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MOB3B – Amyotrophic Lateral Sclerosis

The current evidence linking MOB3B to amyotrophic lateral sclerosis (ALS) is limited. A large-scale screening study of 1019 sporadic ALS patients and 1103 controls identified a handful of rare, amino acid–altering variants, including one instance of c.123A>T (p.Lys41Asn) (PMID:23141412). However, no significant enrichment of rare variants was observed, and segregation data were lacking. In addition, a recent multi‑trait association study identified MOB3B among several genes with shared risk for frontotemporal dementia and ALS (PMID:37979250), yet the overall genetic evidence remains inconclusive due to the isolated nature of the findings.

Functional studies have so far failed to demonstrate robust experimental evidence for a direct role of MOB3B in ALS pathogenesis. The absence of confirmatory in vitro or in vivo assays and the lack of clear mechanistic insights limit the support for a pathogenic effect. Additional evidence from independent replication cohorts and functional validations will be required before MOB3B variant assessment can be reliably integrated into diagnostic decision‑making.

Key Take‑home: While preliminary genetic associations and shared risk signals exist, current data do not provide sufficient support for the clinical utility of MOB3B in diagnosing ALS.

References

  • Neurobiology of aging • 2013 • Screening for rare variants in the coding region of ALS‑associated genes at 9p21.2 and 19p13.3. PMID:23141412
  • Neurobiology of aging • 2024 • Identifying risk loci for FTD and shared genetic component with ALS: A large‑scale multitrait association analysis. PMID:37979250

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Screening in 1019 sporadic ALS patients and 1103 controls did not reveal significant variant enrichment, with only isolated instances detected (PMID:23141412). Although a GWAS identified a shared risk signal with FTD (PMID:37979250), the overall evidence remains limited.

Genetic Evidence

Limited

Few rare variants, such as c.123A>T (p.Lys41Asn), were observed in isolation without familial segregation data, reducing the strength of the genetic support.

Functional Evidence

Limited

There is a lack of robust functional or experimental data demonstrating a clear mechanistic link between MOB3B and ALS pathogenesis.