{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:15:53Z","timestamp":1788315353049,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471650"],"award-info":[{"award-number":["82471650"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","award":["2024YFFK0267"],"award-info":[{"award-number":["2024YFFK0267"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Male infertility, often caused by structural and functional sperm defects, remains genetically unexplained in a substantial proportion of cases.\n                    <jats:italic>ATP1A4<\/jats:italic>\n                    encodes a testis\u2010specific isoform of the Na\n                    <jats:sup>+<\/jats:sup>\n                    , K\n                    <jats:sup>+<\/jats:sup>\n                    \u2010ATPase, a membrane enzyme crucial for maintaining cellular ionic homeostasis. Previous studies on\n                    <jats:italic>Atp1a4<\/jats:italic>\n                    knockout mice have demonstrated severe defects in sperm motility and flagellar architecture; however, the contribution of\n                    <jats:italic>ATP1A4<\/jats:italic>\n                    variants to human male reproduction remains to be elucidated. In this study, we identified compound biallelic variants in\n                    <jats:italic>ATP1A4<\/jats:italic>\n                    , a missense variant (c.2578\u2009T&gt;A, p.Tyr860Asn) and a frameshift variant (c.2582del, p.Gly861Aspfs*5), in a patient presenting with severe oligoasthenoteratozoospermia. Both variants markedly affected ATP1A4 protein expression. Morphological analyses revealed coiled and folded flagella, disrupted mitochondrial sheaths, and irregular head morphology in the patient's spermatozoa. Expression profiling revealed that ATP1A4 was highly enriched in post\u2010meiotic spermatids and localized along the entire flagellum of mature sperm in both humans and mice, indicating a critical role in flagellar assembly and structural integrity. Notably, intracytoplasmic sperm injection (ICSI) in this patient resulted in low fertilization efficiency and failed implantation, suggesting a potential adverse impact of ATP1A4 deficiency on sperm functional competence beyond motility. These findings broaden the genetic spectrum of oligoasthenoteratozoospermia and highlight\n                    <jats:italic>ATP1A4<\/jats:italic>\n                    as a potential gene associated with human male infertility.\n                  <\/jats:p>","DOI":"10.1111\/cge.70205","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:51:34Z","timestamp":1782910294000},"page":"415-425","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biallelic Variants in\n                    <i>ATP1A4<\/i>\n                    Are Associated with Oligoasthenoteratozoospermia and Male Infertility"],"prefix":"10.1111","volume":"110","author":[{"given":"Yantong","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"West China School of Medicine Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingteng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3418-4394","authenticated-orcid":false,"given":"Keyu","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"West China School of Medicine Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Yang","sequence":"additional","affiliation":[{"name":"Reproduction Medical Center, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunchuan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE West China Second University Hospital, Sichuan University  Chengdu 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