Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

MED13L

HGNC:22962 (protein-coding gene)

mediator complex subunit 13L

Unique Cases:
63
Disorders:
ID, ASD, EP, SCZ, CP
Last Updated:
November 4, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
MED13L is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene Function
Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene- specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcripti... (Source: Uniprot)
Previous symbols
THRAP2
Alias symbols
KIAA1025, TRAP240L
Chromosomal Location
12q24.21
Genomic Coordinates
GRCh37:chr12:116396381-116714991
GRCh38:chr12:115958576-116277693
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

7.11

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.06

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Strong

ClinGen Classification (ClinGen)

Definitive1

Limited1

GenCC Classification (GenCC)

Definitive2 Strong2 Supportive1 Limited1

Publications:

Guo H et. al., Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes., Genet Med, 2019
Howrigan DP et. al., Exome sequencing in schizophrenia-affected parent-offspring trios reveals risk conferred by protein-coding de novo mutations., Nat Neurosci, 2020
Smol T et. al., MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype., Neurogenetics, 2018
Ewans LJ et. al., Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders., Genet Med, 2018
Codina-Solà M et. al., Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders., Mol Autism, 2015
Iossifov I et. al., De novo gene disruptions in children on the autistic spectrum., Neuron, 2012
Iossifov I et. al., The contribution of de novo coding mutations to autism spectrum disorder., Nature, 2014
Deciphering Developmental Disorders Study. et. al., Large-scale discovery of novel genetic causes of developmental disorders., Nature, 2015
Beighley JS et. al., Clinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes., Biol Psychiatry, 2020
Redin C et. al., Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing., J Med Genet, 2014
Guo H et. al., Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model., Mol Autism, 2018
Tørring PM et. al., Is MED13L-related intellectual disability a recognizable syndrome?, Eur J Med Genet, 2019
Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019
Cafiero C et. al., Novel de novo heterozygous loss-of-function variants in MED13L and further delineation of the MED13L haploinsufficiency syndrome., Eur J Hum Genet, 2015
Chérot E et. al., Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients., Clin Genet, 2018
van Haelst MM et. al., Further confirmation of the MED13L haploinsufficiency syndrome., Eur J Hum Genet, 2015
Asadollahi R et. al., Dosage changes of MED13L further delineate its role in congenital heart defects and intellectual disability., Eur J Hum Genet, 2013
Munnich A et. al., Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder., Mol Autism, 2019
Wang T et. al., De novo genic mutations among a Chinese autism spectrum disorder cohort., Nat Commun, 2016
Iglesias A et. al., The usefulness of whole-exome sequencing in routine clinical practice., Genet Med, 2014
Arteche-López A et. al., Towards a Change in the Diagnostic Algorithm of Autism Spectrum Disorders: Evidence Supporting Whole Exome Sequencing as a First-Tier Test., Genes (Basel), 2021
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021
Mainali A et. al., Diagnostic yield of clinical exome sequencing in adulthood in medical genetics clinics., Am J Med Genet A, 2022
Lindstrand A et. al., Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability., Genet Med, 2022
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NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.
Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.
DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.
SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.
ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.
GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
gnomAD
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