The human gene ATP6AP2 (ATPase H+ transporting accessory protein 2) is implicated in several neurological diseases: intellectual disability, X-linked syndromic, Hedera type (MIM:300423) and Parkinsonism with spasticity, X-linked (MIM:300911). ATP6AP2 encodes a transmembrane protein that is an essential accessory component of a vacuolar ATPase thought to be required for lysosomal degradative functions and autophagy. There is a single orthologous gene in Drosophila, ATP6AP2, for which a loss-of-function mutation, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
A UAS construct with a tagged wild-type human Hsap\ATP6AP2 has been introduced into flies; partial heterologous rescue (functional complementation) of the Dmel\ATP6AP2 amorphic phenotypes has been observed.
Animals homozygous for an amorphic allele of Dmel\ATP6AP2 die in the larval stage; in somatic clones, planar cell polarity defects are observed. Neuronal loss of function of ATP6AP2 effected by RNAi results in locomotor, memory, and neuroanatomy defects. Physical and genetic interactions have been described for Dmel\ATP6AP2; see below and in the ATP6AP2 gene report.
Recently, specific variants of human ATP6AP2 have been implicated in a congenital disorder of glycosylation (FBhh0000788).
[updated Apr. 2018 by FlyBase; FBrf0222196]
Mutations in ATP6AP2 have been associated with neurological disorders exhibiting Parkinsonism, spasticity, epilepsy, and intellectual disability. [from MIM:300423 and MIM:300911; 2018.04.12]
The ATP6AP2 gene encodes a transmembrane protein that is an essential accessory component of the vacuolar ATPase required for lysosomal degradative functions and autophagy (summary by Korvatska et al., 2013; pubmed:23595882). [from MIM:300556; 2018.04.12]
One to one (1 human to 1 Drosophila).
Moderate- to high-scoring ortholog of human ATP6AP2 (1 Drosophila to 1 human). Dmel\ATP6AP2 shares 26% identity and 47% similarity with the human gene.
