{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent studies have demonstrated that the germ‐cell nuclear antigen (GCNA) is not only a robust marker of the germline but also plays an essential functional role in maintaining genome integrity during meiosis. GCNA is highly expressed in early germ cells—present in prospermatogonia, spermatogonia, and early spermatocytes—with its expression typically declining as germ cells differentiate. Such a defined spatial and temporal expression pattern indicates that GCNA is intimately associated with key developmental transitions within the germ cell lineage."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, genomic analyses in both animal models and human patients have revealed that pathogenic variants in the X‐linked GCNA gene—ranging from early frameshift (stop gain) mutations to functionally disruptive missense substitutions within conserved domains—are associated with severe spermatogenic failure (including azoospermia and oligo‐astheno‐terato‐zoospermia). These mutations likely compromise the protein’s ability to safeguard genome integrity during the extensive mitotic and meiotic divisions of male germ cells, ultimately leading to germ cell arrest and infertility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, GCNA functions as a critical genome integrity factor during germ cell division while also serving as a developmental marker throughout early gametogenesis. Disruption of GCNA structure and/or function can arrest germ cell division, underscoring its pivotal role in proper germline development and male fertility.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "G C Enders, J J May "}, {"type": "b", "children": [{"type": "t", "text": "Developmentally regulated expression of a mouse germ cell nuclear antigen examined from embryonic day 11 to adult in male and female mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Biol (1994)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/dbio.1994.1152"}], "href": "https://doi.org/10.1006/dbio.1994.1152"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "8200475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/8200475"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "D Wang, G C Enders "}, {"type": "b", "children": [{"type": "t", "text": "Expression of a specific mouse germ cell nuclear antigen (GCNA1) by early embryonic testicular teratoma cells in 129/Sv-Sl/+ mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (1996)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/0304-3835(95)04068-4"}], "href": "https://doi.org/10.1016/0304-3835(95"}, {"type": "t", "text": "04068-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "8620450"}], "href": "https://pubmed.ncbi.nlm.nih.gov/8620450"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jimmaline J Hardy, Margot J Wyrwoll, William Mcfadden, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants in GCNA, X-linked germ-cell genome integrity gene, identified in men with primary spermatogenic failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-021-02287-y"}], "href": "https://doi.org/10.1007/s00439-021-02287-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33963445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33963445"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Maram Arafat, Sandra E Kleiman, Ali AbuMadighem, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pathogenic variations in Germ Cell Nuclear Acidic Peptidase (GCNA) are associated with human male infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41431-021-00946-2"}], "href": "https://doi.org/10.1038/s41431-021-00946-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34413498"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34413498"}]}]}]}