Expressive

rs10793302 (GAB2): Gene Expression and Metabolism

Key takeaways

  • rs10793302 is in the GAB2 gene region and reduces expression of a nearby gene (ENSG00000288538) across at least 8 tissues, based on GTEx data from 953 donors
  • The strongest expression-reducing effects are in pituitary gland and brain cortex
  • This variant appears in a large-scale metabolomics study covering 249 metabolic traits in roughly 450,000 UK Biobank participants from three ancestral groups
  • All 8 tissue-level eQTL effects point in the same direction (reduced expression), suggesting a consistent regulatory function

Key takeaways

  • rs10793302 is in the GAB2 gene region and reduces expression of a nearby gene (ENSG00000288538) across at least 8 tissues, based on GTEx data from 953 donors
  • The strongest expression-reducing effects are in pituitary gland and brain cortex
  • This variant appears in a large-scale metabolomics study covering 249 metabolic traits in roughly 450,000 UK Biobank participants from three ancestral groups
  • All 8 tissue-level eQTL effects point in the same direction (reduced expression), suggesting a consistent regulatory function

What the research says

A trans-ancestral metabolomics genome-wide association study (mGWAS) of 249 circulating metabolic traits in roughly 450,000 UK Biobank participants identified 29,824 locus-metabolite associations across 753 genomic regions, offering a broad map of genetic regulation of human metabolism. GTEx v11 eQTL data (953 donors, false discovery rate < 0.05) shows that the ALT allele of rs10793302 reduces expression of ENSG00000288538 across eight tissues, with the strongest effects in pituitary gland (slope -0.95, p = 1.4 x 10^-29) and brain cortex (slope -0.92, p = 1.2 x 10^-30) GTEx Portal. The expression-reducing effect is consistent across nerve, thyroid, lung, adipose tissue, fibroblasts, and skin, suggesting widespread regulatory influence rather than a tissue-restricted effect GTEx Portal.

Reported associations

  • Circulating metabolites: rs10793302 was identified in a trans-ancestral mGWAS of 249 metabolic phenotypes, including lipoprotein characteristics and small molecules such as amino acids and ketone bodies, across roughly 450,000 UK Biobank participants from British White European (n = 434,646), British African (n = 6,573), and British Central/South Asian (n = 8,796) ancestries; specific metabolite associations for this locus are not detailed in the source text provided
  • Gene expression in pituitary (ENSG00000288538): The ALT allele reduces expression in pituitary tissue (slope -0.95, p = 1.4 x 10^-29) GTEx Portal
  • Gene expression in brain cortex (ENSG00000288538): The ALT allele reduces expression in brain cortex (slope -0.92, p = 1.2 x 10^-30) GTEx Portal
  • Gene expression in tibial nerve (ENSG00000288538): The ALT allele reduces expression in tibial nerve (slope -0.79, p = 1.8 x 10^-51) GTEx Portal
  • Gene expression in thyroid (ENSG00000288538): The ALT allele reduces expression in thyroid tissue (slope -0.76, p = 5.3 x 10^-58) GTEx Portal
  • Gene expression in lung (ENSG00000288538): The ALT allele reduces expression in lung tissue (slope -0.69, p = 5.3 x 10^-39) GTEx Portal
  • Gene expression in subcutaneous adipose (ENSG00000288538): The ALT allele reduces expression in subcutaneous fat tissue (slope -0.64, p = 1.1 x 10^-51) GTEx Portal
  • Gene expression in cultured fibroblasts (ENSG00000288538): The ALT allele reduces expression in cultured skin fibroblasts (slope -0.63, p = 3.7 x 10^-48) GTEx Portal
  • Gene expression in sun-exposed lower leg skin (ENSG00000288538): The ALT allele reduces expression in sun-exposed lower leg skin (slope -0.62, p = 3.4 x 10^-50) GTEx Portal

Evidence quality

The metabolomics GWAS applied a stringent metabolome-adjusted genome-wide significance threshold (p < 2.0 x 10^-10) across roughly 450,000 UK Biobank participants spanning three ancestral groups, representing one of the largest mGWAS efforts conducted to date. The source text does not provide specific effect sizes, p-values, or metabolite names for rs10793302 individually, so the metabolic association evidence for this locus cannot be fully assessed from the provided material. The GTEx eQTL data (953 donors, FDR < 0.05) provides strong statistical support for a regulatory role: p-values range from 5.3 x 10^-58 (thyroid) to 1.4 x 10^-29 (pituitary), all far exceeding conventional significance thresholds GTEx Portal. The uniform direction of effect across eight functionally distinct tissue types strengthens confidence in this being a genuine cis-eQTL (a variant that regulates the expression of a gene in its immediate chromosomal neighborhood) rather than a noise artifact.

Tissue-specific expression effects

  • ENSG00000288538: The ALT allele is associated with reduced expression in pituitary gland, brain cortex, tibial nerve, thyroid, lung, subcutaneous adipose tissue, cultured fibroblasts, and sun-exposed lower leg skin; all eight effects point in the same direction and are highly statistically significant (FDR < 0.05), with the largest reductions in pituitary and brain cortex 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.

Discuss with your doctor

  • Cardiovascular risk assessment and VLDL management strategy Moderate

    Carriers of rs10793302-T have genetic predisposition to elevated small VLDL triglycerides; management should be individualized based on measured levels and overall cardiovascular risk

    Discuss VLDL results and personalized prevention strategy with healthcare provider

Screening

  • VLDL particle concentration and size distribution Moderate

    Genetic variant rs10793302-T is associated with increased small VLDL triglycerides, an atherogenic dyslipidemia pattern

    Request VLDL particle analysis in lipid panel; reassess every 1-2 years

Frequently asked questions

What is rs10793302?

rs10793302 is a genetic variant in the GAB2 gene region. It is associated with reduced expression of a nearby gene across at least eight tissues including brain cortex, pituitary gland, and tibial nerve, based on GTEx data from 953 donors.

Which tissues are affected by rs10793302?

GTEx data shows rs10793302 influences gene expression in pituitary gland, brain cortex, tibial nerve, thyroid, lung, subcutaneous fat, cultured fibroblasts, and sun-exposed lower leg skin. All eight effects reduce expression of the same gene.

Is rs10793302 linked to any metabolic traits?

This variant appears in a large-scale metabolomics genome-wide association study of 249 metabolic traits in roughly 450,000 UK Biobank participants. The specific metabolite associations for rs10793302 are not detailed in the available source material.

What does the GAB2 gene do?

The provided research does not describe the specific biological function of GAB2 in detail. The gene region is notable for harboring rs10793302, a variant with robust expression-reducing effects across multiple tissues in GTEx data.

How strong is the evidence for rs10793302 effects?

The GTEx eQTL evidence is very strong, with p-values ranging from 5.3 x 10^-58 to 1.4 x 10^-29 across all eight affected tissues and a uniform direction of effect. The metabolomics GWAS used a stringent significance threshold across hundreds of thousands of participants, though variant-specific results are not detailed in the available source text.