeletal muscle, esophagus, thyroid, and fibroblasts.

Which genes does rs114058530 affect?

Based on GTEx expression data (953 donors), the alternative allele reduces STIMATE and ITIH4 expression in skeletal muscle and reduces GLT8D1 in fibroblasts, while increasing TKT expression in esophageal mucosa and thyroid and increasing PBRM1 in fibroblasts.

Is rs114058530 linked to any disease or health condition?

The research available for this variant does not establish a direct link to clinical disease. Current evidence is limited to effects on gene expression levels in healthy donor tissue, and the health implications of these expression changes have not been confirmed in the provided studies.

What is the TKT gene near rs114058530?

TKT is one of the genes in the chromosomal region surrounding rs114058530. Individuals carrying the alternative allele tend to show higher TKT gene activity in esophageal and thyroid tissue, according to GTEx expression data from 953 donors.

Which tissues are affected by rs114058530?

Based on GTEx expression data, rs114058530 has documented effects in skeletal muscle, cultured fibroblasts, esophageal mucosa, and thyroid tissue. Effects range from reduced STIMATE and ITIH4 levels in skeletal muscle to increased TKT activity in esophagus and thyroid.