WNT1 Gene - Function, Mutations, and Associated Diseases | NCBI, UniProt, OMIM

WNT1 (Wnt family member 1) encodes a secreted signaling glycoprotein that is a member of the WNT gene family. It plays a critical role in embryonic development, particularly in the formation of the neural tube and the midbrain. In adults, WNT1 is essential for bone homeostasis by promoting osteoblast differentiation and bone formation. Mutations in WNT1 cause autosomal recessive osteogenesis imperfecta type XV and early-onset osteoporosis. Aberrant WNT1 signaling is also implicated in various cancers, including breast and lung cancer.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Wnt signaling pathway (KEGG hsa04310)

• Signaling by WNT (Reactome R-HSA-195721)

• Beta-catenin independent WNT signaling (Reactome R-HSA-3858494)

• Osteoblast differentiation (Reactome R-HSA-8940973)

WNT1 is a 370-amino-acid secreted glycoprotein with a signal peptide, a conserved Wnt domain, and multiple cysteine residues critical for proper folding and function. It binds to Frizzled receptors and LRP5/6 co-receptors to activate the canonical Wnt/β-catenin pathway, leading to transcription of target genes involved in cell proliferation, differentiation, and bone formation. Post-translational modifications include glycosylation and palmitoylation, which are essential for secretion and receptor binding.