KDF1 was first reported in relation to AD KDF1-related tooth agenesis with or without ectodermal dysplasia in 2017 (Shamseldin et al., PMID: 27838789). KDF1-related tooth agenesis with or without ectodermal dysplasia is characterized by tooth agenesis; however some patients may also display variable ectodermal dysplasia. 8 unique missense variants that have been reported in 8 probands in 8 publications (PMIDs: 27838789, 30384154, 30977908, 35641834, 36293320, 37144643, 38501196, 40554824) are included in this curation. The mechanism of pathogenicity is thought to be gain of function. This gene-disease relationship is also supported by animal models, expression studies, protein-protein interactions, functional alteration in patient cells, and biochemical function (PMIDs: 24075906, 30384154, 32239614, 36293320, 36831017). In summary, there is definitive evidence supporting the relationship between KDF1 and AD KDF1-related tooth agenesis with or without ectodermal dysplasia. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Craniofacial Malformations GCEP on the meeting date March 20th, 2025 (SOP Version 11).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.