HELP     Sign In
Search

Relevance to Autism

Six de novo variants in the CHD2 gene (four truncating variants and two missense variants disrupting highly conserved residues in the SNF2-related helicase/ATPase domain) were identified in individuals with a wide range of epileptic encephalopathies; all six of these individuals exhibited moderate-to-severe intellectual disability, and two individuals also displayed ASD (Carvill et al., 2013). De novo variants affecting this gene have also been found in individuals with ASD (Neale et al., 2012) and intellectual disability (Rauch et al., 2012).

Molecular Function

The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.
Epilepsy
ID, ASD, DD
Positive Association
De Novo Coding Variants Are Strongly Associated with Tourette Disorder.
Tourette syndrome
Positive Association
De novo mutations in epileptic encephalopathies.
Epilepsy
IS, LGS, DD, ID, ASD, ADHD
Support
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability
ID
Support
Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study
DD, epilepsy/seizures
Support
Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.
ID
Epilepsy, ASD
Support
Genomic backgrounds of Japanese patients with undiagnosed neurodevelopmental disorders
DD, epilepsy/seizures
Autistic features, ID
Support
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
ASD
Support
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Support
Chromatin remodeling dysfunction extends the etiological spectrum of schizophrenia: a case report
SCZ, epilepsy/seizures
Support
CHD2-epilepsy: Polygraphic documentation of self-induced seizures due to fixation-off sensitivity
Epilepsy/seizures
Support
Exome sequencing analysis in a pair of monozygotic twins re-evaluates the genetics behind their intellectual disability and reveals a CHD2 mutation
ASD, DD/ID, epilepsy/seizures
Support
De novo variants in neurodevelopmental disorders-experiences from a tertiary care center
DD, epilepsy/seizures
Support
Patterns and rates of exonic de novo mutations in autism spectrum disorders.
ASD
Support
Exome sequencing findings in 27 patients with myoclonic-atonic epilepsy: Is there a major genetic factor?
ASD, ID, epilepsy/seizures
Support
Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.
ASD
Support
De novo mutations in moderate or severe intellectual disability.
ID
Microcephaly
Support
De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism.
OCD
Support
Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder.
ASD
Support
Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci.
ASD
Support
Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
ASD, DD
ID
Support
Deletion of the RMGA and CHD2 genes in a child with epilepsy and mental deficiency.
Epilepsy
DD
Support
Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.
ADHD, epilepsy/seizures, speech delay
Support
Clinical exome sequencing: results from 2819 samples reflecting 1000 families.
DD, epilepsy/seizures
Support
De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder.
Support
CHD2-related epilepsy: novel mutations and new phenotypes.
Epilepsy/seizures
DD, ID, Afs
Support
Autism spectrum disorder recurrence, resulting of germline mosaicism for a CHD2 gene missense variant.
ASD
ID, epilepsy/seizures
Support
CHD2 mutations are a rare cause of generalized epilepsy with myoclonic-atonic seizures
ID, epilepsy/seizures
Support
Genotype-phenotype correlates of infantile-onset developmental & epileptic encephalopathy syndromes in South India: A single centre experience
Epilepsy/seizures
Support
Disruption of chromodomain helicase DNA binding protein 2 (CHD2) causes scoliosis
DD
Support
The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders.
Epilepsy/seizures
DD
Support
De novo genic mutations among a Chinese autism spectrum disorder cohort.
ASD
Support
De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies.
DD, ID, epilepsy/seizures
Support
Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes
ASD
Support
CHD2 mutations: Only epilepsy? Description of cognitive and behavioral profile in a case with a new mutation
ID, epilepsy/seizures
Autistic features
Support
CHD2 myoclonic encephalopathy is frequently associated with self-induced seizures
DD, ID, epilepsy/seizures
ASD, ADHD
Support
Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use.
ASD
Support
Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
ASD
Support
Application of whole-exome sequencing to unravel the molecular basis of undiagnosed syndromic congenital neutropenia with intellectual disability
DD, ID, epilepsy/seizures
Support
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.
ASD
Support
Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder.
ASD
Support
Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.
ASD
Support
Large-scale discovery of novel genetic causes of developmental disorders.
DD, ID, Epilepsy
Support
Juvenile myoclonic epilepsy mimic associated with CHD2 gene mutation
ASD, epilepsy/seizures
Support
Autism-linked CHD gene expression patterns during development predict multi-organ disease phenotypes.
Support
Genome-wide characteristics of de novo mutations in autism
ASD
Support
Next-generation gene panel testing in adolescents and adults in a medical neuropsychiatric genetics clinic
ID
DD, epilepsy/seizures
Support
CHD2 mutations in Lennox-Gastaut syndrome
Epilepsy/seizures
Support
Clinical utility of multigene panel testing in adults with epilepsy and intellectual disability.
ID, epilepsy/seizures
Support
Genomic diagnosis for children with intellectual disability and/or developmental delay.
ASD, ID, epilepsy/seizures
ADHD, OCD
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
The first reported case of an inherited pathogenic CHD2 variant in a clinically affected mother and daughter.
DD, ID, epilepsy/seizures, ADHD
Recent Recommendation
Chd2 Is Necessary for Neural Circuit Development and Long-Term Memory.
Recent Recommendation
Low load for disruptive mutations in autism genes and their biased transmission.
ASD
Recent Recommendation
CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems.
DD, ID, Epilepsy
ASD, TS, ADHD
Recent Recommendation
De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome.
Epilepsy/seizures, ID
ASD, ADHD

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN548R001 
 frameshift_variant 
 c.4233_4236del 
 p.Glu1412GlyfsTer64 
 De novo 
 NA 
  
 GEN548R002 
 stop_gained 
 c.361C>T 
 p.Arg121Ter 
 De novo 
 NA 
  
 GEN548R003 
 frameshift_variant 
  
 p.Gly491ValfsTer13 
 De novo 
 NA 
  
 GEN548R004 
 frameshift_variant 
 c.4931_4932del 
 p.Arg1644LysfsTer22 
 De novo 
 NA 
  
 GEN548R005 
 missense_variant 
 c.1642T>C 
 p.Trp548Arg 
 De novo 
 NA 
  
 GEN548R006 
 missense_variant 
 c.2468T>C 
 p.Leu823Pro 
 De novo 
 NA 
  
 GEN548R007 
 missense_variant 
 c.2567A>G 
 p.Asp856Gly 
 De novo 
 NA 
 Simplex 
 GEN548R008 
 frameshift_variant 
 c.1809+1del 
  
 De novo 
 NA 
 Simplex 
 GEN548R009 
 copy_number_loss 
  
  
 De novo 
 NA 
 Simplex 
 GEN548R010 
 splice_site_variant 
 c.1503G>A 
 p.Lys501= 
 De novo 
 NA 
  
 GEN548R011 
 splice_site_variant 
 c.1810-2A>C 
  
 De novo 
 NA 
  
 GEN548R012 
 stop_gained 
 c.4971G>A 
 p.Trp1657Ter 
 De novo 
 NA 
  
 GEN548R013 
 stop_gained 
 c.1396C>T 
 p.Arg466Ter 
 De novo 
 NA 
  
 GEN548R014 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN548R015 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN548R016 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN548R017 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN548R018 
 copy_number_loss 
  
  
 De novo 
 NA 
 Multiplex 
 GEN548R019 
 frameshift_variant 
 c.2892_2895del 
 p.Asn964LysfsTer4 
 De novo 
 NA 
 Simplex 
 GEN548R020 
 frameshift_variant 
 c.4949dup 
 p.Gly1651TrpfsTer16 
 De novo 
 NA 
 Simplex 
 GEN548R021 
 stop_gained 
 c.4909C>T 
 p.Arg1637Ter 
 De novo 
 NA 
 Simplex 
 GEN548R022 
 frameshift_variant 
 c.4797_4812del 
 p.His1599GlnfsTer210 
 De novo 
 NA 
 Simplex 
 GEN548R023 
 missense_variant 
 c.1942C>T 
 p.Pro648Ser 
 De novo 
 NA 
 Simplex 
 GEN548R024 
 missense_variant 
 c.3521G>A 
 p.Gly1174Asp 
 De novo 
 NA 
  
 GEN548R025 
 missense_variant 
 c.2999G>A 
 p.Arg1000Gln 
 De novo 
 NA 
  
 GEN548R026 
 missense_variant 
 c.2699G>A 
 p.Arg900Gln 
 De novo 
 NA 
  
 GEN548R027 
 frameshift_variant 
 c.1903_1906del 
 p.Asp635SerfsTer8 
 De novo 
 NA 
  
 GEN548R028 
 3_prime_UTR_variant 
 c.*2273G>A 
  
 De novo 
 NA 
 Simplex 
 GEN548R029 
 missense_variant 
 c.5054G>A 
 p.Arg1685His 
 De novo 
 NA 
  
 GEN548R030 
 missense_variant 
 c.2068C>T 
 p.His690Tyr 
 De novo 
 NA 
  
 GEN548R031 
 missense_variant 
 c.4459G>A 
 p.Asp1487Asn 
 De novo 
 NA 
 Simplex 
 GEN548R032 
 missense_variant 
 c.2699G>A 
 p.Arg900Gln 
 De novo 
 NA 
  
 GEN548R033 
 stop_gained 
 c.4921C>T 
 p.Gln1641Ter 
 De novo 
 NA 
  
 GEN548R034 
 missense_variant 
 c.4216A>G 
 p.Ser1406Gly 
 De novo 
 NA 
 Multiplex 
 GEN548R035 
 stop_gained 
 c.2716C>T 
 p.Gln906Ter 
 Unknown 
  
 Simplex 
 GEN548R036 
 stop_gained 
 c.335C>G 
 p.Ser112Ter 
 De novo 
 NA 
 Simplex 
 GEN548R037 
 missense_variant 
 c.1566C>G 
 p.Phe522Leu 
 De novo 
 NA 
 Simplex 
 GEN548R038 
 frameshift_variant 
  
  
 De novo 
 NA 
  
 GEN548R039 
 frameshift_variant 
 c.3787dup 
 p.Val1263GlyfsTer4 
 De novo 
 NA 
  
 GEN548R040 
 missense_variant 
 c.272A>G 
 p.Glu91Gly 
 De novo 
 NA 
 Simplex 
 GEN548R041 
 missense_variant 
 c.1934C>T 
 p.Thr645Met 
 De novo (germline mosaicism) 
  
 Multiplex 
 GEN548R042 
 splice_site_variant 
 c.693-1G>T 
  
 De novo 
 NA 
 Simplex 
 GEN548R043 
 stop_gained 
 c.2173C>T 
 p.Gln725Ter 
 De novo 
 NA 
 Simplex 
 GEN548R044 
 splice_site_variant 
 c.390C>T 
 p.Ser130= 
 De novo 
 NA 
 Simplex 
 GEN548R045 
 stop_gained 
 c.628G>T 
 p.Glu210Ter 
 Familial 
 Maternal 
 Simplex 
 GEN548R046 
 splice_site_variant 
 c.2506-2A>G 
  
 De novo 
 NA 
 Simplex 
 GEN548R047 
 missense_variant 
 c.3237G>T 
 p.Lys1079Asn 
 De novo 
 NA 
 Simplex 
 GEN548R048 
 missense_variant 
 c.3947A>G 
 p.Tyr1316Cys 
 De novo 
 NA 
  
 GEN548R049 
 frameshift_variant 
 c.3787dup 
 p.Val1263GlyfsTer4 
 Unknown 
  
  
 GEN548R050 
 missense_variant 
 c.2636C>T 
 p.Ala879Val 
 De novo 
 NA 
 Unknown 
 GEN548R051 
 splice_site_variant 
 c.2352+1G>A 
  
 De novo 
 NA 
 Simplex 
 GEN548R052 
 stop_gained 
 c.3782G>A 
 p.Trp1261Ter 
 De novo 
 NA 
  
 GEN548R053 
 missense_variant 
 c.5120G>A 
 p.Arg1707Gln 
 De novo 
 NA 
  
 GEN548R054 
 frameshift_variant 
 c.4052_4053del 
 p.Lys1351SerfsTer11 
 De novo 
 NA 
 Simplex 
 GEN548R055 
 splice_site_variant 
 c.5153+2T>C 
  
 Familial 
 Paternal 
 Simplex 
 GEN548R056 
 missense_variant 
 c.2644G>T 
 p.Val882Phe 
 De novo 
 NA 
 Simplex 
 GEN548R057 
 frameshift_variant 
 c.4156dup 
 p.Ser1386LysfsTer23 
 De novo 
 NA 
 Multi-generational 
 GEN548R058 
 missense_variant 
 c.5232G>A 
 p.Met1744Ile 
 Familial 
 Paternal 
 Multi-generational 
 GEN548R059 
 stop_gained 
 c.5007G>A 
 p.Trp1669Ter 
 De novo 
 NA 
 Simplex 
 GEN548R060 
 stop_gained 
 c.2410C>T 
 p.Arg804Ter 
 De novo 
 NA 
 Simplex 
 GEN548R061 
 frameshift_variant 
 c.1778dup 
 p.Thr594AsnfsTer4 
 Unknown 
  
 Simplex 
 GEN548R062 
 frameshift_variant 
 c.4173dup 
 p.Gln1392ThrfsTer17 
 De novo 
 NA 
 Simplex 
 GEN548R063 
 frameshift_variant 
 c.3734dup 
 p.Tyr1246IlefsTer13 
 De novo 
 NA 
 Simplex 
 GEN548R064 
 missense_variant 
 c.2537G>A 
 p.Arg846Gln 
 De novo 
 NA 
 Simplex 
 GEN548R065 
 stop_gained 
 c.4636C>T 
 p.Arg1546Ter 
 De novo 
 NA 
 Simplex 
 GEN548R066 
 missense_variant 
 c.2609G>A 
 p.Gly870Asp 
 De novo 
 NA 
 Simplex 
 GEN548R067 
 frameshift_variant 
 c.4278+1del 
  
 De novo 
 NA 
 Simplex 
 GEN548R068 
 missense_variant 
 c.2740C>T 
 p.Arg914Cys 
 De novo 
 NA 
 Simplex 
 GEN548R069 
 missense_variant 
 c.1566C>G 
 p.Phe522Leu 
 De novo 
 NA 
 Simplex 
 GEN548R070 
 stop_gained 
 c.4921C>T 
 p.Gln1641Ter 
 De novo 
 NA 
 Simplex 
 GEN548R071 
 missense_variant 
 c.4459G>A 
 p.Asp1487Asn 
 De novo 
 NA 
 Simplex 
 GEN548R072 
 intron_variant 
 c.2727+46A>G 
  
 De novo 
 NA 
 Simplex 
 GEN548R073 
 frameshift_variant 
 c.995_999del 
 p.Val332GlyfsTer25 
 Unknown 
  
 Simplex 
 GEN548R074 
 stop_gained 
 c.988C>T 
 p.Gln330Ter 
 De novo 
 NA 
  
 GEN548R075 
 missense_variant 
 c.1049A>C 
 p.Gln350Pro 
 De novo 
 NA 
  
 GEN548R076 
 stop_gained 
 c.1345A>T 
 p.Asn449Tyr 
 De novo 
 NA 
  
 GEN548R077 
 missense_variant 
 c.2699G>A 
 p.Arg900Gln 
 De novo 
 NA 
  
 GEN548R078 
 missense_variant 
 c.2702C>G 
 p.Ala901Gly 
 De novo 
 NA 
  
 GEN548R079 
 missense_variant 
 c.2740C>T 
 p.Arg914Cys 
 De novo 
 NA 
  
 GEN548R080 
 missense_variant 
 c.4555G>A 
 p.Ala1519Thr 
 De novo 
 NA 
  
 GEN548R081 
 stop_gained 
 c.327C>G 
 p.Val109%3D 
 Unknown 
  
  
 GEN548R082 
 frameshift_variant 
 c.1265del 
 p.Tyr422PhefsTer40 
 Unknown 
  
  
 GEN548R083 
 frameshift_variant 
 c.11_14del 
 p.Asn4ArgfsTer89 
 Unknown 
  
  
 GEN548R084 
 frameshift_variant 
 c.522del 
 p.Val175Ter 
 Unknown 
  
  
 GEN548R085 
 stop_gained 
 c.934A>T 
 p.Lys312Ter 
 Unknown 
  
  
 GEN548R086 
 missense_variant 
 c.4483G>A 
 p.Val1495Met 
 De novo 
 NA 
  
 GEN548R087 
 missense_variant 
 c.4033C>T 
 p.Arg1345Trp 
 Familial 
 Paternal 
  
 GEN548R088 
 missense_variant 
 c.3346C>T 
 p.Arg1116Cys 
 Unknown 
  
  
 GEN548R089 
 missense_variant 
 c.595C>T 
 p.Arg199Cys 
 Unknown 
  
  
 GEN548R090 
 missense_variant 
 c.667C>T 
 p.Arg223Cys 
 Unknown 
  
  
 GEN548R091 
 missense_variant 
 c.5362C>T 
 p.Arg1788Cys 
 Unknown 
  
  
 GEN548R092 
 missense_variant 
 c.1234G>A 
 p.Glu412Lys 
 Unknown 
  
  
 GEN548R093 
 missense_variant 
 c.5129G>A 
 p.Arg1710Gln 
 Unknown 
  
  
 GEN548R094 
 frameshift_variant 
 c.3998dup 
 p.Gly1334TrpfsTer29 
 Familial 
 Maternal 
  
 GEN548R095a 
 missense_variant 
 c.2843G>A 
 p.Arg948Gln 
 Familial 
 Both parents 
  
 GEN548R096 
 missense_variant 
 c.2095C>T 
 p.Arg699Trp 
 Unknown 
  
  
 GEN548R097 
 missense_variant 
 c.2095C>T 
 p.Arg699Trp 
 Unknown 
  
  
 GEN548R098 
 missense_variant 
 c.5071C>T 
 p.Pro1691Ser 
 Unknown 
  
  
 GEN548R099 
 missense_variant 
 c.5369C>A 
 p.Pro1790His 
 Unknown 
  
  
 GEN548R100 
 missense_variant 
 c.5369C>A 
 p.Pro1790His 
 Unknown 
  
  
 GEN548R101 
 missense_variant 
 c.4516C>T 
 p.Leu1506%3D 
 Unknown 
  
  
 GEN548R102 
 missense_variant 
 c.4034G>A 
 p.Arg1345Gln 
 Unknown 
  
  
 GEN548R103 
 missense_variant 
 c.4034G>A 
 p.Arg1345Gln 
 Unknown 
  
  
 GEN548R104 
 missense_variant 
 c.4507C>T 
 p.Arg1503Trp 
 Unknown 
  
  
 GEN548R105 
 translocation 
  
  
 De novo 
 NA 
  
 GEN548R106 
 frameshift_variant 
 c.4173dup 
 p.Gln1392ThrfsTer17 
 De novo 
 NA 
  
 GEN548R107 
 frameshift_variant 
  
 p.Gly491ValfsTer13 
 De novo 
 NA 
  
 GEN548R108 
 stop_gained 
  
 p.Arg121Ter 
 De novo 
 NA 
  
 GEN548R109 
 frameshift_variant 
  
 p.Arg1644LysfsTer22 
 De novo 
 NA 
  
 GEN548R110 
 missense_variant 
  
 p.Leu823Pro 
 De novo 
 NA 
  
 GEN548R111 
 frameshift_variant 
  
 p.Glu1412GlyfsTer64 
 De novo 
 NA 
  
 GEN548R112 
 frameshift_variant 
  
 p.Gly1575ValfsTer 
 De novo 
 NA 
  
 GEN548R113 
 frameshift_variant 
  
 p.Leu1591Terfs 
 De novo 
 NA 
  
 GEN548R114 
 stop_gained 
  
 p.Gln909Ter 
 De novo 
 NA 
  
 GEN548R115 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN548R116 
 missense_variant 
  
 p.Trp548Arg 
 De novo 
 NA 
  
 GEN548R117 
 frameshift_variant 
 c.4256del 
 p.Lys1419SerfsTer58 
 De novo 
 NA 
 Simplex 
 GEN548R118 
 frameshift_variant 
 c.4173dup 
 p.Gln1392ThrfsTer17 
 De novo 
 NA 
 Multiplex (monozygotic twins) 
 GEN548R119 
 frameshift_variant 
 c.5094dup 
 p.Pro1699AlafsTer3 
 Unknown 
 Not maternal 
  
 GEN548R120 
 frameshift_variant 
 c.4164del 
 p.Met1388IlefsTer18 
 De novo 
 NA 
 Simplex 
 GEN548R121 
 nonsynonymous_variant 
 c.2005G>T 
 p.Glu669Ter 
 De novo 
 NA 
  
 GEN548R122 
 missense_variant 
 c.1861C>T 
 p.Arg621Trp 
 De novo 
 NA 
  
 GEN548R123 
 stop_gained 
 c.3931C>T 
 p.Gln1311Ter 
 De novo 
 NA 
 Simplex 
 GEN548R124 
 splice_site_variant 
 c.693-1G>T 
  
 De novo 
 NA 
 Simplex 
 GEN548R125 
 stop_gained 
 c.4003G>T 
 p.Glu1335Ter 
 De novo 
 NA 
 Simplex 
 GEN548R126 
 stop_gained 
  
  
 De novo 
 NA 
  
 GEN548R127 
 stop_gained 
 c.4489G>T 
 p.Glu1497Ter 
 Unknown 
  
  
 GEN548R128 
 missense_variant 
 c.3454C>G 
 p.Arg1152Gly 
 De novo 
 NA 
 Simplex 
 GEN548R129 
 frameshift_variant 
 c.4173dup 
 p.Gln1392ThrfsTer17 
 Unknown 
  
  
 GEN548R130 
 stop_gained 
 c.4636G>T 
 p.Arg1546Ter 
 Unknown 
  
  

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
15
Duplication
 66
  construct
15
Duplication
 1
 
15
Duplication
 1
 
15
Duplication
 1
 
15
Duplication
 1
 
15
Deletion-Duplication
 27
 
15
Duplication
 1
 

Model Summary

Both Chd2 nulls and hets show embryonic or perinatal lethality, defects in hematopoiesis, and cardiovascular abnormalities. Mutant cells demonstrate accumulative DNA damage markers and exhibit a decreased response to X-ray irradiation. Lordokyphosis and high incidence of lymphoma are also observed in Chd2 hets.

References

Type
Title
Author, Year
Primary
Role of chromodomain helicase DNA-binding protein 2 in DNA damage response signaling and tumorigenesis.
Additional
Chd2 Is Necessary for Neural Circuit Development and Long-Term Memory.

M_CHD2_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: A splice-acceptor beta-geo cassette (beta-galactosidase-neomycin fusion gene) was integrated within intro 27 (1563 base pairs from the beginning of the intron) of the Chd2 gene, which resulted in a hypomorphic allele.
Allele Type: Gene trapped
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Not specified

M_CHD2_1_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: A splice-acceptor beta-geo cassette (beta-galactosidase-neomycin fusion gene) was integrated within intro 27 (1563 base pairs from the beginning of the intron) of the Chd2 gene, which resulted in a hypomorphic allele.
Allele Type: Gene trapped
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Not specified

M_CHD2_3_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Heterozygous null mice were genrated by crossing transgenic mice with floxed exon 3 and beta actin Cre mouse line. Chd2-flox mice were mated with a hemizygous glutamic acid decarboxylase - enhanced green fluorescence protein (GAD67-GFP) knockin line maint
Allele Type: knockout
Strain of Origin:
Genetic Background:
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_CHD2_3_KO_HT_MGE-PROGENITORS

Model Type: RESCUE-Transplantation
Model Genotype: Heterozygous
Mutation: 5x10^5 MGE progenitors were obtained from E13.5 b-actin:GFP donor mice, and injected bilaterally into the hippocampus of neonatal M_CHD2_3_KO_HT recipients at P5.
Allele Type: knockout
Strain of Origin:
Genetic Background:
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_CHD2_4_CKO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Conditional deletion of exon 3 of the Chd2 gene Nkx2.1-Cre, in interneurons. The CKO was also crossed with the reporter lines: an Ai14 tdTomato reporter or a hemizygous glutamic acid decarboxylase enhanced green fluorescence protein (GAD67-GFP) knockin line.
Allele Type: Conditional loss-of-function
Strain of Origin:
Genetic Background:
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_CHD2_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Mortality/lethality: embryonic1
Increased
Description: Homozygous mutants died at embryonic or perinatal stage
Exp Paradigm: General observation
 General observations
 Neonatal
Cardiovascular development and function1
Decreased
Description: Decreased in the extent of the vascular structure; hemorrhages were presented in the mutants; occasional atrial enlargement in mutant mice
Exp Paradigm: General observation
 General observations
 E12.5 or p1
Cell differentiation: hematopoiesis1
Decreased
Description: Increased numbers of megakaryocytes and less organized hematopoietic cell islands in neonatal livers; decreased ability to differentiate into the erythroid lineage in the mutant livers
Exp Paradigm: H&e histochemistry; increased percentage of cd71+ter119- proerythroblasts and decreased number of cd71+ter119+ early basophilic erythroblasts in the mutant livers (similar results by using ter119 and cd117)-histology
 Histology
 Neonatal
Cell differentiation: hematopoiesis1
Decreased
Description: Increased numbers of megakaryocytes and less organized hematopoietic cell islands in neonatal livers; decreased ability to differentiate into the erythroid lineage in the mutant livers
Exp Paradigm: H&e histochemistry; increased percentage of cd71+ter119- proerythroblasts and decreased number of cd71+ter119+ early basophilic erythroblasts in the mutant livers (similar results by using ter119 and cd117)- flow cytometric analysis
 Flow cytometric analysis
 Neonatal
Targeted expression1
Decreased
Description: Decreased levels of chd2 wild-type mrna in the mutant mice
Exp Paradigm: Rt-pcr
 Polymerase chain reaction (pcr)
 E14.5
Dna repair1
Decreased
Description: Decreased dna repair or decreased attenuation of the h2ax signal after repair in the mutant mef cells
Exp Paradigm: Mouse embryonic fibroblasts were grown on glass chamber slides and exposed to 4 gy x-ray irradiation.
 Immunostaining
 E13.5-e14.5
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_CHD2_1_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Vertebrae morphology1
Abnormal
Description: Lordokyphosis was observed in the heterozygous mutant mice
Exp Paradigm: General observation
 General observations
 8-10 months
Size/growth1
Decreased
Description: Decreased size in mutant newborns and mice after 8-10 months but no change in the size of 3-4 month old mutant mice
Exp Paradigm: General observation
 General observations
 P1, 8-10 months
Mortality/lethality1
Increased
Description: Heterozygous mutants died at embryonic or perinatal stage
Exp Paradigm: General observation
 Kaplan-meier survival curve
 Neonatal
Cardiovascular development and function1
Decreased
Description: Decreased in the extent of the vascular structure; hemorrhages were presented in the mutants
Exp Paradigm: General observation
 General observations
 E12.5
Dna repair1
Decreased
Description: Decreased dna repair or decreased attenuation of the h2ax signal after repair in the mutant mef cells
Exp Paradigm: Mouse embryonic fibroblasts were grown on glass chamber slides and exposed to 4 gy x-ray irradiation.
 Immunostaining
 E13.5-e14.5
Cell proliferation1
Increased
Description: Increased incidence of t-cell lymphomas (splenic, lymphnode, and thymic lymphomas as well as lymphoid hyperplasias ) in the mutant mice
Exp Paradigm: The earliest incidence occurred at 26 weeks and 14 out 21 mutant mice suffered from lymphomas within 56 weeks; there were no difference in the total number of b cells but increased number of t cells in the lymphocytes from mutant spleen and lymph nodes
 Flow cytometric analysis
 6 months-2 years
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_CHD2_3_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuronal number: excitatory neurons1
Decreased
Description: Het mutants show a decrease in gad67 negative and neun positive interneurons excitatory interneurons in the somatosensory cortex but not in the hippocampus compared with controls.
Exp Paradigm: NA
 Immunostaining
 1 month
Hippocampal morphology: dentate gyrus1
Increased
Description: Het mutants show increase in cellular phenotypes of epilepsy in the dentate gyrus revealing no mossy fiber sprouting into the inner molecular layer compared with controls.
Exp Paradigm: NA
 Immunostaining
 1 month
Neuronal number: inhibitory neurons1
Decreased
Description: Het mutants show decrease in numbers of gad67 positive gabaergic inhibitory interneurons in the somatosensory cortex and ca1 hippocampus compared with controls. het mutants show decreased gabaergic subtypes of parvalbumin, somatostatin and reelin positive neurons.
Exp Paradigm: NA
 Immunostaining
 1 month
Cell proliferation: neural precursors1
Decreased
Description: Het mutants show decrease in proliferation of neural precursors in the developing forebrain compared with controls, measured by ki67 positive cells in the vz, svz. mge, a decrease in
Exp Paradigm: NA
 NA
 NA
Neuronal number: inhibitory neurons1
Decreased
Description: Het mutants show a decrease in the density of gad67-gfp+ cells in somatosensory
Exp Paradigm: NA
 NA
 NA
Action potential property: firing rate1
Increased
Description: Het mutants show an increase in action potential firing compared with controls, in ca1 pyramidal neurons.
Exp Paradigm: Electrophysiological properties of ca1 pyramidal
 Whole-cell patch clamp
 NA
Membrane potential1
Decreased
Description: Het mutants show no change in resting membrane potential
Exp Paradigm: Electrophysiological properties of ca1 pyramidal
 Whole-cell patch clamp
 NA
Decay kinetics of evoked post synaptic currents1
Decreased
Description: Het mutants show no change in time constant
Exp Paradigm: Electrophysiological properties of ca1 pyramidal
 Whole-cell patch clamp
 NA
Miniature post synaptic current frequency: inhibitory1
Decreased
Description: Het mutants show decrease in miniature inhibitory postsynaptic current (mipsc) frequency compared with controls.
Exp Paradigm: NA
 Whole-cell patch clamp
 1 month
Action potential property: amplitude1
Decreased
Description: Het mutants show no change in spike amplitude
Exp Paradigm: Electrophysiological properties of ca1 pyramidal
 Whole-cell patch clamp
 NA
Intrinsic membrane properties1
Decreased
Description: Het mutants show no change in input resistance
Exp Paradigm: Electrophysiological properties of ca1 pyramidal
 Whole-cell patch clamp
 NA
Adaptation of action potential firing1
Decreased
Description: Het mutants show a decrease in spike adptation compared with controls
Exp Paradigm: Electrophysiological properties of ca1 pyramidal
 Whole-cell patch clamp
 NA
Miniature post synaptic current amplitude: inhibitory1
NA
Description: Het mutants show no change in miniature inhibitory postsynaptic current (mipsc) amplitudes compared with controls.
Exp Paradigm: NA
 Whole-cell patch clamp
 1 month
Electroencephalogram (eeg) signature1
Increased
Description: Het mutants show increase in alpha (813 hz) and gamma (3070 hz) frequency
Exp Paradigm: NA
 NA
 NA
Action potential property: threshold1
Decreased
Description: Het mutants show no change in spike threshold
Exp Paradigm: Electrophysiological properties of ca1 pyramidal
 Whole-cell patch clamp
 NA
Miniature post synaptic current amplitude: excitatory1
Increased
Description: Het mutants show an increase in miniature excitatory postsynaptic current (mepsc) amplitudes compared with controls.
Exp Paradigm: Miniature excitatory and inhibitory synaptic
 Whole-cell patch clamp
 NA
Decay kinetics of miniature post synaptic currents1
Increased
Description: Het mutants show faster decay kinetics compared with controls in excitatory but not inhibitory synaptic events.
Exp Paradigm: NA
 Whole-cell patch clamp
 1 month
Vertebrae morphology1
Decreased
Description: Het mutants show lordokyphosis compared with controls.
Exp Paradigm: NA
 General observations
 2 months
Size/growth1
Decreased
Description: Het mutants show decrease in body weight compared with controls.
Exp Paradigm: NA
 Body weight measurement
 Not reported
Anxiety1
Decreased
Description: Het mutants spend more time in the center of the open field compared with controls.
Exp Paradigm: NA
 Open field test
 1.4- 2 months
Object recognition memory1
Decreased
Description: Het mutants spend equal time exploring novel and familiar objects compared with controls that spend more time exploring the novel object.
Exp Paradigm: NA
 Novel object recognition test
 1.4- 2 months
Spatial working memory1
Decreased
Description: Het mutants spend equal time exploring relocated and non-relocated objects compared with controls that spend more time exploring the relocated object.
Exp Paradigm: NA
 Object-place recognition test
 1.4- 2 months
Targeted expression1
Decreased
Description: Het mutants show half the expression of chd2 protein compared with controls.
Exp Paradigm: NA
 Western blot
 1 month
Gene expression1
Abnormal
Description: Het mutants show differential gene expression compared with controls.
Exp Paradigm: Polya+ rna sequencing on tissue micro-dissected from neocortex and
 Rna sequencing
 NA
Gene expression1
Abnormal
Description: Het mutants show differential gene expression compared with controls including slc6a13, myo7a, vipr, hddc3, ago2, lgr6, cacna1g, ctnnd2m, hexa, grin2b, ktm2a, and shank2.
Exp Paradigm: NA
 Quantitative pcr (qrt-pcr)
 E13.5, adult
Mortality/lethality1
 No change
 General observations
 Adult
General locomotor activity: ambulatory activity1
 No change
 Open field test
 1.4- 2 months
Cortical lamination1
 No change
 Immunostaining
 1 month
Glial number1
 No change
 Immunostaining
 1 month
Hippocampal morphology1
 No change
 Immunostaining
 1 month
Neuronal number: inhibitory neurons1
 No change
 Immunostaining
 1 month
Number of oligodendrocytes1
 No change
 Immunostaining
 1 month
Apoptosis: brain cells1
 No change
 Immunostaining
 P7
Epsp-spike relationship1
 No change
 Whole-cell patch clamp
 NA
Local field potential1
 No change
 In vivo local field potential (lfp) recordings
 1.4- 2 months
Membrane potential1
 No change
 Whole-cell patch clamp
 NA
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp
 NA
Presynaptic function: paired-pulse facilitation1
 No change
 Whole-cell patch clamp
 1 month
Reproductive function1
 No change
 General observations
 Adult
Seizures1
 No change
 Electroencephalogram (eeg)
 1.4- 2 months
 Not Reported: Circadian sleep/wake cycle, Communications, Immune response, Maternal behavior, Physiological parameters, Repetitive behavior, Sensory, Social behavior

M_CHD2_3_KO_HT_MGE-PROGENITORS

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Spatial working memory1
Ameliorated
Description: Mice with grafted mge progenitor cells show improvement in the novel object location task compared with controls.
Exp Paradigm: NA
 Object-place recognition test
 1.4- 2 months
Object recognition memory1
Refractory
Description: Mice with grafted mge progenitor cells show no improvement in novel object recognition task compared with controls.
Exp Paradigm: NA
 Novel object recognition test
 1.4- 2 months
Gene expression1
Restored
Description: Mice with grafted cells show enriched expression of olig2, dlx5, lhx6, pou3f4 and gad1 in the mge and neocortex compared with mutants.
Exp Paradigm: NA
 Rna sequencing
 E13.5
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Maternal behavior, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_CHD2_4_CKO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuronal number: interneurons1
Decreased
Description: Mice with chd2 happloinsufficiency in inhibitory interneurons show reduced interneuron density in the hippocampus compared with controls.
Exp Paradigm: Gaba
 Immunofluorescence staining
 1.4- 2 months
Spatial working memory1
Decreased
Description: Mice with chd2 happloinsufficiency in inhibitory interneurons spend equal time exploring relocated and non-relocated objects compared with controls that spend more time exploring the relocated object.
Exp Paradigm: NA
 Object-place recognition test
 1.4- 2 months
Object recognition memory1
Decreased
Description: Mice with chd2 happloinsufficiency in inhibitory interneurons spend equal time exploring novel and familiar objects compared with controls that spend more time exploring the novel object.
Exp Paradigm: NA
 Novel object recognition test
 1.4- 2 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
ADARB2 adenosine deaminase, RNA-specific, B2 105 Q9NS39 LC-MS/MS
Vertegaal AC , et al. 2006
ALDH18A1 aldehyde dehydrogenase 18 family, member A1 5832 P54886 LC-MS/MS
Vertegaal AC , et al. 2006
ARID5B AT rich interactive domain 5B (MRF1-like) 84159 Q14865 LC-MS/MS
Vertegaal AC , et al. 2006
BCKDK branched chain ketoacid dehydrogenase kinase 10295 A8MY43 LC-MS/MS
Vertegaal AC , et al. 2006
BEND7 BEN domain containing 7 222389 Q8N7W2 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
BRCA1 breast cancer 1, early onset 672 P38398 LC-MS/MS
Vertegaal AC , et al. 2006
CENPV centromere protein V 201161 Q7Z7K6 LC-MS/MS
Vertegaal AC , et al. 2006
CHD8 chromodomain helicase DNA binding protein 8 57680 Q9HCK8 ChIP-chip
Subtil-Rodrguez A , et al. 2013
FAM120C family with sequence similarity 120C 54954 Q9NX05 LC-MS/MS
Vertegaal AC , et al. 2006
FMR1 fragile X mental retardation 1 2332 G8JLE9 PAR-CLIP
Ascano M Jr , et al. 2012
H3F3A H3 histone, family 3A 3020 P84243 IP/WB
Luijsterburg MS , et al. 2016
INO80B INO80 complex subunit B 83444 Q9C086 LC-MS/MS
Vertegaal AC , et al. 2006
MID2 midline 2 11043 Q9UJV3 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
OGT O-linked N-acetylglucosamine (GlcNAc) transferase 8473 O15294 LC-MS/MS
Vertegaal AC , et al. 2006
PARP1 poly (ADP-ribose) polymerase 1 142 P09874 IP/WB; SILAC/MS
Luijsterburg MS , et al. 2016
RBAK RB-associated KRAB zinc finger 57786 Q9NYW8 LC-MS/MS
Vertegaal AC , et al. 2006
RREB1 ras responsive element binding protein 1 6239 Q92766 LC-MS/MS
Vertegaal AC , et al. 2006
RSBN1 round spermatid basic protein 1 54665 Q5VWQ0 LC-MS/MS
Vertegaal AC , et al. 2006
SIRT7 sirtuin 7 51547 Q9NRC8 LC-MS/MS
Tsai YC , et al. 2012
SPATA12 spermatogenesis associated 12 353324 Q7Z6I5 Y2H; bimolecular fluorescence complementation assay
Zhang Y , et al. 2013
SPTBN1 spectrin, beta, non-erythrocytic 1 6711 Q01082 LC-MS/MS
Vertegaal AC , et al. 2006
SUMO1 SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae) 7341 P63165 LC-MS/MS
Matafora V , et al. 2009
SUMO2 SMT3 suppressor of mif two 3 homolog 2 (S. cerevisiae) 6613 P61956 LC-MS/MS
Golebiowski F , et al. 2009
TEKT1 tektin 1 83659 Q969V4 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
THAP1 THAP domain containing, apoptosis associated protein 1 NM_018105 Q9NVV9 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
TOP3B topoisomerase (DNA) III beta 8940 O95985 HITS-CLIP
Xu D , et al. 2013
TRIM41 tripartite motif containing 41 90933 Q8WV44 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
UBC ubiquitin C 7316 P63279 LC-MS/MS
Danielsen JM , et al. 2010
WDR33 WD repeat domain 33 55339 Q9C0J8 LC-MS/MS
Vertegaal AC , et al. 2006
XRCC6 X-ray repair complementing defective repair in Chinese hamster cells 6 2547 P12956 IP/WB
Luijsterburg MS , et al. 2016
ZC3HAV1 zinc finger CCCH-type, antiviral 1 56829 Q7Z2W4 LC-MS/MS
Vertegaal AC , et al. 2006
ZMYND11 zinc finger, MYND-type containing 11 10771 Q5BJG6 LC-MS/MS
Vertegaal AC , et al. 2006
ZNF174 zinc finger protein 174 7727 Q15697 LC-MS/MS
Vertegaal AC , et al. 2006
ZNF317 zinc finger protein 317 57693 Q96PQ6 LC-MS/MS
Vertegaal AC , et al. 2006
ZNF462 zinc finger protein 462 58499 Q96JM2 LC-MS/MS
Vertegaal AC , et al. 2006
ZNF592 zinc finger protein 592 9640 Q92610 LC-MS/MS
Vertegaal AC , et al. 2006
ZNF687 zinc finger protein 687 57592 Q8N1G0 LC-MS/MS
Vertegaal AC , et al. 2006
ZNF768 zinc finger protein 768 79724 Q9H5H4 LC-MS/MS
Vertegaal AC , et al. 2006
ZSCAN12 zinc finger and SCAN domain containing 12 9753 O43309 LC-MS/MS
Vertegaal AC , et al. 2006
Acta1 actin, alpha 1, skeletal muscle 11459 P68134 ChIP-Seq; ChIP-qPCR
Harada A , et al. 2012
Ank1 ankyrin 1, erythroid 11733 Q02357 ChIP-Seq; ChIP-qPCR
Harada A , et al. 2012
Cdkn1a cyclin-dependent kinase inhibitor 1A (P21) 12575 P39689 ChIP-Seq; ChIP-qPCR
Harada A , et al. 2012
Dmd dystrophin, muscular dystrophy 13405 P11531 ChIP-Seq; ChIP-qPCR
Harada A , et al. 2012
H3f3a H3 histone, family 3A 15078 P84244 IP/WB; Proximity ligation assay; Co-localization
Harada A , et al. 2012
Myl3 myosin, light chain 3, alkali; ventricular, skeletal, slow 17897 P09542 ChIP-Seq; ChIP-qPCR
Harada A , et al. 2012
Myod1 myogenic differentiation 1 17927 P10085 IP/WB; Proximity ligation assay; ChIP-reChIP
Harada A , et al. 2012
Myog myogenin (myogenic factor 4) 17928 P12979 ChIP-Seq; ChIP-qPCR
Harada A , et al. 2012

HELP
Copyright © 2017 MindSpec, Inc.