NCF2: Neutrophil Cytosolic Factor 2
Key Component of the NADPH Oxidase Complex in Innate Immunity
Gene Information Card
| Symbol | NCF2 |
|---|---|
| Full Name | Neutrophil Cytosolic Factor 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q25.3 |
| NCBI Gene ID | 4688 ncbi.nlm.nih.gov/gene/4688 |
| Ensembl ID | ENSG00000116701 |
| UniProt ID | P19878 |
| OMIM ID | 608515 |
| HGNC ID | 7661 |
| Aliases | NOXA2, p67-phox, NCF-2, P67PHOX |
Description
The NCF2 gene encodes the neutrophil cytosolic factor 2 (p67-phox), a 67 kDa cytosolic subunit of the NADPH oxidase complex. This enzyme is critical for the production of superoxide anions in phagocytes, enabling the respiratory burst essential for killing invading microorganisms. NCF2 interacts with other oxidase components (e.g., p47-phox, p40-phox, Rac) and translocates to the membrane upon activation. Mutations in NCF2 cause autosomal recessive chronic granulomatous disease (CGD), characterized by recurrent bacterial and fungal infections.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic granulomatous disease (CGD), autosomal recessive | Loss-of-function mutations in NCF2 impair NADPH oxidase assembly, preventing superoxide production and leading to defective microbial killing in phagocytes. | ClinVar, OMIM |
| Inflammatory bowel disease (IBD)-like colitis | Reduced NADPH oxidase activity in intestinal phagocytes may disrupt mucosal immunity and promote chronic inflammation. | NCBI Gene, PubMed |
| Systemic lupus erythematosus (SLE) | Polymorphisms in NCF2 have been associated with increased risk of SLE, possibly due to altered oxidative burst and immune complex clearance. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Whole blood | 12.3 | Medium |
| Spleen | 8.7 | Medium |
| Bone marrow | 7.1 | Medium |
| Lung | 4.2 | Low |
| Small intestine | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HL-60 (promyeloblast) | 15.2 | High expression; inducible upon differentiation |
| THP-1 (monocyte) | 10.8 | Moderate expression |
| K-562 (lymphoblast) | 2.1 | Low expression |
| HeLa (cervical carcinoma) | 0.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.304C>T (p.Arg102*) | Nonsense | <0.01% in general population | Premature stop; loss of p67-phox function; causes CGD |
| c.782G>A (p.Arg261Gln) | Missense | <0.01% | Impaired binding to Rac; reduced oxidase activity |
| c.1084C>T (p.Arg362Trp) | Missense | <0.01% | Disrupts p47-phox interaction; leads to CGD |
| c.1529A>G (p.Tyr510Cys) | Missense | <0.01% | Alters SH3 domain; decreased membrane translocation |
Mutation functional classification
Loss of Function (LOF)
Most NCF2 mutations are loss-of-function, leading to absent or non-functional p67-phox protein, resulting in chronic granulomatous disease due to defective NADPH oxidase activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NCF2.
Dominant Negative (DN)
No dominant-negative mutations have been described; NCF2-associated CGD is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• NADPH oxidase complex (Reactome: R-HSA-5668599)
• Fcgamma receptor (FCGR) dependent phagocytosis (Reactome: R-HSA-2029480)
• Toll-like receptor cascades (Reactome: R-HSA-168898)
• Neutrophil degranulation (Reactome: R-HSA-6798695)
Protein Summary
The NCF2 protein (p67-phox) is a 526-amino-acid cytosolic component of the phagocyte NADPH oxidase. It contains four tetratricopeptide repeat (TPR) domains at the N-terminus that mediate binding to Rac-GTP, a central activation domain, and two SH3 domains that interact with p47-phox and p40-phox. Upon cell activation, p67-phox translocates to the membrane to form the active oxidase complex, enabling electron transfer from NADPH to oxygen to produce superoxide. Defects in p67-phox abolish the respiratory burst, leading to severe immunodeficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NCF2 Knockout HEK293 Cell Line | EDJ-KQ5305 | Human | 4688 | Details Get a Quote |
| NCF2 Knockout A-549 Cell Line | EDJ-KQ28368 | Human | 4688 | Details Get a Quote |
| NCF2 Knockout HeLa Cell Line | EDJ-KQ28369 | Human | 4688 | Details Get a Quote |
| NCF2 Knockout HCT 116 Cell Line | EDJ-KQ70921 | Human | 4688 | Details Get a Quote |
