NCF1 Gene - Neutrophil Cytosolic Factor 1: Function, Mutations, and Disease

The NCF1 gene encodes neutrophil cytosolic factor 1, also known as p47phox, a 47 kDa cytosolic subunit of the NADPH oxidase complex. This enzyme complex is essential for the production of reactive oxygen species (ROS) in phagocytes, playing a critical role in host defense against microbial pathogens. NCF1 is primarily expressed in myeloid cells and is required for the assembly and activation of the NADPH oxidase upon phagocyte stimulation. Mutations in NCF1 are a major cause of autosomal recessive chronic granulomatous disease (CGD), characterized by recurrent bacterial and fungal infections.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• NADPH oxidase complex (Reactome: R-HSA-1222556)

• Innate immune system (Reactome: R-HSA-168249)

• Fcgamma receptor-mediated phagocytosis (KEGG: hsa04666)

The NCF1 protein, p47phox, is a 390-amino acid cytosolic factor containing two SH3 domains, a PX domain, and a proline-rich region. It serves as an adaptor that translocates to the membrane upon cell activation, binding to membrane-bound cytochrome b558 (gp91phox and p22phox) to assemble the active NADPH oxidase. This complex catalyzes the reduction of oxygen to superoxide, a precursor to microbicidal ROS. Phosphorylation of p47phox by protein kinase C is a key regulatory step in oxidase activation.