Expressive

rs111807267 (DOCK3): Gene expression variant across tissues

Key takeaways

  • rs111807267 is an eQTL that affects at least five genes across multiple body tissues.
  • The variant reduces DOCK3 expression in non-sun-exposed skin and increases TEX264 expression in esophageal muscle, subcutaneous fat, tibial artery, and tibial nerve.
  • A robust association links this variant to increased GRM2 expression in tibial nerve.
  • No direct disease associations are reported in the provided studies; findings are at the level of gene expression only.

Key takeaways

  • rs111807267 is an expression-quantitative trait locus (eQTL) affecting at least five genes across multiple body tissues.
  • The variant reduces DOCK3 expression in non-sun-exposed skin, and increases TEX264 expression in four separate tissues: esophageal muscle, subcutaneous fat, tibial artery, and tibial nerve.
  • A statistically robust association also links this variant to increased GRM2 (glutamate metabotropic receptor 2) expression in tibial nerve.
  • No direct disease associations are reported in the provided studies; all documented findings are at the level of gene expression, not disease outcomes.

What the research says GTEx v11 data from 953 donors identifies rs111807267 as a cis-eQTL (a variant influencing nearby gene expression) with effects spanning at least five genes across eight tissue-type associations GTEx Portal. The strongest effect is increased TEX264 expression in esophageal muscularis (slope +0.46, p=2.0e-10), while the weakest is increased expression of an annotated but unnamed gene (ENSG00000288988) in brain cortex (p=2.0e-4), which warrants more cautious interpretation GTEx Portal. A proteomics genome-wide association study measuring 1301 circulating protein levels in 2935 participants from the Qatar Biobank found that protein-level genetic signals largely replicate between European and Arab populations, with approximately 81.8% of signals colocalizing across both groups, and European-derived polygenic scores performing roughly 20% better when applied to Europeans compared to Arabs.

Reported associations

  • DOCK3 expression (non-sun-exposed skin): The alternative allele is linked to reduced DOCK3 expression in suprapubic skin (slope -0.39, p=5.2e-6) GTEx Portal
  • TEX264 expression (esophagus muscularis): The alternative allele is linked to increased TEX264 expression in esophageal muscle tissue (slope +0.46, p=2.0e-10) GTEx Portal
  • TEX264 expression (subcutaneous adipose tissue): The alternative allele is linked to increased TEX264 expression in subcutaneous fat (slope +0.36, p=3.8e-8) GTEx Portal
  • TEX264 expression (tibial artery): The alternative allele is linked to increased TEX264 expression in tibial artery (slope +0.32, p=9.3e-8) GTEx Portal
  • TEX264 expression (tibial nerve): The alternative allele is linked to increased TEX264 expression in tibial nerve (slope +0.31, p=3.1e-7) GTEx Portal
  • GRM2 expression (tibial nerve): The alternative allele is linked to increased GRM2 (glutamate metabotropic receptor 2) expression in tibial nerve (slope +0.38, p=8.6e-10) GTEx Portal
  • ENSG00000288988 expression (brain cortex): The alternative allele is linked to increased expression of an annotated but unnamed gene in brain cortex (slope +0.63, p=2.0e-4); this association is notably weaker than others at this locus GTEx Portal
  • IQCF6 expression (testis): The alternative allele is linked to reduced IQCF6 expression in testis (slope -0.30, p=2.2e-7) GTEx Portal

Evidence quality All eQTL associations come from GTEx v11, which analyzed 953 donors using a cis-window approach at a false discovery rate (FDR) below 0.05 GTEx Portal. P-values across the reported associations range from 2.0e-10 (TEX264 in esophageal muscularis) to 2.0e-4 (ENSG00000288988 in brain cortex) GTEx Portal. The brain cortex finding is markedly weaker than the others and should be treated as preliminary evidence only. The TEX264 associations across four tissues and the GRM2 tibial nerve association are statistically robust within the GTEx framework. A related proteomics study in 2935 Qatar Biobank participants measuring 1301 blood proteins found that approximately 81.8% of protein-level genetic signals colocalize between European and Arab populations, and that European-derived polygenic scores explain roughly one-third of genetic protein heritability while performing about 20% better in Europeans than in Arabs. This cross-population limitation is relevant context when interpreting findings derived primarily from European reference datasets.

Tissue-specific expression effects

  • TEX264: The alternative allele is associated with increased expression in esophagus muscularis (the strongest effect documented at this locus), subcutaneous adipose tissue, tibial artery, and tibial nerve GTEx Portal
  • GRM2: The alternative allele is associated with increased expression in tibial nerve GTEx Portal
  • ENSG00000288988: The alternative allele is associated with increased expression in brain cortex; this is the weakest association at this locus and should be interpreted with caution GTEx Portal
  • DOCK3: The alternative allele is associated with reduced expression in non-sun-exposed (suprapubic) skin GTEx Portal
  • IQCF6: The alternative allele is associated with reduced expression in testis GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What does the DOCK3 gene do?

DOCK3 (Dedicator of Cytokinesis 3) is a signaling gene involved in cytoskeletal organization. The rs111807267 variant is associated with reduced DOCK3 expression specifically in non-sun-exposed skin, though the functional impact of this specific change has not been further characterized in the provided studies.

Which tissues are affected by rs111807267?

GTEx data links rs111807267 to expression changes in non-sun-exposed skin (DOCK3, reduced), esophageal muscle, subcutaneous fat, tibial artery, and tibial nerve (all TEX264, increased), tibial nerve (GRM2, increased), brain cortex (one uncharacterized gene, increased), and testis (IQCF6, reduced).

Is rs111807267 associated with any diseases?

The provided studies do not report any direct disease associations for rs111807267. The documented findings are changes in gene expression across tissues, which are considered mechanistic data rather than confirmed disease outcomes.

What is a cis-eQTL?

A cis-eQTL (cis expression quantitative trait locus) is a genetic variant that changes how much a nearby gene is expressed in a cell. rs111807267 acts as a cis-eQTL for several genes, meaning it influences how actively those genes are turned on or off in various tissues.

What is TEX264 and why does rs111807267 affect it?

TEX264 is a protein involved in cellular autophagy, the process by which cells break down and recycle their own components. rs111807267 is associated with increased TEX264 expression in four different tissues, making it the gene most broadly and consistently influenced by this variant based on available GTEx data.