Expressive

rs11074934 (CIITA): immune gene expression variant

Key takeaways

  • rs11074934 is a regulatory variant for CIITA with expression effects confirmed at genome-wide significance across four tissue types.
  • The alternate allele increases CIITA expression in subcutaneous fat, breast tissue, and skeletal muscle, but reduces it in cultured fibroblasts.
  • Two neighboring genes show strongly reduced expression in spleen and EBV-transformed lymphocyte cell lines in carriers of the alternate allele.
  • No direct clinical disease associations for this variant appear in the provided studies; these expression effects reflect gene regulation, not confirmed health outcomes.

Key takeaways

  • rs11074934 is a regulatory variant for the CIITA gene, with expression effects confirmed at genome-wide significance across four tissue types.
  • The alternate allele increases CIITA expression in subcutaneous fat, breast tissue, and skeletal muscle, but reduces it in cultured fibroblasts.
  • Two neighboring genes (Ensembl IDs ENSG00000262488 and ENSG00000302410) show strongly reduced expression in spleen and EBV-transformed lymphocyte cell lines in carriers of the alternate allele.
  • No direct clinical disease associations for this variant appear in the provided studies; these expression effects reflect potential regulatory mechanisms, not confirmed health outcomes.

What the research says GTEx v11 analysis of 953 donors (FDR < 0.05, a threshold controlling the proportion of false-positive findings among significant results) identifies rs11074934 as a significant cis-eQTL (a variant that alters how much a nearby gene is expressed) for CIITA across four tissues: the alternate allele increases expression in subcutaneous adipose tissue (slope +0.21, p = 5.4 x 10^-10), breast mammary tissue (slope +0.16, p = 3.9 x 10^-6), and skeletal muscle (slope +0.15, p = 2.6 x 10^-5), while reducing it in cultured fibroblasts (slope -0.18, p = 1.1 x 10^-7) GTEx Portal. The variant is also associated with reduced expression of two neighboring genes, ENSG00000262488 and ENSG00000302410 (Ensembl database identifiers for genes in this chromosomal region), in spleen (slopes -0.65 and -0.55, p = 1.0 x 10^-20 and 4.8 x 10^-13 respectively) and EBV-transformed lymphocyte cell lines (immune cells maintained in laboratory culture; slopes -0.38 and -0.35, p = 2.9 x 10^-9 and 2.2 x 10^-6) GTEx Portal.

Reported associations

  • CIITA expression (subcutaneous adipose tissue): The alternate allele is associated with increased expression (slope +0.21, p = 5.4 x 10^-10) GTEx Portal
  • CIITA expression (breast mammary tissue): The alternate allele is associated with increased expression (slope +0.16, p = 3.9 x 10^-6) GTEx Portal
  • CIITA expression (skeletal muscle): The alternate allele is associated with increased expression (slope +0.15, p = 2.6 x 10^-5) GTEx Portal
  • CIITA expression (cultured fibroblasts): The alternate allele is associated with reduced expression (slope -0.18, p = 1.1 x 10^-7) GTEx Portal
  • ENSG00000262488 expression (spleen): The alternate allele is associated with strongly reduced expression (slope -0.65, p = 1.0 x 10^-20) GTEx Portal
  • ENSG00000262488 expression (EBV-transformed lymphocytes): The alternate allele is associated with reduced expression (slope -0.38, p = 2.9 x 10^-9) GTEx Portal
  • ENSG00000302410 expression (spleen): The alternate allele is associated with strongly reduced expression (slope -0.55, p = 4.8 x 10^-13) GTEx Portal
  • ENSG00000302410 expression (EBV-transformed lymphocytes): The alternate allele is associated with reduced expression (slope -0.35, p = 2.2 x 10^-6) GTEx Portal

Evidence quality All associations for rs11074934 derive from GTEx v11 eQTL analysis (953 donors, cis-window, FDR < 0.05) GTEx Portal. The strongest signal is reduced ENSG00000262488 expression in spleen (p = 1.0 x 10^-20); all eight eQTL associations are highly significant, with effect sizes (log2-normalized expression slopes, where each unit corresponds to a twofold change in expression) ranging from -0.65 to +0.21 GTEx Portal. Neither of the two accompanying GWAS papers (one assessing 731 immune-cell traits in 3,757 Sardinians and one modeling the genomic architecture of adiposity across the lifespan) specifically reports rs11074934, so clinical disease associations are absent and all findings here should be treated as preliminary expression-mechanism evidence only.

Tissue-specific expression effects

  • CIITA: Increased expression in subcutaneous adipose tissue, breast mammary tissue, and skeletal muscle; reduced expression in cultured fibroblasts. The alternate allele shows opposite directional effects on this locus depending on tissue context GTEx Portal
  • ENSG00000262488: Reduced expression in both spleen and EBV-transformed lymphocyte cell lines, with the spleen signal among the strongest eQTL effects for this variant (p = 1.0 x 10^-20) GTEx Portal
  • ENSG00000302410: Reduced expression in both spleen and EBV-transformed lymphocyte cell lines GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What does rs11074934 do?

rs11074934 is a regulatory genetic variant that influences how much the CIITA gene is expressed in different tissues. Depending on the tissue type, it can either increase or decrease how active CIITA is.

Which tissues does rs11074934 affect?

GTEx data shows effects in subcutaneous adipose tissue, breast mammary tissue, skeletal muscle, cultured fibroblasts, spleen, and EBV-transformed lymphocyte cell lines. CIITA expression increases in fat and muscle but decreases in fibroblasts.

Is rs11074934 linked to autoimmune disease?

The provided studies do not report a direct link to autoimmune disease. The variant affects gene expression in immune-relevant tissues such as spleen and lymphocyte cell lines, but whether this translates to disease risk has not been established in the available evidence.

What is CIITA?

CIITA is a gene whose expression level varies considerably by tissue type, as shown by GTEx data for rs11074934. This variant acts as a regulatory switch for the gene, altering how much of it is produced in tissues ranging from adipose to immune-related cells.

What other genes does rs11074934 affect besides CIITA?

GTEx data shows it also affects two neighboring genes identified as ENSG00000262488 and ENSG00000302410. Both show reduced expression in spleen and lymphocyte cell lines in carriers of the alternate allele.