The Human Aminophospholipid-Transporting ATPase Gene ATP10C Maps Adjacent to UBE3A and Exhibits Similar Imprinted Expression

Abstract

Maternal duplications of the imprinted 15q11-13 domain result in an estimated 1%-2% of autism-spectrum disorders, and linkage to autism has been identified within 15q12-13. UBE3A, the Angelman syndrome gene, has, to date, been the only maternally expressed, imprinted gene identified within this region, but mutations have not been found in autistic patients. Here we describe the characterization of ATP10C, a new human imprinted gene, which encodes a putative protein homologous to the mouse aminophospholipid-transporting ATPase Atp10c. ATP10C maps within 200 kb distal to UBE3A and, like UBE3A, also demonstrates imprinted, preferential maternal expression in human brain. The location and imprinted expression of ATP10C thus make it a candidate for chromosome 15-associated autism and suggest that it may contribute to the Angelman syndrome phenotype.

Mitochondrial dysfunction in autistic patients with 15q inverted duplication

“…19 The ATP10C gene encodes a haloacid dehalogenase hydrolase that is apparently involved in ion transport. 19 Because both of our cases had a very similar marker chromosome 15, it is uncertain that all autistic children with similar marker chromosomes, or those with interstitial 15q inv dup, are similarly affected. It will require a larger study to determine the critical region involved in this phenotype and whether the gene dosage is related to the degree of metabolic or clinical deficit.…”

Clinical and genetic aspects of Angelman syndrome

“…85,86 UBE3A displays predominant maternal expression in human fetal brain and adult frontal cortex. [87][88][89] In mouse, maternal allele-specific expression is detected in specific brain subregions including hippocampus, cerebellum, olfactory bulb, and visual cortex. 83,84,90 Other brain regions may also show this type of allele-specific expression.…”

Mutational analysis of the Lem3p-Dnf1p putative phospholipid-translocating P-type ATPase reveals novel regulatory roles for Lem3p and a carboxyl-terminal region of Dnf1p independent of the phospholipid-translocating activity of Dnf1p in yeast

“…FIC1 (ATP8B) mutations cause familial intrahepatic cholestasis, a defect in bile secretion [5,6]. The ATP10C gene has been linked to Angelman syndrome and autism in some patients [7,8]. However, little is known about the detailed cellular function of type 4 Ptype ATPases, including these gene products.…”