PHB2 – Chronic Granulomatous Disease

Evidence linking PHB2 (HGNC:30306) to chronic granulomatous disease (MONDO_0018305) remains limited from a genetic standpoint while being supported by several functional studies. Although PHB2 has been included in multi‐gene panels evaluating chronic granulomatous disease, no definitive, reportable pathogenic variants have been documented in unrelated probands (PMID:10910929, PMID:28577521). Consequently, case‐level and segregation data are lacking, and no conclusive familial co‐segregation has been observed for PHB2 in affected individuals.

In contrast, functional assays suggest that PHB2 might modulate NADPH oxidase activity. In vitro experiments have demonstrated that alterations in the protein interactions involving p22(phox) and its phosphorylation status can influence reactive oxygen species production (PMID:19948736). Additionally, studies examining the stability and electron transfer efficiency of the NADPH oxidase complex point to a contributory role for PHB2 in maintaining oxidase function (PMID:21659519).

Despite the absence of robust genetic evidence, the concordance of these functional findings provides moderate experimental support. The available data suggest that PHB2 may act as a modulatory factor in the NADPH oxidase complex, potentially influencing the clinical phenotype of chronic granulomatous disease.

The overall integration of evidence indicates that while PHB2’s contribution to chronic granulomatous disease is supported by functional studies, its genetic association remains limited due to the lack of specific pathogenic variants and segregation data in patient cohorts. Further research is needed to definitively determine its causal role.

Key Take‑home sentence: Although genetic evidence for PHB2 in chronic granulomatous disease is currently limited, functional studies highlight its potential role in modulating NADPH oxidase activity, which may have implications for diagnostic decision‑making.

References

• The Journal of biological chemistry • 2010 • Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding PMID:19948736
• The Journal of biological chemistry • 2011 • Role of putative second transmembrane region of Nox2 protein in the structural stability and electron transfer of the phagocytic NADPH oxidase PMID:21659519
• Asian Pacific journal of allergy and immunology • 2018 • Seven chronic granulomatous disease cases in a single‑center experience and a review of the literature PMID:28577521

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