Human Gene Module / Chromosome 2 / MYT1L

MYT1LMyelin transcription factor 1-like

Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
10 / 21
Rare Variants / Common Variants
44 / 1
Aliases
MYT1L, NZF1,  ZC2HC4B
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Syndromic, Genetic Association
Chromosome Band
2p25.3
Associated Disorders
ASD
Relevance to Autism

A de novo LoF variant and a de novo likely damaging missense variant in the MYT1L gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2017 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report identified MYT1L as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene. De novo LoF variants in MYT1L were also identified in two sporadic cases in De Rocker et al., 2015: one in a patient presenting with ASD and intellectual disability, and the other in a patient presenting with intellectual disability and autistic features (PMID 25232846). Two additional de novo LoF variants in the MYT1L gene were identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016 (PMID 27824329), and an ASD proband from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017 (PMID 28263302). MYT1L has been proposed as a causative gene for intellectual disability and other phenotypes observed in cases with 2p25.3 deletions (PMID 21990140, 25232846). Copy number variants affecting the MYT1L gene have also been implicated in schizophrenia (Vrijenhoek et al., 2008; Lee et al., 2012; Van Den Bossche et al., 2013).

Molecular Function

May function as a panneural transcription factor associated with neuronal differentiation and may play a role in the development of neurons and oligodendroglia in the CNS.

Reports related to MYT1L (21 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Recurrent CNVs disrupt three candidate genes in schizophrenia patients. Vrijenhoek T , et al. (2008) No -
2 Support Common SNPs in myelin transcription factor 1-like (MYT1L): association with major depressive disorder in the Chinese Han population. Wang T , et al. (2010) No -
3 Support MYT1L is a candidate gene for intellectual disability in patients with 2p25.3 (2pter) deletions. Stevens SJ , et al. (2011) No ASD
4 Primary Germline mosaic transmission of a novel duplication of PXDN and MYT1L to two male half-siblings with autism. Meyer KJ , et al. (2011) Yes -
5 Support Microduplications disrupting the MYT1L gene (2p25.3) are associated with schizophrenia. Lee Y , et al. (2012) No -
6 Support Identification of rare copy number variants in high burden schizophrenia families. Van Den Bossche MJ , et al. (2013) No -
7 Recent Recommendation Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity. De Rocker N , et al. (2014) No ASD
8 Recent Recommendation Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
9 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
10 Recent Recommendation Low load for disruptive mutations in autism genes and their biased transmission. Iossifov I , et al. (2015) Yes -
11 Support De novo genic mutations among a Chinese autism spectrum disorder cohort. Wang T , et al. (2016) Yes -
12 Support The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies. Redin C , et al. (2016) No -
13 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
14 Recent Recommendation Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates. Mall M , et al. (2017) No -
15 Recent Recommendation MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothala... Blanchet P , et al. (2017) No ASD
16 Support A novel MYT1L mutation in a patient with severe early-onset obesity and intellectual disability. Loid P , et al. (2018) No Obesity, behavioral abnormalities
17 Support Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder. Munnich A , et al. (2019) Yes -
18 Support Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort. Wu H , et al. (2019) Yes Microcephaly
19 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
20 Support Nine newly identified individuals refine the phenotype associated with MYT1L mutations. Windheuser IC , et al. (2020) No ASD
21 Support Genome-wide detection of tandem DNA repeats that are expanded in autism Trost B et al. (2020) Yes -
Rare Variants   (44)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain - - - 18940311 Vrijenhoek T , et al. (2008)
- - translocation De novo NA - 27841880 Redin C , et al. (2016)
- - minisatellite Unknown - Unknown 32717741 Trost B et al. (2020)
- - copy_number_loss Unknown - - 28859103 Blanchet P , et al. (2017)
- - copy_number_loss De novo NA - 21990140 Stevens SJ , et al. (2011)
- - copy_number_loss Unknown - Multiplex 21990140 Stevens SJ , et al. (2011)
- - copy_number_loss De novo NA Simplex 32065501 Windheuser IC , et al. (2020)
c.2542C>T p.Gln848Ter stop_gained De novo NA - 27824329 Wang T , et al. (2016)
- - copy_number_gain Familial Maternal Multiplex 22157634 Meyer KJ , et al. (2011)
c.1709+1G>A - splice_site_variant De novo NA - 28859103 Blanchet P , et al. (2017)
c.2677C>T p.Arg893Ter stop_gained De novo NA - 28859103 Blanchet P , et al. (2017)
c.2227G>T p.Glu743Ter stop_gained De novo NA Simplex 31674007 Wu H , et al. (2019)
CA>C p.Leu381fs frameshift_variant De novo NA - 28859103 Blanchet P , et al. (2017)
c.1559T>C p.Leu520Pro missense_variant De novo NA - 28859103 Blanchet P , et al. (2017)
c.1570C>A p.His524Asn missense_variant De novo NA - 28859103 Blanchet P , et al. (2017)
c.1579G>A p.Gly527Arg missense_variant De novo NA - 28859103 Blanchet P , et al. (2017)
c.1678C>T p.His560Tyr missense_variant De novo NA - 28859103 Blanchet P , et al. (2017)
c.1706G>A p.Arg569Gln missense_variant De novo NA - 28859103 Blanchet P , et al. (2017)
c.591C>A p.Tyr197Ter stop_gained De novo NA Simplex 25363760 De Rubeis S , et al. (2014)
c.2642+1G>A - splice_site_variant De novo NA Simplex 25232846 De Rocker N , et al. (2014)
c.1917T>G p.Tyr639Ter stop_gained De novo NA Simplex 25232846 De Rocker N , et al. (2014)
c.223C>T p.Arg75Ter stop_gained De novo NA Simplex 32065501 Windheuser IC , et al. (2020)
c.2769-2A>G - splice_site_variant De novo NA Simplex 32065501 Windheuser IC , et al. (2020)
- - copy_number_gain Familial Paternal Multiplex 23505263 Van Den Bossche MJ , et al. (2013)
c.565G>A p.Glu189Lys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.770G>A p.Gly257Glu missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.995G>A p.Arg332Gln missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1531G>T p.Gly511Ter stop_gained De novo NA Simplex 32065501 Windheuser IC , et al. (2020)
c.1510T>C p.Cys504Arg missense_variant De novo NA Simplex 25363768 Iossifov I et al. (2014)
c.1579G>C p.Gly527Arg missense_variant De novo NA Simplex 31406558 Munnich A , et al. (2019)
c.2990A>T p.Glu997Val missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2236del p.Met746CysfsTer5 frameshift_variant De novo NA - 28859103 Blanchet P , et al. (2017)
c.1566C>G p.His522Gln missense_variant De novo NA Simplex 25363760 De Rubeis S , et al. (2014)
c.1700G>C p.Arg567Pro missense_variant De novo NA Simplex 32065501 Windheuser IC , et al. (2020)
c.1711G>A p.Gly571Arg missense_variant De novo NA Simplex 32065501 Windheuser IC , et al. (2020)
c.2319G>A p.Leu773= synonymous_variant De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
c.2460C>T p.Pro820= synonymous_variant De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
c.3118A>T p.Lys1040Ter stop_gained Familial Paternal Simplex 32065501 Windheuser IC , et al. (2020)
c.995G>A p.Arg332Gln missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2215_2224del p.Leu739AlafsTer9 frameshift_variant De novo NA Simplex 30055078 Loid P , et al. (2018)
c.3052G>T p.Val1018Phe missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.3333del p.Glu1111AspfsTer14 frameshift_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.761_764del p.Asp254ValfsTer14 frameshift_variant De novo NA Multiplex 28263302 C Yuen RK et al. (2017)
c.2579del p.Val860GlyfsTer20 frameshift_variant De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.291G>A p.(=) synonymous_variant - - - 21048971 Wang T , et al. (2010)
SFARI Gene score
1

High Confidence

A de novo LoF variant and a de novo likely damaging missense variant in the MYT1L gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2017 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report identified MYT1L as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene. De novo LoF variants in MYT1L were also identified in two sporadic cases in De Rocker et al., 2015: one in a patient presenting with ASD and intellectual disability, and the other in a patient presenting with intellectual disability and autistic features (PMID 25232846). Two additional de novo LoF variants in the MYT1L gene were identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016 (PMID 27824329), and an ASD proband from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017 (PMID 28263302). MYT1L has been proposed as a causative gene for intellectual disability and other phenotypes observed in cases with 2p25.3 deletions (PMID 21990140, 25232846). Copy number variants affecting the MYT1L gene have also been implicated in schizophrenia (Vrijenhoek et al., 2008; Lee et al., 2012; Van Den Bossche et al., 2013).

Score Delta: Score remained at 1

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.

7/1/2020
1
icon
1

Score remained at 1

Description

A de novo LoF variant and a de novo likely damaging missense variant in the MYT1L gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2017 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report identified MYT1L as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene. De novo LoF variants in MYT1L were also identified in two sporadic cases in De Rocker et al., 2015: one in a patient presenting with ASD and intellectual disability, and the other in a patient presenting with intellectual disability and autistic features (PMID 25232846). Two additional de novo LoF variants in the MYT1L gene were identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016 (PMID 27824329), and an ASD proband from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017 (PMID 28263302). MYT1L has been proposed as a causative gene for intellectual disability and other phenotypes observed in cases with 2p25.3 deletions (PMID 21990140, 25232846). Copy number variants affecting the MYT1L gene have also been implicated in schizophrenia (Vrijenhoek et al., 2008; Lee et al., 2012; Van Den Bossche et al., 2013).

1/1/2020
1
icon
1

Score remained at 1

Description

A de novo LoF variant and a de novo likely damaging missense variant in the MYT1L gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2017 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report identified MYT1L as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene. De novo LoF variants in MYT1L were also identified in two sporadic cases in De Rocker et al., 2015: one in a patient presenting with ASD and intellectual disability, and the other in a patient presenting with intellectual disability and autistic features (PMID 25232846). Two additional de novo LoF variants in the MYT1L gene were identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016 (PMID 27824329), and an ASD proband from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017 (PMID 28263302). MYT1L has been proposed as a causative gene for intellectual disability and other phenotypes observed in cases with 2p25.3 deletions (PMID 21990140, 25232846). Copy number variants affecting the MYT1L gene have also been implicated in schizophrenia (Vrijenhoek et al., 2008; Lee et al., 2012; Van Den Bossche et al., 2013).

10/1/2019
1
icon
1

Score remained at 1

New Scoring Scheme
Description

A de novo LoF variant and a de novo likely damaging missense variant in the MYT1L gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2017 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report identified MYT1L as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene. De novo LoF variants in MYT1L were also identified in two sporadic cases in De Rocker et al., 2015: one in a patient presenting with ASD and intellectual disability, and the other in a patient presenting with intellectual disability and autistic features (PMID 25232846). Two additional de novo LoF variants in the MYT1L gene were identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016 (PMID 27824329), and an ASD proband from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017 (PMID 28263302). MYT1L has been proposed as a causative gene for intellectual disability and other phenotypes observed in cases with 2p25.3 deletions (PMID 21990140, 25232846). Copy number variants affecting the MYT1L gene have also been implicated in schizophrenia (Vrijenhoek et al., 2008; Lee et al., 2012; Van Den Bossche et al., 2013).

7/1/2019
1
icon
1

Score remained at 1

Description

A de novo LoF variant and a de novo likely damaging missense variant in the MYT1L gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2017 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report identified MYT1L as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene. De novo LoF variants in MYT1L were also identified in two sporadic cases in De Rocker et al., 2015: one in a patient presenting with ASD and intellectual disability, and the other in a patient presenting with intellectual disability and autistic features (PMID 25232846). Two additional de novo LoF variants in the MYT1L gene were identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016 (PMID 27824329), and an ASD proband from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017 (PMID 28263302). MYT1L has been proposed as a causative gene for intellectual disability and other phenotypes observed in cases with 2p25.3 deletions (PMID 21990140, 25232846). Copy number variants affecting the MYT1L gene have also been implicated in schizophrenia (Vrijenhoek et al., 2008; Lee et al., 2012; Van Den Bossche et al., 2013).

7/1/2018
1.1
icon
1

Score remained at 1

Description

A de novo LoF variant and a de novo likely damaging missense variant in the MYT1L gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2017 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report identified MYT1L as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene. De novo LoF variants in MYT1L were also identified in two sporadic cases in De Rocker et al., 2015: one in a patient presenting with ASD and intellectual disability, and the other in a patient presenting with intellectual disability and autistic features (PMID 25232846). Two additional de novo LoF variants in the MYT1L gene were identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016 (PMID 27824329), and an ASD proband from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017 (PMID 28263302). MYT1L has been proposed as a causative gene for intellectual disability and other phenotypes observed in cases with 2p25.3 deletions (PMID 21990140, 25232846). Copy number variants affecting the MYT1L gene have also been implicated in schizophrenia (Vrijenhoek et al., 2008; Lee et al., 2012; Van Den Bossche et al., 2013).

10/1/2017
1
icon
1

Score remained at 1

Description

A de novo LoF variant and a de novo likely damaging missense variant in the MYT1L gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2017 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report identified MYT1L as a gene meeting high statistical significance with a 0.05 < FDR ? 0.1, meaning that this gene had a ? 90% chance of being a true autism gene. De novo LoF variants in MYT1L were also identified in two sporadic cases in De Rocker et al., 2015: one in a patient presenting with ASD and intellectual disability, and the other in a patient presenting with intellectual disability and autistic features (PMID 25232846). Two additional de novo LoF variants in the MYT1L gene were identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016 (PMID 27824329), and an ASD proband from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017 (PMID 28263302). MYT1L has been proposed as a causative gene for intellectual disability and other phenotypes observed in cases with 2p25.3 deletions (PMID 21990140, 25232846). Copy number variants affecting the MYT1L gene have also been implicated in schizophrenia (Vrijenhoek et al., 2008; Lee et al., 2012; Van Den Bossche et al., 2013).

4/1/2017
1
icon
1

Score remained at 1

Description

A de novo LoF variant and a de novo likely damaging missense variant in the MYT1L gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). De novo LoF variants in MYT1L were also identified in two sporadic cases, one in a patient presenting with ASD and intellectual disability and the other in a patient presenting with intellectual disability and autistic features (PMID 25232846). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MYT1L as a gene meeting high statistical significance with a 0.05< FDR ?0.1, meaning that this gene had a ?90% chance of being a true autism gene (PMID 25363760). MYT1L has been proposed as a causative gene for intellectual disability and other phenotypes observed in cases with 2p25.3 deletions (PMID 21990140, 25232846). A third de novo LoF variant in the MYT1L gene was identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016.

10/1/2016
2
icon
1

Decreased from 2 to 1

Description

A de novo LoF variant and a de novo likely damaging missense variant in the MYT1L gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). De novo LoF variants in MYT1L were also identified in two sporadic cases, one in a patient presenting with ASD and intellectual disability and the other in a patient presenting with intellectual disability and autistic features (PMID 25232846). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MYT1L as a gene meeting high statistical significance with a 0.05

1/1/2016
2
icon
2

Decreased from 2 to 2

Description

A de novo LoF variant and a de novo likely damaging missense variant in the MYT1L gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). De novo LoF variants in MYT1L were also identified in two sporadic cases, one in a patient presenting with ASD and intellectual disability and the other in a patient presenting with intellectual disability and autistic features (PMID 25232846). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MYT1L as a gene meeting high statistical significance with a 0.05

10/1/2014
icon
2

Increased from to 2

Description

A de novo LoF variant and a de novo likely damaging missense variant in the MYT1L gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760). De novo LoF variants in MYT1L were also identified in two sporadic cases, one in a patient presenting with ASD and intellectual disability and the other in a patient presenting with intellectual disability and autistic features (PMID 25232846). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MYT1L as a gene meeting high statistical significance with a 0.05

Krishnan Probability Score

Score 0.61290551338736

Ranking 154/25841 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.
ExAC Score

Score 0.99996398937701

Ranking 557/18225 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
Iossifov Probability Score

Score 0.897

Ranking 144/239 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
Sanders TADA Score

Score 0.026721972805188

Ranking 37/18665 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).
Larsen Cumulative Evidence Score

Score 24

Ranking 83/461 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.
Zhang D Score

Score 0.39990694077103

Ranking 1465/20870 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.
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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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