NCF4 Gene (Neutrophil Cytosolic Factor 4)
Key regulator of NADPH oxidase activity in phagocytes
Gene Information Card
| Symbol | NCF4 |
|---|---|
| Full Name | Neutrophil Cytosolic Factor 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q12.3 |
| NCBI Gene ID | 4689 ncbi.nlm.nih.gov/gene/4689 |
| Ensembl ID | ENSG00000100368 |
| UniProt ID | Q15080 |
| OMIM ID | 601488 |
| HGNC ID | 7661 |
| Aliases | p40phox, NCF-4, SH3PXD4 |
Description
NCF4 encodes the cytosolic subunit p40phox of the NADPH oxidase complex, which is essential for the production of superoxide anions in phagocytes. The protein contains an N-terminal PX domain that binds phosphatidylinositol 3-phosphate, targeting the oxidase complex to phagosomal membranes. Mutations in NCF4 can lead to chronic granulomatous disease (CGD) and have been associated with susceptibility to inflammatory bowel disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic granulomatous disease (CGD) | Loss-of-function mutations impair superoxide production, leading to recurrent infections and granuloma formation. | OMIM #601488; NCBI Gene |
| Inflammatory bowel disease (IBD) | Variants in NCF4 may alter NADPH oxidase activity, affecting intestinal immune responses. | ClinVar; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Whole blood | 12.5 | High |
| Spleen | 8.2 | Medium |
| Lung | 4.1 | Low |
| Bone marrow | 6.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HL-60 (promyeloblast) | 15.3 | Differentiated to neutrophil-like cells |
| THP-1 (monocyte) | 10.1 | Macrophage model |
| K-562 (lymphoblast) | 2.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.268C>T (p.Arg90*) | Nonsense | <0.1% | Loss of function; associated with CGD |
| c.332G>A (p.Arg111Gln) | Missense | 0.2% | Reduced oxidase activity; IBD risk |
| c.502G>A (p.Gly168Arg) | Missense | 0.05% | Impaired membrane targeting |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg90*) abolish p40phox expression or function, causing CGD.
Gain of Function (GOF)
Not reported for NCF4.
Dominant Negative (DN)
Rare missense variants may interfere with complex assembly, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • NADPH oxidase activity | • superoxide-generating NADPH oxidase activator activity |
| • phosphatidylinositol-3-phosphate binding | • phagocytosis |
| • innate immune response | • protein-containing complex assembly |
Pathways
• NADPH oxidase complex (Phagosome)
• Fc gamma receptor-mediated phagocytosis
• Toll-like receptor signaling
Protein Summary
p40phox is a 339-amino acid cytosolic protein with a PX domain that binds PI(3)P, a PB1 domain for interaction with p67phox, and an SH3 domain. It stabilizes the NADPH oxidase complex and enhances superoxide production during phagocytosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NCF4 Knockout HEK293 Cell Line | EDJ-KQ5307 | Human | 4689 | Details Get a Quote |
| NCF4 Knockout HeLa Cell Line | EDJ-KQ53965 | Human | 4689 | Details Get a Quote |
| NCF4 Knockout A-549 Cell Line | EDJ-KQ62455 | Human | 4689 | Details Get a Quote |
| NCF4 Knockout HCT 116 Cell Line | EDJ-KQ70922 | Human | 4689 | Details Get a Quote |
