ZNF512B and Amyotrophic Lateral Sclerosis

The studies assessing the association between ZNF512B and amyotrophic lateral sclerosis (ALS) provide conflicting evidence. A retrospective analysis of 176 ALS patients identified a novel single‑nucleotide polymorphism (SNP) in ZNF512B (rs2275294) that was significantly associated with a poorer survival prognosis (PMID:23168171), suggesting a potential prognostic role for the gene. However, a subsequent large-scale case‑control study in a Chinese cohort involving 953 ALS patients and 1039 controls failed to replicate this association (PMID:26668144), underscoring the genetic heterogeneity and conflicting nature of the findings.

In addition to the case‑control data, functional studies of ZNF512B in a non‑ALS context demonstrated that the protein binds to the NuRD complex via a conserved interaction motif (PMID:39460621). Although these functional assays provide insight into the molecular behavior of ZNF512B, they do not directly substantiate its role in ALS. Given the lack of segregation data and the inconsistency between studies, the overall gene‑disease association remains disputed. Key take‑home: while ZNF512B may influence ALS prognosis in select populations, the conflicting genetic data necessitate further rigorous studies before its clinical utility can be fully integrated into ALS diagnostic decision‑making.

References

• Journal of the neurological sciences • 2013 • ZNF512B gene is a prognostic factor in patients with amyotrophic lateral sclerosis PMID:23168171
• Chinese medical journal • 2015 • Single‑nucleotide Polymorphism rs2275294 in ZNF512B is not Associated with Susceptibility to Amyotrophic Lateral Sclerosis in a Large Chinese Cohort PMID:26668144
• Nucleic acids research • 2024 • ZNF512B binds RBBP4 via a variant NuRD interaction motif and aggregates chromatin in a NuRD complex‑independent manner PMID:39460621

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