CYBB — Cytochrome b-245, Beta Polypeptide

CYBB — Cytochrome b-245, Beta Polypeptide

title: CYBB Gene
<div class="infobox infobox-gene"> [@choi2022]

| Gene Symbol | CYBB | [@marden2019]
|---|---|
| Full Name | Cytochrome b-245, Beta Polypeptide (NADPH Oxidase Subunit) |
| Chromosomal Location | Xp21.1 |
| NCBI Gene ID | [1539](https://www.ncbi.nlm.nih.gov/gene/1539) |
| OMIM | [306500](https://www.omim.org/entry/306500) |
| Ensembl ID | ENSG00165195 |
| UniProt ID | [P04839](https://www.uniprot.org/uniprot/P04839) |
| Associated Diseases | Chronic Granulomatous Disease, Parkinson's Disease, Alzheimer's Disease |

</div>

Overview

...

CYBB — Cytochrome b-245, Beta Polypeptide

title: CYBB Gene
<div class="infobox infobox-gene"> [@choi2022]

| Gene Symbol | CYBB | [@marden2019]
|---|---|
| Full Name | Cytochrome b-245, Beta Polypeptide (NADPH Oxidase Subunit) |
| Chromosomal Location | Xp21.1 |
| NCBI Gene ID | [1539](https://www.ncbi.nlm.nih.gov/gene/1539) |
| OMIM | [306500](https://www.omim.org/entry/306500) |
| Ensembl ID | ENSG00165195 |
| UniProt ID | [P04839](https://www.uniprot.org/uniprot/P04839) |
| Associated Diseases | Chronic Granulomatous Disease, Parkinson's Disease, Alzheimer's Disease |

</div>

Overview

The CYBB gene (also known as NOX2) encodes the gp91^phox^ subunit, the catalytic core of the NADPH oxidase enzyme complex. This gene is located on chromosome Xp21.1 and is essential for the production of superoxide anion (O2•-), the primary [reactive oxygen species](/entities/reactive-oxygen-species) (ROS) generated by phagocytic cells [1]. In the nervous system, NOX2 plays complex roles in microglial activation, neuroimmune communication, and redox signaling. Dysregulated NOX2 activity has been implicated in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS) [2][3][4]. The gene is also notable for causing Chronic Granulomatous Disease (CGD) when mutated, making it one of the few genes with clear links to both immunodeficiency and neurodegeneration.

Function

The CYBB gene encodes the gp91^phox^ subunit (also called NOX2), which is the catalytic core of the NADPH oxidase (NOX2) enzyme complex. This enzyme is responsible for generating superoxide anion (O₂•⁻), the primary reactive oxygen species (ROS) produced by phagocytic cells.

Structure

• gp91^phox^ is a 570-amino acid transmembrane protein
• Contains six transmembrane helices and binding sites for heme and FAD
• Forms a heterodimer with p22^phox^ (encoded by [CYBA](/genes/cyba)) to create the cytochrome b558 complex
• The C-terminal cytosolic domain contains the NADPH-binding site

Normal Function in the Nervous System

In the central nervous system, NOX2 is expressed in:

• [Microglia](/cell-types/microglia-neuroinflammation): The brain's resident immune cells, where it mediates oxidative burst in response to pathogens
• [Neurons](/entities/neurons): Lower expression, but contributes to synaptic plasticity and redox signaling
• [Astrocytes](/entities/astrocytes): Involved in astrocyte-neuron communication

NOX2-derived ROS serve as signaling molecules in:

• Synaptic transmission and plasticity
• Neuroimmune communication
• Cellular stress responses

Disease Associations

Neurodegenerative Diseases

Parkinson's Disease

• Increased NOX2 activity observed in substantia nigra of PD patients
• Contributes to dopaminergic neuron death through oxidative stress
• NOX2 activation by [alpha-synuclein](/proteins/alpha-synuclein) aggregates promotes microglial inflammation [2]

Alzheimer's Disease

• Elevated NOX2 expression in microglia surrounding amyloid plaques
• Mediates neuroinflammation and oxidative damage in AD brain
• NOX2-derived ROS amplifies [amyloid-beta](/proteins/amyloid-beta) toxicity [3]

Amyotrophic Lateral Sclerosis (ALS)

• NOX2 upregulation in motor neurons and microglia
• Contributes to oxidative stress-mediated motor neuron death [4]

Chronic Granulomatous Disease (CGD)

• X-linked recessive disorder caused by CYBB mutations
• Defective NADPH oxidase function leads to recurrent infections
• May provide insight into neuroinflammation pathways

Expression

Brain Expression

• High expression: Substantia nigra, [hippocampus](/brain-regions/hippocampus), cerebral [cortex](/brain-regions/cortex)
• Microglial expression: Highly upregulated in response to neuroinflammation
• Expression increases with age in certain brain regions

Expression Databases

• [Allen Brain Atlas](https://human.brain-map.org/): High expression in thalamus and substantia nigra
• [GTEx](https://gtexportal.org/): Moderate expression in brain tissue

Therapeutic Targeting

NOX2 Inhibitors

• Apocynin: Natural NOX2 inhibitor, shown to reduce oxidative stress in PD models
• GKT137831: Dual NOX1/NOX4 inhibitor, in clinical trials for diabetic nephropathy
• VAS2870: Pan-NOX inhibitor, neuroprotective in preclinical models

Research Status

• NOX2 as therapeutic target remains controversial due to dual roles in protection and damage
• [Microglia](/cell-types/microglia)specific NOX2 inhibition may be preferable to global inhibition [4]

Key Publications

[Zhang et al., NOX2-mediated oxidative stress in Parkinson's disease pathogenesis (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.03.012)

[Hernandes et al., NADPH oxidase as a therapeutic target in Alzheimer's disease (2020)](https://doi.org/10.1016/j.jad.2020.01.080)

[Choi et al., Targeting NADPH oxidases in neurodegenerative diseases (2022)](https://doi.org/10.1016/j.pharmthera.2022.108176)

[Marden et al., NOX2 activation in ALS pathogenesis (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.06.012)

Cross-References

• [CYBB Protein](/proteins/cybb-protein)
• [Oxidative Stress Pathway](/mechanisms/oxidative-stress)
• [Microglial Activation in Neurodegeneration](/mechanisms/microglial-phagocytosis))
• [NADPH Oxidase Family](/proteins/nadph-oxidase)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)

See Also

• [Genes Directory](/genes)
• [Oxidative Stress Genes](/content/genes)
• [Neurodegeneration Genes](/content/genes)
• [Microglia-Related Genes](/content/genes)

External Links

• [NCBI Gene: CYBB](https://www.ncbi.nlm.nih.gov/gene/1539)
• [UniProt: CYBB (P04839)](https://www.uniprot.org/uniprot/P04839)
• [OMIM: CYBB](https://www.omim.org/entry/306500)
• [Ensembl: CYBB](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000165195)
• [Allen Brain Atlas: CYBB](https://human.brain-map.org/)

References

[Smith et al., Structure and function of CYBB (2018) (2018)]([DOI:10.1016/j.bbamcr.2018.01.005](https://doi.org/10.1016/j.bbamcr.2018.01.005))

[Zhang et al., NOX2-mediated oxidative stress in Parkinson's disease pathogenesis (2020) (2020)]([DOI:10.1016/j.neurobiolaging.2020.03.012](https://doi.org/10.1016/j.neurobiolaging.2020.03.012))

[Hernandes et al., NADPH oxidase as a therapeutic target in Alzheimer's disease (2020) (2020)]([DOI:10.1016/j.jad.2020.01.080](https://doi.org/10.1016/j.jad.2020.01.080))

[Choi et al., Targeting NADPH oxidases in neurodegenerative diseases (2022) (2022)]([DOI:10.1016/j.pharmthera.2022.108176](https://doi.org/10.1016/j.pharmthera.2022.108176))

[Marden et al., NOX2 activation in ALS pathogenesis (2019) (2019)]([DOI:10.1016/j.neurobiolaging.2019.06.012](https://doi.org/10.1016/j.neurobiolaging.2019.06.012))

Pathway Diagram

The following diagram shows the key molecular relationships involving CYBB — Cytochrome b-245, Beta Polypeptide discovered through SciDEX knowledge graph analysis: