• nervous system disease

Three human genes within the sodium/potassium-transporting ATPase alpha subunit gene family, ATP1A1, ATP1A2, and ATP1A3, are associated with neurologic disorders. ATP1A1 is implicated in Charcot-Marie-Tooth disease, axonal, type 2DD (MIM:618036; FBhh0001579) and a syndromic intellectual developmental disorder (MIM:616418). ATP1A2 is implicated in familial hemiplegic migraine (MIM:602481; FBhh0000548) and alternating hemiplegia of childhood (MIM:104290). ATP1A3 is also implicated in a form of alternating hemiplegia of childhood (MIM:614820), in rapid-onset dystonia-parkinsonism (MIM:128235), and in CAPOS syndrome (MIM:601338). All of these diseases exhibit autosomal dominant inheritance. There is one high-scoring ortholog of ATP1A1, ATP1A2 and ATP1A3 in Drosophila, Atpα, for which classical hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

The human Hsap\ATP1A3 gene has been introduced into flies, but has not been used in the context of a disease model. The human ATP1A1 and ATP1A2 genes have not been introduced into flies.

Homozygous loss-of-function mutations of Dmel\Atpα are lethal in the embryonic stage. Heterozygous and viable mutant combinations cause stress-sensitivity, temperature-sensitive paralysis, reduced or increased longevity, altered tracheal development, and progressive locomotor defects. A large collection of missense mutations have been generated, mapped, and characterized. One such missense mutation is analogous to an amino acid substitution in ATP1A2 that has been associated with familial hemiplegic migraine 2 (see FBhh0000548). In additional, a collection missense mutations analogous to those implicated in Charcot-Marie-Tooth disease, axonal, type 2DD (FBhh0001579) has been generated by homologous recombination. See the 'Disease-Implicated Variants' table below.

[updated Oct. 2024 by FlyBase; FBrf0222196]