Expressive

rs12406924 (LRRC8C): Multi-tissue Expression Variant

Key takeaways

  • The alternate allele at rs12406924 raises LRRC8C expression in 8 tissues, from whole blood to adrenal glands.
  • The effect is consistent in direction across all 8 tissues, suggesting a broad regulatory role.
  • Strongest expression effects appear in adrenal gland and prostate, with slopes of +0.41.
  • The variant was detected in a large-scale GWAS of over 400,000 UK Biobank participants.
  • Phenotypic disease associations are not documented in the available study sources.

Key takeaways

  • The alternate allele at rs12406924 is linked to increased expression of LRRC8C across at least 8 distinct tissues in GTEx v11 data from 953 donors.
  • The strongest expression increases occur in adrenal gland and prostate, with effect slopes of +0.41 in both tissues.
  • Consistent direction of effect across all 8 tissues (blood, lung, nerve, skin, and fat depots) suggests a broad regulatory influence.
  • This variant was identified in a large-scale GWAS of 405,088 UK Biobank participants using a machine learning-enhanced method called Quickdraws.
  • Phenotypic disease associations for this variant are not described in the available study sources.

What the research says A genome-wide association study using Quickdraws, a machine learning-enhanced linear mixed-model algorithm, analyzed 13.3 million genetic variants across 79 quantitative and 50 binary traits in 405,088 UK Biobank participants (Loya et al., Nature Genetics, 2025). GTEx v11 eQTL (expression quantitative trait locus, meaning a genetic variant linked to differences in gene expression levels) data from 953 donors shows the alternate allele at this locus is associated with increased LRRC8C (Ensembl: ENSG00000231613) expression in 8 tissues, with effect slopes from +0.24 in subcutaneous adipose tissue to +0.41 in adrenal gland and prostate GTEx Portal. The available Quickdraws study excerpt does not specify which phenotypic trait this variant was associated with, so only molecular expression-level associations can be documented here.

Reported associations

  • LRRC8C gene expression (eQTL, molecular phenotype): The alternate allele is associated with increased LRRC8C expression in 8 tissues, including whole blood, lung, and multiple fat depots, with effect slopes from +0.24 to +0.41 GTEx Portal.

Evidence quality The molecular-level evidence for rs12406924 comes from GTEx v11, a large reference eQTL dataset covering 953 donors, with associations reported at FDR (false discovery rate, a statistical threshold controlling the expected proportion of false positives) < 0.05 across tissues. P-values range from 1.2e-4 in subcutaneous adipose tissue to 4.9e-8 in whole blood, with all effects pointing in the direction of increased expression GTEx Portal. The Quickdraws GWAS (Loya et al., Nature Genetics, 2025) covered 405,088 UK Biobank participants and 13.3 million variants across 79 quantitative and 50 binary traits, but the available excerpt does not include phenotypic association details, p-values, or replication data for this specific variant. No conflicting findings are present in the provided sources.

Tissue-specific expression effects

  • LRRC8C: The alternate allele is associated with increased expression in adrenal gland and prostate (slope +0.41 each), visceral adipose tissue (slope +0.32), whole blood, lung, and tibial nerve (slope +0.31 each), sun-exposed lower-leg skin (slope +0.27), and subcutaneous adipose tissue (slope +0.24, the smallest reported effect) GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs12406924 and why does it matter?

rs12406924 is a single-letter DNA variant where the alternate allele is linked to increased expression of the LRRC8C gene across eight different tissues. This makes it notable as a regulatory variant with an unusually broad tissue reach, according to GTEx v11 eQTL data from 953 donors.

Which tissues are affected by rs12406924?

According to GTEx v11 data from 953 donors, the alternate allele raises LRRC8C expression in adrenal gland, prostate, visceral adipose tissue, whole blood, lung, tibial nerve, sun-exposed lower-leg skin, and subcutaneous adipose tissue.

Is rs12406924 linked to any disease?

The available study sources do not describe specific disease or trait associations for rs12406924. The variant was detected in a large-scale UK Biobank GWAS covering 79 quantitative and 50 binary traits, but the specific phenotypic findings for this variant are not included in the provided excerpt.

How was rs12406924 discovered?

This variant was identified in the context of a genome-wide association study of 405,088 UK Biobank participants, using a method called Quickdraws that applies machine learning and a spike-and-slab prior on variant effects to detect more genetic associations than conventional tools.

What does the LRRC8C gene do?

The provided sources do not describe the biological function of LRRC8C directly. What the GTEx v11 eQTL data show is that rs12406924's alternate allele is associated with higher LRRC8C expression across multiple tissue types, from fat tissue to whole blood to adrenal glands.