RIMS1 – Autism Spectrum Disorder

In a single-family case report, one of two siblings with ASD carried a rare de novo heterozygous RIMS1 mutation, implicating RIMS1 as an ASD candidate gene (PMID:30949922). A large whole-exome sequencing study of 787 ASD trios identified clustering of de novo frameshift indels in RIMS1, further suggesting a contributory role of RIMS1 variants in ASD risk (PMID:25284784). No multi-generational segregation or recurrent founder alleles have been reported to date, and overall case counts remain low.

Biochemical and genetic studies demonstrate that RIM1 is essential for synaptic vesicle release: the N-terminal domain binds Rab3-GTP to regulate exocytosis (PMID:11431472), and deletion of RIM1 in yeast leads to impaired meiosis-associated gene expression and spore formation (PMID:8367297). While these data establish RIM1’s role in neurotransmitter dynamics, ASD-specific functional assays or animal models are lacking. Key take-home: Current evidence for RIMS1 in ASD is limited but justifies further genetic and functional studies to clarify its clinical diagnostic utility.

References

• Behavior genetics • 2019 • Exome Sequencing of Two Siblings with Sporadic Autism Spectrum Disorder and Severe Speech Sound Disorder Suggests Pleiotropic and Complex Effects PMID:30949922
• Cell Reports • 2014 • De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder PMID:25284784
• The Journal of Biological Chemistry • 2001 • Rim1 and rabphilin-3 bind Rab3-GTP by composite determinants partially related through N-terminal alpha-helix motifs PMID:11431472
• Nucleic Acids Research • 1993 • Molecular characterization of the yeast meiotic regulatory gene RIM1 PMID:8367297

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