Human Gene Module / Chromosome 16 / CTCF

CTCFCCCTC-binding factor

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
10 / 25
Rare Variants / Common Variants
80 / 0
EAGLE Score
10.45
Moderate Learn More
Aliases
CTCF, MRD21
Associated Syndromes
Tourette syndrome
Chromosome Band
16q22.1
Associated Disorders
DD/NDD, ID, ASD
Genetic Category
Rare Single Gene Mutation, Syndromic, Functional
Relevance to Autism

Two de novo loss-of-function variants and several de novo missense variants in the CTCF gene have been identified in ASD probands from the Simons Simplex Collection, the MSSNG cohort, and the SPARK cohort (Iossifov et al., 2014; Krumm et al., 2015; Zhou et al., 2022). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368). Konrad et al., 2019 found that 39 individuals with CTCF variants presented with a variable neurodevelopmental disorder frequently characterized by feeding difficulties/failure to thrive, developmental delay/intellectual disability, and behavioral abnormalities, including autism and autistic features. A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified CTCF as a gene reaching exome-wide significance (P < 2.5E-06).

Molecular Function

This gene is a member of the BORIS + CTCF gene family and encodes a transcriptional regulator protein with 11 highly conserved zinc finger (ZF) domains. This nuclear protein is able to use different combinations of the ZF domains to bind different DNA target sequences and proteins. Depending upon the context of the site, the protein can bind a histone acetyltransferase (HAT)-containing complex and function as a transcriptional activator or bind a histone deacetylase (HDAC)-containing complex and function as a transcriptional repressor. If the protein is bound to a transcriptional insulator element, it can block communication between enhancers and upstream promoters, thereby regulating imprinted expression.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CTCF (25 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary CTCF-dependent chromatin insulator is linked to epigenetic remodeling Ishihara K , et al. (2006) No -
2 Recent Recommendation Identification of CTCF as a master regulator of the clustered protocadherin genes Golan-Mashiach M , et al. (2012) No -
3 Recent Recommendation De novo mutations in the genome organizer CTCF cause intellectual disability Gregor A , et al. (2013) No DD
4 Recent Recommendation Role of CTCF protein in regulating FMR1 locus transcription Lanni S , et al. (2013) No -
5 Recent Recommendation Dual effect of CTCF loss on neuroprogenitor differentiation and survival Watson LA , et al. (2014) No -
6 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
7 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
8 Support Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
9 Support Genome-wide characteristics of de novo mutations in autism Yuen RK et al. (2016) Yes -
10 Positive Association De Novo Coding Variants Are Strongly Associated with Tourette Disorder Willsey AJ , et al. (2017) No -
11 Support Identification of a novel CTCF mutation responsible for syndromic intellectual disability - a case report Bastaki F , et al. (2017) No -
12 Support CTCF deletion syndrome: clinical features and epigenetic delineation Hori I , et al. (2017) No Autistic features, dysmorphic features
13 Support Three additional de novo CTCF mutations in Chinese patients help to define an emerging neurodevelopmental disorder Chen F , et al. (2019) No -
14 Recent Recommendation CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum Konrad EDH , et al. (2019) Yes Feeding difficulties, vision anomalies, microcepha
15 Support De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism Cappi C , et al. (2019) No -
16 Support Autism risk in offspring can be assessed through quantification of male sperm mosaicism Breuss MW , et al. (2019) Yes -
17 Recent Recommendation Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes ID
18 Support - Brunet T et al. (2021) No -
19 Support - Hiraide T et al. (2021) No ASD
20 Support - Li D et al. (2022) Yes -
21 Support - Davis L et al. (2022) No -
22 Recent Recommendation - Zhou X et al. (2022) Yes -
23 Support - Yuan B et al. (2023) Yes -
24 Support - Tan B et al. (2023) No Epilepsy/seizures
25 Support - et al. () Yes -
Rare Variants   (80)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - - 37664546 Tan B et al. (2023)
- - copy_number_loss De novo - - 23746550 Gregor A , et al. (2013)
- - copy_number_loss De novo - Simplex 28848059 Hori I , et al. (2017)
- - copy_number_loss De novo - Simplex 31239556 Konrad EDH , et al. (2019)
c.1385A>G p.Tyr462Cys missense_variant Unknown - - 34968013 Li D et al. (2022)
c.-32-5538dup - frameshift_variant De novo - - 23746550 Gregor A , et al. (2013)
c.638G>A p.Arg213His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.792G>C p.Lys264Asn missense_variant De novo - - 33004838 Wang T et al. (2020)
c.995T>C p.Val332Ala missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1024C>T p.Arg342Cys missense_variant De novo - - 33004838 Wang T et al. (2020)
c.1094A>G p.Lys365Arg missense_variant De novo - - 33004838 Wang T et al. (2020)
c.1102C>T p.Arg368Cys missense_variant De novo - - 33004838 Wang T et al. (2020)
c.1118A>T p.His373Leu missense_variant De novo - - 33004838 Wang T et al. (2020)
c.1129C>T p.Arg377Cys missense_variant De novo - - 33004838 Wang T et al. (2020)
c.1244G>A p.Arg415Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1807C>T p.Arg603Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1481G>A p.Arg494His missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1541A>C p.Lys514Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.*956T>A - 3_prime_UTR_variant De novo - Simplex 27525107 Yuen RK et al. (2016)
c.-32-5225del - frameshift_variant De novo - - 31239556 Konrad EDH , et al. (2019)
c.773_776del p.Lys258ArgfsTer4 frameshift_variant Unknown - - 38438125 et al. ()
c.1176C>A p.Tyr392Ter stop_gained De novo - Simplex 35982159 Zhou X et al. (2022)
c.715C>T p.Arg239Trp missense_variant De novo - - 23746550 Gregor A , et al. (2013)
c.-32-5584dup - frameshift_variant De novo - Simplex 30893510 Chen F , et al. (2019)
c.-32-5140_-32-5137del - frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.-32-5381_-32-5375del - frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.853G>T p.Glu285Ter stop_gained De novo - Simplex 31873310 Breuss MW , et al. (2019)
c.1016G>A p.Arg339Gln missense_variant De novo - - 31239556 Konrad EDH , et al. (2019)
c.1024C>T p.Arg342Cys missense_variant De novo - - 31239556 Konrad EDH , et al. (2019)
c.1103G>A p.Arg368His missense_variant De novo - - 31239556 Konrad EDH , et al. (2019)
c.1168G>A p.Asp390Asn missense_variant De novo - - 31239556 Konrad EDH , et al. (2019)
c.782-2A>G - splice_site_variant Unknown - Simplex 31239556 Konrad EDH , et al. (2019)
c.55del p.His19ThrfsTer15 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.848G>A p.Arg283His missense_variant De novo - Simplex 33004838 Wang T et al. (2020)
c.-32-5299del - frameshift_variant De novo - Simplex 28619046 Bastaki F , et al. (2017)
c.-32-5765dup - frameshift_variant De novo - Simplex 31239556 Konrad EDH , et al. (2019)
c.373+2201del - frameshift_variant De novo - Simplex 31239556 Konrad EDH , et al. (2019)
c.1699C>T p.Arg567Trp missense_variant De novo - Simplex 30893510 Chen F , et al. (2019)
c.958C>G p.Arg320Gly missense_variant De novo - Unknown 33619735 Brunet T et al. (2021)
c.1016G>A p.Arg339Gln missense_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.1004del p.Gly335GlufsTer27 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1430A>C p.His477Pro missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.1244G>A p.Arg415Gln missense_variant De novo - Simplex 31771860 Cappi C , et al. (2019)
c.-32-4772_-32-4771del - frameshift_variant De novo - - 31239556 Konrad EDH , et al. (2019)
c.2000-1G>A - splice_site_variant Familial Paternal Simplex 33004838 Wang T et al. (2020)
c.202dup p.Arg68LysfsTer13 frameshift_variant De novo - - 23746550 Gregor A , et al. (2013)
c.1102C>T p.Arg368Cys missense_variant De novo - Simplex 33644862 Hiraide T et al. (2021)
c.1699C>T p.Arg567Trp missense_variant De novo - Simplex 33644862 Hiraide T et al. (2021)
c.260G>A p.Arg87Gln missense_variant De novo - Simplex 28472652 Willsey AJ , et al. (2017)
c.778_781del p.Lys260ValfsTer2 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.833G>T p.Arg278Leu missense_variant De novo - Simplex 31239556 Konrad EDH , et al. (2019)
c.848G>A p.Arg283His missense_variant De novo - Simplex 31239556 Konrad EDH , et al. (2019)
c.979T>A p.Cys327Ser missense_variant De novo - Simplex 31239556 Konrad EDH , et al. (2019)
c.615_618del p.Lys206ProfsTer15 frameshift_variant De novo - - 36881370 Yuan B et al. (2023)
c.-32-5298_-32-5295del - frameshift_variant De novo - Simplex 30893510 Chen F , et al. (2019)
c.1006G>C p.Glu336Gln missense_variant De novo - Simplex 31239556 Konrad EDH , et al. (2019)
c.1024C>T p.Arg342Cys missense_variant De novo - Simplex 31239556 Konrad EDH , et al. (2019)
c.1102C>T p.Arg368Cys missense_variant De novo - Simplex 31239556 Konrad EDH , et al. (2019)
c.1117C>G p.His373Asp missense_variant De novo - Simplex 31239556 Konrad EDH , et al. (2019)
c.1118A>C p.His373Pro missense_variant Unknown - Simplex 31239556 Konrad EDH , et al. (2019)
c.1130G>A p.Arg377His missense_variant De novo - Simplex 31239556 Konrad EDH , et al. (2019)
c.1343G>A p.Arg448Gln missense_variant De novo - Simplex 31239556 Konrad EDH , et al. (2019)
c.1585G>A p.Asp529Asn missense_variant Unknown - Simplex 31239556 Konrad EDH , et al. (2019)
c.1078A>C p.Ser360Arg missense_variant Unknown - Unknown 31239556 Konrad EDH , et al. (2019)
c.1226G>A p.Cys409Tyr missense_variant De novo - Unknown 31239556 Konrad EDH , et al. (2019)
c.1130G>A p.Arg377His missense_variant De novo - Multiplex 31239556 Konrad EDH , et al. (2019)
c.1133C>T p.Pro378Leu missense_variant De novo - Multiplex 31239556 Konrad EDH , et al. (2019)
c.1343G>A p.Arg448Gln missense_variant De novo - Multiplex 31239556 Konrad EDH , et al. (2019)
c.855_869del p.Glu285_Pro289del inframe_deletion De novo - Simplex 37664546 Tan B et al. (2023)
c.1960C>T p.Arg654Ter stop_gained Familial Maternal Simplex 31239556 Konrad EDH , et al. (2019)
c.71dup p.Cys25ValfsTer56 frameshift_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.615_618del p.Lys206ProfsTer15 frameshift_variant De novo - - 31239556 Konrad EDH , et al. (2019)
c.782-1G>T - splice_site_variant Unknown Not maternal Simplex 31239556 Konrad EDH , et al. (2019)
c.773_776del p.Lys258ArgfsTer4 frameshift_variant De novo - Simplex 31239556 Konrad EDH , et al. (2019)
c.1699C>T p.Arg567Trp missense_variant De novo - Multi-generational 31239556 Konrad EDH , et al. (2019)
c.615_618del p.Lys206ProfsTer15 frameshift_variant Unknown - Simplex 31239556 Konrad EDH , et al. (2019)
c.1025G>A p.Arg342His missense_variant Familial Paternal Multi-generational 31239556 Konrad EDH , et al. (2019)
c.118C>T p.Arg40Cys missense_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.881A>C p.His294Pro missense_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.1133C>T p.Pro378Leu missense_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
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."

1/1/2021
1
icon
1

Score remained at 1

Description

A de novo loss-of-function variant in the CTCF gene was identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368). Konrad et al., 2019 found that 39 individuals with CTCF variants presented with a variable neurodevelopmental disorder frequently characterized by feeding difficulties/failure to thrive, developmental delay/intellectual disability, and behavioral abnormalities, including autism and autistic features.

Reports Added
[De novo variants in neurodevelopmental disorders-experiences from a tertiary care center2021] [Genetic and phenotypic analysis of 101 patients with developmental delay or intellectual disability using whole-exome sequencing2021]
10/1/2020
1
icon
1

Score remained at 1

Description

A de novo loss-of-function variant in the CTCF gene was identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368). Konrad et al., 2019 found that 39 individuals with CTCF variants presented with a variable neurodevelopmental disorder frequently characterized by feeding difficulties/failure to thrive, developmental delay/intellectual disability, and behavioral abnormalities, including autism and autistic features.

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
1/1/2020
1
icon
1

Score remained at 1

Description

A de novo loss-of-function variant in the CTCF gene was identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368). Konrad et al., 2019 found that 39 individuals with CTCF variants presented with a variable neurodevelopmental disorder frequently characterized by feeding difficulties/failure to thrive, developmental delay/intellectual disability, and behavioral abnormalities, including autism and autistic features.

Reports Added
[De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism.2019] [Autism risk in offspring can be assessed through quantification of male sperm mosaicism.2019]
10/1/2019
3S
icon
1

Decreased from 3S to 1

New Scoring Scheme
Description

A de novo loss-of-function variant in the CTCF gene was identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368). Konrad et al., 2019 found that 39 individuals with CTCF variants presented with a variable neurodevelopmental disorder frequently characterized by feeding difficulties/failure to thrive, developmental delay/intellectual disability, and behavioral abnormalities, including autism and autistic features.

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3S

Decreased from 3 to 3S

Description

A de novo loss-of-function variant in the CTCF gene was identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368). Konrad et al., 2019 found that 39 individuals with CTCF variants presented with a variable neurodevelopmental disorder frequently characterized by feeding difficulties/failure to thrive, developmental delay/intellectual disability, and behavioral abnormalities, including autism and autistic features.

Reports Added
[CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum.2019]
4/1/2019
3
icon
3

Decreased from 3 to 3

Description

A de novo loss-of-function variant in the CTCF gene was identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368).

Reports Added
[Three additional de novo CTCF mutations in Chinese patients help to define an emerging neurodevelopmental disorder.2019]
10/1/2017
3
icon
3

Decreased from 3 to 3

Description

A de novo loss-of-function variant in the CTCF gene was identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368).

Reports Added
[CTCF deletion syndrome: clinical features and epigenetic delineation.2017]
7/1/2017
3
icon
3

Decreased from 3 to 3

Description

A de novo loss-of-function variant in the CTCF gene was identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368).

Reports Added
[Identification of a novel CTCF mutation responsible for syndromic intellectual disability - a case report.2017]
4/1/2017
3
icon
3

Decreased from 3 to 3

Description

A de novo loss-of-function variant in the CTCF gene was identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368).

Reports Added
[The contribution of de novo coding mutations to autism spectrum disorder2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [De novo mutations in the genome organizer CTCF cause intellectual disability.2013] [CTCF-dependent chromatin insulator is linked to epigenetic remodeling.2006] [Identification of CTCF as a master regulator of the clustered protocadherin genes.2012] [Role of CTCF protein in regulating FMR1 locus transcription.2013] [Dual effect of CTCF loss on neuroprogenitor differentiation and survival.2014] [Excess of rare, inherited truncating mutations in autism.2015] [Genome-wide characteristics of de novo mutations in autism2016] [De Novo Coding Variants Are Strongly Associated with Tourette Disorder.2017]
7/1/2016
3
icon
3

Decreased from 3 to 3

Description

A de novo loss-of-function variant in the CTCF gene was identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368).

Reports Added
[Genome-wide characteristics of de novo mutations in autism2016]
4/1/2015
3
icon
3

Decreased from 3 to 3

Description

A de novo loss-of-function variant in the CTCF gene was identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368).

Reports Added
[Excess of rare, inherited truncating mutations in autism.2015]
1/1/2015
3
icon
3

Decreased from 3 to 3

Description

A de novo loss-of-function variant in the CTCF gene was identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368).

Reports Added
[Large-scale discovery of novel genetic causes of developmental disorders.2014]
10/1/2014
icon
3

Increased from to 3

Description

A de novo loss-of-function variant in the CTCF gene was identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). De novo variants in this gene (two frameshift, one missense) were previously identified in individuals presenting with developmental delay/intellectual disability, microcephaly, and growth retardation; autistic features were also observed in one of these individuals (PMID 23746550). CTCF interacts with the high confidence ASD gene CHD8 (PMID 16949368).

Reports Added
[The contribution of de novo coding mutations to autism spectrum disorder2014]
Krishnan Probability Score

Score 0.59302606652379

Ranking 461/25841 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 0.99792495785254

Ranking 1265/18225 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 0.15479957022551

Ranking 88/18665 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
Larsen Cumulative Evidence Score

Score 4.5

Ranking 298/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.33017816482418

Ranking 2291/20870 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
CENPE centromere protein E, 312kDa Human Protein Binding 1062 Q02224
DGCR8 DiGeorge syndrome critical region gene 8 Human Protein Binding 54487 Q8WYQ5
HIST1H1E histone cluster 1, H1e Human Protein Binding 3008 P10412
KIAA0020 KIAA0020 Human Protein Binding 9933 Q15397
LMNA lamin A/C Human Protein Binding 4000 P02545
TAF3 TAF3 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 140kDa Human Protein Binding 83860 Q5VWG9
ZBTB33 zinc finger and BTB domain containing 33 Human Protein Binding 10009 Q86T24
ZBTB48 zinc finger and BTB domain containing 48 Human Protein Binding 3104 P10074
ZCRB1 zinc finger CCHC-type and RNA binding motif 1 Human Protein Binding 85437 Q8TBF4
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