Expressive

rs12146774 (HSPB8/LINC00934): Gene Expression Variant

Key takeaways

  • rs12146774 sits in the HSPB8 heat shock protein and LINC00934 non-coding RNA region
  • The alternate allele reduces expression of a nearby gene (ENSG00000310200) specifically in spleen tissue
  • The same allele also reduces PRKAB1, a subunit of the energy-sensing AMPK enzyme, in fibroblasts
  • No disease associations have been confirmed for this specific variant in the available research

Key takeaways

  • rs12146774 sits in the HSPB8 (Heat Shock Protein Family B Member 8) and LINC00934 (a long intergenic non-coding RNA) region of the genome
  • The alternate allele reduces expression of a nearby gene (ENSG00000310200) specifically in spleen tissue
  • The same allele also reduces PRKAB1, a regulatory subunit of the energy-sensing AMPK enzyme, in cultured fibroblasts
  • No disease associations have been confirmed for this specific variant in the available research

What the research says GTEx v11 eQTL analysis (953 donors, cis-window, FDR < 0.05) links the alternate allele of rs12146774 to reduced expression of ENSG00000310200 in spleen tissue (slope −0.47, p = 8.8×10^-6) GTEx Portal. The same allele is associated with reduced PRKAB1 (AMP-activated protein kinase regulatory subunit beta-1) expression in cultured fibroblasts (slope −0.19, p = 1.6×10^-4) GTEx Portal. No genome-wide-significant disease associations for rs12146774 are reported in the available literature.

Reported associations

  • ENSG00000310200 expression (spleen): The alternate allele is associated with reduced expression in spleen tissue (slope −0.47, p = 8.8×10^-6; GTEx v11, n = 953 donors) GTEx Portal
  • PRKAB1 expression (cultured fibroblasts): The alternate allele is associated with reduced expression of PRKAB1, a regulatory beta-1 subunit of AMPK (AMP-activated protein kinase, a central cellular energy sensor), in cultured fibroblasts (slope −0.19, p = 1.6×10^-4; GTEx v11) GTEx Portal

Evidence quality All reported associations for rs12146774 derive from GTEx v11 cis-eQTL data (953 donors, FDR < 0.05 threshold applied) GTEx Portal. The ENSG00000310200 spleen effect (p = 8.8×10^-6) and the PRKAB1 fibroblast effect (p = 1.6×10^-4) both pass the FDR threshold, but neither has been independently replicated in the provided sources. The available GWAS literature, which includes a multi-institutional study of osteosarcoma (primary bone cancer) survival across 632 patients of European and Brazilian ancestry, does not list this locus among its significant findings. The evidence should therefore be considered preliminary and is limited to tissue-level expression data.

Tissue-specific expression effects

  • ENSG00000310200: The alternate allele is associated with reduced expression in spleen tissue GTEx Portal
  • PRKAB1: The alternate allele is associated with reduced expression in cultured fibroblasts GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is the HSPB8 gene?

HSPB8 (Heat Shock Protein Family B Member 8) is a small heat shock protein that helps protect cells under stress and assists in proper protein folding. LINC00934 is a long non-coding RNA located in the same chromosomal neighborhood whose precise functions are still being studied.

What does rs12146774 do?

Based on large-scale expression data, the alternate allele of rs12146774 is associated with lower expression of nearby genes in spleen tissue and lower PRKAB1 expression in cultured fibroblasts. The downstream biological consequences of these changes are not yet established.

Is rs12146774 linked to any disease?

No confirmed disease associations are reported for rs12146774 in the available research. Current evidence is limited to tissue-level gene expression effects identified in GTEx data.

What is PRKAB1 and why does it appear here?

PRKAB1 encodes a regulatory beta subunit of AMPK (AMP-activated protein kinase), a key enzyme that senses cellular energy levels and coordinates metabolic responses throughout the body. The rs12146774 alternate allele is associated with reduced PRKAB1 expression specifically in cultured fibroblasts.

What is an eQTL?

An eQTL (expression quantitative trait locus) is a genetic variant that influences how much a nearby gene is expressed in specific tissues. GTEx data identifies rs12146774 as an eQTL affecting genes in spleen and fibroblast tissue, providing a possible molecular mechanism to investigate in future disease studies.