{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:19:39Z","timestamp":1778642379009,"version":"3.51.4"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,11,21]],"date-time":"2016-11-21T00:00:00Z","timestamp":1479686400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1"},{"start":{"date-parts":[[2016,11,21]],"date-time":"2016-11-21T00:00:00Z","timestamp":1479686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institute for Health Research","doi-asserted-by":"crossref","award":["G118160216"],"award-info":[{"award-number":["G118160216"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000145","name":"Alberta Innovates - Health Solutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000145","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alberta Health Services Graduate Student Recruitment Studentships"},{"name":"Department of Medical Genetics Recruitment Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2017,2]]},"DOI":"10.1002\/humu.23141","type":"journal-article","created":{"date-parts":[[2016,11,2]],"date-time":"2016-11-02T09:39:35Z","timestamp":1478079575000},"page":"169-179","source":"Crossref","is-referenced-by-count":21,"title":["Comparison of Bioinformatics Prediction, Molecular Modeling, and Functional Analyses of<i>FOXC1<\/i>Mutations in Patients with Axenfeld-Rieger Syndrome"],"prefix":"10.1155","volume":"38","author":[{"given":"Morteza","family":"Seifi","sequence":"first","affiliation":[{"name":"Department of Medical Genetics; Faculty of Medicine & Dentistry; University of Alberta; Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Footz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics; Faculty of Medicine & Dentistry; University of Alberta; Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherry A. M.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics; Faculty of Medicine & Dentistry; University of Alberta; Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics; Faculty of Medicine & Dentistry; University of Alberta; Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,11,21]]},"reference":[{"key":"10.1002\/humu.23141-BIB0001|humu23141-cit-0001","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"},{"key":"10.1002\/humu.23141-BIB0002|humu23141-cit-0002","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1038\/ng.422","article-title":"FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation","volume":"41","author":"Aldinger","year":"2009","journal-title":"Nat Genet"},{"key":"10.1002\/humu.23141-BIB0003|humu23141-cit-0003","doi-asserted-by":"crossref","first-page":"10098","DOI":"10.1074\/jbc.M513629200","article-title":"Regulation of FOXC1 stability and transcriptional activity by an epidermal growth factor-activated mitogen-activated protein kinase signaling cascade","volume":"281","author":"Berry","year":"2006","journal-title":"J Biol Chem"},{"key":"10.1002\/humu.23141-BIB0004|humu23141-cit-0004","doi-asserted-by":"crossref","first-page":"10292","DOI":"10.1074\/jbc.M110266200","article-title":"FOXC1 transcriptional regulation is mediated by N- and C-terminal activation domains and contains a phosphorylated transcriptional inhibitory domain","volume":"277","author":"Berry","year":"2002","journal-title":"J Biol Chem"},{"key":"10.1002\/humu.23141-BIB0005|humu23141-cit-0005","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/prot.340160110","article-title":"An empirical energy function for threading protein sequence through the folding motif","volume":"16","author":"Bryant","year":"1993","journal-title":"Proteins"},{"key":"10.1002\/humu.23141-BIB0006|humu23141-cit-0006","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1167\/iovs.08-2253","article-title":"The transcription factor gene FOXC1 exhibits a limited role in primary congenital glaucoma","volume":"50","author":"Chakrabarti","year":"2009","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1002\/humu.23141-BIB0007|humu23141-cit-0007","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1101\/gr.092619.109","article-title":"Identification of deleterious mutations within three human genomes","volume":"19","author":"Chun","year":"2009","journal-title":"Genome Res"},{"key":"10.1002\/humu.23141-BIB0049|humu23141-cit-0049","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/364412a0","article-title":"Co-crystal structure of the HNF3\/forkhead DNA recognition motif resembles histone H5","volume":"364","author":"Clark","year":"1993","journal-title":"Nature"},{"key":"10.1002\/humu.23141-BIB0008|humu23141-cit-0008","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1167\/iovs.10-5309","article-title":"Expanding the spectrum of FOXC1 and PITX2 mutations and copy number changes in patients with anterior segment malformations","volume":"52","author":"D'haene","year":"2011","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"10.1002\/humu.23141-BIB0009|humu23141-cit-0009","first-page":"1","article-title":"A Novel Mutation of FOXC1 (R127L) in an Axenfeld-Rieger Syndrome Family with Glaucoma and Multiple Congenital Heart Diseases","volume":"6810","author":"Du","year":"2015","journal-title":"Ophthalmic Genet"},{"key":"10.1002\/humu.23141-BIB0010|humu23141-cit-0010","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/j.1399-0004.2009.01210.x","article-title":"Characterization of a novel FOXC1 mutation, P297S, identified in two individuals with anterior segment dysgenesis","volume":"76","author":"Fetterman","year":"2009","journal-title":"Clin Genet"},{"key":"10.1002\/humu.23141-BIB0011|humu23141-cit-0011","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1089\/gtmb.2010.0036","article-title":"Using SIFT and PolyPhen to predict loss-of-function and gain-of-function mutations","volume":"14","author":"Flanagan","year":"2010","journal-title":"Genet Test Mol Biomarkers"},{"key":"10.1002\/humu.23141-BIB0012|humu23141-cit-0012","first-page":"1005","article-title":"Novel mutations in the FOXC1 gene in Japanese patients with Axenfeld-Rieger syndrome","volume":"13","author":"Fuse","year":"2007","journal-title":"Mol Vis"},{"key":"10.1002\/humu.23141-BIB0013|humu23141-cit-0013","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/ajmg.a.35697","article-title":"Cardiac anomalies in Axenfeld-Rieger syndrome due to a novel FOXC1 mutation","volume":"161","author":"Gripp","year":"2013","journal-title":"Am J Med Genet Part A"},{"key":"10.1002\/humu.23141-BIB0014|humu23141-cit-0014","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1002\/elps.1150181505","article-title":"SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling","volume":"18","author":"Guex","year":"1997","journal-title":"Electrophoresis"},{"key":"10.1002\/humu.23141-BIB0015|humu23141-cit-0015","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1167\/iovs.08-3032","article-title":"Severe molecular defects of a novel FOXC1 W152G mutation result in aniridia","volume":"50","author":"Ito","year":"2009","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1002\/humu.23141-BIB0016|humu23141-cit-0016","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1001\/archopht.125.1.128","article-title":"Analyses of a novel L130F missense mutation in FOXC1","volume":"125","author":"Ito","year":"2007","journal-title":"Arch Ophthalmol"},{"key":"10.1002\/humu.23141-BIB0017|humu23141-cit-0017","doi-asserted-by":"crossref","DOI":"10.1093\/jnci\/djv148","article-title":"Diagnosis of basal-like breast cancer using a FOXC1-based assay","volume":"107","author":"Jensen","year":"2015","journal-title":"J Natl Cancer Inst"},{"key":"10.1002\/humu.23141-BIB0018|humu23141-cit-0018","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0925-4773(96)00539-4","article-title":"Five years on the wings of fork head","volume":"57","author":"Kaufmann","year":"1996","journal-title":"Mech Dev"},{"key":"10.1002\/humu.23141-BIB0019|humu23141-cit-0019","first-page":"1366","article-title":"Molecular analysis of FOXC1 in subjects presenting with severe developmental eye anomalies","volume":"15","author":"Kaur","year":"2009","journal-title":"Mol Vis"},{"key":"10.1002\/humu.23141-BIB0020|humu23141-cit-0020","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1006\/dbio.1999.9314","article-title":"The Forkhead\/Winged-Helix gene, Mf1, is necessary for the normal development of the cornea and formation of the anterior chamber in the mouse eye","volume":"211","author":"Kidson","year":"1999","journal-title":"Dev Biol"},{"key":"10.1002\/humu.23141-BIB0021|humu23141-cit-0021","first-page":"1843","article-title":"Ocular developmental abnormalities and glaucoma associated with interstitial 6p25 duplications and deletions","volume":"43","author":"Lehmann","year":"2002","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"10.1002\/humu.23141-BIB0022|humu23141-cit-0022","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1086\/321194","article-title":"Chromosomal duplication involving the forkhead transcription factor gene FOXC1 causes iris hypoplasia and glaucoma","volume":"67","author":"Lehmann","year":"2000","journal-title":"Am J Hum Genet"},{"key":"10.1002\/humu.23141-BIB0023|humu23141-cit-0023","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1093\/bioinformatics\/btp528","article-title":"Automated inference of molecular mechanisms of disease from amino acid substitutions","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"10.1002\/humu.23141-BIB0024|humu23141-cit-0024","doi-asserted-by":"crossref","first-page":"e1310","DOI":"10.7717\/peerj.1310","article-title":"Expression of temperature-sensitive ion channel TRPM8 in sperm cells correlates with vertebrate evolution","volume":"3","author":"Majhi","year":"2015","journal-title":"Peer J"},{"key":"10.1002\/humu.23141-BIB0025|humu23141-cit-0025","doi-asserted-by":"crossref","first-page":"e1004725","DOI":"10.1371\/journal.pcbi.1004725","article-title":"Towards increasing the clinical relevance of in silico methods to predict pathogenic missense variants","volume":"12","author":"Masica","year":"2016","journal-title":"PLoS Comput Biol"},{"key":"10.1002\/humu.23141-BIB0026|humu23141-cit-0026","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0119272","article-title":"Hypo- and hypermorphic FOXC1 mutations in dominant glaucoma: transactivation and phenotypic variability","volume":"10","author":"Medina-Trillo","year":"2015","journal-title":"PLoS One"},{"key":"10.1002\/humu.23141-BIB0027|humu23141-cit-0027","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/sj.ejhg.5200354","article-title":"Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25","volume":"8","author":"Mirzayans","year":"2000","journal-title":"Eur J Hum Genet"},{"key":"10.1002\/humu.23141-BIB0028|humu23141-cit-0028","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1167\/iovs.04-0167","article-title":"The wing 2 region of the FOXC1 forkhead domain is necessary for normal DNA-binding and transactivation functions","volume":"45","author":"Murphy","year":"2004","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"10.1002\/humu.23141-BIB0029|humu23141-cit-0029","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"},{"key":"10.1002\/humu.23141-BIB0030|humu23141-cit-0030","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1146\/annurev.genom.7.080505.115630","article-title":"Predicting the effects of amino acid substitutions on protein function","volume":"7","author":"Ng","year":"2006","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"10.1002\/humu.23141-BIB0031|humu23141-cit-0031","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1002\/humu.22987","article-title":"Variation interpretation predictors: principles, types, performance, and choice","volume":"37","author":"Niroula","year":"2016","journal-title":"Hum Mutat"},{"key":"10.1002\/humu.23141-BIB0032|humu23141-cit-0032","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1086\/318183","article-title":"A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye","volume":"68","author":"Nishimura","year":"2001","journal-title":"Am J Hum Genet"},{"key":"10.1002\/humu.23141-BIB0033|humu23141-cit-0033","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/493","article-title":"The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25","volume":"19","author":"Nishimura","year":"1998","journal-title":"Nat Genet"},{"key":"10.1002\/humu.23141-BIB0034|humu23141-cit-0034","doi-asserted-by":"crossref","first-page":"3870","DOI":"10.1158\/0008-5472.CAN-09-4120","article-title":"FOXC1 is a potential prognostic biomarker with functional significance in basal-like breast cancer","volume":"70","author":"Ray","year":"2010","journal-title":"Cancer Res"},{"key":"10.1002\/humu.23141-BIB0035|humu23141-cit-0035","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"},{"key":"10.1002\/humu.23141-BIB0036|humu23141-cit-0036","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1086\/318792","article-title":"Analyses of the effects that disease-causing missense mutations have on the structure and function of the winged-helix protein FOXC1","volume":"68","author":"Saleem","year":"2001","journal-title":"Am J Hum Genet"},{"key":"10.1002\/humu.23141-BIB0037|humu23141-cit-0037","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1093\/hmg\/ddg324","article-title":"Structural and functional analyses of disease-causing missense mutations in the forkhead domain of FOXC1","volume":"12","author":"Saleem","year":"2003a","journal-title":"Hum Mol Genet"},{"key":"10.1002\/humu.23141-BIB0038|humu23141-cit-0038","doi-asserted-by":"crossref","first-page":"4182","DOI":"10.1093\/nar\/gkh742","article-title":"Essential structural and functional determinants within the forkhead domain of FOXC1","volume":"32","author":"Saleem","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"10.1002\/humu.23141-BIB0039|humu23141-cit-0039","doi-asserted-by":"crossref","first-page":"4608","DOI":"10.1167\/iovs.03-0090","article-title":"Identification and analysis of a novel mutation in the FOXC1 Forkhead domain","volume":"44","author":"Saleem","year":"2003b","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"10.1002\/humu.23141-BIB0040|humu23141-cit-0040","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/ng1296-392","article-title":"Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome","volume":"14","author":"Semina","year":"1996","journal-title":"Nat Genet"},{"key":"10.1002\/humu.23141-BIB0041|humu23141-cit-0041","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1093\/hmg\/9.7.1021","article-title":"Haploinsufficiency of the transcription factors {FOXC1} and {FOXC2} results in aberrant ocular development","volume":"9","author":"Smith","year":"2000","journal-title":"Hum Mol Genet"},{"key":"10.1002\/humu.23141-BIB0042|humu23141-cit-0042","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1167\/iovs.06-0472","article-title":"Genotype-phenotype correlations in Axenfeld-Rieger malformation and glaucoma patients with FOXC1 and PITX2 mutations","volume":"48","author":"Strungaru","year":"2007","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"10.1002\/humu.23141-BIB0043|humu23141-cit-0043","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1136\/jmg.2005.033878","article-title":"Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral","volume":"43","author":"Tavtigian","year":"2005","journal-title":"J Med Genet"},{"key":"10.1002\/humu.23141-BIB0044|humu23141-cit-0044","doi-asserted-by":"crossref","DOI":"10.1002\/humu.20939","article-title":"The proportion of mutations predicted to have a deleterious effect differs between gain and loss of function genes in neurodegenerative disease","volume":"30","author":"Valdmanis","year":"2009","journal-title":"Hum Mutat"},{"key":"10.1002\/humu.23141-BIB0045|humu23141-cit-0045","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s13277-012-0629-3","article-title":"High expression of FOXC1 is associated with poor clinical outcome in non-small cell lung cancer patients","volume":"34","author":"Wei","year":"2013","journal-title":"Tumour Biol"},{"key":"10.1002\/humu.23141-BIB0046|humu23141-cit-0046","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.1167\/iovs.06-0343","article-title":"Novel mutations of FOXC1 and PITX2 in patients with Axenfeld-Rieger malformations","volume":"47","author":"Weisschuh","year":"2006","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"10.1002\/humu.23141-BIB0047|humu23141-cit-0047","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1111\/j.1399-0004.2008.01025.x","article-title":"A novel mutation in the FOXC1 gene in a family with Axenfeld-Rieger syndrome and Peters'anomaly","volume":"74","author":"Weisschuh","year":"2008","journal-title":"Clin Genet"},{"key":"10.1002\/humu.23141-BIB0048|humu23141-cit-0048","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/hep.26029","article-title":"Overexpression of forkhead box C1 promotes tumor metastasis and indicates poor prognosis in hepatocellular carcinoma","volume":"57","author":"Xia","year":"2013","journal-title":"Hepatology"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhumu.23141","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/onlinelibrary.wiley.com\/wol1\/doi\/10.1002\/humu.23141\/fullpdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T16:54:58Z","timestamp":1672332898000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/humu.23141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,21]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,2]]}},"URL":"https:\/\/doi.org\/10.1002\/humu.23141","archive":["Portico"],"relation":{},"ISSN":["1059-7794"],"issn-type":[{"value":"1059-7794","type":"print"}],"subject":[],"published":{"date-parts":[[2016,11,21]]}}}