Alternative titles; symbols
HGNC Approved Gene Symbol: STX2
Cytogenetic location: 12q24.33 Genomic coordinates (GRCh38): 12:130,789,600-130,839,250 (from NCBI)
Hirai et al. (1992) identified a novel 150-kD protein expressed on the surface of mesenchymal cells of mouse embryonic tissues. A monoclonal antibody to this molecule inhibited various processes of epithelial morphogenesis, such as hair follicle growth and lung epithelial tubular formation, in organ cultures of these tissues. Sequence analysis of cDNA encoding this protein showed that it had 289 amino acids with a hydrophobic stretch at the C terminus. NIH-3T3 cells transfected with the cDNA expressed the exogenous 150-kD protein on their surface. When lung epithelial cells were cocultured with these transfected cells, they showed normal tubular morphogenesis, but not when cocultured with untransfected NIH-3T3 cells. Hirai et al. (1992) interpreted these results as indicating that the protein, termed epimorphin, plays a central role in epithelial-mesenchymal interactions.
Zha et al. (1996) mapped the rat, mouse, and human epimorphin genes. They used a rat epimorphin DNA probe, mouse rat somatic cell hybrids, and fluorescence in situ hybridization to map epimorphin to rat chromosome 12q16. By analyzing epimorphin RFLPs segregating in 2 genetic crosses, Zha et al. (1996) mapped epimorphin to mouse chromosome 5, a region homologous to parts of human chromosomes 7 and 12. They determined that epimorphin is a new member of the synteny group conserved between mouse chromosome 5 and rat chromosome 5 that also includes Tcf1 (142410), Mdh2 (154100), and Gus. Zha et al. (1996) noted that mouse epimorphin maps near the developmental mutation bf (buff), which is characterized by alteration of coat color in non-agouti mice. Zha et al. (1996) mapped the epimorphin gene to human chromosome 7 by in situ hybridization.
Low et al. (2003) found that 2 members of the SNARE membrane fusion machinery, syntaxin-2 and Vamp8 (603177), localized to the midbody during cytokinesis in rat and canine kidney cell lines. Inhibition of syntaxin-2 and Vamp8 function by overexpression of nonmembrane-anchored mutants caused failure of cytokinesis leading to the formation of binucleated cells. Time-lapse microscopy showed that only midbody abscission and not further upstream events, such as furrowing, were affected.
Associations Pending Confirmation
In a cohort of 131 infertile Japanese men clinically diagnosed with nonobstructive azoospermia, Nakamura et al. (2018) analyzed the STX2 gene and identified 1 patient who was homozygous for a 5-bp deletion (c.8_12delACCGG) in exon 1, causing a frameshift predicted to result in a premature termination codon (Asp3AlafsTer8). The patient was a 32-year-old man who had bilateral small testes, with normal testosterone and luteinizing hormone (LH; see 152780) levels and mildly elevated follicle stimulating hormone (FSH; see 136530). Histologic analysis of his testis revealed universal maturation arrest with multinucleated spermatocytes. The patient had been previously studied by Nakamura et al. (2017) (patient 4), and had been found to carry 2 rare variants in the SPATA7 (609868) and MEI1 (608797) genes. Nakamura et al. (2018) stated that although the latter genes might be associated with the risk of nonobstructive azoospermia, multinucleation of the germ cells was more consistent with mutation in the STX2 gene.
Wang et al. (2006) found that male Epim -/- mice were sterile due to abnormal testicular development and impaired spermatogenesis. Intestinal growth was increased in Epim -/- mice due to augmented crypt cell proliferation and crypt fission during the suckling period that was mediated, at least in part, by changes in Bmp (see BMP1; 112264) and Wnt (see WNT1; 164820) signaling pathways. Colonic mucosal injury and colitis induced by dextran sodium sulfate were ameliorated in Epim -/- mice, likely due to the increased proliferative capacity of the Epim -/- colon.
Hirai, Y., Takebe, K., Takashina, M., Kobayashi, S., Takeichi, M. Epimorphin: a mesenchymal protein essential for epithelial morphogenesis. Cell 69: 471-481, 1992. [PubMed: 1581962] [Full Text: https://doi.org/10.1016/0092-8674(92)90448-l]
Low, S. H., Li, X., Miura, M., Kudo, N., Quinones, B., Weimbs, T. Syntaxin 2 and endobrevin are required for the terminal step of cytokinesis in mammalian cells. Dev. Cell 4: 753-759, 2003. [PubMed: 12737809] [Full Text: https://doi.org/10.1016/s1534-5807(03)00122-9]
Nakamura, S., Kobori, Y., Ueda, Y., Tanaka, Y., Ishikawa, H., Yoshida, A., Katsumi, M., Saito, K., Nakamura, A., Ogata, T., Okada, H., Nakai, H., Miyado, M., Fukami, M. STX2 is a causative gene for nonobstructive azoospermia. Hum. Mutat. 39: 830-833, 2018. [PubMed: 29570232] [Full Text: https://doi.org/10.1002/humu.23423]
Nakamura, S., Miyado, M., Saito, K., Katsumi, M., Nakamura, A., Kobori, Y., Tanaka, Y., Ishikawa, H., Yoshida, A., Okada, H., Hata, K., Nakabayashi, K., Okamura, K., Ogata, H., Matsubara, Y., Ogata, T., Nakai, H., Fukami, M. Next-generation sequencing for patients with non-obstructive azoospermia: implications for significant roles of monogenic/oligogenic mutations. Andrology 5: 824-831, 2017. [PubMed: 28718531] [Full Text: https://doi.org/10.1111/andr.12378]
Wang, Y., Wang, L., Iordanov, H., Swietlicki, E. A., Zheng, Q., Jiang, S., Tang, Y., Levin, M. S., Rubin, D. C. Epimorphin-/- mice have increased intestinal growth, decreased susceptibility to dextran sodium sulfate colitis, and impaired spermatogenesis. J. Clin. Invest. 116: 1535-1546, 2006. [PubMed: 16710473] [Full Text: https://doi.org/10.1172/JCI25442]
Zha, H., Remmers, E. F., Szpirer, C., Szpirer, J., Zhang, H., Kozak, C. A., Wilder, R. L. The epimorphin gene is highly conserved among humans, mice, and rats and maps to human chromosome 7, mouse chromosome 5, and rat chromosome 12. Genomics 37: 386-389, 1996. [PubMed: 8938452] [Full Text: https://doi.org/10.1006/geno.1996.0574]