Expressive

rs11869286 (STARD3): Heart and immune eQTL variant

Key takeaways

  • rs11869286 reduces PGAP3 expression in both the left ventricle and heart atrial appendage, per GTEx v11 data from 953 donors
  • The same variant reduces ORMDL3 expression in immune cells - ORMDL3 resides in one of the most-replicated asthma susceptibility regions on chromosome 17
  • STARD3 expression in cultured fibroblasts is reduced by this variant
  • PPP1R1B expression is increased in esophageal tissue by this variant
  • No direct GWAS disease associations for rs11869286 are reported in the studies reviewed

Key takeaways

  • rs11869286 reduces PGAP3 expression in both the left ventricle and heart atrial appendage, per GTEx v11 data from 953 donors
  • The same variant reduces ORMDL3 expression in immune cells - ORMDL3 resides in one of the most-replicated asthma susceptibility regions on chromosome 17
  • STARD3 expression in cultured fibroblasts is reduced by this variant
  • PPP1R1B expression is increased in esophageal tissue by this variant
  • No direct GWAS disease associations for rs11869286 are reported in the studies reviewed

What the research says GTEx v11 (953 donors, FDR < 0.05) identifies rs11869286 as a cis-eQTL - a variant that alters the activity level of nearby genes - for four genes at the 17q12-21 locus (STARD3 / PGAP3 / ORMDL3 / PPP1R1B): the ALT allele reduces STARD3 expression in cultured fibroblasts, reduces PGAP3 expression in pituitary, both heart chambers, thyroid, and stomach, reduces ORMDL3 expression in EBV-transformed lymphocytes, and increases PPP1R1B expression in esophageal mucosa GTEx Portal. A 2025 genome-wide meta-analysis of asthma (n = 71,481) and chronic rhinosinusitis with nasal polyposis (CRSwNP, n = 9,626) across FinnGen and UK Biobank (685,602 controls) confirmed that the GSDMB/ORMDL3 segment of 17q21 is an established asthma susceptibility locus, providing biological context for the observed ORMDL3 expression effect at this locus.

Reported associations

  • Gene expression - STARD3 (cultured fibroblasts): ALT allele reduces expression (slope -0.36, p = 8.0e-37) GTEx Portal
  • Gene expression - PGAP3 (pituitary): ALT allele reduces expression (slope -0.48, p = 3.5e-24), the largest per-tissue magnitude for this gene across the tissues examined GTEx Portal
  • Gene expression - PGAP3 (heart atrial appendage): ALT allele reduces expression (slope -0.36, p = 1.0e-30) GTEx Portal
  • Gene expression - PGAP3 (heart left ventricle): ALT allele reduces expression (slope -0.31, p = 7.8e-26) GTEx Portal
  • Gene expression - PGAP3 (thyroid): ALT allele reduces expression (slope -0.26, p = 2.2e-30) GTEx Portal
  • Gene expression - PGAP3 (stomach): ALT allele reduces expression (slope -0.26, p = 6.5e-32) GTEx Portal
  • Gene expression - ORMDL3 (EBV-transformed lymphocytes): ALT allele reduces expression (slope -0.50, p = 5.1e-17) GTEx Portal
  • Gene expression - PPP1R1B (esophageal mucosa): ALT allele increases expression (slope +0.33, p = 3.2e-23) GTEx Portal

Evidence quality All reported associations are tissue-specific eQTL findings from GTEx v11 (953 donors), each passing FDR < 0.05 GTEx Portal. No study in the provided literature reports a direct GWAS association between rs11869286 and any clinical trait or disease outcome. The ORMDL3/GSDMB asthma locus at 17q21 is among the best-replicated findings in human respiratory genetics, confirmed in a FinnGen/UK Biobank meta-analysis of 131 genomic associations across asthma and CRSwNP. The functional significance of PGAP3 reduction across cardiac and other tissues, ORMDL3 reduction in lymphocytes, and PPP1R1B increase in esophageal mucosa for clinical outcomes has not been established for this specific variant in the studies provided. Evidence for rs11869286 should be considered preliminary, resting on gene expression data without direct phenotypic outcome data from the sources reviewed.

Tissue-specific expression effects

  • STARD3: Reduced expression in cultured fibroblasts; the ALT allele consistently lowers levels in this cell type GTEx Portal
  • PGAP3: Reduced expression across a broad range of tissues - pituitary, heart atrial appendage, left ventricle, thyroid, and stomach; PGAP3 shows the widest tissue distribution of the four genes affected at this locus, with the pituitary showing the largest reduction GTEx Portal
  • ORMDL3: Reduced expression in EBV-transformed lymphocytes; ORMDL3 is located within the 17q21 region confirmed as an asthma susceptibility locus in large genome-wide studies GTEx Portal
  • PPP1R1B: Increased expression in esophageal mucosa, making it the only gene at this locus with a positive eQTL slope in the tissues examined GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Bloodwork

  • HDL cholesterol Moderate

    This variant is significantly associated with HDL cholesterol levels in large population studies

    Annual lipid panel including HDL-C measurement

Frequently asked questions

What gene is rs11869286 near?

rs11869286 is located near STARD3 on chromosome 17. GTEx data shows it also affects expression of three other nearby genes: PGAP3, ORMDL3, and PPP1R1B, in different tissues.

Is rs11869286 linked to asthma?

rs11869286 reduces expression of ORMDL3 in immune cells, and ORMDL3 sits within the 17q21 region confirmed as a major asthma susceptibility locus in large genome-wide studies. However, rs11869286 itself has not been reported as a direct GWAS hit for asthma in the studies reviewed.

What does rs11869286 do to gene expression in the heart?

According to GTEx v11 data from 953 donors, rs11869286 reduces PGAP3 expression in both the heart atrial appendage (slope -0.36) and left ventricle (slope -0.31). Whether this is relevant to cardiac health has not been established for this specific variant in the studies reviewed.

What is a cis-eQTL?

A cis-eQTL is a genetic variant that influences how much a nearby gene is expressed in cells or tissues. rs11869286 is a cis-eQTL that lowers STARD3, PGAP3, and ORMDL3 expression and raises PPP1R1B expression, depending on the tissue.

How strong is the current evidence for rs11869286?

Evidence is limited to tissue-level gene expression data from GTEx v11 (953 donors), with all associations passing FDR < 0.05. No large-scale GWAS has directly linked rs11869286 to a clinical disease outcome in the studies reviewed, so evidence should be considered preliminary.