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Relevance to Autism

A de novo in-frame deletion variant in the BRD4 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2012; functional characterization in Korb et al., 2017 demonstrated that this variant prevented a Brd4-induced increase in spine formation in transfected neurons compared to wild-type Brd4, suggesting a loss-of-function effect. Korb et al., 2017 also demonstrated that Brd4 was upregulated in a mouse model of Fragile X syndrome (FXS), and that inhibition of Brd4 function by the inhibitor JQ1 alleviated many of the phenotypes associated with Fragile X syndrome that were observed in FXS mice. De novo missense variants in BRD4 have also been identified in ASD probands from the Simons Simplex Collection (Krumm et al., 2015).

Molecular Function

BRD4 encodes a chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. The protein encoded by the BRD4 gene remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De novo gene disruptions in children on the autistic spectrum.
ASD
Support
Excess of rare, inherited truncating mutations in autism.
ASD
Recent Recommendation
Excess Translation of Epigenetic Regulators Contributes to Fragile X Syndrome and Is Alleviated by Brd4 Inhibition.
Recent Recommendation
BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange-like syndrome.
DD, ID
Microcephaly, OCD

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN970R001 
 inframe_deletion 
 c.651del 
 p.Val218CysfsTer22 
 De novo 
 NA 
 Simplex 
 GEN970R002 
 missense_variant 
 c.878A>G 
 p.Asp293Gly 
 De novo 
 NA 
 Simplex 
 GEN970R003 
 missense_variant 
  
  
 De novo 
 NA 
 Simplex 
 GEN970R004 
 copy_number_loss 
  
  
 De novo 
 NA 
 Simplex 
 GEN970R005 
 missense_variant 
 c.1289A>G 
 p.Tyr430Cys 
 De novo 
 NA 
 Simplex 
 GEN970R006 
 frameshift_variant 
 c.1224delinsCA 
 p.Glu408AspfsTer4 
 De novo 
 NA 
 Simplex 
 GEN970R007 
 frameshift_variant 
 c.691del 
 p.Asp231ThrfsTer9 
 De novo 
 NA 
 Simplex 

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
19
Deletion-Duplication
 16
 
19
Deletion
 4
 
19
Duplication
 1
 
19
Duplication
 1
 
19
Deletion
 2
 
19
Duplication
 2
 
19
Deletion-Duplication
 5
 
19
Duplication
 1
 
19
Duplication
 1
 

No Animal Model Data Available

 

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