NCF4 (Neutrophil cytosol factor 4) variants and mutations

NCF4 (also known as Neutrophil cytosol factor 4) is a human protein-coding gene encoding a neutrophil cytosol factor 4 protein. It helps organize and regulate phagocyte NADPH oxidase complexes and contributes to reactive-oxygen-species generation in innate immune cells. Biallelic pathogenic variants can cause a milder chronic-granulomatous-disease-like immunodeficiency with recurrent infection and inflammation. This analysis covers 655 NCF4 variants and mutations. Of these, 80% have computational variant effect predictions. Disease context includes chronic granulomatous disease, inflammatory bowel disease, and Crohn disease. Example NCF4 variants include A2T, A2S, and A2G.

Variant analysis overview

Gene: NCF4
Protein: Neutrophil cytosol factor 4
UniProt accession: Q15080
Organism: Homo sapiens
Variants analyzed: 655
Variant scope: all variants
Completed: 2026-08-22

Variant and mutation evidence

Variant composition: 485 unspecified-consequence records; 1 natural variant; 67 missense variants; 77 synonymous variants; 11 frameshift variants; 6 stop-gained variants; 5 splice-region variants; 2 in-frame deletions; 1 splice acceptor variant; 1 in-frame insertions; 1 substitution
Prediction scores: 525 variants have prediction scores (80% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: chronic granulomatous disease, inflammatory bowel disease, Crohn disease, dermatitis, psoriasis, atopic eczema, asthma, multiple sclerosis, respiratory system disorder, Eczematoid dermatitis, diabetic ketoacidosis, immunodeficiency 86.

Protein structure and variant hotspots

Protein features: 3 domains; 2 binding sites; 2 post-translational modification sites.
Structural context: 527 variants have structural context.
PTM context: 2 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable NCF4 variants

Examples include A2T, A2S, A2G, A2D, A2A, V3E, V3G, V3L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

NCF4 analysis run — NCF4 (655 variants) — completed 2026-08-22