Human Gene Module / Chromosome 1 / SPEN

SPENspenfamily transcriptional repressor

Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
8 / 0
Associated Syndromes
Genetic Category
Rare Single Gene Mutation
Chromosome Band
Associated Disorders
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.

Reports related to SPEN (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
2 Primary The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
3 Support Excess of rare, inherited truncating mutations in autism. Krumm N , et al. (2015) Yes -
4 Support Genome-wide characteristics of de novo mutations in autism. Yuen RK , et al. (2016) Yes -
5 Support Prevalence and architecture of de novo mutations in developmental disorders. Deciphering Developmental Disorders Study (2017) No -
6 Recent Recommendation Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity. Coe BP , et al. (2018) No -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.986A>C c.986A>C missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.5392C>T p.Gln1798Ter stop_gained De novo - Simplex 27525107 Yuen RK , et al. (2016)
c.4651G>A p.Glu1551Lys missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.8492G>C p.Ser2831Thr missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.7503G>A p.Trp2501Ter stop_gained De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
c.461G>A p.Arg154Gln missense_variant De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
c.3028_3029insA p.Asp1011GlyfsTer11 frameshift_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.6958_6962del p.Lys2320GlyfsTer37 frameshift_variant De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
Common Variants  

No common variants reported.

CNVs associated with SPEN(1 CNVs)
1p36.21-p36.13 1 Deletion-Duplication 2  /  3
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