rs10137082 (EFS-IL25): Brain and Skin Expression Variant

Key takeaways

• This variant reduces EFS (Embryonal Fyn-associated Substrate, a cell-signaling protein) expression in brain cerebellar hemisphere tissue and in both sun-exposed and non-sun-exposed skin
• The same variant increases SLC22A17 (a membrane transport protein) expression in skin, the opposite direction from its effect on EFS
• Expression effects were measured across 953 donors in GTEx v11 at FDR < 0.05, providing statistically robust signals
• EFS and IL25 (interleukin 25, also called IL-17E, a cytokine involved in type 2 immune responses) are the primary genes in this chromosomal region, which has been studied in proteomics and immune disease research
• No clinical drug responses or lifestyle interventions are documented for this variant in the provided evidence

What the research says Tissue-specific expression data from GTEx v11 (953 donors, FDR < 0.05) shows that the ALT allele at this locus reduces EFS expression in brain cerebellar hemisphere tissue and in both sun-exposed lower leg skin and non-sun-exposed suprapubic skin, while simultaneously increasing SLC22A17 expression in those same skin regions GTEx Portal. A large-scale proteogenomics study testing 10.2 million genetic variants against 4,775 plasma proteins in 10,708 participants provides a research framework for connecting loci in this region to protein biology, and a Type 1 diabetes meta-analysis of 9,934 cases and 16,956 controls examined immune-relevant loci across the genome; the neighboring IL25 gene encodes a cytokine involved in immune regulation, situating this locus within a biologically plausible network for immune trait research. The eQTL signals (eQTL stands for expression quantitative trait locus, meaning a genetic variant that influences how much of a gene is produced) are directionally consistent within each gene across tissue types, with EFS reduced in all three affected tissues and SLC22A17 increased in both affected skin tissues GTEx Portal.

Reported associations

• EFS expression, brain cerebellar hemisphere: The ALT allele is associated with reduced EFS expression (p = 5.2e-7) GTEx Portal
• EFS expression, non-sun-exposed suprapubic skin: The ALT allele is associated with reduced EFS expression (p = 3.2e-6) GTEx Portal
• EFS expression, sun-exposed lower leg skin: The ALT allele is associated with reduced EFS expression (p = 4.8e-5) GTEx Portal
• SLC22A17 expression, sun-exposed lower leg skin: The ALT allele is associated with increased SLC22A17 expression (p = 7.1e-8, the strongest signal for this variant across all tissues) GTEx Portal
• SLC22A17 expression, non-sun-exposed suprapubic skin: The ALT allele is associated with increased SLC22A17 expression (p = 1.4e-5) GTEx Portal

Evidence quality All reported associations derive from GTEx v11 expression QTL analysis across 953 donors, all passing FDR < 0.05 GTEx Portal. The EFS expression signals are directionally consistent across three tissue types (reduced in each), and the SLC22A17 signals are concordant across two skin tissue types (increased in each), lending internal consistency to the eQTL data. These are expression-level findings only: demonstrating that changes in EFS or SLC22A17 expression contribute to specific diseases would require additional evidence beyond expression QTL data alone. The broader referenced studies - a 10,708-person proteogenomics screen identifying over 10,000 protein-variant associations and a 26,890-person Type 1 diabetes meta-analysis - provide biological context for the EFS-IL25 chromosomal region but do not supply published association statistics specific to rs10137082 in the provided evidence. Overall evidence for this variant should be considered preliminary and limited to expression-level biology.

Tissue-specific expression effects

• EFS: Reduced expression in brain cerebellar hemisphere tissue, non-sun-exposed suprapubic skin, and sun-exposed lower leg skin; the brain cerebellar hemisphere signal shows the largest magnitude reduction among the three tissues GTEx Portal
• SLC22A17: Increased expression in sun-exposed lower leg skin and non-sun-exposed suprapubic skin; effects are similar in magnitude across both skin tissue types GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.