{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T03:48:16Z","timestamp":1776916096602,"version":"3.51.2"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Department of Science and Technology of Sichuan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>rs7590268 present on the 2p21 locus was identified to be associated with non-syndromic cleft lip with or without cleft palate (NSCL\/P) in several populations, including the Chinese Han population, indicating that 2p21 was a susceptibility locus for NSCL\/P. However, previous studies have only identified common single-nucleotide polymorphism (SNP) within the <jats:italic>THADA<\/jats:italic> gene, neglecting the rare variants and other genes in 2p21; thus, this study was designed to investigate additional variants and novel susceptibility genes in 2p21. A total of 159 NSCL\/P patients and 542 controls were recruited in the discovery phase, whereas 1830 NSCL\/P patients and 2,436 controls were recruited in the replication phase. After targeted region sequencing, we performed association and burden analyses for the common and rare variants, respectively. Furthermore, RNA-seq, proliferation assay and cell cycle analysis were performed to clarify the possible function of the candidate gene <jats:italic>ZFP36L2<\/jats:italic>. Association analysis showed that four SNPs were specifically associated with non-syndromic cleft lip only (NSCLO) and two SNPs were associated with both NSCLO and NSCL\/P. Burden analysis indicated that <jats:italic>ZFP36L2<\/jats:italic> was associated with NSCLO (<jats:italic>p<\/jats:italic> = .0489, OR = 2.41, 95% CI: 0.98\u20135.90). Moreover, SNPs in the <jats:italic>ZFP36L2<\/jats:italic> targeted gene <jats:italic>JUP<\/jats:italic> were also associated with NSCLO. <jats:italic>ZFP36L2<\/jats:italic> also inhibited cell proliferation and induced G2 phase arrest in the GMSM-K cell line. Therefore, we proposed that <jats:italic>ZFP36L2<\/jats:italic> is a novel susceptibility gene of NSCLO in the 2p21 locus, which could lead to NSCLO by modulating cell proliferation and cycle.<\/jats:p>","DOI":"10.3389\/fgene.2022.802229","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T09:51:51Z","timestamp":1644918711000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeted Re-Sequencing of the 2p21 Locus Identifies Non-Syndromic Cleft Lip Only Novel Susceptibility Gene ZFP36L2"],"prefix":"10.3389","volume":"13","author":[{"given":"Mu-Jia","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Yu","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiu-Shuang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong-Lin","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg0720s76","article-title":"Predicting Functional Effect of Human Missense Mutations Using PolyPhen\u20102","volume":"76","author":"Adzhubei","year":"2013","journal-title":"Curr. 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