Relevance to Autism

De novo missense variants that were predicted in silico to be damaging were observed in the MCM6 gene in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014) and an ASD proband from a cohort of 262 Japanese trios (Takata et al., 2018). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as the Japanese ASD cohort from Takata et al., 2018, identified MCM6 as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05).

Molecular Function

The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 4 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of the complex by CDC2 kinase reduces the helicase activity, suggesting a role in the regulation of DNA replication.

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