Expressive

rs117005178 (BCL2L12): Tissue Expression Variant

Key takeaways

  • rs117005178 sits in the BCL2L12 gene, which encodes a protein involved in regulating programmed cell death.
  • The alternate allele reduces FCGRT (an immune antibody-recycling gene) expression in nerve, colon, esophagus, and skin.
  • The same allele increases RCN3 expression in the pituitary and arteries but decreases it in whole blood, showing opposite tissue-specific effects.
  • This allele is also linked to increased CPT1C expression, a fatty acid transport gene, in subcutaneous fat.
  • Evidence is limited to gene expression associations; no clinical outcome links are reported in the provided sources.

Key takeaways

  • rs117005178 sits in the BCL2L12 (BCL2-Like 12) gene, which encodes a protein involved in regulating programmed cell death (apoptosis).
  • The alternate allele reduces expression of FCGRT (the neonatal Fc receptor gene, which recycles IgG antibodies and albumin) in nerve, colon, esophagus, and skin.
  • The same allele increases RCN3 (a calcium-binding protein inside cells) expression in the pituitary and tibial artery but decreases it in whole blood, showing tissue-specific opposite effects.
  • This allele is also linked to increased expression of CPT1C, a fatty acid transport gene, in subcutaneous adipose tissue.
  • Evidence is limited to gene expression data from GTEx; no clinical outcome associations are reported in the provided sources.

What the research says A systematic genome-wide association study of 35 blood and urine biomarkers in UK Biobank participants (n=363,228) identified 1,857 genomic loci containing 3,374 fine-mapped associations with laboratory measurements, providing population-scale context for variants in the BCL2L12 region. GTEx v11 expression data from 953 donors identify rs117005178 as a significant expression quantitative trait locus (eQTL) for three neighboring genes, with the strongest individual signals being reduced FCGRT expression in tibial nerve (p=6.3e-12) and reduced RCN3 expression in whole blood (p=8.5e-13) GTEx Portal. RCN3 shows directionally opposite effects depending on tissue, increasing in the pituitary and tibial artery while decreasing in whole blood, underscoring that expression effects at this locus are tissue-context dependent rather than uniform GTEx Portal.

Reported associations

  • FCGRT expression in nerve, gut, and skin: The alternate allele is linked to reduced expression of FCGRT, the neonatal Fc receptor gene (which salvages IgG antibodies and albumin from degradation), in tibial nerve (slope -0.42, p=6.3e-12), esophageal gastroesophageal junction (slope -0.38, p=2.2e-8), transverse colon (slope -0.31, p=6.2e-7), and non-sun-exposed suprapubic skin (slope -0.29, p=1.8e-6) GTEx Portal.
  • RCN3 expression in pituitary and vasculature (increased): The alternate allele is linked to increased expression of RCN3 (reticulocalbin-3, a calcium-binding protein in the endoplasmic reticulum) in the pituitary gland (slope +0.78, p=1.1e-6) and tibial artery (slope +0.37, p=1.0e-11) GTEx Portal.
  • RCN3 expression in whole blood (decreased): The same alternate allele is linked to reduced RCN3 expression in whole blood (slope -0.34, p=8.5e-13), directionally opposite to the pituitary and arterial effects listed above GTEx Portal.
  • CPT1C expression in subcutaneous adipose: The alternate allele is linked to increased expression of CPT1C (carnitine palmitoyltransferase 1C, an enzyme that shuttles long-chain fatty acids into mitochondria for energy production) in subcutaneous adipose tissue (slope +0.50, p=8.7e-7) GTEx Portal.
  • Blood and urine biomarkers (UK Biobank): A systematic GWAS of 35 laboratory measurements in UK Biobank participants (meta-analysis n=355,891) identified 1,857 associated loci genome-wide; specific association statistics for rs117005178 are not detailed in the available study text.

Evidence quality All quantitative association evidence for rs117005178 comes from GTEx v11 eQTL data (953 donors), a systematically collected, multi-tissue expression atlas. Reported p-values range from 6.3e-12 (FCGRT in tibial nerve) to 8.7e-7 (CPT1C in subcutaneous adipose), all meeting the FDR < 0.05 threshold applied by GTEx v11. The directionally opposite RCN3 effects between whole blood (decreased) and pituitary or tibial artery (increased) reflect tissue-specific regulatory architecture and are not contradictory; they are a finding in their own right about how this locus acts differently across cell types. The UK Biobank biomarker GWAS (n=363,228) is included as a large-cohort framework for the genomic region, but specific association statistics for rs117005178 are not available in the provided excerpt, limiting any interpretation of clinical trait links. No replication studies, clinical outcome data, ClinVar classifications, or pharmacogenomic annotations are present in the provided sources; the evidence base is preliminary and confined to expression-level effects.

Tissue-specific expression effects

  • FCGRT: The alternate allele is linked to reduced expression of this neonatal Fc receptor gene across four tissues: tibial nerve, esophageal gastroesophageal junction, transverse colon, and non-sun-exposed suprapubic skin GTEx Portal.
  • RCN3: The alternate allele is linked to increased expression of this calcium-binding endoplasmic reticulum protein in the pituitary gland and tibial artery, but reduced expression in whole blood, showing directionally opposite tissue-specific effects GTEx Portal.
  • CPT1C: The alternate allele is linked to increased expression of this mitochondrial fatty acid transport enzyme in subcutaneous adipose tissue GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs117005178?

rs117005178 is a single nucleotide variant located in the BCL2L12 gene, which encodes a protein in the BCL-2 family that helps regulate apoptosis (programmed cell death). GTEx expression data show it influences the activity of several neighboring genes across multiple tissues.

What gene is rs117005178 in?

rs117005178 is located in BCL2L12 (BCL2-Like 12). The variant also has measurable effects on the expression of neighboring genes FCGRT, RCN3, and CPT1C in various tissues, based on GTEx eQTL data.

Is rs117005178 linked to any disease or health condition?

No disease associations for rs117005178 are reported in the provided studies. The variant is documented in the context of a large UK Biobank biomarker study and shows gene expression associations, but no clinical outcome links are established in the available sources.

What does the FCGRT gene do and why might expression changes matter?

FCGRT encodes the neonatal Fc receptor, a protein that salvages IgG antibodies and albumin from being broken down, extending how long they circulate in the body. Reduced FCGRT expression in tissues like tibial nerve and colon, as linked to the alternate allele of rs117005178, is a mechanistic finding; the functional consequences of this tissue-level reduction have not been established in the provided sources.

Why does rs117005178 have opposite effects on RCN3 in blood versus arteries?

GTEx eQTL data show the same alternate allele increases RCN3 expression in the pituitary and tibial artery while decreasing it in whole blood. This reflects tissue-specific regulatory differences, such as variation in chromatin state or transcription factor activity across cell types, and is a notable finding about the locus rather than a contradiction in the data.