Expressive

rs12156009 (FAM167A): Multi-tissue expression variant

Key takeaways

  • rs12156009 is a regulatory variant near FAM167A and FAM167A-AS1 that alters the activity of at least five genes across multiple tissue types.
  • The alternate allele is linked to reduced expression in immune cells, heart, and brain tissue, and increased expression in fat and connective tissue cells.
  • A nearby gene, BLK (B lymphocyte kinase), shows higher activity in fibroblasts when the alternate allele is present.
  • FAM66A, another gene at this locus, shows lower activity in blood vessel tissue with the alternate allele.
  • All eQTL effects are statistically robust (FDR < 0.05), with p-values ranging from 1.0 x 10^-20 to 3.4 x 10^-13.

Key takeaways

  • rs12156009 is a regulatory variant near FAM167A and FAM167A-AS1 that alters the activity of at least five genes across multiple tissue types.
  • The alternate allele is linked to reduced expression in immune cells, heart, and brain tissue, and increased expression in fat and connective tissue cells.
  • A nearby gene, BLK (B lymphocyte kinase), shows higher activity in fibroblasts when the alternate allele is present.
  • FAM66A, another gene at this locus, shows lower activity in blood vessel tissue with the alternate allele.
  • All eQTL effects are statistically robust (FDR < 0.05), with p-values ranging from 1.0 x 10^-20 to 3.4 x 10^-13.

What the research says GTEx v11 eQTL (expression quantitative trait locus) analysis across 953 donors identifies rs12156009 as a cis-regulatory variant associated with altered expression of at least five distinct genes spanning immune, cardiac, brain, adipose, fibroblast, and vascular tissues GTEx Portal. The alternate allele reduces expression of gene models ENSG00000255310 and ENSG00000290829 in heart atrial appendage and cerebellar brain regions respectively, while increasing expression of ENSG00000269954 in subcutaneous fat and cultured fibroblasts GTEx Portal. Named genes at this locus, FAM66A and BLK, show directionally opposite expression effects, with FAM66A reduced in tibial artery and BLK increased in fibroblasts, when the alternate allele is present GTEx Portal.

Reported associations

  • Gene expression in immune cells (ENSG00000255310): The alternate allele is associated with reduced expression in EBV-transformed lymphocytes (effect size -0.51 log2 units, p=3.4 x 10^-20) GTEx Portal.
  • Gene expression in heart (ENSG00000255310): Reduced expression in heart atrial appendage with the alternate allele (effect size -0.40 log2 units, p=3.7 x 10^-16) GTEx Portal.
  • Gene expression in cerebellar hemisphere (ENSG00000290829): Reduced expression in the cerebellar hemisphere with the alternate allele (effect size -0.57 log2 units, p=7.6 x 10^-16) GTEx Portal.
  • Gene expression in cerebellum (ENSG00000290829): Reduced expression in the cerebellum with the alternate allele (effect size -0.52 log2 units, p=3.4 x 10^-13) GTEx Portal.
  • Gene expression in adipose tissue (ENSG00000269954): Increased expression in subcutaneous adipose tissue with the alternate allele (effect size +0.38 log2 units, p=4.9 x 10^-16) GTEx Portal.
  • Gene expression in fibroblasts (ENSG00000269954): Increased expression in cultured fibroblasts with the alternate allele (effect size +0.38 log2 units, p=1.0 x 10^-20) GTEx Portal.
  • Gene expression in tibial artery (FAM66A): Reduced FAM66A expression in tibial artery with the alternate allele (effect size -0.41 log2 units, p=3.2 x 10^-17) GTEx Portal.
  • Gene expression in fibroblasts (BLK): Increased BLK expression in cultured fibroblasts with the alternate allele (effect size +0.34 log2 units, p=1.3 x 10^-17) GTEx Portal.

Evidence quality All associations reported here come from GTEx v11 eQTL analysis (953 donors, cis-window, FDR < 0.05). P-values across the eight reported tissue-gene effects range from 1.0 x 10^-20 to 3.4 x 10^-13, all well beyond standard genome-wide significance thresholds. The four studies provided as source material for this entry lack PubMed identifiers, and their available text excerpts do not explicitly name rs12156009 or the FAM167A locus; as a result, no GWAS disease-trait associations can be directly cited here. The available evidence for this variant is therefore limited to gene-expression regulation. Whether these eQTL effects translate to clinical phenotypes or disease risk remains unestablished in the available source material.

Tissue-specific expression effects

  • ENSG00000255310: Reduced expression in EBV-transformed lymphocytes and heart atrial appendage with the alternate allele GTEx Portal.
  • ENSG00000290829: Reduced expression in cerebellar hemisphere and cerebellum with the alternate allele GTEx Portal.
  • ENSG00000269954: Increased expression in subcutaneous adipose tissue and cultured fibroblasts with the alternate allele GTEx Portal.
  • FAM66A: Reduced expression in tibial artery with the alternate allele GTEx Portal.
  • BLK: Increased expression in cultured fibroblasts with the alternate allele GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What gene is rs12156009 associated with?

rs12156009 is located near FAM167A and FAM167A-AS1. GTEx eQTL data also links it to expression changes in FAM66A and BLK across nearby tissue types.

What does rs12156009 do to gene expression?

The alternate allele reduces nearby gene activity in immune cells, heart, and cerebellar brain tissue, while increasing activity in fat cells and fibroblasts. FAM66A activity drops in blood vessel tissue and BLK activity rises in fibroblasts.

Is rs12156009 linked to any diseases?

No disease associations have been established in the source studies available for this entry. Current evidence describes gene-expression effects only, which are mechanistic observations rather than clinical findings.

What is FAM167A-AS1?

FAM167A-AS1 is an antisense RNA gene adjacent to FAM167A. Antisense RNA genes are transcribed from the opposite strand of DNA and often play regulatory roles. Both genes sit near rs12156009.

Why does BLK matter in the context of rs12156009?

BLK encodes B lymphocyte kinase, an enzyme involved in B cell signaling. GTEx v11 data shows the alternate allele of rs12156009 increases BLK expression in cultured fibroblasts, pointing to a regulatory connection between this variant and immune-related gene activity.