HELP     Sign In
Search

Relevance to Autism

De novo and inherited dominant variants in the SIN3A gene were identified in individuals presenting with a syndrome characterized by intellectual disability, ASD, brain abnormalities detected by MRI, dysmorphic facial features, microcephaly, and short stature; this phenotype is similar to that of individuals with atypical 15q24 microdeletions, whose shortest region of overlap (approximately 260 kb) includes the SIN3A gene (Witteveen et al., 2016). Knockdown of SIN3A in the developing mouse brain in Witteveen et al., 2016 resulted in a decrease in cortical progenitors, altered cortical neuronal identity, and aberrant corticocortical projections.

Molecular Function

The protein encoded by this gene is a transcriptional regulatory protein.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Haploinsufficiency of MeCP2-interacting transcriptional co-repressor SIN3A causes mild intellectual disability by affecting the development of cort...
ID
ASD, epilepsy/seizures
Support
Transcriptional corepressor SIN3A regulates hippocampal synaptic plasticity via Homer1/mGluR5 signaling.
Support
The contribution of de novo coding mutations to autism spectrum disorder
ASD
Support
Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
ASD
Support
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Support
Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.
ASD
Microcephaly
Support
Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
ASD
Support
Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype
Witteveen-Kolk syndrome, DD, ID
ASD, ADHD, epilepsy/seizures
Support
Exome Pool-Seq in neurodevelopmental disorders.
ID
ADHD
Support
Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
ASD, DD
Support
Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnose...
ASD
Support
Behavior and cognitive functioning in Witteveen-Kolk syndrome
Witteveen-Kolk syndrome
ASD
Support
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability
ID

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN837R001 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN837R002 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN837R003 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN837R004 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN837R005 
 frameshift_variant 
 c.803dup 
 p.Leu269ThrfsTer37 
 De novo 
 NA 
  
 GEN837R006 
 frameshift_variant 
 c.1010_1013del 
 p.Lys337SerfsTer16 
 De novo 
 NA 
  
 GEN837R007 
 frameshift_variant 
 c.1759del 
 p.Ser587ProfsTer12 
 Familial 
 Paternal 
 Multiplex 
 GEN837R008 
 frameshift_variant 
 c.2955_2956del 
 p.Glu985AspfsTer29 
 De novo 
 NA 
  
 GEN837R009 
 stop_gained 
 c.3310C>T 
 p.Arg1104Ter 
 Familial 
 Maternal 
 Multiplex 
 GEN837R010 
 missense_variant 
 c.2585C>T 
 p.Pro862Leu 
 De novo 
 NA 
  
 GEN837R011 
 missense_variant 
 c.1813T>C 
 p.Tyr605His 
 De novo 
 NA 
 Simplex 
 GEN837R012 
 synonymous_variant 
 c.246T>C 
 p.His82= 
 De novo 
 NA 
  
 GEN837R013 
 frameshift_variant 
  
 p.Gln827LysfsTer3 
 De novo 
 NA 
  
 GEN837R014 
 frameshift_variant 
 c.3118_3119del 
 p.Gln1040GlufsTer15 
 Unknown 
 Not maternal 
  
 GEN837R015 
 missense_variant 
 c.95G>A 
 p.Arg32Gln 
 Familial 
 Maternal 
 Simplex 
 GEN837R016 
 missense_variant 
 c.3811A>G 
 p.Lys1271Glu 
 De novo 
 NA 
 Simplex 
 GEN837R017 
 frameshift_variant 
 c.2248_2249insCTCTTAC 
 p.Leu750ProfsTer5 
 De novo 
 NA 
 Simplex 
 GEN837R018 
 frameshift_variant 
 c.1010_1013del 
 p.Lys337SerfsTer16 
 De novo 
 NA 
 Simplex 
 GEN837R019 
 stop_gained 
 c.1675C>T 
 p.Arg559Ter 
 Unknown 
  
  
 GEN837R020 
 frameshift_variant 
 c.1489_1499del 
 p.Arg497CysfsTer13 
 Unknown 
  
  
 GEN837R021 
 stop_gained 
 c.1657C>T 
 p.Arg553Ter 
 Unknown 
  
  
 GEN837R022 
 frameshift_variant 
 c.3706_3709del 
 p.Gly1236ArgfsTer21 
 Unknown 
  
  
 GEN837R023 
 frameshift_variant 
 c.3698_3702del 
 p.Trp1233TyrfsTer3 
 Unknown 
  
  
 GEN837R024 
 stop_gained 
 c.1541T>A 
 p.Leu514Ter 
 Unknown 
  
 Simplex 
 GEN837R025 
 missense_variant 
 c.3034G>A 
 p.Val1012Met 
 Unknown 
  
  
 GEN837R026 
 missense_variant 
 c.3034G>A 
 p.Val1012Met 
 Unknown 
  
  
 GEN837R027 
 missense_variant 
 c.2153G>A 
 p.Arg718Gln 
 Unknown 
  
  
 GEN837R028 
 missense_variant 
 c.2153G>A 
 p.Arg718Gln 
 Unknown 
  
  
 GEN837R029 
 missense_variant 
 c.2966T>A 
 p.Ile989Asn 
 Unknown 
  
  
 GEN837R030 
 missense_variant 
 c.2254G>A 
 p.Glu752Lys 
 Unknown 
  
  
 GEN837R031 
 missense_variant 
 c.1490G>A 
 p.Arg497His 
 Unknown 
  
  
 GEN837R032 
 missense_variant 
 c.1424G>A 
 p.Arg475Gln 
 Unknown 
  
  
 GEN837R033 
 missense_variant 
 c.2003C>T 
 p.Ala668Val 
 Unknown 
  
  
 GEN837R034 
 missense_variant 
 c.3139G>C 
 p.Glu1047Gln 
 Unknown 
  
  
 GEN837R035 
 missense_variant 
 c.2030C>T 
 p.Ala677Val 
 Unknown 
  
  
 GEN837R036 
 stop_gained 
 c.1657C>T 
 p.Arg553Ter 
 Unknown 
  
  
 GEN837R037 
 stop_gained 
 c.1657C>T 
 p.Arg553Ter 
 Unknown 
  
  
 GEN837R038 
 frameshift_variant 
 c.3016dup 
 p.Arg1006LysfsTer9 
 Unknown 
  
  
 GEN837R039 
 frameshift_variant 
 c.2809_2810del 
 p.Lys937GlufsTer2 
 Unknown 
  
  
 GEN837R040 
 frameshift_variant 
 c.975del 
 p.Tyr325Ter 
 Unknown 
  
  
 GEN837R041 
 frameshift_variant 
 c.2983_2984insGTAA 
 p.Phe995CysfsTer21 
 Unknown 
  
  
 GEN837R042 
 missense_variant 
 c.1091G>A 
 p.Arg364His 
 Unknown 
  
  
 GEN837R043 
 missense_variant 
 c.1091G>A 
 p.Arg364His 
 Unknown 
  
  
 GEN837R044 
 missense_variant 
 c.2002G>A 
 p.Ala668Thr 
 Unknown 
  
  
 GEN837R045 
 missense_variant 
 c.1793T>A 
 p.Val598Glu 
 Unknown 
  
  
 GEN837R046 
 frameshift_variant 
 c.1462del 
 p.Val488LeufsTer7 
 De novo 
 NA 
 Simplex 
 GEN837R047 
 stop_gained 
 c.2764C>T 
 p.Arg922Ter 
 De novo 
 NA 
 Simplex 
 GEN837R048 
 frameshift_variant 
 c.588del 
 p.Asn197MetfsTer4 
 De novo 
 NA 
 Simplex 
 GEN837R049 
 missense_variant 
 c.377C>T 
 p.Ala126Val 
 De novo 
 NA 
 Simplex 
 GEN837R050 
 frameshift_variant 
 c.1245_1246del 
 p.Asn415LysfsTer24 
 De novo 
 NA 
 Simplex 
 GEN837R051 
 frameshift_variant 
 c.775dup 
 p.His259ProfsTer47 
 De novo 
 NA 
 Simplex 
 GEN837R052 
 frameshift_variant 
 c.824del 
 p.Pro275HisfsTer12 
 De novo 
 NA 
 Simplex 
 GEN837R053 
 frameshift_variant 
 c.2248_2251del 
 p.Leu750MetfsTer43 
 De novo 
 NA 
 Simplex 
 GEN837R054 
 frameshift_variant 
 c.2339del 
 p.Ala780GlyfsTer14 
 De novo 
 NA 
 Simplex 
 GEN837R055 
 stop_gained 
 c.889C>T 
 p.Gln297Ter 
 De novo 
 NA 
 Simplex 
 GEN837R056 
 frameshift_variant 
 c.1715_1722delinsCCCAAGTGTA 
 p.Gly572AlafsTer11 
 De novo 
 NA 
 Simplex 
 GEN837R057 
 stop_gained 
 c.3323C>G 
 p.Ser1108Ter 
 De novo 
 NA 
 Simplex 
 GEN837R058 
 stop_gained 
 c.3490A>T 
 p.Lys1164Ter 
 De novo 
 NA 
 Simplex 
 GEN837R059 
 stop_gained 
 c.46C>T 
 p.Gln16Ter 
 Familial 
 Maternal 
  
 GEN837R060 
 frameshift_variant 
 c.2809_2810del 
 p.Lys937GlufsTer2 
 De novo 
 NA 
 Simplex 
 GEN837R061 
 frameshift_variant 
 c.1489_1499del 
 p.Arg497CysfsTer13 
 De novo 
 NA 
 Simplex 
 GEN837R062 
 missense_variant 
 c.3317T>C 
 p.Met1106Thr 
 De novo 
 NA 
 Simplex 
 GEN837R063 
 stop_gained 
 c.1675C>T 
 p.Arg559Ter 
 De novo 
 NA 
 Simplex 
 GEN837R064 
 stop_gained 
 c.3303C>G 
 p.Tyr1101Ter 
 De novo 
 NA 
 Simplex 
 GEN837R065 
 frameshift_variant 
 c.1570_1577del 
 p.Tyr524ValfsTer26 
 De novo 
 NA 
 Simplex 
 GEN837R066 
 frameshift_variant 
 c.2185_2186del 
 p.Leu729GlyfsTer8 
 De novo 
 NA 
 Simplex 
 GEN837R067 
 frameshift_variant 
 c.3441_3445del 
 p.Lys1148ArgfsTer12 
 De novo 
 NA 
 Simplex 
 GEN837R068 
 frameshift_variant 
 c.1319_1320insGAAGAAACCCAAACTGCTCAATCTGAAGGATTCTTCTATGGCAGATGCCAGCAAACATGGTGGTGGAACAGAATCGTTATTTTTTG 
 p.Pro442LysfsTer34 
 De novo 
 NA 
 Simplex 
 GEN837R069 
 stop_gained 
 c.1773G>A 
 p.Trp591Ter 
 De novo 
 NA 
 Simplex 
 GEN837R070 
 missense_variant 
 c.463A>G 
 p.Lys155Glu 
 De novo 
 NA 
 Simplex 
 GEN837R071 
 stop_gained 
 c.2803C>T 
 p.Arg935Ter 
 De novo 
 NA 
 Simplex 
 GEN837R072 
 frameshift_variant 
 c.1888dup 
 p.Ile630AsnfsTer17 
 De novo 
 NA 
 Simplex 

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
15
Duplication
 66
  construct
15
Duplication
 1
 
15
Deletion
 3
 
15
Deletion
 1
 
15
Duplication
 2
 
15
Deletion
 8
 
15
Duplication
 1
 
15
Deletion
 9
 
15
Duplication
 1
 

Model Summary

Sin3A-VDRC105852 mutants showed no change in habituation. Sin3A-VDRC10808 mutants' initial jump response was impaired.

References

Type
Title
Author, Year
Primary
Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.

F_SIN3A_1_KD_GAL4:UAS;RNAI-VDRC105852

Model Type: Genetic
Model Genotype: Wild type
Mutation: Sin3A-Gal4 driver line expressing UAS-Sin3A-RNAi.
Allele Type: Loss-of-function
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line:
Mutant ES Cell Line:
Model Source:

F_SIN3A_2_KD_GAL4:UAS;RNAI-VDRC10808

Model Type: Genetic
Model Genotype: Wild type
Mutation: Sin3A-Gal4 driver line expressing UAS-Sin3A-RNAi.
Allele Type: Loss-of-function
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line:
Mutant ES Cell Line:
Model Source:

F_SIN3A_1_KD_GAL4:UAS;RNAI-VDRC105852

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Habituation to aversive stimuli1
 No change
 Light-off startle jump
 adult stage
Startle response1
 No change
 Light-off startle jump
 adult stage
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

F_SIN3A_2_KD_GAL4:UAS;RNAI-VDRC10808

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Startle response1
Decreased
Description: When challenged in the light-off jump paradigm, the mutants' initial jump response was impaired (23% frequency of initial jumping), thus precluding proper assessment of habituation.
 Light-off startle jump
 adult stage
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
C13ORF31 Laccase domain-containing protein 1 Q8IV20 IP; LC-MS/MS
Huttlin EL , et al. 2015
DDX41 DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 51428 Q9UJV9 IP; LC-MS/MS
Huttlin EL , et al. 2015
FAM60A family with sequence similarity 60, member A 58516 Q9NP50 IP; LC-MS/MS
Huttlin EL , et al. 2015
HDAC1 histone deacetylase 1 3065 Q13547 IP/WB
Zhang Y , et al. 1999
HDAC1 histone deacetylase 1 3065 Q13547 IP; LC-MS/MS
Huttlin EL , et al. 2015
ING2 Inhibitor of growth protein 2 Q9H160 IP; LC-MS/MS
Huttlin EL , et al. 2015
KMT2E lysine (K)-specific methyltransferase 2E 55904 Q8IZD2 IP; LC-MS/MS
Ding X , et al. 2015
MBD4 methyl-CpG binding domain protein 4 8930 O95243 IP/WB; GST
Kondo E , et al. 2005
MDK midkine (neurite growth-promoting factor 2) 4192 P21741 IP; LC-MS/MS
Huttlin EL , et al. 2015
MIER2 mesoderm induction early response 1, family member 2 54531 Q8N344 IP; LC-MS/MS
Huttlin EL , et al. 2015
MXD1 MAX dimerization protein 1 4084 B7ZLI7 IP; LC-MS/MS
Huttlin EL , et al. 2015
MXD3 Max dimerization protein 3 Q9BW11-3 IP; LC-MS/MS
Huttlin EL , et al. 2015
PHF23 PHD finger protein 23 79142 Q9BUL5 IP; LC-MS/MS
Huttlin EL , et al. 2015
RBBP7 retinoblastoma binding protein 7 5931 Q16576 IP; LC-MS/MS
Huttlin EL , et al. 2015
SAP30 Sin3A-associated protein, 30kDa NM_003864 O75446 IP/WB
Zhang Y , et al. 1999
Snai1 snail family zinc finger 1 20613 Q02085 IP/WB
Peinado H , et al. 2003
SUDS3 suppressor of defective silencing 3 homolog (S. cerevisiae) 64426 Q9H7L9 IP; LC-MS/MS
Huttlin EL , et al. 2015
TFAP4 transcription factor AP-4 (activating enhancer binding protein 4) 7023 Q01664 IP; LC-MS/MS
Huttlin EL , et al. 2015
TOP3B topoisomerase (DNA) III beta 8940 O95985 HITS-CLIP
Xu D , et al. 2013
Ncor1 nuclear receptor co-repressor 1 20185 Q60974 Y2H; in vitro binding assay
Nagy L , et al. 1997
Rara retinoic acid receptor, alpha 19401 P11416 in vitro binding assay
Nagy L , et al. 1997
Rxra retinoid X receptor alpha 20181 P28700 in vitro binding assay
Nagy L , et al. 1997
MECP2 methyl CpG binding protein 2 (Rett syndrome) 29386 Q00566 GST; IP/WB
Nan X , et al. 1998
MIB1 mindbomb E3 ubiquitin protein ligase 1 307594 D3ZUV2 Affinity chromatography; LC-MS/MS
Mertz J , et al. 2015

HELP
Copyright © 2017 MindSpec, Inc.