The human Neurobeachin gene (NBEA) has been identified as a candidate susceptibility locus for autism spectrum disorder (rated in SFARI as high confidence). NBEA encodes an anchor protein that binds to the regulatory subunit of protein kinase A (PKA), confining it to specific subcellular sites. There is a single orthologous gene in Drosophila, rg, for which classical amorphic and loss-of-function alleles, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\rg is also orthologous to a second human gene, LRBA.
The human NBEA gene has not been introduced into flies. The orthologous mouse gene, Mmus\Nbea, has been introduced into flies; partial functional complementation of rg learning and neural phenotypes is observed.
Animals homozygous for amorphic or hypomorphic alleles of rg are viable and fertile, with a rough eye phenotype; they exhibit learning defects, defective social interactions, impaired habituation, aberrant locomotion, and hyperactivity; neuroanatomy defects are observed in both larvae and adults.
[updated Apr. 2022 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 association for NBEA as high confidence (score 1). [2020.11.05]
The SFARI Gene autism database ( https:gene.sfari.org ) rates the gene-autism association for LRBA as suggestive evidence (score 3). [2020.11.05]
Neurobeachin (NBEA) encodes a member of a large, diverse group of A-kinase anchor proteins that target the activity of protein kinase A to specific subcellular sites by binding to its type II regulatory subunits. [Gene Cards, NBEA; 2017.03.18]
Many to one (2 human to 1 Drosophila); the human genes are NBEA and LRBA.
Moderate- to high-scoring ortholog of human NBEA and LRBA (1 Drosophila to 2 human). Dmel\rg shares 39% identity and 54% similarity with human NBEA.
