Human Gene Module / Chromosome 8 / CHD7

CHD7chromodomain helicase DNA binding protein 7

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
20 / 46
Rare Variants / Common Variants
59 / 0
EAGLE Score
8.1
Moderate Learn More
Aliases
CHD7, FLJ20357,  FLJ20361,  IS3,  KAL5,  KIAA1416
Associated Syndromes
CHARGE syndrome
Chromosome Band
8q12.2
Associated Disorders
DD/NDD, ID, ASD, EPS
Genetic Category
Rare Single Gene Mutation, Syndromic, Functional
Relevance to Autism

This gene has been associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. In particular, rare mutations of the CHD7 gene have been identified with CHARGE syndrome (Vissers et al., 2004), and a rare mutation in the CHD7 gene has been identified in an individual with ASD (ORoak et al., 2012).

Molecular Function

This gene encodes a protein that contains several helicase family domains. Mutations in this gene have been found in some patients with the CHARGE syndrome.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome Informatics
Fruit fly
Entrez Gene
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CHD7 (46 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Mutations in a new member of the chromodomain gene family cause CHARGE syndrome Vissers LE , et al. (2004) No ASD
2 Support CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome Batsukh T , et al. (2010) No -
3 Support Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
4 Recent Recommendation Chromatin remodeling by the CHD7 protein is impaired by mutations that cause human developmental disorders Bouazoune K and Kingston RE (2012) No -
5 Recent Recommendation The chromatin remodeler CHD7 regulates adult neurogenesis via activation of SoxC transcription factors Feng W , et al. (2013) No -
6 Support Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing Jiang YH , et al. (2013) Yes -
7 Support Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with autism spectrum disorder Koshimizu E , et al. (2013) Yes ID, epilepsy
8 Recent Recommendation CHD7, the gene mutated in CHARGE syndrome, regulates genes involved in neural crest cell guidance Schulz Y , et al. (2014) No -
9 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
10 Recent Recommendation Low load for disruptive mutations in autism genes and their biased transmission Iossifov I , et al. (2015) Yes -
11 Recent Recommendation De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies Homsy J , et al. (2016) No DD, learning disabilities
12 Recent Recommendation Chd7 cooperates with Sox10 and regulates the onset of CNS myelination and remyelination He D , et al. (2016) No -
13 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH et al. (2016) No -
14 Support De novo genic mutations among a Chinese autism spectrum disorder cohort Wang T , et al. (2016) Yes -
15 Support The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies Redin C , et al. (2016) No -
16 Support Clinical exome sequencing: results from 2819 samples reflecting 1000 families Trujillano D , et al. (2016) No ASD, ID
17 Recent Recommendation The chromatin remodeling factor CHD7 controls cerebellar development by regulating reelin expression Whittaker DE , et al. (2017) No -
18 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
19 Recent Recommendation Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme Feng W , et al. (2017) No -
20 Support Genomic diagnosis for children with intellectual disability and/or developmental delay Bowling KM , et al. (2017) No -
21 Support Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands Jin SC , et al. (2017) No Neurodevelopmental disorders (NDD)
22 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
23 Support Oligodendrocyte precursor survival and differentiation requires chromatin remodeling by Chd7 and Chd8 Marie C , et al. (2018) No -
24 Support Autism-linked CHD gene expression patterns during development predict multi-organ disease phenotypes Kasah S , et al. (2018) No -
25 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model Guo H , et al. (2018) Yes -
26 Support Comprehensive Analysis of Rare Variants of 101 Autism-Linked Genes in a Hungarian Cohort of Autism Spectrum Disorder Patients Balicza P , et al. (2019) Yes CHARGE syndrome
27 Support Autism-associated missense genetic variants impact locomotion and neurodevelopment in Caenorhabditis elegans Wong WR , et al. (2019) Yes -
28 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
29 Support Should autism spectrum disorder be considered part of CHARGE syndrome? A cross-sectional study of 46 patients Abadie V et al. (2020) No -
30 Support - Zhang R et al. (2021) Yes -
31 Recent Recommendation - Coll-Tané M et al. (2021) No -
32 Support - Reddy NC et al. (2021) No -
33 Support - Brea-Fernández AJ et al. (2022) Yes -
34 Support - Chuan Z et al. (2022) No -
35 Support - Hu C et al. (2022) Yes -
36 Support - Zhang W et al. (2022) No -
37 Support - Zhou X et al. (2022) Yes -
38 Support - More RP et al. (2023) Yes -
39 Support - Hodorovich DR et al. (2023) No -
40 Support - Spataro N et al. (2023) No -
41 Support - Hu C et al. (2023) Yes -
42 Recent Recommendation - Timberlake AT et al. (2023) No -
43 Support - Tuncay IO et al. (2023) Yes -
44 Support - Sheth F et al. (2023) Yes DD, ID, epilepsy/seizures
45 Support - et al. () Yes -
46 Support - et al. () No -
Rare Variants   (59)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation - - - 15300250 Vissers LE , et al. (2004)
- - translocation De novo - - 27841880 Redin C , et al. (2016)
c.2839C>T p.Arg947Ter stop_gained De novo - - 38321498 et al. ()
- - copy_number_loss De novo - - 15300250 Vissers LE , et al. (2004)
c.1717-5658C>T - stop_gained De novo - - 28991257 Jin SC , et al. (2017)
c.3973T>C p.Tyr1325His missense_variant Unknown - - 38003033 et al. ()
c.1717-11683C>T - stop_gained De novo - - 28991257 Jin SC , et al. (2017)
c.1717-20232C>T - stop_gained De novo - - 26785492 Homsy J , et al. (2016)
c.469C>T p.Arg157Ter stop_gained - - - 15300250 Vissers LE , et al. (2004)
c.1078G>T p.Gly360Ter stop_gained - - - 15300250 Vissers LE , et al. (2004)
c.6051T>A p.Cys2017Ter stop_gained - - - 15300250 Vissers LE , et al. (2004)
c.6070C>T p.Arg2024Ter stop_gained - - - 15300250 Vissers LE , et al. (2004)
G>A p.? splice_site_variant De novo - - 15300250 Vissers LE , et al. (2004)
c.7252C>T p.Arg2418Ter stop_gained De novo - - 35571021 Chuan Z et al. (2022)
c.1714C>T p.Gln572Ter stop_gained De novo - - 15300250 Vissers LE , et al. (2004)
c.3640C>G p.Gln1214Glu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.5050G>A p.Gly1684Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.7708C>T p.Pro2570Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.8326C>T p.Pro2776Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.8692A>G p.Met2898Val missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1717-20205del - frameshift_variant De novo - - 31134136 Balicza P , et al. (2019)
c.5418C>G p.Tyr1806Ter stop_gained De novo - - 15300250 Vissers LE , et al. (2004)
c.7824T>A p.Tyr2608Ter stop_gained De novo - - 15300250 Vissers LE , et al. (2004)
c.1644G>A p.Pro548%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.5181C>G p.Tyr1727Ter stop_gained De novo - - 27479843 Lelieveld SH et al. (2016)
c.2959C>T p.Arg987Ter stop_gained De novo - - 27848944 Trujillano D , et al. (2016)
c.2643T>A p.Tyr881Ter stop_gained Unknown - - 34088660 Coll-Tané M et al. (2021)
c.5202C>A p.His1734Gln missense_variant De novo - - 37492102 Tuncay IO et al. (2023)
c.5181C>G p.Tyr1727Ter stop_gained Unknown - - 34088660 Coll-Tané M et al. (2021)
ACCAGTGTCTG>A - frameshift_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.1263A>G p.Pro421= synonymous_variant De novo - - 31452935 Feliciano P et al. (2019)
c.304C>T p.His102Tyr missense_variant Familial Paternal - 35741772 Hu C et al. (2022)
c.3082A>G p.Ile1028Val missense_variant De novo - - 15300250 Vissers LE , et al. (2004)
c.3770T>G p.Leu1257Arg missense_variant De novo - - 15300250 Vissers LE , et al. (2004)
c.6955C>T p.Arg2319Cys missense_variant De novo - - 28554332 Bowling KM , et al. (2017)
c.2701G>A p.Val901Met missense_variant Familial Maternal - 37007974 Hu C et al. (2023)
c.4851-31C>T - intron_variant Familial Maternal Simplex 33948885 Zhang R et al. (2021)
c.4851-31C>T - intron_variant Familial Paternal Simplex 33948885 Zhang R et al. (2021)
c.6307G>A p.Gly2103Ser missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.844C>T p.Gln282Ter stop_gained De novo - - 35322241 Brea-Fernández AJ et al. (2022)
c.7013A>T p.Gln2338Leu missense_variant De novo - Simplex 35837997 Zhang W et al. (2022)
c.1717-17396C>T - intron_variant Familial Paternal Simplex 33948885 Zhang R et al. (2021)
c.4516G>A p.Gly1506Ser missense_variant Familial Maternal - 27824329 Wang T , et al. (2016)
c.4516G>A p.Gly1506Ser missense_variant Familial Paternal - 27824329 Wang T , et al. (2016)
c.2176G>T p.Asp726Tyr missense_variant Familial - Multiplex 36702863 More RP et al. (2023)
c.7880G>A p.Arg2627Gln missense_variant De novo - Simplex 29346770 Takata A , et al. (2018)
c.2986G>A p.Gly996Ser missense_variant De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
c.7652C>A p.Thr2551Asn missense_variant Unknown - Unknown 24066114 Koshimizu E , et al. (2013)
c.7880G>A p.Arg2627Gln missense_variant Unknown - Unknown 24066114 Koshimizu E , et al. (2013)
- - copy_number_loss De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.7193G>A p.Arg2398His missense_variant Familial Paternal Simplex 30564305 Guo H , et al. (2018)
c.7502C>A p.Ser2501Tyr missense_variant Unknown Not maternal Simplex 30564305 Guo H , et al. (2018)
c.6904G>A p.Glu2302Lys missense_variant Unknown - Extended multiplex 37543562 Sheth F et al. (2023)
c.3566G>A p.Arg1189His missense_variant Familial Paternal Simplex 23849776 Jiang YH , et al. (2013)
c.2245del p.Leu749Ter frameshift_variant Familial Maternal Simplex 23160955 O'Roak BJ , et al. (2012)
c.4493_4506del p.Ile1498ArgfsTer9 frameshift_variant Unknown - - 34088660 Coll-Tané M et al. (2021)
c.2352dup p.Asn785GlnfsTer12 frameshift_variant Unknown Not maternal - 36980980 Spataro N et al. (2023)
c.2657G>A p.Arg886Gln missense_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.8941_8942insA p.Leu2981HisfsTer5 frameshift_variant Familial Paternal Simplex 23160955 O'Roak BJ , et al. (2012)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met
See SFARI Gene'scoring criteria
1

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.

S

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."

4/1/2021
1
icon
1

Score remained at 1

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[An Intronic Variant of CHD7 Identified in Autism Patients Interferes with Neuronal Differentiation and Development2021]
4/1/2020
1
icon
1

Score remained at 1

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[Should autism spectrum disorder be considered part of CHARGE syndrome? A cross-sectional study of 46 patients2020]
10/1/2019
S
icon
1

Increased from S to 1

New Scoring Scheme
Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]
7/1/2019
S
icon
S

Increased from S to S

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[Comprehensive Analysis of Rare Variants of 101 Autism-Linked Genes in a Hungarian Cohort of Autism Spectrum Disorder Patients.2019] [Autism-associated missense genetic variants impact locomotion and neurodevelopment in Caenorhabditis elegans.2019]
1/1/2019
S
icon
S

Increased from S to S

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.2018]
10/1/2018
S
icon
S

Increased from S to S

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[Autism-linked CHD gene expression patterns during development predict multi-organ disease phenotypes.2018]
7/1/2018
S
icon
S

Increased from S to S

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[Oligodendrocyte precursor survival and differentiation requires chromatin remodeling by Chd7 and Chd8.2018]
10/1/2017
S
icon
S

Increased from S to S

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.2017]
4/1/2017
S
icon
S

Increased from S to S

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Mutations in a new member of the chromodomain gene family cause CHARGE syndrome.2004] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome.2010] [Chromatin remodeling by the CHD7 protein is impaired by mutations that cause human developmental disorders.2012] [The chromatin remodeler CHD7 regulates adult neurogenesis via activation of SoxC transcription factors.2013] [CHD7, the gene mutated in CHARGE syndrome, regulates genes involved in neural crest cell guidance.2014] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies.2016] [Chd7 cooperates with Sox10 and regulates the onset of CNS myelination and remyelination.2016] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [The chromatin remodeling factor CHD7 controls cerebellar development by regulating reelin expression.2017] [Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme.2017] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]
1/1/2017
S
icon
S

Increased from S to S

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[The chromatin remodeling factor CHD7 controls cerebellar development by regulating reelin expression.2017]
10/1/2016
S
icon
S

Increased from S to S

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Clinical exome sequencing: results from 2819 samples reflecting 1000 families.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016]
7/1/2016
S
icon
S

Increased from S to S

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016]
1/1/2016
S
icon
S

Increased from S to S

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Mutations in a new member of the chromodomain gene family cause CHARGE syndrome.2004] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome.2010] [Chromatin remodeling by the CHD7 protein is impaired by mutations that cause human developmental disorders.2012] [The chromatin remodeler CHD7 regulates adult neurogenesis via activation of SoxC transcription factors.2013] [CHD7, the gene mutated in CHARGE syndrome, regulates genes involved in neural crest cell guidance.2014] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies.2016] [Chd7 cooperates with Sox10 and regulates the onset of CNS myelination and remyelination.2016]
1/1/2015
S
icon
S

Increased from S to S

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[Large-scale discovery of novel genetic causes of developmental disorders.2014]
7/1/2014
No data
icon
S

Increased from No data to S

Description

Multiple independent reports have observed a relationship between individuals with CHARGE syndrome, resulting from mutations in CHD7, and autism. Included here are: 3/3 cases in PMID 10355813, 12/ 31 cases in PMID 15633180, 6/10 cases in PMID 15688419, and 25/31 cases in PMID 19709852. However, no relationship to autism was observed in PMID 16532469. CHD7 has been shown to interact with CDH8, which has also been implicated in autism (PMID 20453063).

Reports Added
[Mutations in a new member of the chromodomain gene family cause CHARGE syndrome.2004] [CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome.2010] [Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.2012] [Chromatin remodeling by the CHD7 protein is impaired by mutations that cause human developmental disorders.2012] [The chromatin remodeler CHD7 regulates adult neurogenesis via activation of SoxC transcription factors.2013] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [CHD7, the gene mutated in CHARGE syndrome, regulates genes involved in neural crest cell guidance.2014]
Krishnan Probability Score

Score 0.57086008214275

Ranking 857/25841 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 0.99999999999975

Ranking 35/18225 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
Iossifov Probability Score

Score 0.968

Ranking 63/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Original Source
Sanders TADA Score

Score 0.94156868009779

Ranking 14981/18665 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 0.020188730328192

Ranking 8075/20870 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
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ARID2 AT rich interactive domain 2 (ARID, RFX-like) Human Protein Binding 196528 Q68CP9
BAF155 SWI/SNF complex subunit SMARCC1 Human Protein Binding 6599 Q92922
BAF170 SWI/SNF complex subunit SMARCC2 Human Protein Binding 6601 Q8TAQ2
BRD7 bromodomain containing 7 Human Protein Binding 29117 Q9NPI1
BRG1 Transcription activator BRG1 Human Protein Binding 6597 P51532
CCNC cyclin C Mouse DNA Binding 51813 Q62447
CDK8 cyclin-dependent kinase 8 Mouse DNA Binding 264064 Q8R3L8
CMTM3 CKLF-like MARVEL transmembrane domain containing 3 Mouse DNA Binding 68119 Q99LJ5
CORO1C coronin, actin binding protein 1C Mouse DNA Binding 23790 Q9WUM4
CPD carboxypeptidase D Mouse DNA Binding 12874 O89001
Creb3l2 cAMP responsive element binding protein 3-like 2 Rat Direct Regulation 362339 Q6QDP7
CSRP1 cysteine and glycine-rich protein 1 Mouse DNA Binding 1465 P97315
CTCF CCCTC-binding factor (zinc finger protein) Human Protein Binding 10664 B5MC38
E2F1 E2F transcription factor 1 Mouse Protein Binding 13555 Q61501
EEF1E1 eukaryotic translation elongation factor 1 epsilon 1 Mouse DNA Binding 66143 Q9D1M4
EIF1AY eukaryotic translation initiation factor 1A, X-linked Mouse DNA Binding 66235 Q8BMJ3
EP300 E1A binding protein p300 Mouse Protein Binding 328572 B2RWS6
FAM190B granule cell antiserum positive 14 Mouse DNA Binding 72972 Q3UHI0
FGD4 FYVE, RhoGEF and PH domain containing 4 Mouse DNA Binding 224014 Q91ZT5
FRMD4B FERM domain containing 4B Mouse DNA Binding 232288 Q920B0
GATAD2A GATA zinc finger domain containing 2A Mouse Protein Binding 234366 Q8CHY6
Gbx2 Homeobox protein GBX-2 Mouse DNA Binding 14472 P48031
GLI3 GLI-Kruppel family member GLI3 Mouse DNA Binding 14634 Q61602
GRIA2 glutamate receptor, ionotropic, AMPA2 (alpha 2) Mouse DNA Binding 14800 P23819
HES5 hairy and enhancer of split 5 (Drosophila) Mouse DNA Binding 15208 P70120
ITGA6 integrin alpha 6 Mouse DNA Binding 16403 Q61739
JAG1 jagged 1 Mouse DNA Binding 16449 Q9QXX0
KCTD17 potassium channel tetramerisation domain containing 17 Mouse DNA Binding 72844 E0CYQ0
KLF15 Kruppel-like factor 15 Mouse DNA Binding 66277 Q9EPW2
LSM6 LSM6 homolog, U6 small nuclear RNA associated (S. cerevisiae) Mouse DNA Binding 78651 P62313
Mbp myelin basic protein Rat Direct Regulation 24547 P02688
MITF microphthalmia-associated transcription factor Human Protein Binding 4286 O75030
MOB3B MOB kinase activator 3B Mouse DNA Binding 214944 Q8VE04
Myrf myelin regulatory factor Rat Direct Regulation 293736 D4A352
NANOG Nanog homeobox Mouse Protein Binding 71950 Q80Z64
NLK nemo-like kinase Human Protein Binding 51701 Q9UBE8
NRAS neuroblastoma ras oncogene Mouse DNA Binding 18176 P08556
OLIG1 oligodendrocyte transcription factor 1 Mouse Protein Binding 116448 Q9JKN5
Olig2 oligodendrocyte lineage transcription factor 2 Rat DNA Binding 304103 G3V612
Otx2 Homeobox protein OTX2 Mouse DNA Binding P80206
OXCT1 3-oxoacid CoA transferase 1 Mouse DNA Binding 67041 Q9D0K2
p53 Cellular tumor antigen p53 Mouse DNA Binding 22059 P02340
PFKFB3 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 Mouse DNA Binding 170768 A7UAK4
RAB33B RAB33B, member of RAS oncogene family Mouse DNA Binding 19338 O35963
RBPJ recombination signal binding protein for immunoglobulin kappa J region Mouse DNA Binding 19664 P31266
RGS8 regulator of G-protein signaling 8 Mouse DNA Binding 67792 Q8BXT1
SEC63 SEC63-like (S. cerevisiae) Mouse DNA Binding 140740 Q8VHE0
SLC25A36 solute carrier family 25, member 36 Mouse DNA Binding 192287 Q922G0
SMAD5 SMAD family member 5 Mouse Protein Binding 17129 P97454
SMAD8 Mothers against decapentaplegic homolog 9 Mouse Protein Binding 55994 Q9JIW5
SMARCD3 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 3 Human Protein Binding 6604 Q6P9Z1
Sox3 Mouse DNA Binding P53784
SOX9 SRY (sex determining region Y)-box 9 Human DNA Binding 6662 P48436
Sp7 Sp7 transcription factor Rat Direct Regulation 300260 Q6IMK2
SPEG SPEG complex locus Mouse DNA Binding 11790 Q62407
STAT3 signal transducer and activator of transcription 3 Mouse Protein Binding 20848 P42227
SUZ12 suppressor of zeste 12 homolog (Drosophila) Mouse Protein Binding 52615 Q80U70
TADA1 transcriptional adaptor 1 Mouse DNA Binding 27878 Q99LM9
TGFBR2 transforming growth factor, beta receptor II Mouse DNA Binding 21813 Q62312
TMEM132C transmembrane protein 132C Mouse DNA Binding 208213 Q8CEF9
TPM1 tropomyosin 1, alpha Mouse DNA Binding 22003 P58771
TULP3 tubby-like protein 3 Mouse DNA Binding 22158 O88413
TWIST1 twist homolog 1 (Drosophila) Human DNA Binding 7291 Q15672
Ugt8 UDP glycosyltransferase 8 Rat DNA Binding 50555 Q09426
ZBTB20 zinc finger and BTB domain containing 20 Human Protein Binding 26137 Q9HC78
ZFX zinc finger protein X-linked Mouse Protein Binding 22764 P17012
ZHX3 zinc fingers and homeoboxes 3 Mouse DNA Binding 320799 Q8C0Q2
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