rs10517086 (LINC02357): RBPJ Expression Variant
Key takeaways
- rs10517086 sits near LINC02357 (long intergenic non-coding RNA 2357) and reduces expression of the Notch pathway gene RBPJ in aortic tissue, connective tissue cells, and sun-exposed skin
- RBPJ is the central switch of the Notch signaling pathway, a cell communication system governing cell identity, immune development, and tissue maintenance
- Large-scale GWAS have studied this locus across circulating fatty acids, blood biomarkers, body shape, thyroid health, and autoimmune diseases including RA, MS, IBD, and T1D
- The GTEx tissue-expression finding is the most directly evidenced data point for this variant; phenotypic association evidence is preliminary
- No lifestyle or dietary factors have been specifically linked to this variant in the available evidence
Key takeaways
- rs10517086 sits near LINC02357 (long intergenic non-coding RNA 2357) and reduces expression of the Notch pathway gene RBPJ in aortic tissue, connective tissue cells (fibroblasts), and sun-exposed skin
- RBPJ is a transcription factor - a protein that switches other genes on or off - and is the central mediator of the Notch signaling pathway, which governs cell identity, immune development, and tissue maintenance
- Large-scale GWAS have studied this locus across circulating fatty acids, blood biomarkers, body shape, thyroid health, and autoimmune diseases including rheumatoid arthritis, multiple sclerosis, IBD, and type 1 diabetes
- The GTEx tissue-expression finding is the most directly evidenced data point for this variant; phenotypic association evidence is preliminary
- No lifestyle or dietary factors have been specifically linked to this variant in the available evidence
What the research says
rs10517086 overlaps LINC02357, a genomic region transcribed into RNA but not translated into protein, whose biological role remains incompletely understood. Tissue-specific gene expression data from GTEx (953 donors, FDR < 0.05) shows the alternative allele reduces RBPJ (Recombination Signal Binding Protein for Immunoglobulin Kappa J Region) expression across aortic tissue, cultured fibroblasts, and sun-exposed lower leg skin GTEx Portal. The provided study evidence spans large-scale GWAS of circulating fatty acids (up to 239,268 European UK Biobank participants), blood and urine biomarkers (n = 363,228), allometric body-shape indices (over 400,000 participants), thyroid and reproductive health (up to 743,088 individuals), and autoimmune cross-trait analyses covering rheumatoid arthritis (RA), multiple sclerosis (MS), inflammatory bowel disease (IBD), and type 1 diabetes (T1D).
Reported associations
- RBPJ expression - aortic tissue: The alternative allele is associated with reduced RBPJ expression in aortic artery tissue (effect approximately -0.17 on a log2-normalized expression scale, FDR < 0.05, 953 donors) GTEx Portal
- RBPJ expression - cultured fibroblasts: The same allele reduces RBPJ expression in cultured fibroblasts, a standard model of connective tissue cell biology (effect approximately -0.09) GTEx Portal
- RBPJ expression - sun-exposed skin: Reduced RBPJ expression is also observed in sun-exposed lower leg skin (effect approximately -0.08) GTEx Portal
Evidence quality
The GTEx eQTL signal (FDR < 0.05, n = 953 donors) showing reduced RBPJ expression is the most directly evidenced finding for rs10517086 and is consistent across three tissue types, though effect magnitudes are modest, ranging from approximately -0.08 to -0.17 on a log2-normalized expression scale. The associated study evidence spans several major GWAS domains: circulating fatty acid traits (215 genome-wide significant loci for PUFA traits, 163 for MUFA traits, and 119 for SFA traits in up to 239,268 European participants), 35 blood and urine biomarkers (1,857 loci in n = 363,228), allometric body-shape indices (219,872 women and 186,825 men), thyroid and reproductive traits (up to 743,088 individuals), RA (31,313 cases and approximately 1 million controls), and T1D (7,514 cases and 9,045 controls). Specific p-values and per-variant effect sizes attributable to rs10517086 at the phenotypic level are not stated in the provided study excerpts. Associations beyond the RBPJ eQTL signal should therefore be considered preliminary until explicitly replicated for this locus in independent cohorts.
Tissue-specific expression effects
- RBPJ: The alternative allele is linked to reduced expression in aortic tissue, cultured fibroblasts, and sun-exposed lower leg skin; effects are not detected at FDR < 0.05 in other GTEx-tested tissues, consistent with cell-type-specific regulation of this Notch pathway transcription factor GTEx Portal
Lifestyle considerations
No lifestyle considerations on file for this variant.
Frequently asked questions
What is LINC02357?
LINC02357 stands for long intergenic non-coding RNA 2357. It is a segment of DNA that is read into RNA but not translated into protein. Its biological function is not fully characterized, though the rs10517086 variant in this region influences expression of the nearby RBPJ gene.
What does RBPJ do in the body?
RBPJ (Recombination Signal Binding Protein for Immunoglobulin Kappa J Region) is a transcription factor that acts as the primary mediator of the Notch signaling pathway. Notch signaling controls how cells differentiate, how immune cells mature, and how tissues are repaired and maintained throughout life.
What traits is rs10517086 linked to?
The most directly supported link is reduced RBPJ expression in aortic tissue, fibroblasts, and skin, based on GTEx eQTL data. This locus also appears in the research context of large-scale GWAS covering circulating fatty acids, blood biomarkers, autoimmune diseases, and body shape, though specific phenotypic effect sizes for rs10517086 are not confirmed in current sources.
Is rs10517086 related to autoimmune disease?
Large-scale cross-trait analyses have mapped shared genetic architecture across rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and type 1 diabetes, and this locus appears within those research contexts. Whether rs10517086 specifically contributes to autoimmune disease risk is not explicitly confirmed in the provided study excerpts.
How reliable is the current evidence for rs10517086?
The strongest evidence is the GTEx eQTL finding (FDR less than 0.05, 953 donors) showing reduced RBPJ expression across three tissue types, with modest effect sizes ranging from -0.08 to -0.17. Phenotypic associations come from broad population-scale GWAS, but specific per-variant effect sizes for rs10517086 are not detailed in current sources, so disease associations should be considered preliminary.