{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T19:03:22Z","timestamp":1773255802313,"version":"3.50.1"},"reference-count":0,"publisher":"The Korean Society for Reproductive Medicine","content-domain":{"domain":["ecerm.org"],"crossmark-restriction":true},"short-container-title":["Clin Exp Reprod Med"],"abstract":"The family with sequence similarity (<i>FAM<\/i>) gene family links pathological mechanisms of male infertility and oncogenesis. This review focuses on five key FAM members (<i>FAM71D, FAM46C, FAM170A, FAM83D<\/i>, and <i>FAM172A<\/i>), which were selected based on: clinical relevance (<i>FAM83D<\/i> as a breast cancer prognostic biomarker, hazard ratio, 1.29, p<0.05; <i>FAM71D<\/i> homozygous mutation c.440G>A associated with asthenoteratospermia); adequate experimental validation (<i>in vitro<\/i> assays, <i>in vivo<\/i> models, and clinical samples\u2014for example, <i>FAM170A<\/i> knockout mice exhibit male infertility, with reduced transcription observed in patients); and recent impact (\u226530 PubMed-indexed studies within 5 years and clearly defined mechanisms). In reproduction, <i>FAM71D<\/i> maintains sperm motility via calmodulin- plasma membrane Ca<sup>2+<\/sup>-ATPase (PMCA)- Ca<sup>2+<\/sup> signaling, <i>FAM46C<\/i> anchors the sperm head-flagellum junction, and <i>FAM170A<\/i> regulates chromatin remodeling through ubiquitin- specific protease 7 (USP7)-mediated H2B deubiquitination. In oncology, <i>FAM83D<\/i> activates mitogen-activated protein kinase kinase\/extracellular signal-regulated kinase signaling to drive hepatocellular carcinoma, whereas <i>FAM172A<\/i> dysregulates p38 mitogen-activated protein kinase in thyroid cancer. Translational advances include FAM83B nanodetection, the Fam20C inhibitor FL-1607 (IC<sub>50<\/sub>=2.1 \u03bcM), and clustered regularly interspaced short palindromic repeats (CRISPR)-corrected <i>FAM170A<\/i>. Cross-species functional divergence remains a challenge. <i>FAM<\/i> genes enable novel diagnostics and targeted therapies for reproductive and oncological care, with near-term clinical applications in personalized assisted reproductive technology and cancer precision medicine.<\/jats:p>","DOI":"10.5653\/cerm.2025.08767","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T02:05:47Z","timestamp":1773194747000},"update-policy":"https:\/\/doi.org\/10.5653\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n FAM<\/i>\n gene family and its bridging of male infertility and oncogenic signaling mechanisms: A comprehensive review"],"prefix":"10.5653","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4133-7476","authenticated-orcid":true,"given":"Peng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiu","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4462-616X","authenticated-orcid":true,"given":"Hemei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3624","published-online":{"date-parts":[[2026,3,11]]},"container-title":["Clinical and Experimental Reproductive Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ecerm.org\/upload\/pdf\/cerm-2025-08767.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T02:05:48Z","timestamp":1773194748000},"score":1,"resource":{"primary":{"URL":"http:\/\/ecerm.org\/journal\/view.php?doi=10.5653\/cerm.2025.08767"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":0,"URL":"https:\/\/doi.org\/10.5653\/cerm.2025.08767","relation":{},"ISSN":["2233-8233","2233-8241"],"issn-type":[{"value":"2233-8233","type":"print"},{"value":"2233-8241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,11]]},"assertion":[{"value":"2025-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-11","order":2,"name":"published","label":"Published online","group":{"name":"publication_history","label":"Publication History"}}]}}