Human Gene Module / Chromosome 12 / MED13L

MED13LMediator complex subunit 13-like

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
8 / 16
Rare Variants / Common Variants
34 / 0
Aliases
MED13L, PROSIT240,  THRAP2,  TRAP240L
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
12q24.21
Associated Disorders
ASD, DD/NDD, ID
Relevance to Autism

Two de novo loss-of-function variants in the MED13L gene have been identified in ASD probands from the Simons Simplex Collection (refs).

Molecular Function

The protein encoded by this gene is a subunit of the Mediator complex, a large complex of proteins that functions as a transcriptional coactivator for most RNA polymerase II-transcribed genes. The encoded protein is involved in early development of the heart and brain. Defects in this gene are a cause of transposition of the great arteries, dextro-looped (DTGA) [MIM:608808].

Reports related to MED13L (16 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De novo gene disruptions in children on the autistic spectrum. Iossifov I , et al. (2012) Yes -
2 Support Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing. Redin C , et al. (2014) No -
3 Support De novo mutations in moderate or severe intellectual disability. Hamdan FF , et al. (2014) No Speech delay, motor delay
4 Recent recommendation The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
5 Support Large-scale discovery of novel genetic causes of developmental disorders. Deciphering Developmental Disorders Study (2014) Yes -
6 Support Novel de novo heterozygous loss-of-function variants in MED13L and further delineation of the MED13L haploinsufficiency syndrome. Cafiero C , et al. (2015) No -
7 Recent recommendation Redefining the MED13L syndrome. Adegbola A , et al. (2015) No Autistic features (2 cases
8 Support Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders. Codina-Sol M , et al. (2015) Yes -
9 Recent recommendation Low load for disruptive mutations in autism genes and their biased transmission. Iossifov I , et al. (2015) Yes -
10 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability. Lelieveld SH , et al. (2016) No -
11 Support De novo mutations in genes of mediator complex causing syndromic intellectual disability: mediatorpathy or transcriptomopathy? Caro-Llopis A , et al. (2016) No Autistic behavior (1/2 cases)
12 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior. Doan RN , et al. (2016) Yes -
13 Support De novo genic mutations among a Chinese autism spectrum disorder cohort. Wang T , et al. (2016) Yes -
14 Support Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Stessman HA , et al. (2017) Yes -
15 Support MED13L haploinsufficiency syndrome: A de novo frameshift and recurrent intragenic deletions due to parental mosaicism. Yamamoto T , et al. (2017) No DD, ID
16 Support Genomic diagnosis for children with intellectual disability and/or developmental delay. Bowling KM , et al. (2017) No -
Rare Variants   (34)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.5364dupG p.Glu1788fs splice_site_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.6118_6125del p.Gly2040AsnfsTer32 frameshift_variant De novo - Simplex 25167861 Redin C , et al. (2014)
c.1708_1709delCT p.Ser570PhefsTer27 frameshift_variant De novo - Simplex 25356899 Hamdan FF , et al. (2014)
c.4076G>A p.Trp1359Ter stop_gained De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.1690C>T p.Arg564Ter stop_gained De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.329G>A p.Trp110Ter stop_gained De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.4103delG p.Arg1368fs frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.6005C>T p.Ser2002Leu missense_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
CTGTGT/CT - frameshift_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.5695G>A p.Gly1899Arg missense_variant De novo - Simplex 25533962 Deciphering Developmental Disorders Study (2014)
c.3765delC p.Cys1256ValfsTer2 frameshift_variant De novo - Simplex 25712080 Cafiero C , et al. (2015)
c.607dupT p.Ser203SerfsTer32 frameshift_variant De novo - Simplex 25712080 Cafiero C , et al. (2015)
c.4420A>T p.Lys1474Ter stop_gained De novo - Simplex 25712080 Cafiero C , et al. (2015)
- - copy_number_gain De novo - - 25758992 Adegbola A , et al. (2015)
- - copy_number_loss De novo - - 25758992 Adegbola A , et al. (2015)
- - copy_number_gain De novo - - 25758992 Adegbola A , et al. (2015)
- - copy_number_gain De novo - - 25758992 Adegbola A , et al. (2015)
- - copy_number_loss De novo - - 25758992 Adegbola A , et al. (2015)
delGA p.Gln1984AlafsTer31 frameshift_variant De novo - - 25758992 Adegbola A , et al. (2015)
- - copy_number_gain Familial Maternal - 25758992 Adegbola A , et al. (2015)
- - copy_number_loss De novo - - 25758992 Adegbola A , et al. (2015)
c.1708_1709delAG p.Ser570PhefsTer27 frameshift_variant De novo - Simplex 25969726 Codina-Sol M , et al. (2015)
c.3392G>A p.Cys1131Tyr missense_variant De novo - - 27479843 Lelieveld SH , et al. (2016)
c.5695G>A p.Gly1899Arg missense_variant De novo - - 27500536 Caro-Llopis A , et al. (2016)
c.2524C>T p.Arg842Ter stop_gained De novo - - 27500536 Caro-Llopis A , et al. (2016)
G>CT - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
c.2395_2396del p.Gln799GlyfsTer10 frameshift_variant De novo - - 27824329 Wang T , et al. (2016)
c.6317C>T p.Ala2106Ile missense_variant Familial Maternal - 27824329 Wang T , et al. (2016)
c.6301G>T p.Val2101Leu missense_variant Familial Paternal - 27824329 Wang T , et al. (2016)
c.2344G>T p.Glu782Ter stop_gained De novo - - 28191889 Stessman HA , et al. (2017)
c.257delT p.Phe86SerfsTer9 frameshift_variant De novo - - 28371282 Yamamoto T , et al. (2017)
c.311_2569del - copy_number_loss Familial Maternal Multiplex 28371282 Yamamoto T , et al. (2017)
c.124dupG p.Asp42Glyfs frameshift_variant De novo - - 28554332 Bowling KM , et al. (2017)
c.6485C>T p.Thr2162Met missense_variant De novo - - 28554332 Bowling KM , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two de novo LoF variants in the MED13L gene (one splice-site, one nonsense) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768). A third de novo LoF variant in MED13L was identified in a patient from the Deciphering Developmental Disorders Study presenting with ASD and developmental delay (PMID 25533962). Variants in MED13L that result in haploinsufficiency are also associated with intellectual disability with or without congenital heart defects (PMIDs 23403903, 24781760, 25712080).

2

Strong Candidate

See all Category 2 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
2

Initial score established: 2

Description

Two de novo LoF variants in the MED13L gene (one splice-site, one nonsense) were identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 25363768). A third de novo LoF variant in MED13L was identified in a patient from the Deciphering Developmental Disorders Study presenting with ASD and developmental delay (PMID 25533962). Variants in MED13L that result in haploinsufficiency are also associated with intellectual disability with or without congenital heart defects (PMIDs 23403903, 24781760, 25712080).

Reports Added
[De novo gene disruptions in children on the autistic spectrum.2012] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.2015] [Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [The contribution of de novo coding mutations to autism spectrum disorder.2014] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Redefining the MED13L syndrome.2015] [De novo genic mutations among a Chinese autism spectrum disorder cohort.2016] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017] [De novo mutations in moderate or severe intellectual disability.2014] [Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.2017] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability.2016] [De novo mutations in genes of mediator complex causing syndromic intellectual disability: mediatorpathy or transcriptomopathy?2016] [MED13L haploinsufficiency syndrome: A de novo frameshift and recurrent intragenic deletions due to parental mosaicism.2017] [Novel de novo heterozygous loss-of-function variants in MED13L and further delineation of the MED13L haploinsufficiency syndrome.2015]
CNVs associated with MED13L(1 CNVs)
12q24.21 7 Deletion-Duplication 10  /  17
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
MED19 Mediator of RNA polymerase II transcription subunit 19 Human Protein Binding 219541 A0JLT2
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