Aliases: ATPIIA, NEDGBA
Chromosome No: 20
Chromosome Band: 20q13.2
Genetic Category: Rare single gene variant-Syndromic-Syndromic/Functional-Rare single gene variant/Functional
ASD Reports: 6
Recent Reports: 0
Annotated variants: 15
Associated CNVs: 4
Evidence score: null
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Relevance to Autism
Cordovado et al., 2025 reported five individuals with de novo missense variants in the ATP9A gene presenting with non-syndromic intellectual disability characterized by developmental delay, language impairment, autistic features (including stereotyped movements and/or ritualized/rigid behavior), and epilepsy; functional studies demonstrated that overexpression of selected ATP9A missense variants in HeLa cells and primary neuronal cultures resulted in either retention in the endoplasmic reticulum or a loss of mature dendritic spines. A de novo loss-of-function variant and a de novo missense variant predicted to be deleterious have been reported in ATP9A in ASD probands from the SPARK cohort and the Autism Sequencing Consortium, respectively (Satterstrom et al., 2020; Zhou et al., 2022). Biallelic variants in the ATP9A gene are responsible for neurodevelopmental disorder with poor growth and behavioral abnormalities (NEDGBA; OMIM 20242), an autosomal recessive disorder characterized by global developmental delay, moderately to severely impaired intellectual development, often with absent speech, behavioral abnormalities (including hyperactivity, short attention span, and ADHD), and failure to thrive with poor overall growth; Mattioli et al., 2021 reported that one individual from a consanguineous Iranian family with a homozygous splice-site variant presented with autistic features and stereotyped movements in addition to features frequently associated with NEDGBA. Meng et al., 2023 found that Atp9a-null mice displayed behavioral abnormalities, including impaired muscle strength, impaired hippocampus-dependent spatial learning and memory, and hyperactive/hyperkinetic movements, as well as reduced dendritic arborization and reduced density of dendritic spines in pyramidal and hippocampal neurons.
Molecular Function
Enables protease binding activity. Involved in negative regulation of exosomal secretion; regulation of endocytic recycling; and regulation of retrograde transport, endosome to Golgi. Located in several cellular components, including endosome; perinuclear region of cytoplasm; and trans-Golgi network membrane. Implicated in neurodevelopmental disorder with poor growth and behavioral abnormalities.
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