Expressive

rs1047586 (RARRES2): LRRC61 Multi-Tissue eQTL

Key takeaways

  • rs1047586 consistently increases LRRC61 expression across 8 distinct tissues with no opposing effects reported
  • The strongest statistical signal is in thyroid tissue, confirmed in GTEx data from 953 donors
  • Brain regions including cerebellum and nucleus accumbens both show increased LRRC61 expression
  • This is a molecular expression effect; downstream health consequences are not established from current evidence

Key takeaways

  • rs1047586 is labeled near the RARRES2 gene and consistently increases expression of LRRC61 (Leucine Rich Repeat Containing 61) across at least 8 tissue types
  • The alternate allele raises LRRC61 expression in every reported tissue with no opposing direction found in the GTEx data
  • The strongest statistical signal is in thyroid tissue; the largest magnitude effect is in brain cerebellum
  • These are molecular expression signals; downstream health consequences are not established from the currently available evidence

What the research says GTEx v11 data from 953 donors identifies rs1047586 as an eQTL (expression quantitative trait locus, a variant that influences how much of a gene is expressed) for LRRC61 in eight tissues, with increased expression in all of them GTEx Portal. A whole-genome sequencing study of the plasma proteome in 1,852 Black adults (Katz et al., Circulation 2022) and a genome-wide association analysis of educational attainment in approximately 1.1 million individuals (Lee et al., Nature Genetics 2019) are also included as contextual evidence, with the former identifying 569 protein-genetic associations across 438 unique genomic regions and the latter identifying 1,271 genome-wide-significant loci enriched for brain-development genes.

Reported associations

  • LRRC61 expression, thyroid: Increased LRRC61 expression (slope +0.61 on a log2-normalized scale, p=5.9e-105); the strongest statistical eQTL signal across all reported tissues GTEx Portal
  • LRRC61 expression, skeletal muscle: Increased expression (slope +0.89, p=3.7e-92) GTEx Portal
  • LRRC61 expression, esophagus mucosa: Increased expression (slope +0.69, p=1.7e-91) GTEx Portal
  • LRRC61 expression, tibial nerve: Increased expression (slope +0.62, p=5.8e-88) GTEx Portal
  • LRRC61 expression, cultured fibroblasts: Increased expression (slope +0.84, p=1.6e-86) GTEx Portal
  • LRRC61 expression, testis: Increased expression (slope +0.84, p=1.6e-83) GTEx Portal
  • LRRC61 expression, brain nucleus accumbens (basal ganglia): Increased expression (slope +1.02, p=2.3e-62) GTEx Portal
  • LRRC61 expression, brain cerebellum: Increased expression (slope +1.14, p=1.1e-46); the largest magnitude effect among all reported tissues GTEx Portal

Evidence quality All association data for rs1047586 in the provided evidence base comes from GTEx v11, a systematically generated reference dataset from 953 donors analyzed at FDR below 0.05 within a cis-window. Effect size slopes range from +0.61 to +1.14 across tissues, and p-values span approximately 10^-46 to 10^-105, well beyond standard significance thresholds. The consistency of direction (increased expression in all eight tissues) strengthens confidence in the molecular signal. Two large-scale GWAS studies are included as contextual evidence: the plasma proteome study by Katz et al. (Circulation 2022, n=1,852) and the educational attainment GWAS by Lee et al. (Nature Genetics 2019, n=approximately 1.1 million). The excerpts provided from these studies do not include specific association statistics for rs1047586; the evidence presented here should be treated as preliminary and mechanistic rather than clinically established.

Tissue-specific expression effects

  • LRRC61: Increased expression in thyroid (strongest statistical signal), skeletal muscle, esophagus mucosa, tibial nerve, cultured fibroblasts, testis, brain nucleus accumbens (basal ganglia), and brain cerebellum; the effect direction is consistently positive across all eight tissues, with the largest magnitude effects in brain regions and the most statistically robust signal in thyroid GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What does rs1047586 do?

rs1047586 increases the amount of LRRC61 gene product made across multiple tissues, including brain regions, skeletal muscle, thyroid, and nerve tissue. This type of effect is called an eQTL (expression quantitative trait locus), meaning the variant influences gene expression levels rather than the structure of a resulting protein. The health implications of this expression change are not established from the currently available evidence.

What gene is rs1047586 near?

rs1047586 is labeled near RARRES2 (Retinoic Acid Receptor Responder 2). The measured molecular effect in GTEx data is on a neighboring gene called LRRC61 (Leucine Rich Repeat Containing 61).

Which tissues are affected by rs1047586?

GTEx v11 data shows rs1047586 influences LRRC61 expression in thyroid, skeletal muscle, esophagus mucosa, tibial nerve, cultured fibroblasts, testis, brain nucleus accumbens, and brain cerebellum. The effect is increased expression in all eight tissues.

Is rs1047586 linked to any diseases?

The studies included in this entry do not establish a specific disease link for rs1047586. The available evidence describes a molecular expression effect on LRRC61 across multiple tissues. Whether this translates to measurable health differences requires further research.

How reliable is the evidence for rs1047586?

The eQTL data comes from GTEx v11, a well-established reference dataset from 953 donors analyzed at stringent significance thresholds. The consistency of effect direction across all eight tissues strengthens confidence in the molecular signal. Two additional large-scale GWAS studies are included as contextual evidence, though specific data for rs1047586 was not available in the provided excerpts from those studies.