{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWEE2 is an oocyte‐specific kinase that plays a central role in controlling meiotic arrest and ensuring proper fertilization. Investigations in both animal models and human patients have revealed that loss‐of‐function mutations in WEE2 result in defective fertilization. In affected individuals, these mutations—either as missense alterations or frameshift truncations—lead to markedly reduced protein levels and abnormal serine phosphorylation of WEE2, which is correlated with decreased tyrosine 15 phosphorylation of Cdc2. This defective post‐translational modification disrupts the resumption of the cell cycle necessary for pronucleus formation after sperm–oocyte fusion. Such genetic defects follow a Mendelian recessive pattern and have been demonstrated to cause recurrent fertilization failure, with rescue experiments via WEE2 cRNA injection restoring the fertilization process and subsequent embryonic development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the mechanistic level, WEE2 functions as a regulator of cell cycle progression during the critical transition from oocyte to zygote. Its kinase activity is essential for modulating the phosphorylation state of key cell cycle regulators such as Cdc2, ensuring that the oocyte appropriately exits meiotic arrest and enters into the developmental program following fertilization. Disruptions in these phosphorylation events—as evidenced by abnormal serine phosphorylation patterns in mutant proteins—highlight the pivotal role of WEE2 in orchestrating events that lead to pronuclear formation and successful embryogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its well‐established function in reproduction, the genomic locus of WEE2 also gives rise to an antisense long noncoding RNA, WEE2‑AS1, which appears to exert oncogenic effects in the context of hepatitis B virus–associated hepatocellular carcinoma (HCC). Upregulation of WEE2‑AS1 is associated with aggressive tumor features—including enhanced cell proliferation, migration, invasion, and aberrant cell cycle progression—thereby implicating a novel HBx–WEE2‑AS1–FERMT3 pathway in the pathogenesis of HCC. This observation extends the significance of the WEE2 genomic region beyond fertilization, suggesting that its regulatory network may also be critical for cell cycle control in non‐reproductive tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Qing Sang, Bin Li, Yanping Kuang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homozygous Mutations in WEE2 Cause Fertilization Failure and Female Infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2018.02.015"}], "href": "https://doi.org/10.1016/j.ajhg.2018.02.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29606300"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29606300"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhihua Zhang, Jian Mu, Junli Zhao, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "New biallelic mutations in WEE2: expanding the spectrum of mutations that cause fertilization failure or poor fertilization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fertil Steril (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.fertnstert.2018.11.013"}], "href": "https://doi.org/10.1016/j.fertnstert.2018.11.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30827523"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30827523"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shuai Zhao, Tailai Chen, Mengru Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel WEE2 gene variants identified in patients with fertilization failure and female infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fertil Steril (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.fertnstert.2018.11.018"}], "href": "https://doi.org/10.1016/j.fertnstert.2018.11.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30827524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30827524"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xiaopei Zhou, Lixia Zhu, Meiqi Hou, et al. 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