Human Gene Module / Chromosome 2 / MYT1L

MYT1LMyelin transcription factor 1-like

Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
6 / 14
Rare Variants / Common Variants
24 / 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 germline mosiac duplication of the PXDN and MYT1L genes was transmitted from a psychiatrically normal mother to two male half-siblings with autism (Meyer et al., 2012). Genetic 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) and intellectual disability (Stevens et al., 2011).

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 (14 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 (1 patient)
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 -
Rare Variants   (24)
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)
- - copy_number_gain - - - 18940311 Vrijenhoek T , et al. (2008)
- - copy_number_loss Unknnown - Multiplex 21990140 Stevens SJ , et al. (2011)
- - copy_number_loss De novo - - 21990140 Stevens SJ , et al. (2011)
- - copy_number_loss De novo - - 21990140 Stevens SJ , et al. (2011)
- - copy_number_loss De novo - - 21990140 Stevens SJ , et al. (2011)
- - copy_number_gain Familial Maternal Multiplex 22157634 Meyer KJ , et al. (2011)
- - copy_number_gain Familial Paternal Multiplex 23505263 Van Den Bossche MJ , et al. (2013)
c.2636+1C>T - splice_site_variant De novo - Simplex 25232846 De Rocker N , et al. (2014)
c.1917T>G p.Tyr639Ter stop_gained De novo - Simplex 25232846 De Rocker N , et al. (2014)
c.591C>A p.Tyr197Ter stop_gained De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.1566C>G p.His522Gln missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.3046C>A p.His1016Asn missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.995G>A p.Arg332Gln missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
del(TCAA) - frameshift_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.565G>A p.Glu189Lys missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.2990A>T p.Glu997Val missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1510T>C p.Cys504Arg missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.2542C>T p.Gln848Ter stop_gained De novo - - 27824329 Wang T , et al. (2016)
- - translocation De novo - - 27841880 Redin C , et al. (2016)
- - translocation De novo - - 27841880 Redin C , et al. (2016)
c.761_764del p.Asp254fs frameshift_variant De novo - Multiplex 28263302 C Yuen RK , et al. (2017)
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 (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.

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.

04-01-2017
1

Initial score established: 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.

CNVs associated with MYT1L(1 CNVs)
2p25.3 29 Deletion-Duplication 49  /  107
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