Relevance to Autism

De novo likely gene-disruptive (LGD) variants in the SPEN gene have been identified in two probands with ASD (Iossifov et al., 2014; Yuen et al., 2016) and two probands with unspecified developmental disorders (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified SPEN as a gene with an excess of LGD variants (false discovery rata < 5%, count >1) (Coe et al., 2018). De novo missense variants in SPEN have also been observed in ASD probands (De Rubeis et al., 2014; Iossifov et al., 2014; Krumm et al., 2015).

Molecular Function

his gene encodes a hormone inducible transcriptional repressor. Repression of transcription by this gene product can occur through interactions with other repressors, by the recruitment of proteins involved in histone deacetylation, or through sequestration of transcriptional activators. The product of this gene contains a carboxy-terminal domain that permits binding to other corepressor proteins. This domain also permits interaction with members of the NuRD complex, a nucleosome remodeling protein complex that contains deacetylase activity. In addition, this repressor contains several RNA recognition motifs that confer binding to a steroid receptor RNA coactivator; this binding can modulate the activity of both liganded and nonliganded steroid receptors.

External Links

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