Expressive

rs11625099 (STYX): liver pQTL and multi-tissue eQTL

Key takeaways

  • rs11625099 was identified as a protein-level variant (pQTL) linked to STYX expression in a study of 287 human liver samples
  • GTEx data from 953 donors shows this variant increases expression of ENSG00000285664 in six tissue types including spleen, testis, skin, lung, and adipose tissue
  • The variant reduces GNPNAT1 expression specifically in liver tissue
  • Protein-level variants like this one are often undetectable by standard mRNA-based genetic studies, pointing to post-transcriptional regulation
  • No drug response or lifestyle associations are documented in the current evidence

Key takeaways

  • rs11625099 was identified as a protein-level variant (pQTL) linked to STYX expression in a study of 287 human liver samples
  • GTEx data from 953 donors shows this variant increases expression of ENSG00000285664 in six tissue types including spleen, testis, skin, lung, and adipose tissue
  • The variant reduces GNPNAT1 expression specifically in liver tissue
  • Protein-level variants like this one are often undetectable by standard mRNA-based genetic studies, pointing to post-transcriptional regulation
  • No drug response or lifestyle associations are documented in the current evidence

What the research says A genome-wide pQTL (protein quantitative trait locus, meaning a genetic variant statistically linked to differences in protein abundance) study conducted in 287 normal human liver samples identified rs11625099 as a variant associated with STYX protein expression; the study used a data-independent acquisition total protein approach (DIA-TPA), a high-throughput mass spectrometry method for absolute protein quantification, and identified 900 local and 4,026 distant pQTL variants, of which over 2,000 were not reported in prior mRNA-level eQTL studies, suggesting extensive post-transcriptional regulation in the liver. GTEx v11 eQTL data from 953 donors independently links rs11625099 to expression changes in three genes, including STYX and GNPNAT1, across eight tissue and cell types GTEx Portal.

Reported associations

  • STYX protein expression (liver, pQTL): rs11625099 was identified in a liver proteomics study of 287 samples as a pQTL variant associated with STYX protein expression
  • STYX expression in cultured fibroblasts (eQTL): this variant is associated with increased STYX expression in cultured fibroblasts (log2-normalized slope +0.21, p=1.3e-23) GTEx Portal
  • ENSG00000285664 expression (multi-tissue eQTL): this variant is associated with increased expression of gene ENSG00000285664 in spleen (slope +0.67, p=1.3e-16), testis (+0.53, p=1.2e-20), non-sun-exposed suprapubic skin (+0.43, p=2.7e-18), subcutaneous adipose tissue (+0.39, p=1.2e-18), lung (+0.37, p=2.5e-14), and sun-exposed lower-leg skin (+0.34, p=8.8e-15) GTEx Portal
  • GNPNAT1 expression (liver, eQTL): this variant is associated with reduced GNPNAT1 expression in liver tissue (slope -0.33, p=3.3e-17) GTEx Portal

Evidence quality The pQTL association with STYX protein expression in liver derives from a single study of 287 samples using high-throughput mass spectrometry; independent replication of this specific variant has not been reported in the sources provided. The GTEx eQTL associations are based on 953 donors across multiple tissue types, all at FDR<0.05, providing robust statistical support for the tissue-specific expression effects. Both pQTL and eQTL findings are statistical associations between genotype and expression levels and do not on their own establish functional mechanisms or clinical significance. No conflicting findings are reported in the available sources.

Tissue-specific expression effects

  • ENSG00000285664: increased expression in spleen, testis, non-sun-exposed skin, subcutaneous adipose tissue, lung, and sun-exposed skin GTEx Portal
  • GNPNAT1: reduced expression in liver tissue GTEx Portal
  • STYX: increased expression in cultured fibroblasts GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11625099?

rs11625099 is a genetic variant located near the STYX gene. It has been identified as a protein quantitative trait locus (pQTL) in human liver tissue and is associated with gene expression changes in multiple tissues including spleen, testis, skin, lung, and fibroblasts.

What is a pQTL and how is it different from an eQTL?

A pQTL (protein quantitative trait locus) is a genetic variant linked to differences in protein abundance, measured directly by proteomics. An eQTL (expression quantitative trait locus) is linked to differences in mRNA levels. Research shows thousands of pQTL variants do not overlap with eQTLs, meaning many genetic effects on protein expression are invisible to mRNA-only studies.

Which tissues does rs11625099 affect gene expression in?

GTEx v11 eQTL data from 953 donors links rs11625099 to expression changes in eight tissue types: spleen, testis, non-sun-exposed skin, subcutaneous adipose tissue, lung, sun-exposed skin, liver, and cultured fibroblasts.

Is rs11625099 linked to any diseases?

The available evidence does not link rs11625099 to any specific disease. The liver pQTL study noted that pQTL variants broadly were analyzed in the context of liver disease trait associations, but no disease association specific to this variant was reported in the sources reviewed.

What genes does rs11625099 affect?

Based on the studies reviewed, rs11625099 is associated with STYX protein expression in liver and STYX mRNA expression in cultured fibroblasts. It also reduces GNPNAT1 expression in liver and increases expression of gene ENSG00000285664 across spleen, testis, skin, lung, and adipose tissue.