UNC5A Gene - Netrin Receptor, Tumor Suppressor, and Axon Guidance | NCBI, UniProt, OMIM

UNC5A (unc-5 netrin receptor A) is a protein-coding gene that encodes a member of the UNC5 family of netrin receptors. The encoded protein is a transmembrane receptor that mediates axon guidance, cell migration, and apoptosis in response to netrin-1. UNC5A functions as a dependence receptor, inducing apoptosis in the absence of netrin-1. It is implicated in tumor suppression, particularly in colorectal and breast cancers, where loss of expression or function contributes to tumor progression.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Netrin-1 signaling (Reactome: R-HSA-373752)

• Apoptosis (KEGG: hsa04210)

• Axon guidance (KEGG: hsa04360)

UNC5A is a 931-amino acid transmembrane protein belonging to the UNC5 family. It contains two immunoglobulin-like domains and two thrombospondin type-1 domains in the extracellular region, and a death domain in the intracellular region. The protein acts as a dependence receptor: in the presence of netrin-1, it promotes cell survival and migration; in the absence of netrin-1, it triggers apoptosis via caspase activation. UNC5A is widely expressed in neural tissues and at lower levels in epithelial tissues. Loss of UNC5A expression is frequently observed in cancers due to promoter hypermethylation or mutation.