Neutrophil cytosolic factor 4

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Protein NCF4 PDB 1h6h

Neutrophil cytosolic factor 4 (NCF4) is a gene that encodes a protein known as p40phox. This protein is a crucial component of the NADPH oxidase complex found in neutrophils, which plays a vital role in the immune system's defense against pathogens. Mutations in the NCF4 gene can lead to immunodeficiency disorders, specifically chronic granulomatous disease (CGD), where the immune system is unable to effectively combat bacterial and fungal infections.

Structure and Function[edit | edit source]

The NCF4 gene is located on chromosome 22q13.1 and consists of 12 exons that encode the p40phox protein. p40phox is a cytosolic subunit of the NADPH oxidase complex, which is responsible for generating reactive oxygen species (ROS) in neutrophils. ROS production is essential for the oxidative burst, a process that helps neutrophils kill engulfed pathogens.

Clinical Significance[edit | edit source]

Mutations in the NCF4 gene can result in impaired ROS production by neutrophils, leading to CGD. Individuals with CGD are highly susceptible to recurrent bacterial and fungal infections, as their immune system is unable to effectively eliminate pathogens. Treatment for CGD often involves antimicrobial therapy and, in severe cases, hematopoietic stem cell transplantation.

Research[edit | edit source]

Research on NCF4 and CGD continues to provide insights into the molecular mechanisms underlying immune system function and dysfunction. Understanding the role of p40phox in NADPH oxidase activation may lead to the development of novel therapeutic strategies for treating immunodeficiency disorders.

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Contributors: Prab R. Tumpati, MD