Human Gene Module / Chromosome 9 / SET

SETSETnuclear proto-oncogene

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 4
Rare Variants / Common Variants
10 / 0
Aliases
SET, 2PP2A,  I2PP2A,  IGAAD,  IPP2A2,  MRD58,  PHAPII,  TAF-I,  TAF-IBETA
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
9q34.11
Associated Disorders
-
Relevance to Autism

De novo likely gene-disruptive (LGD) variants in the SET gene have been identifed in two probands with ASD (Yuen et al., 2017) and three 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 SET as a gene with an excess of LGD variants (false discovery rata < 5%, count >1) that passed a Bonferroni family-wise error rare (FWER) correction indicating exome-wide significance (P < 5.0E-07); SET was similarly identified as a gene with an excess of de novo LGD variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018). Stevens et al., 2018 identified four individuals with de novo SET variants, as well as an affected mother and son with a SET frameshift variant, who presented with non-syndromic intellectual disability (autosomal dominant mental retardation-58; OMIM 618106).

Molecular Function

The protein encoded by this gene inhibits acetylation of nucleosomes, especially histone H4, by histone acetylases (HAT). This inhibition is most likely accomplished by masking histone lysines from being acetylated, and the consequence is to silence HAT-dependent transcription. Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning.

Reports related to SET (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Prevalence and architecture of de novo mutations in developmental disorders. Deciphering Developmental Disorders Study (2017) No -
2 Primary Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
3 Support De novo mutations in the SET nuclear proto-oncogene, encoding a component of the inhibitor of histone acetyltransferases (INHAT) complex in patient... Stevens SJC , et al. (2018) No -
4 Recent Recommendation Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity. Coe BP , et al. (2018) No -
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.165_168del4 p.Gln56AspfsTer11 frameshift_variant De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
c.459_460del p.Lys154ArgfsTer6 frameshift_variant De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
c.165_168del4 p.Gln56AspfsTer11 frameshift_variant De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
c.112+1G>C p.? splice_site_variant De novo - Simplex 28263302 C Yuen RK , et al. (2017)
c.112+1G>C p.? splice_site_variant De novo - Simplex 28263302 C Yuen RK , et al. (2017)
c.167_170del p.Arg57LeufsTer10 frameshift_variant Familial Maternal Multi-generational 29688601 Stevens SJC , et al. (2018)
c.283T>G p.Trp95Gly missense_variant De novo - - 29688601 Stevens SJC , et al. (2018)
c.352C>T p.His118Tyr missense_variant De novo - - 29688601 Stevens SJC , et al. (2018)
c.417+1G>C p.? splice_site_variant De novo - - 29688601 Stevens SJC , et al. (2018)
c.689_690dup p.Gln231TyrfsTer29 frameshift_variant De novo - - 29688601 Stevens SJC , et al. (2018)
Common Variants  

No common variants reported.

CNVs associated with SET(1 CNVs)
9q34.11 12 Deletion-Duplication 22  /  44
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