CRB3 Gene - Crumbs Cell Polarity Complex Component 3 | Function, Mutations & Disease

CRB3 (Crumbs Cell Polarity Complex Component 3) encodes a transmembrane protein that is a core component of the Crumbs polarity complex, essential for establishing and maintaining apical-basal cell polarity in epithelial cells and retinal photoreceptors. The protein localizes to the apical membrane and interacts with PALS1 and PATJ to regulate tight junction formation and cell adhesion. Alternative splicing produces two isoforms (CRB3A and CRB3B) with distinct C-terminal PDZ-binding motifs. CRB3 is critical for epithelial morphogenesis, retinal integrity, and lumen formation. Loss of CRB3 function is associated with retinal degeneration and cancer progression.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Apical-basal polarity (Crumbs complex) – REACT: R-HSA-446353

• Tight junction organization – REACT: R-HSA-420029

• Epithelial cell differentiation – REACT: R-HSA-446388

• Retina morphogenesis – REACT: R-HSA-5619507

CRB3 is a 120-amino acid transmembrane protein with a single extracellular EGF-like domain and a short cytoplasmic tail containing a PDZ-binding motif. It localizes to the apical membrane of epithelial cells and photoreceptors, where it forms the Crumbs polarity complex with PALS1 and PATJ. This complex is essential for establishing apical-basal polarity, maintaining tight junctions, and regulating cell proliferation. CRB3 also interacts with the PAR complex to coordinate cell division orientation. In the retina, CRB3 is required for photoreceptor morphogenesis and survival. Alternative splicing generates two isoforms: CRB3A (canonical) and CRB3B (with a distinct C-terminal motif). Loss of CRB3 leads to polarity defects, increased cell migration, and tumorigenic properties in epithelial cancers.