ArticleHuman molecular genetics2015
A single nucleotide polymorphism associated with isolated cleft lip and palate, thyroid cancer and hypothyroidism alters the activity of an oral epithelium and thyroid enhancer near FOXE1.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 4 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 4 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Exploration of the association between FOXE1 gene polymorphism and differentiated thyroid cancer: a meta-analysis.BMC medical genetics · 2018Pooled it
- Genome-wide meta-analyses of nonsyndromic orofacial clefts identify novel associations between FOXE1 and all orofacial clefts, and TP63 and cleft lip with or without cleft palate.Human genetics · 2017Pooled it
- Imputation of orofacial clefting data identifies novel risk loci and sheds light on the genetic background of cleft lip ± cleft palate and cleft palate only.Human molecular genetics · 2017Pooled it
- Identification of functional non-coding variants associated with orofacial cleft.Nature communications · 2025Article
- Functional Validation of Noncoding Variants Associated With Nonsyndromic Orofacial Cleft.Human mutation · 2025Review
- Transcriptional and epigenetic characterization of a new in vitro platform to model the formation of human pharyngeal endoderm.Genome biology · 2024Article
- Identification of GermlineInternational journal of molecular sciences · 2024Article
- Reduced expression ofFrontiers in endocrinology · 2024Article
- Disruption of theFrontiers in cell and developmental biology · 2023Article
- The length of FOXE1 polyalanine tract in congenital hypothyroidism: Evidence for a pathogenic role from familial, molecular and cohort studies.Frontiers in endocrinology · 2023Article
- Integration of single-cell transcriptomes and chromatin landscapes reveals regulatory programs driving pharyngeal organ development.Nature communications · 2022Article
- Genetic predisposition of SNPs in miRNA-149 (rs2292832) and FOXE1 (rs3758249) in thyroid Cancer.Molecular biology reports · 2021Article
- Identification of microRNAs and gene regulatory networks in cleft lip common in humans and mice.Human molecular genetics · 2021Article
- Article
- Analysis of zebrafish periderm enhancers facilitates identification of a regulatory variant near humaneLife · 2020Article
- PBX-WNT-P63-IRF6 pathway in nonsyndromic cleft lip and palate.Birth defects research · 2020Article
- Non-syndromic Cleft Palate: An Overview on Human Genetic and Environmental Risk Factors.Frontiers in cell and developmental biology · 2020Review
- Association of low-frequency genetic variants in regulatory regions with nonsyndromic orofacial clefts.American journal of medical genetics. Part A · 2019Article
- Article
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Three common diseases, isolated cleft lip and cleft palate (CLP), hypothyroidism and thyroid cancer all map to the FOXE1 locus, but causative variants have yet to be identified. In patients with CLP, the frequency of coding mutations in FOXE1 fails to account for the risk attributable to this locus, suggesting that the common risk alleles reside in nearby regulatory elements. Using a combination of zebrafish and mouse transgenesis, we screened 15 conserved non-coding sequences for enhancer activity, identifying three that regulate expression in a tissue specific pattern consistent with endogenous foxe1 expression. These three, located -82.4, -67.7 and +22.6 kb from the FOXE1 start codon, are all active in the oral epithelium or branchial arches. The -67.7 and +22.6 kb elements are also active in the developing heart, and the -67.7 kb element uniquely directs expression in the developing thyroid. Within the -67.7 kb element is the SNP rs7850258 that is associated with all three diseases. Quantitative reporter assays in oral epithelial and thyroid cell lines show that the rs7850258 allele (G) associated with CLP and hypothyroidism has significantly greater enhancer activity than the allele associated with thyroid cancer (A). Moreover, consistent with predicted transcription factor binding differences, the -67.7 kb element containing rs7850258 allele G is significantly more responsive to both MYC and ARNT than allele A. By demonstrating that this common non-coding variant alters FOXE1 expression, we have identified at least in part the functional basis for the genetic risk of these seemingly disparate disorders.
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