A prevalent disease-associated SNP in the human <i>ID3</i> gene regulates E-protein activity and cellular proliferation.

ABSTRACT: The helix-loop-helix transcription factor ID3 is a critical regulator of tissue development and homeostasis. Aberrations in ID3 are strongly associated with numerous human disease processes including Burkitt's lymphoma. We previously identified that a single-nucleotide polymorphism (SNP) in ID3 at rs11574 is associated with increased vascular disease burden in three independent cohorts; however, the mechanisms by which this SNP alters ID3 function and impacts vascular cells are unknown. Here, we show that the minor allele of rs11574 specifically disrupts ID3's ability to bind the E-protein E12. Computational analysis and confirmatory biochemical experiments revealed that rs11574's effects on ID3:E12 dimerization are dependent upon a key residue within E12's unique loop domain. Funct

SUBMITTER: Henderson CA 

PROVIDER: S-EPMC12869245 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature