{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T22:31:42Z","timestamp":1787524302177,"version":"build-2736575974"},"reference-count":59,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2027,2,13]],"date-time":"2027-02-13T00:00:00Z","timestamp":1802476800000},"content-version":"am","delay-in-days":318,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100007137","name":"Texas Children's Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007137","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD098458"],"award-info":[{"award-number":["R01 HD098458"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R24OD022005"],"award-info":[{"award-number":["R24OD022005"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016958","name":"National Institutes of Health Office of Research Infrastructure Programs","doi-asserted-by":"publisher","award":["R24OD031447"],"award-info":[{"award-number":["R24OD031447"]}],"id":[{"id":"10.13039\/100016958","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016958","name":"National Institutes of Health Office of Research Infrastructure Programs","doi-asserted-by":"publisher","award":["U54OD030165"],"award-info":[{"award-number":["U54OD030165"]}],"id":[{"id":"10.13039\/100016958","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U24HG013300"],"award-info":[{"award-number":["U24HG013300"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1105008"],"award-info":[{"award-number":["1105008"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1102971"],"award-info":[{"award-number":["1102971"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1195236"],"award-info":[{"award-number":["1195236"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1172897"],"award-info":[{"award-number":["1172897"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1195955"],"award-info":[{"award-number":["1195955"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1160893"],"award-info":[{"award-number":["1160893"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1116976"],"award-info":[{"award-number":["1116976"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017236","name":"Huffington Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017236","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U24HG011746"],"award-info":[{"award-number":["U24HG011746"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U01HG011744"],"award-info":[{"award-number":["U01HG011744"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U01HG011745"],"award-info":[{"award-number":["U01HG011745"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U01HG011758"],"award-info":[{"award-number":["U01HG011758"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U01HG011762"],"award-info":[{"award-number":["U01HG011762"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U01HG011755"],"award-info":[{"award-number":["U01HG011755"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["gimjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Genetics in Medicine"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1016\/j.gim.2026.101685","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T00:38:52Z","timestamp":1768610332000},"page":"101685","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rare heterozygous de novo variants in RAPGEF2 are associated with a neurodevelopmental disorder"],"prefix":"10.1016","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1602-3605","authenticated-orcid":false,"given":"Ali H.","family":"Bereshneh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1870-620X","authenticated-orcid":false,"given":"Kirkland A.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4453-4971","authenticated-orcid":false,"given":"Xueyang","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8984-4773","authenticated-orcid":false,"given":"Shabab B.","family":"Hannan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan A.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jullianne","family":"Diaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1852-2849","authenticated-orcid":false,"given":"Eyby","family":"Leon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6209-8301","authenticated-orcid":false,"given":"Tiana M.","family":"Moses","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8543-8284","authenticated-orcid":false,"given":"Mahshid S.","family":"Azamian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1460-5169","authenticated-orcid":false,"given":"Daryl A.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9533-7217","authenticated-orcid":false,"given":"Ping Yee","family":"Billie Au","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1112-7002","authenticated-orcid":false,"given":"Juan Pablo","family":"Appendino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2311-2174","authenticated-orcid":false,"given":"Ingrid E.","family":"Scheffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6576-5862","authenticated-orcid":false,"given":"Antony","family":"Kaspi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5132-0774","authenticated-orcid":false,"given":"Melanie","family":"Bahlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2739-0515","authenticated-orcid":false,"given":"Michael S.","family":"Hildebrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-7405","authenticated-orcid":false,"given":"Angela T.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8257-1864","authenticated-orcid":false,"given":"Ekanem","family":"Ekure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Milosavljevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise G.","family":"Lanza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxue","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D.","family":"Heaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Rogers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Posey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A.","family":"Rosenfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay C.","family":"Burrage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramin Zahedi","family":"Darshoori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandesh C.S.","family":"Nagamani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon-Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Ramamurthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Ramanathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhandong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Shulman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedhelm","family":"Hildebrandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4814-6765","authenticated-orcid":false,"given":"Jennifer E.","family":"Posey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-0875","authenticated-orcid":false,"given":"Paul","family":"Kruszka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5557-3709","authenticated-orcid":false,"given":"Eric","family":"Vilain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2172-8036","authenticated-orcid":false,"given":"Shinya","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5438-0879","authenticated-orcid":false,"given":"Oguz","family":"Kanca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7517-4302","authenticated-orcid":false,"given":"Seth","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5992-5989","authenticated-orcid":false,"given":"Hugo J.","family":"Bellen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.gim.2026.101685_bib1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1152\/physrev.00003.2012","article-title":"Regulation of small GTPases by GEFs, GAPs, and GDIs","volume":"93","author":"Cherfils","year":"2013","journal-title":"Physiol Rev"},{"issue":"2-3","key":"10.1016\/j.gim.2026.101685_bib2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0167-4889(02)00365-8","article-title":"Characterisation of PDZ-GEFs, a family of guanine nucleotide exchange factors specific for Rap1 and Rap2","volume":"1593","author":"Kuiperij","year":"2003","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"10.1016\/j.gim.2026.101685_bib3","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s00018-023-04999-y","article-title":"The guanine nucleotide exchange factor RapGEF2 is required for ERK-dependent immediate-early gene (Egr1) activation during fear memory formation","volume":"81","author":"Jiang","year":"2024","journal-title":"Cell Mol Life Sci"},{"issue":"6","key":"10.1016\/j.gim.2026.101685_bib4","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The Genotype-Tissue Expression (GTEx) project","volume":"45","year":"2013","journal-title":"Nat Genet"},{"issue":"5","key":"10.1016\/j.gim.2026.101685_bib5","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0248-17.2017","article-title":"NCS-Rapgef2, the protein product of the neuronal Rapgef2 gene, is a specific activator of D1 dopamine receptor-dependent ERK phosphorylation in mouse brain","volume":"4","author":"Jiang","year":"2017","journal-title":"eNeuro"},{"issue":"45","key":"10.1016\/j.gim.2026.101685_bib6","doi-asserted-by":"crossref","first-page":"34901","DOI":"10.1074\/jbc.M005327200","article-title":"Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction","volume":"275","author":"Rebhun","year":"2000","journal-title":"J Biol Chem"},{"issue":"9","key":"10.1016\/j.gim.2026.101685_bib7","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S0960-9822(00)00473-5","article-title":"The guanine nucleotide exchange factor CNrasGEF activates RAS in response to cAMP and cGMP","volume":"10","author":"Pham","year":"2000","journal-title":"Curr Biol"},{"key":"10.1016\/j.gim.2026.101685_bib8","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1186\/1471-2105-12-357","article-title":"An integrative approach to ortholog prediction for disease-focused and other functional studies","volume":"12","author":"Hu","year":"2011","journal-title":"BMC Bioinform"},{"issue":"1","key":"10.1016\/j.gim.2026.101685_bib9","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13041-017-0342-7","article-title":"The Rap activator Gef26 regulates synaptic growth and neuronal survival via inhibition of BMP signaling","volume":"10","author":"Heo","year":"2017","journal-title":"Mol Brain"},{"issue":"1","key":"10.1016\/j.gim.2026.101685_bib10","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.yexcr.2019.04.024","article-title":"Corrigendum to \u201cThe PDZ-GEF Gef26 regulates synapse development and function via FasII and Rap 1 at the Drosophila neuromuscular junction\u201d","volume":"381","author":"Ou","year":"2019","journal-title":"Exp Cell Res"},{"issue":"10","key":"10.1016\/j.gim.2026.101685_bib11","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/humu.22844","article-title":"GeneMatcher: a matching Tool for connecting investigators with an interest in the same gene","volume":"36","author":"Sobreira","year":"2015","journal-title":"Hum Mutat"},{"key":"10.1016\/j.gim.2026.101685_bib12","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.76077","article-title":"An expanded toolkit for Drosophila gene tagging using synthesized homology donor constructs for CRISPR-mediated homologous recombination","volume":"11","author":"Kanca","year":"2022","journal-title":"Elife"},{"key":"10.1016\/j.gim.2026.101685_bib13","article-title":"In vivo functional study of disease-associated rare human variants using Drosophila","volume":"150","author":"Harnish","year":"2019","journal-title":"J Vis Exp"},{"issue":"11","key":"10.1016\/j.gim.2026.101685_bib14","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1242\/dev.088757","article-title":"A versatile platform for creating a comprehensive UAS-ORFeome library in Drosophila","volume":"140","author":"Bischof","year":"2013","journal-title":"Development"},{"issue":"5806","key":"10.1016\/j.gim.2026.101685_bib15","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1126\/science.1134426","article-title":"P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster","volume":"314","author":"Venken","year":"2006","journal-title":"Science"},{"issue":"5","key":"10.1016\/j.gim.2026.101685_bib16","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.ajhg.2023.03.012","article-title":"Bi-allelic variants in INTS11 are associated with a complex neurological disorder","volume":"110","author":"Tepe","year":"2023","journal-title":"Am J Hum Genet"},{"issue":"2","key":"10.1016\/j.gim.2026.101685_bib17","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.jneumeth.2011.08.037","article-title":"Increased throughput assays of locomotor dysfunction in Drosophila larvae","volume":"203","author":"Sinadinos","year":"2012","journal-title":"J Neurosci Methods"},{"issue":"4","key":"10.1016\/j.gim.2026.101685_bib18","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1038\/s41380-022-01879-y","article-title":"Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development","volume":"28","author":"Kaspi","year":"2023","journal-title":"Mol Psychiatry"},{"issue":"7","key":"10.1016\/j.gim.2026.101685_bib19","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.tig.2020.11.002","article-title":"To NMD or not to NMD: nonsense-mediated mRNA decay in cancer and other genetic diseases","volume":"37","author":"Supek","year":"2021","journal-title":"Trends Genet"},{"issue":"5","key":"10.1016\/j.gim.2026.101685_bib20","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1186\/1479-7364-2-5-274","article-title":"Human SNPs resulting in premature stop codons and protein truncation","volume":"2","author":"Savas","year":"2006","journal-title":"Hum Genomics"},{"issue":"6","key":"10.1016\/j.gim.2026.101685_bib21","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.ajhg.2017.04.010","article-title":"MARRVEL: integration of human and model organism genetic resources to facilitate functional annotation of the human genome","volume":"100","author":"Wang","year":"2017","journal-title":"Am J Hum Genet"},{"issue":"4","key":"10.1016\/j.gim.2026.101685_bib22","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ajhg.2017.09.001","article-title":"DOMINO: using machine learning to predict genes associated with dominant disorders","volume":"101","author":"Quinodoz","year":"2017","journal-title":"Am J Hum Genet"},{"issue":"7993","key":"10.1016\/j.gim.2026.101685_bib23","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41586-023-06045-0","article-title":"A genomic mutational constraint map using variation in 76,156 human genomes","volume":"625","author":"Chen","year":"2024","journal-title":"Nature"},{"issue":"web server issue","key":"10.1016\/j.gim.2026.101685_bib24","doi-asserted-by":"crossref","first-page":"W452","DOI":"10.1093\/nar\/gks539","article-title":"SIFT web server: predicting effects of amino acid substitutions on proteins","volume":"40","author":"Sim","year":"2012","journal-title":"Nucleic Acids Res"},{"issue":"13","key":"10.1016\/j.gim.2026.101685_bib25","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1093\/nar\/gkg509","article-title":"SIFT: predicting amino acid changes that affect protein function","volume":"31","author":"Ng","year":"2003","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"10.1016\/j.gim.2026.101685_bib26","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat Methods"},{"issue":"8","key":"10.1016\/j.gim.2026.101685_bib27","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nmeth0810-575","article-title":"MutationTaster evaluates disease-causing potential of sequence alterations","volume":"7","author":"Schwarz","year":"2010","journal-title":"Nat Methods"},{"issue":"5","key":"10.1016\/j.gim.2026.101685_bib28","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"issue":"1","key":"10.1016\/j.gim.2026.101685_bib29","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/s41576-023-00633-6","article-title":"Integrating non-mammalian model organisms in the diagnosis of rare genetic diseases in humans","volume":"25","author":"Yamamoto","year":"2024","journal-title":"Nat Rev Genet"},{"issue":"6584","key":"10.1016\/j.gim.2026.101685_bib30","doi-asserted-by":"crossref","DOI":"10.1126\/science.abk2432","article-title":"Fly Cell Atlas: a single-nucleus transcriptomic atlas of the adult fruit fly","volume":"375","author":"Li","year":"2022","journal-title":"Science"},{"issue":"5","key":"10.1016\/j.gim.2026.101685_bib31","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/nsmb1081","article-title":"EJC-independent degradation of nonsense immunoglobulin-mu mRNA depends on 3\u2032 UTR length","volume":"13","author":"B\u00fchler","year":"2006","journal-title":"Nat Struct Mol Biol"},{"issue":"10","key":"10.1016\/j.gim.2026.101685_bib32","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1261\/rna.038893.113","article-title":"Comparison of EJC-enhanced and EJC-independent NMD in human cells reveals two partially redundant degradation pathways","volume":"19","author":"Metze","year":"2013","journal-title":"RNA"},{"issue":"5","key":"10.1016\/j.gim.2026.101685_bib33","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.devcel.2013.10.023","article-title":"Control of epithelial cell migration and invasion by the IKK\u03b2- and CK1\u03b1-mediated degradation of RAPGEF2","volume":"27","author":"Magliozzi","year":"2013","journal-title":"Dev Cell"},{"key":"10.1016\/j.gim.2026.101685_bib34","doi-asserted-by":"crossref","DOI":"10.3389\/fncir.2023.1175899","article-title":"Linking neural circuits to the mechanics of animal behavior in Drosophila larval locomotion","volume":"17","author":"Kohsaka","year":"2023","journal-title":"Front Neural Circuits"},{"issue":"2","key":"10.1016\/j.gim.2026.101685_bib35","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0896-6273(00)81169-1","article-title":"Drosophila Futsch\/22C10 is a MAP1B-like protein required for dendritic and axonal development","volume":"26","author":"Hummel","year":"2000","journal-title":"Neuron"},{"key":"10.1016\/j.gim.2026.101685_bib36","first-page":"6","article-title":"Membrane targeted horseradish peroxidase as a marker for correlative fluorescence and electron microscopy studies","volume":"4","author":"Li","year":"2010","journal-title":"Front Neural Circuits"},{"key":"10.1016\/j.gim.2026.101685_bib37","article-title":"Using drosophila larval neuromuscular junction and muscle cells to visualize microtubule network","volume":"200","author":"Zhang","year":"2023","journal-title":"J Vis Exp"},{"issue":"48","key":"10.1016\/j.gim.2026.101685_bib38","doi-asserted-by":"crossref","first-page":"15962","DOI":"10.1523\/JNEUROSCI.2526-14.2014","article-title":"Futsch\/MAP1B mRNA is a translational target of TDP-43 and is neuroprotective in a Drosophila Model of amyotrophic lateral sclerosis","volume":"34","author":"Coyne","year":"2014","journal-title":"J Neurosci"},{"issue":"22","key":"10.1016\/j.gim.2026.101685_bib39","doi-asserted-by":"crossref","first-page":"7966","DOI":"10.1128\/MCB.01275-07","article-title":"The Rap GTPase activator Drosophila PDZ-GEF regulates cell shape in epithelial migration and morphogenesis","volume":"27","author":"Boettner","year":"2007","journal-title":"Mol Cell Biol"},{"issue":"1","key":"10.1016\/j.gim.2026.101685_bib40","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.devcel.2005.11.004","article-title":"Rap-GEF signaling controls stem cell anchoring to their niche through regulating DE-cadherin-mediated cell adhesion in the Drosophila testis","volume":"10","author":"Wang","year":"2006","journal-title":"Dev Cell"},{"issue":"15","key":"10.1016\/j.gim.2026.101685_bib41","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1242\/dev.02449","article-title":"The PDZ-GEF dizzy regulates cell shape of migrating macrophages via Rap1 and integrins in the Drosophila embryo","volume":"133","author":"Huelsmann","year":"2006","journal-title":"Development"},{"issue":"6","key":"10.1016\/j.gim.2026.101685_bib42","doi-asserted-by":"crossref","first-page":"550","DOI":"10.5607\/en.2018.27.6.550","article-title":"A De NovoRAPGEF2 variant identified in a sporadic amyotrophic lateral sclerosis patient impairs microtubule stability and axonal mitochondria distribution","volume":"27","author":"Heo","year":"2018","journal-title":"Exp Neurobiol"},{"issue":"2","key":"10.1016\/j.gim.2026.101685_bib43","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.yexcr.2018.12.008","article-title":"The PDZ-GEF Gef26 regulates synapse development and function via FasII and Rap1 at the Drosophila neuromuscular junction","volume":"374","author":"Ou","year":"2019","journal-title":"Exp Cell Res"},{"issue":"1","key":"10.1016\/j.gim.2026.101685_bib44","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1005810","article-title":"A novel, noncanonical BMP pathway modulates synapse maturation at the drosophila neuromuscular junction","volume":"12","author":"Sulkowski","year":"2016","journal-title":"PLoS Genet"},{"issue":"4","key":"10.1016\/j.gim.2026.101685_bib45","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.neuron.2008.03.007","article-title":"Nervous wreck interacts with thickveins and the endocytic machinery to attenuate retrograde BMP signaling during synaptic growth","volume":"58","author":"O\u2019Connor-Giles","year":"2008","journal-title":"Neuron"},{"key":"10.1016\/j.gim.2026.101685_bib46","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/bs.ctdb.2022.04.001","article-title":"Local BMP signaling: a sensor for synaptic activity that balances synapse growth and function","volume":"150","author":"Vicidomini","year":"2022","journal-title":"Curr Top Dev Biol"},{"issue":"3","key":"10.1016\/j.gim.2026.101685_bib47","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0142-16.2016","article-title":"Crucial role of Rapgef2 and Rapgef6, a family of guanine nucleotide exchange factors for Rap1 small GTPase, in formation of apical surface adherens junctions and neural progenitor development in the mouse cerebral cortex","volume":"3","author":"Maeta","year":"2016","journal-title":"eNeuro"},{"key":"10.1016\/j.gim.2026.101685_bib48","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2024.1352731","article-title":"Interactions between Ras and Rap signaling pathways during neurodevelopment in health and disease","volume":"17","author":"Cherra","year":"2024","journal-title":"Front Mol Neurosci"},{"key":"10.1016\/j.gim.2026.101685_bib49","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2022.945680","article-title":"PXF-1 promotes synapse development at the neuromuscular junction in Caenorhabditis elegans","volume":"15","author":"Lamb","year":"2022","journal-title":"Front Mol Neurosci"},{"issue":"1","key":"10.1016\/j.gim.2026.101685_bib50","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13041-018-0370-y","article-title":"Comprehensive behavioral analysis of mice deficient in Rapgef2 and Rapgef6, a subfamily of guanine nucleotide exchange factors for Rap small GTPases possessing the Ras\/Rap-associating domain","volume":"11","author":"Maeta","year":"2018","journal-title":"Mol Brain"},{"issue":"D1","key":"10.1016\/j.gim.2026.101685_bib51","doi-asserted-by":"crossref","first-page":"D1038","DOI":"10.1093\/nar\/gkac972","article-title":"The International Mouse Phenotyping Consortium: comprehensive knockout phenotyping underpinning the study of human disease","volume":"51","author":"Groza","year":"2023","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"10.1016\/j.gim.2026.101685_bib52","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.bbrc.2009.07.108","article-title":"Impaired vascular development in the yolk sac and allantois in mice lacking RA-GEF-1","volume":"387","author":"Kanemura","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"10.1016\/j.gim.2026.101685_bib53","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1002\/wsbm.44","article-title":"The mammalian phenotype ontology: enabling robust annotation and comparative analysis","volume":"1","author":"Smith","year":"2009","journal-title":"Wiley Interdiscip Rev Syst Biol Med"},{"issue":"4","key":"10.1016\/j.gim.2026.101685_bib54","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.ajhg.2009.03.010","article-title":"DECIPHER: database of chromosomal imbalance and phenotype in humans using Ensembl resources","volume":"84","author":"Firth","year":"2009","journal-title":"Am J Hum Genet"},{"issue":"database issue","key":"10.1016\/j.gim.2026.101685_bib55","doi-asserted-by":"crossref","first-page":"D986","DOI":"10.1093\/nar\/gkt958","article-title":"The Database of Genomic Variants: a curated collection of structural variation in the human genome","volume":"42","author":"MacDonald","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"7809","key":"10.1016\/j.gim.2026.101685_bib56","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"issue":"4","key":"10.1016\/j.gim.2026.101685_bib57","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/s41588-018-0067-2","article-title":"Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy","volume":"50","author":"Ishiura","year":"2018","journal-title":"Nat Genet"},{"issue":"D1","key":"10.1016\/j.gim.2026.101685_bib58","doi-asserted-by":"crossref","first-page":"D1038","DOI":"10.1093\/nar\/gky1151","article-title":"OMIM.org: leveraging knowledge across phenotype-gene relationships. OMIM.org","volume":"47","author":"Amberger","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"27","key":"10.1016\/j.gim.2026.101685_bib59","doi-asserted-by":"crossref","first-page":"20829","DOI":"10.1074\/jbc.M001113200","article-title":"Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs","volume":"275","author":"de Rooij","year":"2000","journal-title":"J Biol Chem"}],"container-title":["Genetics in Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1098360026000031?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1098360026000031?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T23:24:46Z","timestamp":1786663486000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1098360026000031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":59,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["S1098360026000031"],"URL":"https:\/\/doi.org\/10.1016\/j.gim.2026.101685","relation":{},"ISSN":["1098-3600"],"issn-type":[{"value":"1098-3600","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Rare heterozygous de novo variants in RAPGEF2 are associated with a neurodevelopmental disorder","name":"articletitle","label":"Article Title"},{"value":"Genetics in Medicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.gim.2026.101685","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"101685"}}