Summary Statistics:
Gene Score: 4S
Relevance to Autism
Two de novo missense variants and one de novo in-frame deletion variant were identified in the CHD3 gene in ASD probands following whole-exome or whole-genome sequencing (Iossifov et al., 2014; Yuen et al., 2016; Yuen et al., 2017). Snijders Blok et al., 2018 described a cohort of 35 individuals with de novo CHD3 mutations and overlapping phenotypes, including developmental delay/intellectual disability and speech delay/disorder; nine individuals (29%) displayed autism or autistic features, including stereotypic and hand-flapping behavior.
Molecular Function
This gene encodes a member of the CHD family of proteins which are characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. This protein is one of the components of a histone deacetylase complex referred to as the Mi-2/NuRD complex which participates in the remodeling of chromatin by deacetylating histones. Chromatin remodeling is essential for many processes including transcription.
References
Primary
The contribution of de novo coding mutations to autism spectrum disorder
ASD
Support
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
ASD
Support
Snijders Blok-Campeau syndrome, ASD, DD
Support
Genome-wide characteristics of de novo mutations in autism
ASD
Support
Integrating de novo and inherited variants in 42
ASD
Support
A de novo CHD3 variant in a child with intellectual disability, autism, joint laxity, and dysmorphisms
Snijders Blok-Campeau syndrome, ASD, DD, ID
Support
Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes
ASD
Support
Developmental language disorder
Support
Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
ASD
Support
Snijders Blok-Campeau syndrome, DD, ID
ASD, ADHD
Support
Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.
ASD
Recent Recommendation
Inherited variants in CHD3 show variable expressivity in Snijders Blok-Campeau syndrome
Snijders Blok-Campeau syndrome, DD
ASD or autistic features, ID
Recent recommendation
Rare and de novo coding variants in chromodomain genes in Chiari I malformation
Chiari I malformation
Recent Recommendation
A second cohort of CHD3 patients expands the molecular mechanisms known to cause Snijders Blok-Campeau syndrome
Snijders Blok-Campeau syndrome (SNIBCPS)
Autistic features
Recent Recommendation
CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language.
DD, ID
ASD or autistic features
Recent Recommendation
Craniosynostosis
GEN1048R001
missense_variant
c.5452C>T
p.Arg1818Trp
De novo
Simplex
GEN1048R002
missense_variant
c.2902C>G
p.Leu968Val
De novo
Simplex
GEN1048R003
inframe_deletion
c.2284_2286del
p.Lys762del
De novo
Simplex
GEN1048R004
stop_gained
c.1369G>T
p.Glu457Ter
De novo
Simplex
GEN1048R005
missense_variant
c.2657A>G
p.His886Arg
De novo
Simplex
GEN1048R006
missense_variant
c.2745G>T
p.Leu915Phe
De novo
Simplex
GEN1048R007
missense_variant
c.2761G>A
p.Glu921Lys
De novo
Simplex
GEN1048R008
missense_variant
c.2882G>A
p.Gly961Glu
De novo
Simplex
GEN1048R009
missense_variant
c.2953C>T
p.Leu985=
De novo
Simplex
GEN1048R010
missense_variant
c.2953C>T
p.Leu985=
Familial
Maternal
Multiplex
GEN1048R011
missense_variant
c.2953C>T
p.Leu985=
De novo
Simplex
GEN1048R012
missense_variant
c.2953C>T
p.Leu985=
De novo
Simplex
GEN1048R013
missense_variant
c.2953C>T
p.Leu985=
De novo
Simplex
GEN1048R014
missense_variant
c.2954G>A
p.Arg985Gln
De novo
Simplex
GEN1048R015
missense_variant
c.2954G>A
p.Arg985Gln
De novo
Simplex
GEN1048R016
inframe_deletion
c.3325_3327del
p.Tyr1109del
De novo
Simplex
GEN1048R017
missense_variant
c.3357_3358inv
p.Lys1120Gln
De novo
Simplex
GEN1048R018
missense_variant
c.3362G>C
p.Arg1121Pro
De novo
Simplex
GEN1048R019
missense_variant
c.3407C>T
p.Thr1136Ile
De novo
Simplex
GEN1048R020
missense_variant
c.3472T>C
p.Trp1158Arg
De novo
Simplex
GEN1048R021
missense_variant
c.3477C>A
p.Gly1159=
De novo
Simplex
GEN1048R022
missense_variant
c.3482A>G
p.Lys1161Arg
De novo
Multiplex (monozygotic twins)
GEN1048R023
missense_variant
c.3505C>T
p.Arg1169Trp
De novo
Simplex
GEN1048R024
missense_variant
c.3505C>T
p.Arg1169Trp
De novo
Simplex
GEN1048R025
missense_variant
c.3505C>T
p.Arg1169Trp
De novo
Simplex
GEN1048R026
missense_variant
c.3512A>G
p.His1171Arg
De novo
Simplex
GEN1048R027
missense_variant
c.3515G>A
p.Arg1172Gln
De novo
Simplex
GEN1048R028
missense_variant
c.3515G>A
p.Arg1172Gln
De novo
Simplex
GEN1048R029
missense_variant
c.3515G>A
p.Arg1172Gln
De novo
Simplex
GEN1048R030
missense_variant
c.3560G>C
p.Arg1187Pro
De novo
Simplex
GEN1048R031
missense_variant
c.3560G>C
p.Arg1187Pro
De novo
Simplex
GEN1048R032
missense_variant
c.3707T>C
p.Leu1236Pro
De novo
Simplex
GEN1048R033
missense_variant
c.4025G>A
p.Arg1342Gln
De novo
Simplex
GEN1048R034
splice_site_variant
c.4073-2A>G
De novo
Simplex
GEN1048R035
missense_variant
c.5642G>T
p.Arg1881Leu
De novo
Simplex
GEN1048R036
frameshift_variant
c.5767+33_5767+34insAACG
De novo
Simplex
GEN1048R037
missense_variant
c.3509C>T
p.Thr1170Met
De novo
Multiplex
GEN1048R038
frameshift_variant
c.4532_4535del
p.Phe1511TrpfsTer31
De novo
GEN1048R039
missense_variant
c.1796G>A
p.Arg599His
De novo
GEN1048R040
missense_variant
c.1706A>G
p.Gln569Arg
De novo
Multiplex (monozygotic twins)
GEN1048R041
missense_variant
c.2657A>G
p.His886Arg
De novo
Simplex
GEN1048R042
missense_variant
c.2749A>T
p.Asn917Tyr
De novo
Simplex
GEN1048R043
missense_variant
c.2831T>A
p.Phe944Tyr
De novo
Simplex
GEN1048R044
missense_variant
c.2842T>C
p.Ser948Pro
De novo
Simplex
GEN1048R045
missense_variant
c.3073C>T
p.Arg1025Trp
De novo
Simplex
GEN1048R046
missense_variant
c.2896C>T
p.Arg966Trp
De novo
Simplex
GEN1048R047
missense_variant
c.2896C>T
p.Arg966Trp
De novo
Simplex
GEN1048R048
missense_variant
c.2897G>C
p.Arg966Pro
De novo
Simplex
GEN1048R049
missense_variant
c.2905A>G
p.Lys969Glu
De novo
Simplex
GEN1048R050
missense_variant
c.3239T>A
p.Leu1080His
De novo
Simplex
GEN1048R051
missense_variant
c.3515G>A
p.Arg1172Gln
De novo
Simplex
GEN1048R052
inframe_deletion
c.3603_3614del
p.Met1202_Thr1205del
De novo
Simplex
GEN1048R053
inframe_deletion
c.3784_3786del
p.Met1262del
De novo
Simplex
GEN1048R054
missense_variant
c.3784C>T
p.Arg1262Trp
De novo
Simplex
GEN1048R055
missense_variant
c.4243C>T
p.Arg1415Cys
De novo
Simplex
GEN1048R056
missense_variant
c.5863G>T
p.Ala1955Ser
De novo
Simplex
GEN1048R057
stop_gained
c.4280G>A
p.Trp1427Ter
Familial
Maternal
Simplex
GEN1048R058
frameshift_variant
c.1384del
p.Cys462AlafsTer22
Unknown
Simplex
GEN1048R059
frameshift_variant
c.1795dup
p.Arg599ProfsTer47
Unknown
Simplex
GEN1048R060
splice_site_variant
c.4073-3_4078del
De novo
Simplex
GEN1048R061
copy_number_loss
De novo
Simplex
GEN1048R062
copy_number_gain
Unknown
Multiplex
GEN1048R063
missense_variant
c.2896C>T
p.Arg966Trp
De novo
Simplex
GEN1048R064
missense_variant
p.Glu315Lys
De novo
Simplex
GEN1048R065
stop_gained
c.3473G>A
p.Trp1158Ter
Familial
Maternal
Simplex
GEN1048R066
stop_gained
c.3910C>T
p.Arg1304Ter
Familial
Maternal
Simplex
GEN1048R067a
stop_gained
c.4151C>G
p.Ser1384Ter
Familial
Maternal
Simplex
GEN1048R067b
missense_variant
c.4456C>G
p.Gln1486Glu
Familial
Paternal
Simplex
GEN1048R068
stop_gained
c.4280G>A
p.Trp1427Ter
Familial
Maternal
Simplex
GEN1048R069
stop_gained
c.4312C>T
p.Gln1438Ter
Familial
Paternal
Simplex
GEN1048R070
stop_gained
c.5089C>T
p.Arg1697Ter
Familial
Maternal
Simplex
GEN1048R071
stop_gained
c.5461G>T
p.Glu1821Ter
Familial
Maternal
Simplex
GEN1048R072
frameshift_variant
c.2422_3155+60del
Familial
Paternal
Simplex
GEN1048R073
missense_variant
c.1430C>T
p.Ser477Phe
Familial
Paternal
Multiplex
GEN1048R074
missense_variant
c.1888T>C
p.Trp630Arg
Familial
Paternal
Simplex
GEN1048R075
missense_variant
c.2497T>C
p.Phe833Leu
Familial
Maternal
Simplex
GEN1048R076
missense_variant
c.2617G>A
p.Gly873Ser
Familial
Paternal
Simplex
GEN1048R077
missense_variant
c.2947A>G
p.Ile983Val
Familial
Maternal
Simplex
GEN1048R078
missense_variant
c.3137C>T
p.Pro1046Leu
Familial
Maternal
Simplex
GEN1048R079
missense_variant
c.3373C>G
p.Pro1125Ala
Familial
Maternal
Simplex
GEN1048R080
missense_variant
c.4025G>A
p.Arg1342Gln
Familial
Paternal
Simplex
GEN1048R081
missense_variant
c.5117G>A
p.Arg1706Gln
Familial
Maternal
Simplex
GEN1048R082
missense_variant
c.5276G>A
p.Arg1759Gln
Familial
Maternal
Simplex
GEN1048R083
missense_variant
c.5509G>A
p.Glu1837Lys
Familial
Maternal
Simplex
GEN1048R084
missense_variant
c.5663G>A
p.Arg1888Gln
Familial
Maternal
Multiplex
GEN1048R085
missense_variant
c.5915A>C
p.Lys1972Thr
Familial
Maternal
Simplex
GEN1048R086
missense_variant
c.1120G>A
p.Glu374Lys
De novo
GEN1048R087
synonymous_variant
c.5307T>C
p.Asn1769%3D
De novo
GEN1048R088
missense_variant
c.2464A>T
p.Met822Leu
De novo
GEN1048R089
missense_variant
c.3131G>A
p.Arg1044Gln
De novo
GEN1048R090
missense_variant
c.3691C>T
p.Arg1231Trp
De novo
GEN1048R091
missense_variant
c.5432G>A
p.Arg1811Gln
De novo
GEN1048R092
missense_variant
c.6068A>G
p.Asn2023Ser
Unknown
Simplex
GEN1048R093
frameshift_variant
c.5184_5185del
p.Asp1730PhefsTer10
De novo
GEN1048R094
missense_variant
c.3130C>T
p.Arg1044Trp
De novo
GEN1048R095
missense_variant
c.3209G>A
p.Gly1070Asp
De novo
GEN1048R096
missense_variant
c.3673G>C
p.Ala1225Pro
De novo
GEN1048R097
inframe_deletion
c.3325_3327del
p.Tyr1109del
De novo
GEN1048R098
missense_variant
c.3725G>A
p.Arg1242Gln
Familial
Paternal
GEN1048R099
missense_variant
c.3683G>A
p.Arg1228Gln
De novo
GEN1048R100
inframe_deletion
c.3502_3504del
p.Ser1168del
De novo
GEN1048R101
missense_variant
c.3406A>C
p.Thr1136Pro
De novo
GEN1048R102
stop_gained
c.1495C>T
p.Arg499Ter
De novo
GEN1048R103
missense_variant
c.3865G>A
p.Ala1289Thr
Unknown
GEN1048R104
missense_variant
c.4042G>A
p.Ala1348Thr
Familial
Maternal
Multiplex
GEN1048R105
missense_variant
c.2954G>A
p.Arg985Gln
De novo
GEN1048R106
missense_variant
c.3505C>T
p.Arg1169Trp
De novo
GEN1048R107
missense_variant
c.3541A>T
p.Ile1181Phe
De novo
GEN1048R108
missense_variant
c.3541A>T
p.Ile1181Phe
De novo
GEN1048R109
missense_variant
c.3506G>A
p.Arg1169Gln
De novo
GEN1048R110
missense_variant
c.3130C>T
p.Arg1044Trp
De novo
GEN1048R111
missense_variant
c.2327A>G
p.Asp776Gly
Familial
Paternal
Multiplex
No Common Variants Available
17
Deletion-Duplication
29
17
Deletion-Duplication
5
No Interactions Available
