rs12128607 (PRG4): Serum Protein and Brain eQTL

Key takeaways

• rs12128607 sits near the PRG4 gene and was identified as a serum protein variant in a genome-wide proteogenomic study of 5,368 individuals
• The alternate allele raises expression of PDC-AS1 in the putamen and caudate, two basal ganglia regions of the brain
• The same alternate allele lowers expression of ODR4 across six tissues: spinal cord (cervical), cerebellum, nucleus accumbens, anterior cingulate cortex, frontal cortex, and pituitary gland
• The serum protein finding comes from a single study and has not been independently confirmed in the available literature
• Brain and spinal cord eQTL effects are consistent across multiple sites but describe regulatory associations, not established disease outcomes

What the research says A genome-wide proteogenomic study (linking genetic variants to measured protein levels) in 5,368 individuals identified 4,035 independent associations between genetic variants and 2,091 serum proteins, of which 36% were previously unreported, and rs12128607 is among the variant-protein associations for circulating PRG4. The study noted that most genetic signals acted on a single protein, while a subset showed highly pleiotropic (multi-target) effects across multiple proteins, with protein-level variation reflecting properties like tissue specificity and network position. Tissue-specific eQTL (expression quantitative trait loci, meaning genetic effects on gene transcript levels) data from GTEx v11 (953 donors, FDR below 0.05, a standard false discovery rate threshold) further links the alternate allele at this locus to increased expression of PDC-AS1 in brain basal ganglia and reduced expression of ODR4 across multiple central nervous system regions and pituitary tissue GTEx Portal.

Reported associations

• Serum PRG4 protein levels: identified as a variant-protein association (pQTL, or protein quantitative trait locus) in a proteogenomic GWAS of 5,368 individuals that mapped 4,035 independent pQTLs across 2,091 serum proteins
• PDC-AS1 expression (brain basal ganglia): the alternate allele is linked to increased expression in the putamen (p=1.4e-7) and caudate (p=1.9e-6) GTEx Portal
• ODR4 expression (brain, spinal cord, pituitary): the alternate allele is linked to reduced expression in the spinal cord cervical c-1 (p=2.2e-6), cerebellar hemisphere (p=2.6e-7), nucleus accumbens basal ganglia (p=2.2e-6), anterior cingulate cortex BA24 (p=3.2e-7), frontal cortex BA9 (p=7.0e-8), and pituitary (p=2.0e-7) GTEx Portal

Evidence quality The serum protein association is drawn from a single large-scale study of 5,368 individuals that surveyed 2,091 serum proteins and mapped 4,035 independent pQTL associations, 36% of which were novel at the time. No PMID is recorded in the available study metadata, and independent replication of the rs12128607-PRG4 serum association is not documented in the provided materials. The GTEx eQTL signals for PDC-AS1 span two brain regions (p=1.4e-7 and p=1.9e-6), while ODR4 signals span six tissues with p values ranging from 7.0e-8 to 2.2e-6, all in 953 donors and all meeting the FDR<0.05 threshold. The consistency of the ODR4 signal across anatomically diverse central nervous system sites supports it as a robust regulatory effect, though eQTL data describes mechanism rather than clinical outcome.

Tissue-specific expression effects

• PDC-AS1: increased expression in the brain putamen (basal ganglia) and caudate (basal ganglia); the alternate allele drives higher transcript levels in both regions GTEx Portal
• ODR4: reduced expression across the spinal cord (cervical), cerebellar hemisphere, nucleus accumbens (basal ganglia), anterior cingulate cortex (BA24), frontal cortex (BA9), and pituitary gland; the alternate allele is associated with decreased transcript levels at all six sites GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.