{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:37:25Z","timestamp":1790473045533,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T00:00:00Z","timestamp":1579564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["546517"],"award-info":[{"award-number":["546517"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005844","name":"Universitas Diponegoro","doi-asserted-by":"publisher","award":["042.01.2.400898\/2016"],"award-info":[{"award-number":["042.01.2.400898\/2016"]}],"id":[{"id":"10.13039\/501100005844","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005844","name":"Universitas Diponegoro","doi-asserted-by":"publisher","award":["474\u201073\/UN7.P4.3\/PP\/2018"],"award-info":[{"award-number":["474\u201073\/UN7.P4.3\/PP\/2018"]}],"id":[{"id":"10.13039\/501100005844","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>GATA\u2010binding protein 4 (<jats:italic>GATA4<\/jats:italic>) and Friend of GATA 2 protein (<jats:italic>FOG2<\/jats:italic>, also known as <jats:italic>ZFPM2<\/jats:italic>) form a heterodimer complex that has been shown to influence transcription of genes in a number of developmental systems. Recent evidence has also shown these genes play a role in gonadal sexual differentiation in humans. Previously we identified four variants in <jats:italic>GATA4<\/jats:italic> and an unexpectedly large number of variants in <jats:italic>ZFPM2<\/jats:italic> in a cohort of individuals with 46,XY Differences\/Disorders of Sex Development (DSD) (Eggers et al, Genome Biology, 2016; 17: 243).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Here, we review variant curation and test the\u00a0functional activity of <jats:italic>GATA4<\/jats:italic> and <jats:italic>ZFPM2<\/jats:italic> variants. We assess variant transcriptional activity on gonadal specific promoters (<jats:italic>Sox9<\/jats:italic> and <jats:italic>AMH<\/jats:italic>) and variant protein\u2013protein interactions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings support that the majority of <jats:italic>GATA4<\/jats:italic> and <jats:italic>ZFPM2<\/jats:italic> variants we identified are benign in their contribution to 46,XY DSD. Indeed, only one variant, in the conserved N\u2010terminal zinc finger of <jats:italic>GATA4<\/jats:italic>, was considered pathogenic, with functional analysis confirming differences in its ability to regulate <jats:italic>Sox9<\/jats:italic> and <jats:italic>AMH<\/jats:italic> and in protein interaction with <jats:italic>ZFPM2<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study helps define the genetic factors contributing to 46,XY DSD and suggests that the majority of variants we identified in <jats:italic>GATA4<\/jats:italic> and <jats:italic>ZFPM2\/FOG2<\/jats:italic> are not causative.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1095","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T20:22:27Z","timestamp":1579638147000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Analysis of variants in <i>GATA4<\/i> and <i>FOG2<\/i>\/<i>ZFPM2<\/i> demonstrates benign contribution to 46,XY disorders of sex development"],"prefix":"10.1002","volume":"8","author":[{"given":"Jocelyn A.","family":"van den Bergen","sequence":"first","affiliation":[{"name":"Genetics Murdoch Children's Research Institute Parkville Vic. 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