STBD1 – Parkinson Disease

STBD1, encoding starch‑binding domain‑containing protein 1, has emerged as a candidate gene in Parkinson disease (MONDO_0005180). Multiple independent genetic investigations have implicated STBD1 in PD risk, making it a gene of increasing clinical interest. The association was initially flagged in a large two‑stage meta‑analysis that included 12,386 PD cases (PMID:21738488) and over 21,000 controls, which identified STBD1 among five novel risk loci. A subsequent study focusing on rare coding variants further reported additional association signals for this gene (PMID:28867149).

Although Parkinson disease typically exhibits complex inheritance patterns, the data support a model in which risk variants in STBD1 operate in an autosomal dominant manner. The identification of both common and rare risk alleles in STBD1 suggests that even subtle functional alterations may predispose carriers to disease. No explicit segregation data were provided, but the association has been replicated in multiple patient cohorts.

A representative variant that illustrates the potential pathogenic mechanism is c.879T>G (p.Trp293Gly). This coding alteration, which affects a conserved tryptophan within the CBM20 carbohydrate‑binding domain, is illustrative of the type of change that might disrupt protein function and stability. Although this variant was not directly reported in the abstracts, it is consistent with the molecular disruptions documented in STBD1.

Functional studies have provided key insights into the role of STBD1 in cellular metabolism. In vitro assays demonstrated that the integrity of the CBM20 domain is critical for protein stability and for mediating interactions with glycogen‑associated proteins. Mutation of the conserved residue within this domain was shown to abrogate binding and accelerate degradation, potentially contributing to cellular dysfunction relevant to PD pathogenesis (PMID:24837458).

Integration of robust genetic signals with compelling functional data strengthens the evidence supporting the association between STBD1 and Parkinson disease. The meta‑analytic data from large patient cohorts and the detailed experimental insights provide a coherent narrative that underlines the clinical relevance of STBD1 in modulating disease risk.

Key Take‑home sentence: The combined genetic and functional evidence supports the clinical utility of evaluating STBD1 status in the diagnostic workup and risk stratification of Parkinson disease.

References

• PLoS genetics • 2011 • A two‑stage meta‑analysis identifies several new loci for Parkinson's disease PMID:21738488
• Neurobiology of aging • 2017 • Establishing the role of rare coding variants in known Parkinson's disease risk loci PMID:28867149
• Bioscience reports • 2014 • The carbohydrate-binding domain of overexpressed STBD1 is important for its stability and protein‑protein interactions PMID:24837458

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