CHD3chromodomain helicase DNA binding protein 3

SFARI Gene Score

High Confidence, Syndromic Criteria 1.1, Syndromic

Autism Reports / Total Reports

11 / 21

Rare Variants / Common Variants

110 / 0

Aliases

CHD3, Mi-2a, Mi2-ALPHA, ZFH

Associated Syndromes

Snijders Blok-Campeau syndrome (SNIBCPS), Snijders Blok-Campeau syndrome, ASD, DD, ID, Snijders Blok-Campeau syndrome, DD, Snijders Blok-Campeau syndrome, ASD, DD, Snijders Blok-Campeau syndrome, DD, ID, Snijders Blok-Campeau syndrome, ASD, DD, epilepsy/

Chromosome Band

17p13.1

Associated Disorders

ASD

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.

External Links

Gene Card Open Targets Platform gnomAD browser PubMed

Human

Entrez Gene OMIM UniProt HumanBase VariCarta

SFARI Genomic Platforms

GPF browser SFARI genome browser

Reports (21)
Variants (110)
Gene Score

Reports related to CHD3 (21 Reports)

#	Type	Title	Author, Year	Autism Report	Associated Disorders
1	Primary	The contribution of de novo coding mutations to autism spectrum disorder	Iossifov I et al. (2014)	Yes	-
2	Support	Genome-wide characteristics of de novo mutations in autism	Yuen RK et al. (2016)	Yes	-
3	Support	Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder	C Yuen RK et al. (2017)	Yes	-
4	Support	Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder	Lim ET , et al. (2017)	Yes	-
5	Recent Recommendation	CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language	Snijders Blok L , et al. (2018)	No	ASD or autistic features
6	Support	Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks	Ruzzo EK , et al. (2019)	Yes	-
7	Support	Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes	Feliciano P et al. (2019)	Yes	-
8	Recent Recommendation	A second cohort of CHD3 patients expands the molecular mechanisms known to cause Snijders Blok-Campeau syndrome	Drivas TG et al. (2020)	No	Autistic features
9	Recent recommendation	-	Sadler B et al. (2021)	No	-
10	Support	-	Mizukami M et al. (2021)	Yes	-
11	Recent Recommendation	-	van der Spek J et al. (2022)	No	ASD or autistic features, ID
12	Support	-	Zhou X et al. (2022)	Yes	-
13	Support	-	LeBreton L et al. (2023)	Yes	-
14	Recent Recommendation	-	Timberlake AT et al. (2023)	No	-
15	Support	-	Sheth F et al. (2023)	Yes	DD, ID
16	Support	-	Patricia Pascual et al. (2023)	No	ASD, ADHD
17	Support	-	Ashraf Yahia et al. (2024)	No	-
18	Support	-	Noor Smal et al. ()	No	-
19	Support	-	Tomoki T Nomakuchi et al. ()	Yes	-
20	Support	-	Axel Schmidt et al. (2024)	No	ID
21	Support	-	Yuanyuan Gao et al. (2024)	No	ASD

Rare Variants (110)

Allele Change	Residue Change	Variant Type	Inheritance Pattern	Parental Transmission	Family Type	PubMed ID	Author, Year
-	-	copy_number_loss	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
-	-	copy_number_gain	Unknown	-	Multiplex	32483341	Drivas TG et al. (2020)
-	p.Glu315Lys	missense_variant	De novo	-	Simplex	28714951	Lim ET , et al. (2017)
c.1120G>A	p.Glu374Lys	missense_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.2464A>T	p.Met822Leu	missense_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.3131G>A	p.Arg1044Gln	missense_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.3691C>T	p.Arg1231Trp	missense_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.5307T>C	p.Asn1769%3D	synonymous_variant	De novo	-	-	35982159	Zhou X et al. (2022)
c.5432G>A	p.Arg1811Gln	missense_variant	De novo	-	-	36565043	LeBreton L et al. (2023)
c.1796G>A	p.Arg599His	missense_variant	De novo	-	-	31452935	Feliciano P et al. (2019)
c.473C>A	p.Pro158Gln	missense_variant	De novo	-	-	39039281	Axel Schmidt et al. (2024)
c.1495C>T	p.Arg499Ter	stop_gained	De novo	-	-	37761804	Patricia Pascual et al. (2023)
c.3551T>G	p.Phe1184Cys	missense_variant	De novo	-	Simplex	38965372	Noor Smal et al. ()
c.3515G>A	p.Arg1172Gln	missense_variant	De novo	-	-	39039281	Axel Schmidt et al. (2024)
c.3536A>T	p.Asp1179Val	missense_variant	Unknown	-	-	39039281	Axel Schmidt et al. (2024)
c.4202G>A	p.Arg1401Gln	missense_variant	Unknown	-	-	39039281	Axel Schmidt et al. (2024)
c.1708-1G>T	-	splice_site_variant	Unknown	-	Simplex	39050258	Yuanyuan Gao et al. (2024)
c.2902C>G	p.Leu968Val	missense_variant	De novo	-	Simplex	27525107	Yuen RK et al. (2016)
c.6068A>G	p.Asn2023Ser	missense_variant	Unknown	-	Simplex	37543562	Sheth F et al. (2023)
c.4073-3_4078del	-	splice_site_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.5812G>A	p.Ala1938Thr	missense_variant	De novo	-	-	39031459	Tomoki T Nomakuchi et al. ()
c.2657A>G	p.His886Arg	missense_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.2749A>T	p.Asn917Tyr	missense_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.2831T>A	p.Phe944Tyr	missense_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.2842T>C	p.Ser948Pro	missense_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.2896C>T	p.Arg966Trp	missense_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.2897G>C	p.Arg966Pro	missense_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.2905A>G	p.Lys969Glu	missense_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.2954G>A	p.Arg985Gln	missense_variant	De novo	-	-	37761804	Patricia Pascual et al. (2023)
c.3073C>T	p.Arg1025Trp	missense_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.3239T>A	p.Leu1080His	missense_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.3515G>A	p.Arg1172Gln	missense_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.3784C>T	p.Arg1262Trp	missense_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.4243C>T	p.Arg1415Cys	missense_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.5863G>T	p.Ala1955Ser	missense_variant	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.2896C>T	p.Arg966Trp	missense_variant	De novo	-	Simplex	33358638	Mizukami M et al. (2021)
c.3130C>T	p.Arg1044Trp	missense_variant	De novo	-	-	37761804	Patricia Pascual et al. (2023)
c.3209G>A	p.Gly1070Asp	missense_variant	De novo	-	-	37761804	Patricia Pascual et al. (2023)
c.3406A>C	p.Thr1136Pro	missense_variant	De novo	-	-	37761804	Patricia Pascual et al. (2023)
c.3505C>T	p.Arg1169Trp	missense_variant	De novo	-	-	37761804	Patricia Pascual et al. (2023)
c.3506G>A	p.Arg1169Gln	missense_variant	De novo	-	-	37761804	Patricia Pascual et al. (2023)
c.3541A>T	p.Ile1181Phe	missense_variant	De novo	-	-	37761804	Patricia Pascual et al. (2023)
c.3673G>C	p.Ala1225Pro	missense_variant	De novo	-	-	37761804	Patricia Pascual et al. (2023)
c.3683G>A	p.Arg1228Gln	missense_variant	De novo	-	-	37761804	Patricia Pascual et al. (2023)
c.3865G>A	p.Ala1289Thr	missense_variant	Unknown	-	-	37761804	Patricia Pascual et al. (2023)
c.4073-2A>G	-	splice_site_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.5452C>T	p.Arg1818Trp	missense_variant	De novo	-	Simplex	25363768	Iossifov I et al. (2014)
c.1369G>T	p.Glu457Ter	stop_gained	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.3509C>T	p.Thr1170Met	missense_variant	De novo	-	Multiplex	31398340	Ruzzo EK , et al. (2019)
c.2954G>C	p.Arg985Pro	missense_variant	De novo	-	Simplex	39050258	Yuanyuan Gao et al. (2024)
c.3371C>T	p.Ala1124Val	missense_variant	De novo	-	Simplex	39050258	Yuanyuan Gao et al. (2024)
c.4280G>A	p.Trp1427Ter	stop_gained	Familial	Maternal	Simplex	32483341	Drivas TG et al. (2020)
c.2284_2286del	p.Lys762del	inframe_deletion	De novo	-	Simplex	28263302	C Yuen RK et al. (2017)
c.2953C>T	p.Leu985=	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.3784_3786del	p.Met1262del	inframe_deletion	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.3325_3327del	p.Tyr1109del	inframe_deletion	De novo	-	-	37761804	Patricia Pascual et al. (2023)
c.3502_3504del	p.Ser1168del	inframe_deletion	De novo	-	-	37761804	Patricia Pascual et al. (2023)
c.3477C>A	p.Gly1159=	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.2657A>G	p.His886Arg	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.2745G>T	p.Leu915Phe	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.2761G>A	p.Glu921Lys	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.2882G>A	p.Gly961Glu	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.2954G>A	p.Arg985Gln	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.3362G>C	p.Arg1121Pro	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.3407C>T	p.Thr1136Ile	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.3472T>C	p.Trp1158Arg	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.3505C>T	p.Arg1169Trp	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.3512A>G	p.His1171Arg	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.3515G>A	p.Arg1172Gln	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.3560G>C	p.Arg1187Pro	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.3707T>C	p.Leu1236Pro	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.4025G>A	p.Arg1342Gln	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.5642G>T	p.Arg1881Leu	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.1384del	p.Cys462AlafsTer22	frameshift_variant	Unknown	-	Simplex	32483341	Drivas TG et al. (2020)
c.1795dup	p.Arg599ProfsTer47	frameshift_variant	Unknown	-	Simplex	32483341	Drivas TG et al. (2020)
c.4532_4535del	p.Phe1511TrpfsTer31	frameshift_variant	De novo	-	-	31452935	Feliciano P et al. (2019)
c.3473G>A	p.Trp1158Ter	stop_gained	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.3910C>T	p.Arg1304Ter	stop_gained	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.4151C>G	p.Ser1384Ter	stop_gained	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.4280G>A	p.Trp1427Ter	stop_gained	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.4312C>T	p.Gln1438Ter	stop_gained	Familial	Paternal	Simplex	35346573	van der Spek J et al. (2022)
c.5089C>T	p.Arg1697Ter	stop_gained	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.5461G>T	p.Glu1821Ter	stop_gained	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.3725G>A	p.Arg1242Gln	missense_variant	Familial	Paternal	-	37761804	Patricia Pascual et al. (2023)
c.2422_3155+60del	-	frameshift_variant	Familial	Paternal	Simplex	35346573	van der Spek J et al. (2022)
c.3325_3327del	p.Tyr1109del	inframe_deletion	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.3357_3358inv	p.Lys1120Gln	missense_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.5767+33_5767+34insAACG	-	frameshift_variant	De novo	-	Simplex	30397230	Snijders Blok L , et al. (2018)
c.3603_3614del	p.Met1202_Thr1205del	inframe_deletion	De novo	-	Simplex	32483341	Drivas TG et al. (2020)
c.2327A>G	p.Asp776Gly	missense_variant	Familial	Paternal	Multiplex	38300321	Ashraf Yahia et al. (2024)
c.1888T>C	p.Trp630Arg	missense_variant	Familial	Paternal	Simplex	35346573	van der Spek J et al. (2022)
c.2497T>C	p.Phe833Leu	missense_variant	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.2617G>A	p.Gly873Ser	missense_variant	Familial	Paternal	Simplex	35346573	van der Spek J et al. (2022)
c.2947A>G	p.Ile983Val	missense_variant	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.3137C>T	p.Pro1046Leu	missense_variant	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.3373C>G	p.Pro1125Ala	missense_variant	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.4025G>A	p.Arg1342Gln	missense_variant	Familial	Paternal	Simplex	35346573	van der Spek J et al. (2022)
c.4456C>G	p.Gln1486Glu	missense_variant	Familial	Paternal	Simplex	35346573	van der Spek J et al. (2022)
c.5117G>A	p.Arg1706Gln	missense_variant	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.5276G>A	p.Arg1759Gln	missense_variant	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.5509G>A	p.Glu1837Lys	missense_variant	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.5915A>C	p.Lys1972Thr	missense_variant	Familial	Maternal	Simplex	35346573	van der Spek J et al. (2022)
c.5184_5185del	p.Asp1730PhefsTer10	frameshift_variant	De novo	-	-	37761804	Patricia Pascual et al. (2023)
c.1430C>T	p.Ser477Phe	missense_variant	Familial	Paternal	Multiplex	35346573	van der Spek J et al. (2022)
c.2953C>T	p.Leu985=	missense_variant	Familial	Maternal	Multiplex	30397230	Snijders Blok L , et al. (2018)
c.3592_3606del	p.Ala1198_Met1202del	inframe_deletion	De novo	-	Simplex	39050258	Yuanyuan Gao et al. (2024)
c.5663G>A	p.Arg1888Gln	missense_variant	Familial	Maternal	Multiplex	35346573	van der Spek J et al. (2022)
c.4042G>A	p.Ala1348Thr	missense_variant	Familial	Maternal	Multiplex	37761804	Patricia Pascual et al. (2023)
c.1706A>G	p.Gln569Arg	missense_variant	De novo	-	Multiplex (monozygotic twins)	32483341	Drivas TG et al. (2020)
c.3482A>G	p.Lys1161Arg	missense_variant	De novo	-	Multiplex (monozygotic twins)	30397230	Snijders Blok L , et al. (2018)

Common Variants

No common variants reported.

Current Score
Scoring History
3rd Party Scoring

SFARI Gene score

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met

See SFARI Gene'scoring criteria

High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

1/1/2021

Score remained at 1

Description

Reports Added

[Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.2017] [Rare and de novo coding variants in chromodomain genes in Chiari I malformation2021] [A de novo CHD3 variant in a child with intellectual disability, autism, joint laxity, and dysmorphisms2021]

4/1/2020

Score remained at 1

Description

Reports Added

[A second cohort of CHD3 patients expands the molecular mechanisms known to cause Snijders Blok-Campeau syndrome2020]

10/1/2019

Decreased from 4S to 1

New Scoring Scheme

Description

Reports Added

[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]

7/1/2019

Decreased from 4S to 4S

Description

Reports Added

[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]

10/1/2018

Increased from to 4S

Description

Krishnan Probability Score

Score 0.50356225951409

Ranking 1941/25841 scored genes

[Show Scoring Methodology]

Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.

Original Source

ExAC Score

Score 0.99999999551797

Ranking 123/18225 scored genes

[Show Scoring Methodology]

The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt

Original Source

Sanders TADA Score

Score 0.90096203965782

Ranking 6477/18665 scored genes

[Show Scoring Methodology]

The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).

Original Source

Zhang D Score

Score 0.50767055769192

Ranking 472/20870 scored genes

[Show Scoring Methodology]

The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.

Original Source

Human Gene Module / Chromosome 17 / CHD3

CHD3chromodomain helicase DNA binding protein 3

SFARI Gene Score

Autism Reports / Total Reports

Rare Variants / Common Variants

Aliases

Associated Syndromes

Chromosome Band

Associated Disorders

Relevance to Autism

Molecular Function

External Links

Human

SFARI Genomic Platforms

Reports related to CHD3 (21 Reports)

Rare Variants (110)

Common Variants

SFARI Gene score

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met

High Confidence

Syndromic

1/1/2021

Score remained at 1

Description

Reports Added

4/1/2020

Score remained at 1

Description

Reports Added

10/1/2019

Decreased from 4S to 1

New Scoring Scheme

Description

Reports Added

7/1/2019

Decreased from 4S to 4S

Description

Reports Added

10/1/2018

Increased from to 4S

Description

Krishnan Probability Score

Score 0.50356225951409

Ranking 1941/25841 scored genes

ExAC Score

Score 0.99999999551797

Ranking 123/18225 scored genes

Sanders TADA Score

Score 0.90096203965782

Ranking 6477/18665 scored genes

Zhang D Score

Score 0.50767055769192

Ranking 472/20870 scored genes