rs111564639 (ITGA3/PDK2): Plasma Protein pQTL
Key takeaways
- A proteo-genomic study of 10,708 participants identified rs111564639 as a variant linked to plasma protein levels at the ITGA3-PDK2 locus.
- Carriers of the alternate allele show increased expression of a gene (ENSG00000275025) in thyroid tissue.
- The alternate allele is also linked to reduced expression of SLC35B1, a solute carrier gene, in esophageal tissue.
- All current evidence comes from one large European-ancestry study; replication in independent cohorts has not been reported.
Key takeaways
- A proteo-genomic study of 10,708 participants identified rs111564639 as a variant linked to plasma protein levels at the ITGA3-PDK2 locus.
- Carriers of the alternate allele show increased expression of a gene (ENSG00000275025) in thyroid tissue.
- The alternate allele is also linked to reduced expression of SLC35B1, a solute carrier gene, in esophageal tissue at the gastroesophageal junction.
- All current evidence comes from one large European-ancestry study; replication in independent cohorts or other ancestries has not been reported.
What the research says A genome-proteome-wide association analysis in 10,708 generally healthy European-descent participants from the Fenland study tested 10.2 million autosomal and X-chromosomal variants against 4,775 distinct plasma protein targets, identifying 10,674 variant-protein associations including signals at this locus. The study established a cis-anchored proteo-genomic map of 1,859 gene-protein-disease connections, with cis-protein quantitative trait loci (pQTLs, variants located near the protein-encoding gene) showing higher platform replication rates (81.2%) than trans-pQTLs (44.2%). GTEx expression data (953 donors, FDR<0.05) links the alternate allele of rs111564639 to altered expression of two genes in distinct tissues GTEx Portal.
Reported associations
- Plasma protein levels (pQTL): rs111564639 at this locus was detected in a proteo-genomic scan of 4,775 plasma proteins across 10,708 European-descent adults from the Fenland study, which identified 10,674 variant-protein associations overall.
- Thyroid tissue gene expression (eQTL): The alternate allele is associated with increased expression of ENSG00000275025 in thyroid tissue (p=1.7e-8) GTEx Portal.
- Esophageal tissue gene expression (eQTL): The alternate allele is associated with reduced expression of SLC35B1 (a solute carrier involved in sugar-nucleotide transport) in esophagus gastroesophageal junction tissue (p=4.3e-6) GTEx Portal.
Evidence quality The protein-association evidence for rs111564639 comes from a single large study of 10,708 European-descent adults (Fenland study), with associations tested at a genome-wide threshold of p<1.004x10^-11. The study reported that 64% of novel pQTLs validated on a complementary Olink antibody-based platform, with cis-pQTLs replicating at 81.2% versus 44.2% for trans-pQTLs. Specific replication data for this variant are not available in the provided sources. The exclusively European-descent sample limits generalizability to other ancestry groups. The GTEx eQTL signals at this locus (p=1.7e-8 for thyroid; p=4.3e-6 for esophageal junction) provide corroborating evidence of functional gene-regulatory effects, derived from 953 donors at FDR<0.05 GTEx Portal. Overall, evidence is preliminary for this specific variant pending targeted replication.
Tissue-specific expression effects
- ENSG00000275025: The alternate allele is associated with increased expression in thyroid tissue GTEx Portal.
- SLC35B1: The alternate allele is associated with reduced expression in the esophagus (gastroesophageal junction) GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs111564639?
rs111564639 is a genetic variant located at the ITGA3-PDK2 locus. It was identified in a large plasma proteomics study as a protein-quantitative trait locus (pQTL), meaning it is associated with differences in circulating protein levels measured in blood.
What genes are near rs111564639?
rs111564639 lies at a genomic region designated ITGA3-PDK2. ITGA3 encodes integrin subunit alpha 3, a protein involved in cell adhesion and signaling, while PDK2 encodes pyruvate dehydrogenase kinase 2, an enzyme that regulates energy metabolism in mitochondria.
What is a protein-quantitative trait locus or pQTL?
A pQTL is a genetic location where a variant is statistically associated with differences in the measured levels of one or more proteins in blood. Studying pQTLs helps researchers understand how genetic variation influences protein production and may connect genes to disease biology.
Does rs111564639 affect gene expression?
Yes. GTEx data from 953 donors show the alternate allele of rs111564639 is associated with increased expression of a gene (ENSG00000275025) in thyroid tissue and reduced expression of SLC35B1 in the esophagus at the gastroesophageal junction. These are tissue-specific regulatory effects, not clinical outcomes.
How strong is the evidence for rs111564639?
The proteo-genomic evidence comes from a single study of 10,708 European-descent adults, with associations tested at a stringent genome-wide threshold. Independent replication specific to this variant has not been reported in the available sources, so the evidence is currently considered preliminary.