Human Gene Module / Chromosome 12 / MED13L

MED13LMediator complex subunit 13-like

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
8 / 13
Rare Variants / Common Variants
29 / 0
Aliases
MED13L, PROSIT240,  THRAP2,  TRAP240L
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
12q24.21
Associated Disorders
ASD
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 (13 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 Recent recommendation The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
4 Support Large-scale discovery of novel genetic causes of developmental disorders. Deciphering Developmental Disorders Study (2014) Yes -
5 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 -
6 Recent recommendation Redefining the MED13L syndrome. Adegbola A , et al. (2015) No Autistic features (2 cases
7 Support Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders. Codina-Sol M , et al. (2015) Yes -
8 Recent recommendation Low load for disruptive mutations in autism genes and their biased transmission. Iossifov I , et al. (2015) Yes -
9 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability. Lelieveld SH , et al. (2016) No -
10 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)
11 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior. Doan RN , et al. (2016) Yes -
12 Support De novo genic mutations among a Chinese autism spectrum disorder cohort. Wang T , et al. (2016) Yes -
13 Support Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Stessman HA , et al. (2017) Yes -
Rare Variants   (29)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type Author, Year
c.5364dupG p.Glu1788fs splice_site_variant De novo - Simplex Iossifov I , et al. (2012)
c.6118_6125del p.Gly2040AsnfsTer32 frameshift_variant De novo - Simplex Redin C , et al. (2014)
c.4076G>A p.Trp1359Ter stop_gained De novo - Simplex Iossifov I , et al. (2014)
c.1690C>T p.Arg564Ter stop_gained De novo - Simplex Deciphering Developmental Disorders Study (2014)
c.329G>A p.Trp110Ter stop_gained De novo - Simplex Deciphering Developmental Disorders Study (2014)
c.4103delG p.Arg1368fs frameshift_variant De novo - Simplex Deciphering Developmental Disorders Study (2014)
c.6005C>T p.Ser2002Leu missense_variant De novo - Simplex Deciphering Developmental Disorders Study (2014)
CTGTGT/CT - frameshift_variant De novo - Simplex Deciphering Developmental Disorders Study (2014)
c.5695G>A p.Gly1899Arg missense_variant De novo - Simplex Deciphering Developmental Disorders Study (2014)
c.3765delC p.Cys1256ValfsTer2 frameshift_variant De novo - Simplex Cafiero C , et al. (2015)
c.607dupT p.Ser203SerfsTer32 frameshift_variant De novo - Simplex Cafiero C , et al. (2015)
c.4420A>T p.Lys1474Ter stop_gained De novo - Simplex Cafiero C , et al. (2015)
- - copy_number_gain De novo - - Adegbola A , et al. (2015)
- - copy_number_loss De novo - - Adegbola A , et al. (2015)
- - copy_number_gain De novo - - Adegbola A , et al. (2015)
- - copy_number_gain De novo - - Adegbola A , et al. (2015)
- - copy_number_loss De novo - - Adegbola A , et al. (2015)
delGA p.Gln1984AlafsTer31 frameshift_variant De novo - - Adegbola A , et al. (2015)
- - copy_number_gain Familial Maternal - Adegbola A , et al. (2015)
- - copy_number_loss De novo - - Adegbola A , et al. (2015)
c.1708_1709delAG p.Ser570PhefsTer27 frameshift_variant De novo - Simplex Codina-Sol M , et al. (2015)
c.3392G>A p.Cys1131Tyr missense_variant De novo - - Lelieveld SH , et al. (2016)
c.5695G>A p.Gly1899Arg missense_variant De novo - - Caro-Llopis A , et al. (2016)
c.2524C>T p.Arg842Ter stop_gained De novo - - Caro-Llopis A , et al. (2016)
G>CT - intergenic_variant - - Unknown Doan RN , et al. (2016)
c.2395_2396del p.Gln799GlyfsTer10 frameshift_variant De novo - - Wang T , et al. (2016)
c.6317C>T p.Ala2106Ile missense_variant Familial Maternal - Wang T , et al. (2016)
c.6301G>T p.Val2101Leu missense_variant Familial Paternal - Wang T , et al. (2016)
c.2344G>T p.Glu782Ter stop_gained De novo - - Stessman HA , 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.

01-01-2017
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
[]
CNVs associated with MED13L(4 CNVs)
12q24.21 7 Deletion-Duplication 10  /  17
1p13.1-p12 1 Deletion-Duplication 2  /  2
2q14.1 9 Deletion-Duplication 19  /  89
Xq21.2-q24 1 Duplication 1  /  1
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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