The human gene RIMS1 has been identified as a susceptibility locus for the development of autism spectrum disorder (ASD); the SFARI Gene autism database (see below) rates the gene-autism association for RIMS1 as high confidence. RIMS1 is one of several related human genes that regulate synaptic membrane exocytosis. This model uses the single orthologous gene in Drosophila, Rim, for which for which a variety of genetic reagents have been generated, including loss-of-function mutations, RNAi targeting constructs, and alleles caused by insertional mutagenesis.
Dmel\Rim is also orthologous to the other human genes in this family, RIMS2, RIMS3, and RIMS4. Human RISM3 may also be associated with ASD; the available evidence is described as 'suggestive' in SFARI Gene (see below). A UAS construct of the human Hsap\RIMS2 gene has been introduced into flies but has not been characterized. None of the other human genes has been introduced into flies.
Animals homozygous for loss-of-function alleles of Dmel\Rim are generally viable, but may exhibit developmental delay. For a specific tested null allele, neuromuscular junctions in homozygous third instar larvae show a complete lack of synaptic homeostasis; heterozygous animals exhibit normal presynaptic homeostatic plasticity (PHP).
Second site non-complementation with the heterozygous null mutation of Rim has been used to characterize other candidate genes for ASD. Animals heterozygous for the null allele of Rim in addition to being heterozygous for a loss-of-function allele of Dmel\kis, Dmel\Chd1, or Dmel\ash1 exhibit failure of presynaptic homeostatic plasticity (see FBhh0001276, FBhh0001278, FBhh0001280). During testing of deficiencies for candidate genes that impact PHP using the same assumption of second site non-complementation, several deficiencies plus the heterozygous null mutation of Rim exhibit failure of presynaptic homeostatic plasticity.
The PHP phenotypes of different double heterozygous mutation combinations have been used to isolate and characterize genetic modifiers.
RIMS1 is one of a number of genes in human that have been implicated in both autism spectrum disorder and schizophrenia. See the human disease model reports 'schizophrenia, susceptibility to (postulated), RIMS-related' (FBhh0001359) and 'autism co-occurence with schizophrenia' (FBhh0001356).
[updated Jun. 2021 by FlyBase; FBrf0222196]
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996, pubmed:8655659; Risch et al., 1999, pubmed:10417292). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (MIM:608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008; pubmed:18698615). [from MIM:209850; 2017.03.18]
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996, pubmed:8655659; Risch et al., 1999, pubmed:10417292). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (MIM:608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008; pubmed:18698615). [from MIM:209850; 2017.03.18]
The SFARI Gene autism database (https://gene.sfari.org) rates the gene-autism association for RIMS1 as high confidence (score 1). The SFARI Gene autism database rates the gene-autism association for RIMS3 as 'suggestive evidence' (score 3). [2020.11.01]
The protein encoded by RIMS1 is a RAS gene superfamily member that regulates synaptic vesicle exocytosis; it may be required for maintaining normal probability of neurotransmitter release and for regulating release during short-term synaptic plasticity. [Gene Cards, RIMS1; 2020.11.03]
Many to one: 4 human genes to 1 Drosophila gene; the human genes are RIMS1, RIMS2, RIMS3, and RIMS4.
