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Using array\u2010comparative\u2010genomic\u2010hybridization (aCGH),\n                    <jats:italic>potassium\u2010channel\u2010tetramerization\u2010domain\u2010containing\u201013<\/jats:italic>\n                    (\n                    <jats:italic>KCTD13)<\/jats:italic>\n                    encoded at 16p11.2 was identified as a candidate gene involved in hypospadias, cryptorchidism and other genitourinary (GU) tract anomalies. Copy number variants (CNVs) at 16p11.2 are among the most common syndromic genomic variants identified to date. Many patients with CNVs at this locus exhibit GU and\/or neurodevelopmental phenotypes.\n                    <jats:italic>KCTD13<\/jats:italic>\n                    encodes a substrate\u2010specific adapter of a BCR (BTB\u2013CUL3\u2013RBX1) E3\u2013ubiquitin\u2013protein\u2013ligase complex (BCR (BTB\u2013CUL3\u2013RBX1) E3\u2013ubiquitin\u2013protein\u2013ligase complex (B\u2010cell receptor (BCR) [BTB (the BTB domain is a conserved motif involved in protein\u2010protein interactions) Cullin3 complex RING protein Rbx1] E3\u2010ubiqutin\u2010protein\u2010ligase complex), which has essential roles in the regulation of cellular cytoskeleton, migration, proliferation, and neurodevelopment; yet its role in GU development is unknown. The prevalence of\n                    <jats:italic>KCTD13<\/jats:italic>\n                    CNVs in patients with GU anomalies (2.58%) is significantly elevated when compared with patients without GU anomalies or in the general population (0.10%).\n                    <jats:italic>KCTD13<\/jats:italic>\n                    is robustly expressed in the developing GU tract. Loss of\n                    <jats:italic>KCTD13<\/jats:italic>\n                    in cell lines results in significantly decreased levels of nuclear androgen receptor (AR), suggesting that loss of\n                    <jats:italic>KCTD13<\/jats:italic>\n                    affects AR sub\u2010cellular localization.\n                    <jats:italic>Kctd13<\/jats:italic>\n                    haploinsufficiency and homozygous deletion in mice cause a significant increase in the incidence of cryptorchidism and micropenis.\n                    <jats:italic>KCTD13\u2010<\/jats:italic>\n                    deficient mice exhibit testicular and penile abnormalities together with significantly reduced levels of nuclear AR and SOX9. In conclusion, gene\u2010dosage changes of murine\n                    <jats:italic>Kctd13<\/jats:italic>\n                    diminish nuclear AR sub\u2010cellular localization, as well as decrease SOX9 expression levels which likely contribute in part to the abnormal GU tract development in\n                    <jats:italic>Kctd13<\/jats:italic>\n                    mouse models and in patients with CNVs in\n                    <jats:italic>KCTD13<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1096\/fj.202200558r","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T07:45:30Z","timestamp":1664955930000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Gene dosage changes in\n                    <i>KCTD13<\/i>\n                    result in penile and testicular anomalies via diminished androgen receptor 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