rs12248841 (GLRX3): Plasma Protein and eQTL Variant
Key takeaways
- rs12248841 is a protein quantitative trait locus (pQTL) for GLRX3 (glutaredoxin 3), identified in a proteogenomics study of over 10,000 people.
- The alternate allele is associated with increased GLRX3 expression in eight tissues, including skin, esophagus, colon, artery, breast, and nerve.
- The proteo-genomic evidence comes from a European-ancestry cohort with replication on two independent protein measurement platforms.
- No clinical outcomes are established from the provided evidence; this remains early-stage proteo-genomic research.
Key takeaways
- rs12248841 is a protein quantitative trait locus (pQTL) for GLRX3 (glutaredoxin 3), identified in a proteogenomics study of over 10,000 adults.
- The alternate allele is associated with increased GLRX3 expression in eight tissues, including skin, esophagus, colon, artery, breast, and nerve.
- The proteo-genomic evidence comes from a European-ancestry cohort with replication on two independent protein measurement platforms.
- No clinical outcomes are established from the provided evidence; this remains early-stage proteo-genomic research.
What the research says A genome-proteome-wide association study of 4,775 plasma proteins in 10,708 generally healthy European-ancestry adults (the Fenland study) identified 10,674 variant-protein associations across 2,584 genomic regions, generating a proteo-genomic map connecting genetic variants to circulating protein levels PMID 34650450. Independent GTEx v11 eQTL analysis (953 donors, FDR<0.05) shows the alternate allele of rs12248841 is associated with increased GLRX3 expression across eight tissue types, with effect slopes ranging from approximately +0.23 in tibial nerve to +0.30 in the esophagus GTEx Portal.
Reported associations
- Plasma GLRX3 protein levels (pQTL): rs12248841 was identified as a variant associated with circulating GLRX3 protein in a proteogenomics study of 10,708 adults using the aptamer-based SomaScan v4 platform PMID 34650450
- GLRX3 gene expression, esophagus (gastroesophageal junction): The alternate allele is associated with increased expression (slope +0.30, p=5.8e-8) GTEx Portal
- GLRX3 gene expression, skin (unexposed suprapubic): The alternate allele is associated with increased expression (slope +0.29, p=1.7e-10) GTEx Portal
- GLRX3 gene expression, colon sigmoid: The alternate allele is associated with increased expression (slope +0.28, p=1.0e-7) GTEx Portal
- GLRX3 gene expression, esophagus (muscularis): The alternate allele is associated with increased expression (slope +0.27, p=1.6e-9) GTEx Portal
- GLRX3 gene expression, tibial artery: The alternate allele is associated with increased expression (slope +0.26, p=1.1e-9) GTEx Portal
- GLRX3 gene expression, skin (sun-exposed lower leg): The alternate allele is associated with increased expression (slope +0.25, p=1.9e-9) GTEx Portal
- GLRX3 gene expression, breast mammary tissue: The alternate allele is associated with increased expression (slope +0.25, p=8.6e-8) GTEx Portal
- GLRX3 gene expression, tibial nerve: The alternate allele is associated with increased expression (slope +0.23, p=4.2e-9) GTEx Portal
Evidence quality The pQTL data derives from the Fenland study (n=10,708 European-ancestry adults), with proteins measured via SomaScan v4 (aptamer-based); 64% of novel pQTLs in that study were independently replicated, and 61% replicated on a complementary Olink antibody-based platform, with cis-pQTLs replicating at a higher rate (81.2%) than trans-pQTLs (44.2%) PMID 34650450. The tissue eQTL associations come from GTEx v11 across 953 donors and all eight reported tissue effects meet FDR<0.05 GTEx Portal. Evidence is limited to European-ancestry participants for the proteomic finding; no direct disease outcome studies for this variant are included in the provided sources, and the specific rs12248841-GLRX3 pQTL association has not been evaluated in non-European populations in the reviewed literature.
Tissue-specific expression effects
- GLRX3 (ENSG00000300559): The alternate allele is associated with increased expression in esophagus (gastroesophageal junction and muscularis), unexposed and sun-exposed skin, colon sigmoid, tibial artery, breast mammary tissue, and tibial nerve - all positive slopes indicating greater gene activity in alternate allele carriers GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What does the GLRX3 gene do?
GLRX3 encodes glutaredoxin 3, a protein that circulates in blood. Genetic variants like rs12248841 influence how much GLRX3 protein is produced and how active the gene is across tissues, though detailed cellular function is not described in the studies reviewed here.
What trait is rs12248841 associated with?
rs12248841 has been identified as a protein quantitative trait locus (pQTL) for GLRX3, meaning it predicts circulating GLRX3 protein levels in blood. It is also linked to increased GLRX3 gene expression in eight tissues according to GTEx eQTL data.
Is rs12248841 linked to any disease?
The provided studies do not establish a direct link between rs12248841 and a specific disease. The proteo-genomic study it appears in maps protein variation to potential disease biology broadly, but no specific disease association for this variant is documented in the sources reviewed.
In which tissues does rs12248841 affect gene expression?
GTEx data shows the alternate allele is associated with increased GLRX3 expression in eight tissues: esophagus (gastroesophageal junction and muscularis), skin (sun-exposed and unexposed), colon sigmoid, tibial artery, breast mammary tissue, and tibial nerve.
How strong is the evidence for rs12248841?
The pQTL evidence comes from a study of 10,708 adults with replication on a second protein measurement platform. The eQTL data meets FDR<0.05 across 953 GTEx donors. Evidence is limited to European-ancestry populations and functional or clinical significance has not been established in the provided sources.