Chronic granulomatous disease: genes and variants
Chronic granulomatous disease is linked to 6 analyzed proteins (NCF2, NCF4, CYBB, NCF1, IFNGR1 and IFNGR2). 4 DNA variants are known to cause it; 4 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Chronic granulomatous disease
NCF2: Neutrophil cytosol factor 2
It helps activate the phagocyte NADPH oxidase by assembling with membrane and cytosolic partners during the respiratory burst. Biallelic loss-of-function variants cause chronic granulomatous disease and impaired killing of catalase-positive bacteria and fungi.
3 disease-causing and 0 uncertain variants in NCF2 are linked to Chronic granulomatous disease.
NCF4: Neutrophil cytosol factor 4
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.
1 disease-causing and 0 uncertain variants in NCF4 are linked to Chronic granulomatous disease.
CYBB: NADPH oxidase 2
It generates the catalytic electron flow that allows phagocytes to produce microbicidal reactive oxygen species during the respiratory burst. Loss-of-function variants cause X-linked chronic granulomatous disease with severe susceptibility to bacterial and fungal infection.
0 disease-causing and 4 uncertain variants in CYBB are linked to Chronic granulomatous disease.
NCF1: Neutrophil cytosol factor 1
After phagocyte activation, it joins the NADPH oxidase complex to generate microbicidal reactive oxygen species. Biallelic loss-of-function variants cause chronic granulomatous disease with recurrent bacterial and fungal infections.
0 disease-causing and 0 uncertain variants in NCF1 are linked to Chronic granulomatous disease.
IFNGR1: Interferon gamma receptor 1
It binds interferon-gamma and initiates STAT1-dependent antimicrobial and immune-activating programs. Complete or partial loss-of-function variants cause Mendelian susceptibility to mycobacterial disease with severity related to residual signaling.
0 disease-causing and 0 uncertain variants in IFNGR1 are linked to Chronic granulomatous disease.
IFNGR2: Interferon gamma receptor 2
It partners with IFNGR1 to transmit interferon-gamma signals into cells through JAK-STAT pathways. Biallelic loss-of-function variants impair macrophage activation and can cause severe susceptibility to poorly pathogenic mycobacteria and related intracellular organisms.
0 disease-causing and 0 uncertain variants in IFNGR2 are linked to Chronic granulomatous disease.
Known disease-causing variants in Chronic granulomatous disease
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| NCF4 R105Q | 105 | PX | Disease-causing (★★) |
| NCF2 A202V | 202 | Disease-causing (★★) | |
| NCF2 Y394D | 394 | PB1 | Disease-causing (★★) |
| NCF2 A128V | 128 | TPR 3 | Disease-causing (★) |
Same protein, different disease
- Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 is also caused by NCF2 variants; they fall mostly in different places as the Chronic granulomatous disease variants (6 disease-causing).
Diseases related to Chronic granulomatous disease
- Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2, also linked to NCF1, NCF2 and NCF4
- Granulomatous disease, chronic, X-linked, also linked to CYBB
- Systemic lupus erythematosus, also linked to NCF2
- X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency, also linked to CYBB
- Disseminated atypical mycobacterial infection, also linked to IFNGR1
Frequently asked questions
Which genes are linked to Chronic granulomatous disease?
In CATVariant, Chronic granulomatous disease is linked to 6 analyzed proteins: NCF2 (Neutrophil cytosol factor 2), NCF4 (Neutrophil cytosol factor 4), CYBB (NADPH oxidase 2), NCF1 (Neutrophil cytosol factor 1), IFNGR1 (Interferon gamma receptor 1) and IFNGR2 (Interferon gamma receptor 2).
How many genetic variants are linked to Chronic granulomatous disease?
399 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 4 are of uncertain significance or have conflicting reports.
Which uncertain variants in Chronic granulomatous disease look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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