{
  "abstract": "Van der Woude syndrome (VWS) is the most common syndromic form of orofacial clefts (OFCs). The heritability of VWS is largely (~70%) explained by variants in the IRF6 gene. Experimental studies to confirm genetic variant effects are essential but are time intensive and expensive. Advancing next-generation sequencing techniques has made it possible to identify genetic variation quicker than their causal effects in disease processes can be ascertained. Therefore, employing computational tools to reliably predict their causal effects is crucial for advancing translational research. We conducted Sanger sequencing of the IRF6 gene in 46 VWS cases across 34 families to identify likely causal missense variants. We then assessed structure-informed stability changes to the IRF6 protein when these variants were incorporated into the protein, using DDGun3D. We compared DDGun3D predictions to results from previous experimental studies. Among four variants previously shown to prevent functional rescue in zebrafish, only the variant IRF6(NM_006147.4):c.881T>C, shown to cause rupture of zebrafish embryo, exhibited a high free energy change (∆∆Gfold = 3.5 kcal/mol), indicating that substantial predicted thermodynamic destabilization does not capture all disruptive function of IRF6. Our study demonstrates the utility of a protein structure-based computational approach for functional variant interpretation, providing a complementary method for studying genetic variation. Integrating computational predictions with experimental data can enhance our understanding of genetic conditions. However, success depends on fully elucidating protein structures, which is an active area of research.",
  "abstract_shown": true,
  "affiliations": [
    "Iowa Institute for Oral Health Research, University of Iowa, Iowa City, IA 52242, USA.",
    "Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA 52242, USA.",
    "Roy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA.",
    "GKT School of Medical Education, King's College London, London WC2R 2LS, UK.",
    "College of Dentistry, University of Iowa, Iowa City, IA 52242, USA.",
    "School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA.",
    "Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, IA 52242, USA.",
    "Department of General Dentistry, School of Dentistry, Creighton University, Omaha, NE 68178, USA.",
    "Department of Pediatrics, University of KwaZulu-Natal, Pinetown 3605, South Africa.",
    "Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi 00233, Ghana.",
    "Surgical Department, School of Medicine, Addis Ababa University, Addis Ababa P.O. Box 9086, Ethiopia.",
    "Department of Oral and Maxillofacial Surgery, University of Lagos, Lagos 100254, Nigeria.",
    "Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.",
    "Dental and Craniofacial Genomics Core, School of Dental Medicine, University of Puerto Rico, San Juan, PR 00936, USA.",
    "School of Dentistry, University of Dundee, Dundee DD1 4HN, UK."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Mojisola Olujitan",
      "orcid": "0009-0007-9312-1651"
    },
    {
      "affs": [
        2
      ],
      "name": "Rose Gogal"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tamara Busch",
      "orcid": "0009-0006-6252-6966"
    },
    {
      "affs": [
        2
      ],
      "name": "Chloe Ovel"
    },
    {
      "affs": [
        3
      ],
      "name": "Anjolaoluwa Awe"
    },
    {
      "affs": [
        4
      ],
      "name": "Jorge Ceballos"
    },
    {
      "affs": [
        5
      ],
      "name": "Kikanwa Okiosor"
    },
    {
      "affs": [
        0
      ],
      "name": "Natalie Ibarra"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Emmanuel Aladenika",
      "orcid": "0000-0003-1349-1753"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Waheed Awotoye"
    },
    {
      "affs": [
        7
      ],
      "name": "Veronica Sule"
    },
    {
      "affs": [
        0
      ],
      "name": "Babatunde Faparusi"
    },
    {
      "affs": [
        0
      ],
      "name": "Benjamin Bass"
    },
    {
      "affs": [
        0
      ],
      "name": "Rishitha Gadde"
    },
    {
      "affs": [
        8
      ],
      "name": "Thirona Naicker"
    },
    {
      "affs": [
        9
      ],
      "name": "Lord J J Gowans",
      "orcid": "0000-0003-0080-9101"
    },
    {
      "affs": [
        10
      ],
      "name": "Mekonen Eshete"
    },
    {
      "affs": [
        11
      ],
      "name": "Wasiu Lanre Adeyemo"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Aline Petrin",
      "orcid": "0000-0003-2239-8120"
    },
    {
      "affs": [
        12
      ],
      "name": "Martine Dunnwald",
      "orcid": "0000-0002-5182-8874"
    },
    {
      "affs": [
        13
      ],
      "name": "Carmen J Buxo",
      "orcid": "0000-0002-8819-1643"
    },
    {
      "affs": [
        14
      ],
      "name": "Peter Mossey"
    },
    {
      "affs": [
        2
      ],
      "name": "Michael Schnieders",
      "orcid": "0000-0003-1260-4592"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Azeez Butali",
      "orcid": "0000-0002-1229-5964"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/924cgdqjd43cg.bib",
  "cited_by": 0,
  "doi": "10.3390/genes17101223",
  "fulltext_url": "https://europepmc.org/articles/PMC13704330",
  "id": "924cgdqjd43cg",
  "issns": [
    "2073-4425"
  ],
  "landing_url": "https://europepmc.org/article/MED/42938339",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1311|Cleft Lip and Palate Research"
    ]
  ],
  "openalex": "W7216595255",
  "pdf_url": "https://europepmc.org/articles/PMC13704330?pdf=render",
  "pmcid": "PMC13704330",
  "pmid": "42938339",
  "published": "2026-10-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/924cgdqjd43cg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:24Z",
      "native_id": "MED:42938339",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42938339"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Cleft Lip and Palate Research",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Functional Consequence of IRF6 Variants in Van der Woude Syndrome.",
  "title_text": "Functional Consequence of IRF6 Variants in Van der Woude Syndrome.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:24Z",
  "url": "https://research.draconitic.com/paper/924cgdqjd43cg",
  "venue": "Genes",
  "versions": []
}