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AGER (Advanced Glycation End-Product Specific Receptor)

Summary

AGER (Advanced Glycation End-Product Specific Receptor, also known as RAGE) is a multi-ligand transmembrane receptor of the immunoglobulin superfamily. It binds advanced glycation end-products (AGEs), S100/calgranulins, amyloid-beta, and high-mobility group box 1 (HMGB1). Genetic prediction models in OmicsPred have highlighted a robust and consistent cross-ancestry association between predicted AGER blood/plasma levels and hypothyroidism risk.

Biological Role and Disease Association

  • NF-κB Activation: Upon ligand binding, AGER activates the NF-κB signaling pathway (Reactome Pathway R-HSA-445989), which plays a key role in thyroid physiology and thyroid autoimmunity.
  • Hypothyroidism Link: Cross-omic and cross-ancestry Phenome-wide Association Studies (PheWAS) in the Million Veterans Program cohort demonstrated that genetic prediction models for AGER are consistently associated with hypothyroidism, aligning with evidence of dysregulated AGER levels in patients with Hashimoto's thyroiditis.
  • Co-regulated Genes: Other genes mapping to the same NF-κB activation pathway, including NFKB2, NFKBIA, and APP (an AGER ligand), also display significant associations with hypothyroidism.

Citations

  • Foguet, C., et al. (2026). OmicsPred as a centralised resource for genetic prediction of multi-omic traits. medRxiv preprint. DOI: 10.64898/2026.05.15.26353298. Source paper: 2026.05.15.26353298v2.full.pdf
  • Ruggeri, R. M., et al. (2020). Serum levels of advanced glycation end products (AGEs) are increased and their soluble receptor (sRAGE) reduced in Hashimoto's thyroiditis. Journal of Endocrinological Investigation, 43, 1337–1342.