axn2

axn2, also known as AXIN2 or axis inhibition protein 2, is a cytoplasmic scaffold protein that participates in the canonical Wnt/β-catenin signaling pathway. It is a member of the Axin gene family and is conserved across vertebrates.

AXIN2 functions as part of the β-catenin destruction complex, together with APC, GSK3β, and other factors. It promotes phosphorylation and degradation of β-catenin, thereby repressing Wnt target gene expression in the absence of a Wnt signal. Wnt signaling in turn increases AXIN2 transcription via TCF/LEF factors, creating a negative feedback loop that helps terminate signaling.

In terms of structure and interactions, Axin proteins typically contain an N-terminal RGS-like domain and a C-terminal DIX domain that mediate oligomerization and interactions with other pathway components. AXIN2 interacts with APC, GSK3β, β-catenin, and Dishevelled, among others, enabling it to organize and regulate the destruction complex.

Clinical significance of AXIN2 includes associations between germline variants and oligodontia, a congenital tooth agenesis condition, as well as links to increased colorectal cancer risk in some families, though such variants are uncommon. AXIN2 status is sometimes used as a biomarker of Wnt pathway activity in research and, in some contexts, clinical studies.

Researchers study AXIN2 in cell culture and animal models to understand Wnt signaling dynamics. Orthologs of AXIN2 are present across vertebrates, and its regulation is a frequently cited example of Wnt pathway feedback control in developmental biology.