{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:57:27Z","timestamp":1793649447823,"version":"4.5.1"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T00:00:00Z","timestamp":1692316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Infertility affects around 15% of all couples worldwide and is increasingly linked to variants in genes specifically expressed in the testis. Well\u2010established causes of male infertility include pathogenic variants in the genes TEX11<\/jats:italic>, TEX14<\/jats:italic>, and TEX15<\/jats:italic>, while few studies have recently reported variants in TEX13B<\/jats:italic>, TEX13C<\/jats:italic>, FAM9A (TEX39A)<\/jats:italic>, and FAM9B (TEX39B)<\/jats:italic>.<\/jats:p><\/jats:sec>Objectives<\/jats:title>We aimed at screening for novel potential candidate genes among the human TEX<\/jats:italic> (\u201ctestis expressed\u201d) genes as well as verifying previously described disease associations in this set of genes.<\/jats:p><\/jats:sec>Materials and methods<\/jats:title>To this end, we screened the exome sequencing data of 1305 men, including 1056 crypto\u2010 and azoospermic individuals, and determined cell\u2010specific expression by analyzing testis\u2010specific single\u2010cell RNA sequencing data for genes with identified variants. To investigate the overarching role in male fertility, we generated testis\u2010specific knockdown (KD) models of all 10 orthologous TEX<\/jats:italic> genes in Drosophila melanogaster<\/jats:italic>.<\/jats:p><\/jats:sec>Results<\/jats:title>We detected rare potential disease\u2010causing variants in TEX10<\/jats:italic>, TEX13A<\/jats:italic>, TEX13B<\/jats:italic>, TEX13C<\/jats:italic>, TEX13D<\/jats:italic>, ZFAND3 (TEX27)<\/jats:italic>, TEX33<\/jats:italic>, FAM9A (TEX39A)<\/jats:italic>, and FAM9B<\/jats:italic> (TEX39B)<\/jats:italic>, in 28 infertile men, of which 15 men carried variants in TEX10<\/jats:italic>, TEX27<\/jats:italic>, and TEX33<\/jats:italic>. The KD of TEX2<\/jats:italic>, TEX9<\/jats:italic>, TEX10<\/jats:italic>, TEX13<\/jats:italic>, ZFAND3 (TEX27)<\/jats:italic>, TEX28<\/jats:italic>, TEX30<\/jats:italic>, NFX1 (TEX42)<\/jats:italic>, TEX261<\/jats:italic>, and UTP4<\/jats:italic> (TEX292)<\/jats:italic> in Drosophila<\/jats:italic> resulted in normal fertility.<\/jats:p><\/jats:sec>Discussion<\/jats:title>Based on our findings, the autosomal dominant predicted genes TEX10<\/jats:italic> and ZFAND3 (TEX27)<\/jats:italic> and the autosomal recessive predicted gene TEX33<\/jats:italic>, which all three are conceivably required for germ cell maturation, were identified as novel potential candidate genes for human non\u2010obstructive azoospermia. We additionally identified hemizygous loss\u2010of\u2010function (LoF) variants in TEX13B<\/jats:italic>, TEX13C<\/jats:italic>, and FAM9A (TEX39A)<\/jats:italic> as unlikely monogenic culprits of male infertility as LoF variants were also found in control men.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our findings concerning the X\u2010linked genes TEX13B<\/jats:italic>, TEX13C<\/jats:italic>, and FAM9A<\/jats:italic> (TEX39A)<\/jats:italic> contradict previous reports and will decrease false\u2010positive reports in genetic diagnostics of azoospermic men.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13511","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T21:37:00Z","timestamp":1692653820000},"page":"570-584","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Scrutinizing the human TEX<\/i> genes in the context of human male infertility"],"prefix":"10.1111","volume":"12","author":[{"given":"Marie. 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