Submission Details

Autosomal dominant

03/04/2020

The RIMS1 gene is located on chromosome 6 at 6q13 and encodes regulating synaptic membrane exocytosis 1. This protein is a member of the RAS gene superfamily and acts to regulate synaptic vesicle exocytosis, including neurotransmitter release at the active zone. It is highly expressed in the brain, where it also regulates synaptic plasticity. RIMS1 was first reported in association with autism spectrum disorder (autosomal dominant ) in 2012 (22542183, Iossifov et al.). Evidence supporting this gene-disease relationship includes case-level data and experimental data. At least six unique variants (three frameshift, one missense, two stop-gained) have been reported in six unrelated individuals from three publications (22542183: Iossifov et al. 2012; 25284784: Dong et al. 2014; 30564305: Guo et al. 2018); three of these variants occurred de novo. Additional variants have been reported, including those inherited from an unaffected parent, but these did not meet scoring criteria. In addition to expression and biochemical function evidence (29891949: Wang et al. 2018; 22031440: Kang et al. 2011), this gene-disease relationship is also supported by animal model data, in that RIMS1alpha knockout mice display deficits in learning and memory (15066271: Powell et al. 2004). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. MIM603649:Cone-rod dystrophy 7 Of note, this gene-disease association has also been implicated in cone-rod dystrophy. This association will be assessed separately.

22542183 25284784 30564305 29891949 22031440 15066271