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We report eleven individuals from seven families harboring predicted pathogenic biallelic, de novo, and heterozygous variants in the\n                    <jats:italic>NAV3<\/jats:italic>\n                    gene, which encodes the microtubule positive tip protein neuron navigator 3 (NAV3). All affected individuals have intellectual disability (ID), microcephaly, skeletal deformities, ocular anomalies, and behavioral issues. In mouse brain,\n                    <jats:italic>Nav3<\/jats:italic>\n                    is expressed throughout the nervous system, with more prominent signatures in postmitotic, excitatory, inhibiting, and sensory neurons. When overexpressed in HEK293T and COS7 cells, pathogenic variants impaired NAV3 ability to stabilize microtubules. Further, knocking-down\n                    <jats:italic>nav3<\/jats:italic>\n                    in zebrafish led to severe morphological defects, microcephaly, impaired neuronal growth, and behavioral impairment, which were rescued with co-injection of WT\n                    <jats:italic>NAV3<\/jats:italic>\n                    mRNA and not by transcripts encoding the pathogenic variants. Our findings establish the role of\n                    <jats:italic>NAV3<\/jats:italic>\n                    in neurodevelopmental disorders, and reveal its involvement in neuronal morphogenesis, and neuromuscular responses.\n                  <\/jats:p>","DOI":"10.1038\/s42003-024-06466-1","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T09:02:47Z","timestamp":1720429367000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Variants of NAV3, a neuronal morphogenesis protein, cause intellectual disability, developmental delay, and microcephaly"],"prefix":"10.1038","volume":"7","author":[{"given":"Amama","family":"Ghaffar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9691-2097","authenticated-orcid":false,"given":"Tehmeena","family":"Akhter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petter","family":"Str\u00f8mme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doriana","family":"Misceo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amjad","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8387-2247","authenticated-orcid":false,"given":"Eirik","family":"Frengen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Umair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Isidor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Cogn\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma A.","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ange-Line","family":"Bruel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Sorlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-6303","authenticated-orcid":false,"given":"Paul","family":"Kuentz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Chiaverini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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