Human Gene Module / Chromosome 2 / MYT1L

MYT1LMyelin transcription factor 1-like

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
21 / 40
Rare Variants / Common Variants
126 / 1
EAGLE Score
20.35
Strong Learn More
Aliases
MYT1L, NZF1,  ZC2HC4B
Associated Syndromes
-
Chromosome Band
2p25.3
Associated Disorders
ID, ASD
Genetic Category
Rare Single Gene Mutation, Syndromic, Genetic Association, Functional
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). A de novo protein-truncating variant in MYT1L was identified in an ASD proband from the Autism Sequencing Consortium in Satterstrom et al., 2020; subsequent TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in this report identified MYT1L as a candidate gene with a false discovery rate (FDR) 0.01. Coursimault et al., 2021 described 40 previously unreported cases with pathogenic or likely pathogenic variants in the MYT1L gene; developmental delay, intellectual disability, and behavioral disorders were frequently observed in individuals with MYT1L variants, and a formal or informal diagnosis of autism spectrum disorder was made in 17/40 individuals (43%). 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 MYT1L as a gene reaching exome-wide significance (P < 2.5E-06).

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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
Zebrafish
Entrez Gene
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MYT1L (40 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 hypothalamus 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 -
22 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes ID
23 Support - Pode-Shakked B et al. (2021) No -
24 Recent Recommendation - Chen J et al. (2021) No -
25 Support - Mahjani B et al. (2021) Yes -
26 Recent Recommendation - Coursimault J et al. (2021) No ASD, ADHD, ID, epilepsy/seizures, stereotypy, lear
27 Support - Woodbury-Smith M et al. (2022) Yes -
28 Support - Wöhr M et al. (2022) Yes -
29 Support - Carvalho LML et al. (2022) No -
30 Support - Hu C et al. (2022) Yes DD
31 Support - Chen Y et al. (2021) No -
32 Support - Zhou X et al. (2022) Yes -
33 Support - Kim S et al. (2022) No -
34 Recent Recommendation - Weigel B et al. (2023) Yes -
35 Support - Chen J et al. (2023) No -
36 Support - Bouassida M et al. (2023) No ASD
37 Support - Wang J et al. (2023) Yes -
38 Support - Sheth F et al. (2023) Yes DD, ID
39 Support - Silas Yip et al. (2023) Yes -
40 Support - Yasser Al-Sarraj et al. (2024) Yes -
Rare Variants   (126)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation De novo - - 27841880 Redin C , et al. (2016)
- - copy_number_gain - - - 18940311 Vrijenhoek T , et al. (2008)
- - minisatellite Unknown - Unknown 32717741 Trost B et al. (2020)
- - copy_number_loss De novo - - 21990140 Stevens SJ , et al. (2011)
- - copy_number_loss Unknown - - 28859103 Blanchet P , et al. (2017)
- - copy_number_gain De novo - - 37188826 Bouassida M et al. (2023)
- - copy_number_gain Unknown - - 37188826 Bouassida M et al. (2023)
- - copy_number_loss De novo - - 34748075 Coursimault J et al. (2021)
c.2642+1G>A - splice_site_variant De novo - - 35741772 Hu C et al. (2022)
c.223C>T p.Arg75Ter stop_gained De novo - - 33004838 Wang T et al. (2020)
c.535C>T p.Arg179Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.1618+1G>A - splice_site_variant Unknown - - 33004838 Wang T et al. (2020)
- - copy_number_gain Familial Maternal - 37188826 Bouassida M et al. (2023)
- - copy_number_gain Familial Paternal - 37188826 Bouassida M et al. (2023)
- - copy_number_loss Unknown - Multiplex 21990140 Stevens SJ , et al. (2011)
- - copy_number_gain Unknown - Multiplex 37188826 Bouassida M et al. (2023)
c.1975C>T p.Arg659Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.2401C>T p.Gln801Ter stop_gained De novo - - 33004838 Wang T et al. (2020)
- - copy_number_loss De novo - Simplex 32065501 Windheuser IC , et al. (2020)
c.3190G>T p.Glu1064Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.2542C>T p.Gln848Ter stop_gained De novo - - 27824329 Wang T , et al. (2016)
c.1657T>C p.Cys553Arg missense_variant De novo - - 35741772 Hu C et al. (2022)
c.1687A>G p.Ser563Gly missense_variant De novo - - 35741772 Hu C et al. (2022)
c.955G>A p.Asp319Asn missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2519_2520+3del - splice_site_variant Unknown - - 33004838 Wang T et al. (2020)
c.1709+1G>A - splice_site_variant De novo - - 28859103 Blanchet P , et al. (2017)
c.52C>T p.Arg18Ter stop_gained De novo - - 34748075 Coursimault J et al. (2021)
c.1151G>A p.Arg384Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1592C>T p.Pro531Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1675G>A p.Gly559Arg missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1706G>A p.Arg569Gln missense_variant De novo - - 33004838 Wang T et al. (2020)
c.1717G>A p.Gly573Arg missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1954G>A p.Asp652Asn missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2275G>A p.Ala759Thr missense_variant De novo - - 33004838 Wang T et al. (2020)
c.2345C>T p.Pro782Leu missense_variant De novo - - 33004838 Wang T et al. (2020)
c.2770C>T p.Arg924Trp missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1592C>T p.Pro531Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2222C>T p.Thr741Met missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2677C>T p.Arg893Ter stop_gained De novo - - 28859103 Blanchet P , et al. (2017)
c.2227G>T p.Glu743Ter stop_gained De novo - Simplex 31674007 Wu H , et al. (2019)
c.3200A>T p.Gln1067Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.457G>T p.Glu153Ter stop_gained De novo - Simplex 37393044 Wang J et al. (2023)
- - copy_number_gain Familial Maternal Multiplex 22157634 Meyer KJ , et al. (2011)
CA>C p.Leu381fs frameshift_variant De novo - - 28859103 Blanchet P , et al. (2017)
c.2769-1G>T - splice_site_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1789C>T p.Gln597Ter stop_gained De novo - - 34748075 Coursimault J et al. (2021)
c.2671C>T p.Arg891Ter stop_gained De novo - - 34748075 Coursimault J et al. (2021)
c.2824G>T p.Glu942Ter stop_gained De novo - - 34748075 Coursimault J et al. (2021)
c.1509G>C p.Glu503Asp missense_variant Unknown - - 34615535 Mahjani B et al. (2021)
c.3151C>T p.Gln1051Ter stop_gained De novo - - 34748075 Coursimault J et al. (2021)
c.2032+3A>G - splice_region_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1559T>C p.Leu520Pro missense_variant De novo - - 28859103 Blanchet P , et al. (2017)
c.1570C>A p.His524Asn missense_variant De novo - - 28859103 Blanchet P , et al. (2017)
c.1579G>A p.Gly527Arg missense_variant De novo - - 28859103 Blanchet P , et al. (2017)
c.1678C>T p.His560Tyr missense_variant De novo - - 28859103 Blanchet P , et al. (2017)
c.1706G>A p.Arg569Gln missense_variant De novo - - 28859103 Blanchet P , et al. (2017)
c.2711dup p.Cys905ValfsTer7 frameshift_variant De novo - - 35741772 Hu C et al. (2022)
c.505G>A p.Glu169Lys missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.625G>A p.Gly209Ser missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.625G>C p.Gly209Arg missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1706G>A p.Arg569Gln missense_variant De novo - Simplex 35873028 Chen Y et al. (2021)
c.1548C>A p.His516Gln missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1931C>A p.Thr644Asn missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.591C>A p.Tyr197Ter stop_gained De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.2642+1G>A - splice_site_variant De novo - Simplex 25232846 De Rocker N , et al. (2014)
c.1510T>C p.Cys504Arg missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1537G>T p.Gly513Ter missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1579G>A p.Gly527Arg missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1579G>C p.Gly527Arg missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1642T>C p.Cys548Arg missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1657T>A p.Cys553Ser missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1700G>A p.Arg567Gln missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1706G>A p.Arg569Gln missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1712G>A p.Gly571Glu missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1727C>T p.Ala576Val missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1046G>T p.Arg349Met missense_variant Unknown - Simplex 37543562 Sheth F et al. (2023)
c.1917T>G p.Tyr639Ter stop_gained De novo - Simplex 25232846 De Rocker N , et al. (2014)
c.2990C>A p.Ser997Ter stop_gained De novo - Simplex 35597848 Carvalho LML et al. (2022)
c.3070C>A p.Arg1024Ser missense_variant De novo - - 34748075 Coursimault J et al. (2021)
c.223C>T p.Arg75Ter stop_gained De novo - Simplex 32065501 Windheuser IC , et al. (2020)
c.1946dup p.Asn649LysfsTer28 stop_gained De novo - - 34748075 Coursimault J et al. (2021)
c.2769-2A>G - splice_site_variant De novo - Simplex 32065501 Windheuser IC , et al. (2020)
c.1548C>A p.His516Gln missense_variant De novo - Simplex 38136944 Silas Yip et al. (2023)
c.535C>T p.Arg179Ter stop_gained Familial Maternal - 34748075 Coursimault J et al. (2021)
c.2032+5G>A - splice_site_variant Familial Paternal - 34748075 Coursimault J et al. (2021)
c.1531G>T p.Gly511Ter stop_gained De novo - Simplex 32065501 Windheuser IC , et al. (2020)
c.1582_1584delinsGGG p.Ser528Gly missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1510T>C p.Cys504Arg missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1579G>C p.Gly527Arg missense_variant De novo - Simplex 31406558 Munnich A , et al. (2019)
- - 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.1818G>A p.Arg606%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.2236del p.Met746CysfsTer5 frameshift_variant De novo - - 28859103 Blanchet P , et al. (2017)
c.1566C>G p.His522Gln missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.2990A>T p.Glu997Val missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.373G>T p.Glu125Ter stop_gained Unknown Not maternal - 34748075 Coursimault J et al. (2021)
c.3202_3205del p.Leu1068MetfsTer7 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.181del p.Arg61GlufsTer20 frameshift_variant De novo - - 34748075 Coursimault J et al. (2021)
c.3329_3332del p.Ile1110SerfsTer14 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.317del p.Glu106GlyfsTer68 frameshift_variant De novo - - 34748075 Coursimault J et al. (2021)
c.2234del p.Glu745GlyfsTer6 frameshift_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1700G>C p.Arg567Pro missense_variant De novo - Simplex 32065501 Windheuser IC , et al. (2020)
c.1711G>A p.Gly571Arg missense_variant De novo - Simplex 32065501 Windheuser IC , et al. (2020)
c.1706G>A p.Arg569Gln missense_variant De novo - Simplex 34580403 Pode-Shakked B et al. (2021)
c.2319G>A p.Leu773= synonymous_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.2460C>T p.Pro820= synonymous_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.1174dup p.Arg392ProfsTer16 frameshift_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1801del p.Ser601ArgfsTer11 frameshift_variant De novo - - 34748075 Coursimault J et al. (2021)
c.2005del p.Asp669IlefsTer35 frameshift_variant De novo - - 34748075 Coursimault J et al. (2021)
c.2117dup p.Gly707ArgfsTer58 frameshift_variant De novo - - 34748075 Coursimault J et al. (2021)
c.2182del p.Ala728ArgfsTer23 frameshift_variant De novo - - 34748075 Coursimault J et al. (2021)
c.2720del p.Thr907SerfsTer33 frameshift_variant De novo - - 34748075 Coursimault J et al. (2021)
c.1717G>A p.Gly573Arg missense_variant De novo - Unknown 38572415 Yasser Al-Sarraj et al. (2024)
c.470_471del p.Glu157GlyfsTer31 frameshift_variant De novo - - 34748075 Coursimault J et al. (2021)
c.3118A>T p.Lys1040Ter stop_gained Familial Paternal Simplex 32065501 Windheuser IC , et al. (2020)
c.2215_2224del p.Leu739AlafsTer9 frameshift_variant De novo - Simplex 30055078 Loid P , et al. (2018)
c.995G>A p.Arg332Gln missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
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.2924_2925ins22 p.Cys976ArgfsTer92 frameshift_variant De novo - - 34748075 Coursimault J et al. (2021)
c.761_764del p.Asp254ValfsTer14 frameshift_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.2579del p.Val860GlyfsTer20 frameshift_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.2665_2666delinsT p.Asp889SerfsTer51 frameshift_variant De novo - - 34748075 Coursimault J et al. (2021)
c.832del p.Glu278LysfsTer3 frameshift_variant Unknown Not paternal - 34748075 Coursimault J et al. (2021)
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

Score Delta: Score remained at 1

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.

10/1/2020
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).

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
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).

Reports Added
[Genome-wide detection of tandem DNA repeats that are expanded in autism2020]
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).

Reports Added
[Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020] [Nine newly identified individuals refine the phenotype associated with MYT1L mutations.2020]
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).

Reports Added
[Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.2019] [New Scoring Scheme]
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).

Reports Added
[Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder.2019]
7/1/2018
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).

Reports Added
[A novel MYT1L mutation in a patient with severe early-onset obesity and intellectual disability.2018]
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).

Reports Added
[MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothala...2017]
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.

Reports Added
[Germline mosaic transmission of a novel duplication of PXDN and MYT1L to two male half-siblings with autism.2011] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity.2014] [MYT1L is a candidate gene for intellectual disability in patients with 2p25.3 (2pter) deletions.2011] [Common SNPs in myelin transcription factor 1-like (MYT1L): association with major depressive disorder in the Chinese Han population.2010] [Recurrent CNVs disrupt three candidate genes in schizophrenia patients.2008] [Microduplications disrupting the MYT1L gene (2p25.3) are associated with schizophrenia.2012] [Identification of rare copy number variants in high burden schizophrenia families.2013] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates.2017]
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

Reports Added
[De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016]
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

Reports Added
[Germline mosaic transmission of a novel duplication of PXDN and MYT1L to two male half-siblings with autism.2011] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity.2014] [MYT1L is a candidate gene for intellectual disability in patients with 2p25.3 (2pter) deletions.2011] [Common SNPs in myelin transcription factor 1-like (MYT1L): association with major depressive disorder in the Chinese Han population.2010] [Recurrent CNVs disrupt three candidate genes in schizophrenia patients.2008] [Microduplications disrupting the MYT1L gene (2p25.3) are associated with schizophrenia.2012] [Identification of rare copy number variants in high burden schizophrenia families.2013] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014]
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

Reports Added
[Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity.2014] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014]
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.
Original Source
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
Original Source
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
Original Source
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).
Original Source
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.
Original Source
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.
Original Source
Submit New Gene

Report an Error