The human genes ABCA13 and ABCA7 have been identified as candidate susceptibility loci for autism spectrum disorder, among other mental health and neurodegenerative disorders. Each gene is a member of the A subgroup of ABC (adenosine triphosphate (ATP)-binding cassette) transporters, which are membrane transport proteins common to prokaryotes and eukaryotes. Previous work has implicated ABCA13 in schizophrenia, major affective disorder (bipolar disorder), and major depressive disorder (MIM:607807); ABCA7 is implicated in susceptibility to Alzheimer disease (MIM:605414).
Neither human gene, ABCA7 or ABCA13 gene has been introduced into flies.
There are multiple orthologs for ABCA13 and ABCA7 in Drosophila, including Dmel\Abca3. Several RNAi targeting constructs have been generated for Abca3, as well as one targeted mutation for mir-1007, which resides within Abca3, affecting Abca3 as well. Dmel\Abca3 is orthologous to multiple genes in human; it is most closely related to human ABCA3.
Knockdown of Abca3 using a pan-neuronal driver produces flies that maintain greater social space between themselves and other flies (not due to a defect in climbing ability), and early onset of evening activity. Neuromuscular junctions of Abca3-knockdown third instar larvae show an increase in the number of satellite boutons, and a slight decrease in the number of mature boutons and terminal branch length of synapses.
ABCA13 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 report 'autism co-occurence with schizophrenia' (FBhh0001356).
[updated Jul. 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]
The SFARI Gene autism database ( https:gene.sfari.org ) rates the gene-autism associations for ABCA13 and ABCA7 as suggestive evidence (score 3). [2020.11.05]
ABC transporters hydrolyze ATP to transport substances across lipid membranes, and carry several conserved motifs including the Walker A and Walker B motifs and ABC-signature motif. They are categorized into eight groups, labeled A through H, based on the similarity of their nucleotide-binding domains. (Dean et al. 2001, FBrf0159553. See also the ATPA gene group at https://www.genenames.org/data/genegroup/#!/group/805.)
Many to many: multiple human genes to multiple Drosophila genes.
Many to many: multiple human genes to multiple Drosophila genes.
Low-scoring ortholog of human ABCA13 and ABCA7; high-scoring ortholog of human ABCA3. A higher-ranking Drosophila ortholog of both human ABCA13 and ABCA7 is Dmel\CG34120.
Dmel\Abca3 has slightly higher identity with ABCA13 than ABCA3, particularly in the transmembrane domains (Ueoka et al. 2018, FBrf0237540).
Low-ranking ortholog of human ABCA13. Dmel\ABCA has slightly higher identity with ABCA13 than ABCA3, particularly in the transmembrane domains. (Ueoka et al. 2018, FBrf0237540.) A higher-ranking Drosophila ortholog of human ABCA13 is Dmel\CG34120.
