The human gene SCAMP5 has been identified as a candidate susceptibility locus for autism spectrum disorder with intellectual disability and seizures. SCAMP5 is one of five paralogous genes in human encoding secretory carrier membrane proteins that regulate membrane-depolarization and Ca(2+)-induced regulated secretion. There is a single orthologous gene in Drosophila, Dmel\Scamp, for which amorphic mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
UAS constructs for two of the human genes, Hsap\SCAMP1 and Hsap\SCAMP5, have been introduced into flies. In both cases, partial heterologous rescue (functional complementation) is observed for the behavioral phenotypes exhibited by Dmel\Scamp.
Animals with null Scamp genotypes exhibit reduced adult lifespan and progressive behavioral abnormalities including impaired climbing, deficiency in odor associated long-term memory, and a susceptibility to heat-induced seizures. Neuron-specific expression of wild-type Scamp rescues the climbing and memory phenotypes and partially rescues the seizure susceptibility phenotype.
A missense variant in SCAMP5 is postulated to be associated with autism spectrum disorder with intellectual disability and seizures; the analogous mutation has been tested in the fly system. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): G302W in the fly Scamp gene (corresponds to the G180W in the human SCAMP5 gene). Results suggest that this mutation acts as dominant-negative.
Multiple physical interactions have been described for Dmel\Scamp; see below and in the Scamp gene report.
[updated Sep. 2020 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]
Castermans et al. (2010, pubmed:20071347) described the positional cloning of SCAMP5 as a candidate gene for autism, based on finding a de novo chromosomal translocation t1;15(p36.11;q24.2) in a 40-year-old affected male. [from MIM:209850; 2020.09.04]
Secretory Carrier Membrane Proteins (SCAMPs) are evolutionarily conserved tetraspanning integral membrane proteins that regulate membrane dynamics, most prominently membrane-depolarization and Ca(2+)-induced regulated secretion (FBrf0226979 and references cited therein).
SCAMP5 belongs to a family of tetraspanin membrane proteins found in secretory and endocytic compartments of neuronal synapses (FBrf0244649 and references cited therein).
Many to one: 5 human genes to 1 Drosophila gene.
Low- to high-scoring ortholog of human SCAMP1-5 (1 Drosophila to 5 human). Dmel\Scamp shares 36-47% identity and 54-62% similarity with the human genes. SCAMP4 and SCAMP5 encode shorter proteins, lacking amino-terminal sequences found in paralogous genes and in the Drosophila gene.
