Funktion des humanen C15orf2 Gens
Final Report Abstract
In 2000, our group had detected a novel gene in 15q11q13, which was named Chromosome 15 open reading frame 2 (C15orf2). The gene has several interesting features: 1. it is one of the few human genes that do not have a murine orthologue, 2. it appeared to be subject to positive selection in primates, and 3. it is expressed from the paternal allele only, a fact which makes it a candidate gene for some features of Prader-Willi syndrome (PWS). By immunohistochemistry we found C15orf2-immunoreactive neurons in the paraventricular nucleus (PVN) and in the supraoptic nucleus (SON). By RNA in situ analysis C15orf2 expression was restricted to the SON, PVN, and nucleus basalis of Meynert neurons. For identifying the subcellular localization of C15orf2, we overexpressed the gene in Flp-In T-REx-293 cells. By immunohistochemistry and three-dimensional structured illumination microscope we saw that the protein is located at the inner face of the nuclear envelope, where it strongly associates with the nuclear pore complex. Based on these findings, we proposed "Nuclear pore associated protein 1 (NPAP1)" as the new name for C15orf2, which was approved by the HUGO Gene Nomenclature Committee. Although NPAP1 is absent in mice, we identified homologous sequences in all sequenced placental mammals except rodents. Phylogenetic analysis revealed the existence of a gene family - with one mammal-specific and two primate-specific genes - that are related to the vertebrate transmembrane nucleoporin gene POM121. In contrast to POM121, however, the members of this gene family have no or small introns, suggesting that their common ancestor arose by retro-transposition from POM121 during early mammalian evolution.
Publications
- (2010) The C15orf2 gene in the Prader-Willi syndrome region is subject to genomic imprinting and positive selection, Neurogenet 11:153-161
Wawrzik M, Unmehopa UA, Swaab DF, van de Nes J, Buiting K, Horsthemke B
- (2012) The imprinted NPAP1/C15orf2 gene in the Prader-Willi syndrome region encodes a nuclear pore complex associated protein. Hum Mol Genet 21:4038-48
Neumann LC, Markaki Y, Mladenov E, Hoffmann D, Buiting K, Horsthemke B
(See online at https://doi.org/10.1093/hmg/dds228)
