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The structural and functional consequences of caused by an ectodysplasin\u2010A (EDA) mutations on protein phenotype, stability, and posttranslational modifications (PTMs) have not been well investigated. The present investigation involves five missense mutations that cause XLHED (L56P, R155C, P220L, V251M, and V322A) in different domains of EDA (TM, furin, collagen, and tumor necrosis factor [TNF]) from previously published papers. The deleterious nature of EDA mutant variants was identified using several computational algorithm tools. The point mutations induce major drifts in the structural flexibility of EDA mutant variants and have a negative impact on their stability, according to the 3D protein modeling tool assay. Using the molecular docking technique, EDA\/EDA variants were docked to 10 EDA interacting partners, retrieved from the STRING database. We found a novel biomarker CD68 by molecular docking analysis, suggesting all five EDA variants had lower affinity for EDAR, EDA2R, and CD68, implying that they would affect embryonic signaling between the ectodermal and mesodermal cell layers. In silico research such as gene ontology, subcellular localization, protein\u2013protein interaction, and PTMs investigations indicates major functional alterations would occur in EDA variants. According to molecular simulations, EDA variants influence the structural conformation, compactness, stiffness, and function of the EDA protein. Further studies on cell line and animal models might be useful in determining their specific roles in functional annotations.<\/jats:p>","DOI":"10.1002\/jcb.30186","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T12:33:03Z","timestamp":1637843583000},"page":"431-449","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Understanding the impact of missense mutations on the structure and function of the <i><b>EDA<\/b><\/i> gene in X\u2010linked hypohidrotic ectodermal dysplasia: A bioinformatics approach"],"prefix":"10.1002","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4479-4503","authenticated-orcid":false,"given":"Prashant","family":"Ranjan","sequence":"first","affiliation":[{"name":"Centre for Genetic Disorders, Institute of Science Banaras Hindu University  Varanasi Uttar Pradesh 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