CDC6 was first reported in relation to autosomal recessive Meier-Gorlin Syndrome 5 in 2011 (Bicknell et al. 2011, PMID: 21358632). At least 3 variants (2 missense, one nonsense) have been reported. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Meier-Gorlin Syndrome 5 is the only disease entity that CDC6 is associated with.The mechanism of pathogenicity is reported to be loss of function and variants in this gene that have been reported in at least 2 probands in at least 2 publications (PMIDs: 21358632, 35023948) are included in this curation. This gene-disease relationship is also supported by functional alteration in patient cells (PMID: 23516378). CDC6 also has a similar biochemical function to ORC1 and ORC6 (PMID: 23516378). CDC6 is part of the origin recognition complex (ORC); it interacts with ORC1, ORC4, ORC6, CDT1 (PMID: 11477602). Additionally support for this gene-disease relationship comes from an animal model (zebrafish; PMID: 28985365). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date January 17th, 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).
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