rs117399000 (CA10): Plasma Protein Level Variant
Key takeaways
- rs117399000 is a genetic variant linked to variation in circulating CA10 (carbonic anhydrase 10) protein levels in blood
- Three independent studies covering 3,301 to 10,708 participants identified this variant using stringent genome-wide significance thresholds
- Genetic variants affecting circulating proteins can act locally (cis) or at a distance (trans) from the protein-encoding gene
- This is preliminary proteogenomic evidence and does not establish clinical significance or disease risk
Key takeaways
- rs117399000 is a genetic variant linked to variation in circulating levels of CA10 (carbonic anhydrase 10) in blood, identified in large-scale proteogenomic studies
- Three independent studies covering 3,301 to 10,708 participants applied stringent genome-wide significance thresholds and replicated findings across independent cohorts
- Genetic variants affecting circulating proteins can act locally (cis, near the encoding gene) or at a distance (trans, far from the gene)
- This pQTL (protein quantitative trait locus) finding is preliminary and does not establish clinical significance or disease risk
What the research says
Three independent large-scale proteogenomic studies provide the evidentiary basis for the association between rs117399000 and circulating CA10 levels. A study of 5,368 individuals identified 4,035 independent genetic-protein associations spanning 2,091 serum proteins, including 36% that were previously unreported, and highlighted that circulating proteins may originate from virtually any tissue in the body, enabling system-level cross-tissue coordination PMID 35902577. A genome-proteome-wide association study in 10,708 Fenland cohort participants found 10,674 variant-protein associations across 3,892 proteins at p < 1.004 x 10^-11, with 79% of associated genomic regions linked to only a single protein target PMID 34767462. A study of 3,301 healthy INTERVAL study blood donors identified 1,927 significant associations (p < 1.5 x 10^-11) spanning 1,478 proteins and 764 genomic regions, with 88 pQTL regions overlapping established disease susceptibility loci PMID 29875488.
Reported associations
- Circulating CA10 protein levels: Identified as a pQTL for CA10 in a proteogenomic study of 5,368 individuals covering 2,091 serum proteins; specific effect size not reported in available excerpts PMID 35902577
- Circulating CA10 protein levels: Identified in a genome-proteome-wide association study of 10,708 Fenland cohort participants covering 3,892 plasma proteins at p < 1.004 x 10^-11 PMID 34767462
- Circulating CA10 protein levels: Identified in a study of 3,301 healthy INTERVAL study blood donors covering 1,478 proteins at p < 1.5 x 10^-11 PMID 29875488
Evidence quality
The three contributing studies range from 3,301 to 10,708 participants of European descent and each applied stringent genome-wide significance thresholds. Sun et al. replicated 65% of pQTLs overall in 4,998 additional individuals, with replication rates of 81% for cis-acting and 52% for trans-acting associations PMID 29875488. Pietzner et al. replicated 81% of cis-pQTLs and 64% of novel associations using a complementary Olink antibody-based protein assay PMID 34767462. Gudjonsson et al. found 36% of their 4,035 associations were previously unreported in 5,368 individuals PMID 35902577. Specific effect sizes, p-values, and cis-versus-trans classification for rs117399000 are not reported in the available excerpts, limiting characterization of the strength and directionality of this specific association. All three studies recruited primarily European-descent participants, limiting generalizability across ancestral backgrounds.
Lifestyle considerations
No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs117399000?
rs117399000 is a common point of variation in the human DNA sequence (a SNP, or single nucleotide polymorphism) linked to variation in circulating levels of the CA10 protein in blood. It was identified in large-scale studies that simultaneously mapped genetic influences on thousands of circulating proteins.
What is CA10?
CA10 is carbonic anhydrase 10, a protein that circulates in blood. Large-scale proteogenomic research has shown that circulating proteins like CA10 may originate from various tissues and participate in cross-tissue biological communication, though the specific functions of CA10 are not detailed in the available study excerpts.
Is rs117399000 linked to any disease?
The available evidence links rs117399000 to CA10 protein levels, not directly to a disease. Large-scale proteogenomic studies have found that 88 variant regions overlap with known disease susceptibility loci, but no specific disease association is established for rs117399000 in the available evidence.
What is a pQTL and why does it matter?
A protein quantitative trait locus (pQTL) is a genetic variant statistically associated with differences in how much of a specific protein circulates in blood. Identifying pQTLs helps researchers connect genetic variation to protein biology and potentially to disease mechanisms or therapeutic targets.
How large and reliable are the studies behind this variant?
Three studies enrolled 3,301 to 10,708 participants of European descent and each applied stringent genome-wide thresholds. Replication rates reached 81% for cis-acting variants across independent cohorts and complementary protein assay platforms, supporting the reliability of the general pQTL approach.