Alternative titles; symbols
HGNC Approved Gene Symbol: ATP10A
Cytogenetic location: 15q12 Genomic coordinates (GRCh38) : 15:25,672,237-25,865,088 (from NCBI)
Nagase et al. (1998) isolated a partial cDNA from brain encoding ATP10C, which they called KIAA0566. Based on homology analysis, they predicted that ATP10C is a probable calcium-transporting ATPase. RT-PCR analysis detected wide expression, with highest levels in kidney, followed by lung, brain, prostate, testis, ovary, and small intestine.
By radiation hybrid analysis, Nagase et al. (1998) mapped the ATP10C gene to chromosome 15. Halleck et al. (1999) mapped the ATP10C gene, which they called ATPVC, to chromosome 15q11-q13 based on genomic sequence analysis.
The mouse Atp10a gene maps to chromosome 7 (Kayashima et al., 2003).
Imprinting of ATP10A
Lack of a maternal contribution to the genome at the imprinted domain on proximal chromosome 15 causes Angelman syndrome (AS; 105830), which is associated with neurobehavioral anomalies that include severe mental retardation, ataxia, and epilepsy. Although AS patients infrequently have mutations in the UBE3A gene (601623), which encodes a ubiquitin ligase required for long-term synaptic potentiation (LTP), most cases are attributed to de novo maternal deletions of chromosome 15q11-q13. Meguro et al. (2001) reported that the ATP10C gene is maternally expressed, that it maps within the most common interval of deletion responsible for AS, and that ATP10C expression is virtually absent from AS patients with imprinting mutations, as well as from patients with maternal deletions of chromosome 15q11-q13. They noted that maternal inheritance of deletions of the mouse Atp10c gene results in increased body fat (Dhar et al., 2000), and that an obese phenotype has consistently been observed in the mouse model for AS with paternal uniparental disomy (Cattanach et al., 1997). A subset of sporadic patients with AS has been associated with obesity resembling that of Prader-Willi syndrome (PWS; 176270) (Gillessen-Kaesbach et al., 1999). Meguro et al. (2001) speculated that ATP10C may be an aminophospholipid translocase involved in phospholipid transport.
Herzing et al. (2001) reported that ATP10C maps within 200 kb distal to UBE3A and, like UBE3A, demonstrates imprinted, preferential maternal expression in human brain. They suggested that ATP10C is a candidate for chromosome 15-associated autism and the Angelman syndrome phenotype.
Kashiwagi et al. (2003) demonstrated that the mouse Atp10c gene shows tissue-specific maternal expression in the hippocampus and olfactory bulb, which overlaps the region of imprinted Ube3a expression. The data suggested that the imprinted transcript of Atp10c in the specific region of the central nervous system may be associated with neurologic disorders, including AS and autism.
Kayashima et al. (2003) stated that the mouse Atp10a gene is located at the border of an imprinted domain on mouse chromosome 7. RT-PCR detected expression of Atp10a in all mouse tissues examined, with highest expression in brain, lung, spleen, white adipose tissue, and skin. Atp10a was biallelically expressed in all embryonic and adult tissues examined. There was no allele-specific methylation in the promoter region of the gene and no antisense transcripts that could control its expression. Kayashima et al. (2003) concluded that the mouse Atp10a gene escapes genomic imprinting.
By RT-PCR of 16 normal control brain samples, Hogart et al. (2008) found that 10 (62.5%) exhibited biallelic expression and 6 (37.5%) showed monoallelic expression. Contrary to the expectation of a maternally expressed imprinted gene, quantitative RT-PCR revealed significantly reduced ATP10A transcript in PWS brains with 2 maternal chromosomes due to uniparental disomy (PWS-UPD). Furthermore, a PWS-UPD brain sample with monoallelic ATP10A expression demonstrated that monoallelic expression could be independent of imprinting. Hogart et al. (2008) found that gender influenced allelic ATP10A expression, as females were significantly more likely to have monoallelic ATP10A expression than males (p = 0.0128). A promoter polymorphism that disrupted binding of the SP1 (189906) transcription factor potentially contributed to allelic expression differences in females. Hogart et al. (2008) concluded that monoallelic expression of ATP10A is variable in the population and is influenced by both gender and common genetic variation.
Cattanach, B. M., Barr, J. A., Beechey, C. V., Martin, J., Noebels, J., Jones, J. A candidate model for Angelman syndrome in the mouse. Mammalian Genome 8: 472-478, 1997. Note: Erratum: Mammalian Genome 8: 877 only, 1997. [PubMed: 9195990] [Full Text: https://doi.org/10.1007/s003359900479]
Dhar, M., Webb, L. S., Smith, L., Hauser, L., Johnson, D., West, D. B. A novel ATPase on mouse chromosome 7 is a candidate gene for increased body fat. Physiol. Genomics 4: 93-100, 2000. [PubMed: 11074018] [Full Text: https://doi.org/10.1152/physiolgenomics.2000.4.1.93]
Gillessen-Kaesbach, G., Demuth, S., Thiele, H., Theile, U., Lich, C., Horsthemke, B. A previously unrecognised phenotype characterised by obesity, muscular hypotonia, and ability to speak in patients with Angelman syndrome caused by an imprinting defect. Europ. J. Hum. Genet. 7: 638-644, 1999. [PubMed: 10482951] [Full Text: https://doi.org/10.1038/sj.ejhg.5200362]
Halleck, M. S., Lawler, J. F., Jr., Blackshaw, S., Gao, L., Nagarajan, P., Hacker, C., Pyle, S., Newman, J. T., Nakanishi, Y., Ando, H., Weinstock, D., Williamson, P., Schlegel, R. A. Differential expression of putative transbilayer amphipath transporters. Physiol. Genomics 1: 139-150, 1999. [PubMed: 11015572] [Full Text: https://doi.org/10.1152/physiolgenomics.1999.1.3.139]
Herzing, L. B. K., Kim, S.-J., Cook, E. H., Jr., Ledbetter, D. H. The human aminophospholipid-transporting ATPase gene ATP10C maps adjacent to UBE3A and exhibits similar imprinted expression. Am. J. Hum. Genet. 68: 1501-1505, 2001. [PubMed: 11353404] [Full Text: https://doi.org/10.1086/320616]
Hogart, A., Patzel, K. A., LaSalle, J. M. Gender influences monoallelic expression of ATP10A in human brain. Hum. Genet. 124: 235-242, 2008. [PubMed: 18726118] [Full Text: https://doi.org/10.1007/s00439-008-0546-0]
Kashiwagi, A., Meguro, M., Hoshiya, H., Haruta, M., Ishino, F., Shibahara, T., Oshimura, M. Predominant maternal expression of the mouse Atp10c in hippocampus and olfactory bulb. J. Hum. Genet. 48: 194-198, 2003. [PubMed: 12730723] [Full Text: https://doi.org/10.1007/s10038-003-0009-3]
Kayashima, T., Yamasaki, K., Joh, K., Yamada, T., Ohta, T., Yoshiura, K., Matsumoto, N., Nakane, Y., Mukai, T., Niikawa, N., Kishino, T. Atp10a, the mouse ortholog of the human imprinted ATP10A gene, escapes genomic imprinting. Genomics 81: 644-647, 2003. [PubMed: 12782135] [Full Text: https://doi.org/10.1016/s0888-7543(03)00077-6]
Meguro, M., Kashiwagi, A., Mitsuya, K., Nakao, M., Kondo, I., Saitoh, S., Oshimura, M. A novel maternally expressed gene, ATP10C, encodes a putative aminophospholipid translocase associated with Angelman syndrome. Nature Genet. 28: 19-20, 2001. [PubMed: 11326269] [Full Text: https://doi.org/10.1038/ng0501-19]
Nagase, T., Ishikawa, K., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 5: 31-39, 1998. [PubMed: 9628581] [Full Text: https://doi.org/10.1093/dnares/5.1.31]