Expressive

rs11658899 (CEP112): Proteo-genomic Variant

Key takeaways

  • rs11658899 is a genetic variant at the CEP112 (centrosomal protein 112) gene locus, catalogued through a large-scale plasma proteomics study of 10,708 participants.
  • The ALT allele is associated with reduced CEP112 expression in subcutaneous fat tissue, based on GTEx data from 953 donors.
  • This locus is part of a proteo-genomic map linking over 10,000 variant-protein associations across nearly 5,000 proteins and 1,859 disease connections.
  • No disease outcome associations for this specific variant appear in the provided sources; evidence is at the discovery stage.

Key takeaways

  • rs11658899 is a genetic variant at the CEP112 (centrosomal protein 112) gene locus, catalogued through a large-scale plasma proteomics study of 10,708 participants.
  • The ALT allele is associated with reduced CEP112 expression in subcutaneous fat tissue, based on GTEx data from 953 donors.
  • This locus is part of a proteo-genomic map linking over 10,000 variant-protein associations across nearly 5,000 proteins and 1,859 disease connections.
  • No disease outcome associations for this specific variant appear in the provided sources; evidence is at the discovery stage.

What the research says A genome-proteome-wide association study of 10,708 generally healthy European-descent individuals from the Fenland cohort tested 10.2 million genetic variants against 4,775 plasma proteins, identifying 10,674 variant-protein associations for 3,892 protein targets and generating a proteo-genomic map of 1,859 gene-protein-disease connections PMID 34648354. Among 2,584 associated genomic regions, 1,543 were cis (within 500 kb of the protein-encoding gene), and cis-pQTLs (variants that influence plasma levels of their nearest encoded protein) showed an 81.2% directional replication rate on a complementary proteomics platform PMID 34648354. Tissue expression data from GTEx v11 independently shows the ALT allele at rs11658899 is associated with reduced CEP112 gene expression in subcutaneous adipose tissue (slope -0.26 log2-normalized units, p=9.4e-7, n=953 donors) GTEx Portal.

Reported associations

  • Plasma protein levels (cis-pQTL at the CEP112 locus): Identified in a proteo-genomic scan of 3,892 proteins in 10,708 participants that generated a map of 1,859 gene-protein-disease connections PMID 34648354.
  • CEP112 gene expression in subcutaneous adipose tissue: The ALT allele is associated with reduced expression (slope -0.26 log2-normalized units, p=9.4e-7) in 953 tissue donors GTEx Portal.

Evidence quality The proteo-genomic association derives from a single large European-ancestry cohort (n=10,708 in the Fenland study). At the study-wide level, 64% of newly discovered pQTLs replicated directionally (p<0.05) using the complementary Olink platform, with cis variants replicating at 81.2% versus 44.2% for trans variants PMID 34648354. Variant-specific replication data for rs11658899 is not described in the provided text. The GTEx eQTL (an expression-quantitative trait locus, meaning a variant that influences gene activity in a specific tissue) finding reaches a standard significance threshold (p=9.4e-7, n=953) but is limited to one tissue type. No disease endpoints or clinical outcomes are linked to this variant in the provided sources; findings should be regarded as discovery-stage.

Tissue-specific expression effects

  • CEP112: The ALT allele is associated with reduced expression in subcutaneous adipose tissue (fat just beneath the skin); no other tissue reached significance in the GTEx v11 dataset of 953 donors GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11658899?

rs11658899 is a single nucleotide variant (a one-letter change in DNA) located near the CEP112 gene. It was identified in a large proteomics study as part of an effort to map how genetic variants influence protein levels and disease biology.

What does the CEP112 gene do?

CEP112 encodes centrosomal protein 112, a protein associated with the centrosome, a cellular structure involved in organizing cell division. The provided research identifies it as a plasma proteomics target but does not describe its function in clinical detail.

Is rs11658899 linked to any disease?

No disease associations for rs11658899 are reported in the provided sources. It was identified as a protein-quantitative trait locus in a discovery study, and expression data shows a tissue-level effect in fat tissue, but no clinical outcomes have been connected.

What does it mean that rs11658899 affects gene expression in fat tissue?

GTEx data shows the ALT allele at rs11658899 is associated with lower CEP112 gene activity specifically in subcutaneous fat tissue. This is a molecular signal indicating that the variant influences how much of this gene is expressed in that tissue, not a direct health outcome.

How was rs11658899 discovered?

It was flagged in a genome-wide proteomics study that tested over 10 million genetic variants against 4,775 plasma proteins in 10,708 healthy European-ancestry participants from the Fenland cohort, as part of an effort to map genetic influences on human protein levels and disease connections.