{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T02:28:11Z","timestamp":1786588091071,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88887.832293\/2023-00"],"award-info":[{"award-number":["88887.832293\/2023-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100024786","name":"Instituto Oswaldo Cruz","doi-asserted-by":"publisher","award":["2025202510014"],"award-info":[{"award-number":["2025202510014"]}],"id":[{"id":"10.13039\/501100024786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"\n Introduction<\/jats:title>\n \n Orofacial cleft is a congenital anomaly influenced by genetic and environmental factors.\n NECTIN1<\/jats:italic>\n encodes an adhesion protein critical for the adherens junctions and has been associated with orofacial clefts. This study aimed to investigate the contribution of\n NECTIN1<\/jats:italic>\n to the etiology of NSCL\/P in a population from Patagonia, Argentina, a region with a high prevalence of orofacial clefts.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n First, an association study was conducted to evaluate the relationship between orofacial clefts and two\n NECTIN1<\/jats:italic>\n single nucleotide variants: rs3829260 (G\n \n \n \n ><\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n C) and rs7940667 (C\n \n \n \n ><\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n A). Genotyping of 132 affected families was performed. The transmission disequilibrium test was applied, and identified variants were analyzed\n in silico<\/jats:italic>\n using VarSome and ClinVar. No statistically significant association was found for rs3829260 (G\n \n \n \n ><\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n C) or rs7940667 (C\n \n \n \n ><\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n A). Subsequently, all six exons of\n NECTIN1<\/jats:italic>\n were sequenced in 116 probands. Molecular modeling was then performed to evaluate the functional impact on protein structure.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Three rare heterozygous variants were identified in five probands: two non-synonymous variants (p.(Arg199Gln) and p.(Gly44Ser)) and one synonymous variant p.(His394=). Molecular modeling suggested that p.(Arg199Gln) and p.(Gly44Ser) could locally impact the structural dynamics and glycosylation pattern.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These findings show the potential involvement of\n NECTIN1<\/jats:italic>\n in orofacial clefts and suggest that rare genetic variants may contribute to disease susceptibility.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fgene.2026.1894075","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T01:58:10Z","timestamp":1786586290000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Rare missense variants in NECTIN1 alter local protein structure and may contribute to non-syndromic cleft lip with or without palate"],"prefix":"10.3389","volume":"17","author":[{"given":"Ana Luiza","family":"Meneguci Moreira Franco","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Epidemiologia de Malforma\u00e7\u00f5es Cong\u00eanitas (LEMC), Instituto Oswaldo Cruz, FIOCRUZ","place":["Rio de Janeiro, Brazil"]},{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Gen\u00e9tica da Universidade Federal do Rio de Janeiro (PGGen-UFRJ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Antunes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00f4mica Aplicada e Bioinova\u00e7\u00f5es, Instituto Oswaldo Cruz, FIOCRUZ","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina","family":"Proen\u00e7a da Fonseca","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Biomedicina Translacional, Universidade do Grande Rio\/AFYA","place":["Rio de Janeiro, Brazil"]},{"name":"Laborat\u00f3rio de Gen\u00e9tica Humana, Instituto Oswaldo Cruz, FIOCRUZ","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Clara","family":"Rodrigues Moreira Gomes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Epidemiologia de Malforma\u00e7\u00f5es Cong\u00eanitas (LEMC), Instituto Oswaldo Cruz, FIOCRUZ","place":["Rio de Janeiro, Brazil"]},{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Biologia Celular e Molecular, Instituto Oswaldo Cruz, Fiocruz","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina","family":"Ramos Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Gen\u00f4mica Aplicada e Bioinova\u00e7\u00f5es, Instituto Oswaldo Cruz, FIOCRUZ","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ieda Maria","family":"Orioli","sequence":"additional","affiliation":[{"name":"ECLAMC no Departamento de Gen\u00e9tica, Laborat\u00f3rio de Malforma\u00e7\u00f5es Cong\u00eanitas (LMC), Instituto de Biologia, Universidade Federal do Rio de Janeiro","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Martinez de Carvalho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Epidemiologia de Malforma\u00e7\u00f5es Cong\u00eanitas (LEMC), Instituto Oswaldo Cruz, FIOCRUZ","place":["Rio de Janeiro, Brazil"]},{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Gen\u00e9tica da Universidade Federal do Rio de Janeiro (PGGen-UFRJ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"Gromacs: high performance molecular simulations through multi-level parallelism from laptops to supercomputers","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"B2","doi-asserted-by":"publisher","first-page":"153","DOI":"10.3390\/biology11020153","article-title":"To stick or not to stick: adhesions in orofacial clefts","volume":"11","author":"Antiguas","year":"2022","journal-title":"Biology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.1002\/ajmg.a.31367","article-title":"Pvrl1 variants contribute to non-syndromic cleft lip and palate in multiple populations","volume":"140","author":"Avila","year":"2006","journal-title":"Am. 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