RCAN1 (Regulator Of Calcineurin 1) was originally designated Down syndrome critical region gene 1 (DSCR1). Calcineurin participates in a number of cellular processes, including regulation of synaptic vesicle recycling. There is a single fly ortholog of RCAN1, Dmel\sra, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\sra is also orthologous to the human genes RCAN2 and RCAN3.
A UAS construct of a tagged wild-type human Hsap\RCAN1 gene has been introduced into flies and has been made available; it has not been characterized.
Most loss-of-function alleles of sra result in lethality or female sterility. Some insertion alleles are viable and fertile without visible abnormalities, however they exhibit significant learning defects. Overexpression of UAS-sra, using systemic or pan-neuronal GAL4 drivers, also results in animals with learning defects, suggesting that precise regulation of sra is necessary to maintain optimum learning. Transient overexpression of sra is sufficient to cause learning defects, supporting a hypothesis that biochemical defects, rather than impaired neuronal development, contribute to the observed learning impairment. Physical and genetic interactions of sra have been reported; see below and in the sra gene report.
[updated Apr. 2018 by FlyBase; FBrf0222196]
Down syndrome is characterized by a particular combination of phenotypic features that includes mental retardation and characteristic facial structure. Individuals with Down syndrome often have specific major congenital malformations such as those of the heart (30-40% in some studies) and of the gastrointestinal tract. 90% of Down syndrome patients have a significant hearing loss (Mazzoni et al., 1994; pubmed:7881226). A number of other diseases are observed at higher frequency among Down syndrome individuals, including leukemia (Robison, 1992; pubmed:1532221) and Alzheimer disease (Wisniewski et al., 1985; pubmed:3158266). [from MIM:190685; 2016.07.19]
RCAN1 (Regulator Of Calcineurin 1) encodes a protein that interacts with calcineurin A and inhibits calcineurin-dependent signaling pathways (Gene Cards, RCAN1; 2016.07.25). Calcineurin inhibitors impair synaptic vesicle recycling and reduce the total vesicle pool size in synaptic terminals (references cited in FBrf0208963).
Many to one: 3 human to 1 Drosophila; the fly gene sra is orthologous to RCAN1, RCAN2, and RCAN3 in human.
High-scoring ortholog of human genes RCAN1, RCAN2, and RCAN3 (1 Drosophila to 3 human). Dmel\sra shares 33-41% identity and 49-57% similarity with the human genes.
