• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
MED13L (HGNC:22962) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
mediator complex subunit 13L
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
THRAP2
Alias symbols
KIAA1025, TRAP240L
%HI
7.11(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.06(Read more about gnomAD LOEUF score)
Cytoband
12q24.21
Genomic Coordinates
GRCh37/hg19: chr12:116396381-116715498 NCBI Ensembl UCSC
GRCh38/hg38: chr12:115958576-116277693 NCBI Ensembl UCSC
MANE Select Transcript
NM_015335.5 ENST00000281928.9 (Read more about MANE Select)
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)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-21137
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
08/08/2023

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Impaired intellectual development and distinctive facial features with or without cardiac defects Monarch
HI Evidence:
  • PUBMED: 24781760
    van Haelst et al (2015) describe two individuals wit MED13L variants. Patient 1 showed delayed milestones, sandal gap toe, facial asymmetry and macroglossia. Patient 2 presented with recurrent ear infections, speech and motor delay, short stature, and mild retrognathia. Whole exome sequencing of Patient 1 and her parents identified a de novo splice acceptor mutation in exon 5 that resulted in the use of a cryptic splice acceptor site 45 nucleotides into exon 5. This 45 bp deletion is in a highly conserved region of the protein and was presumed to disrupt gene product function. The analysis of Patient 2 by aCGH showed a 41 kb deletion of exons 6-20, also presumed to result in loss of function.
  • PUBMED: 25712080
    Cafiero et al (2015) report three individuals with de novo pathogenic variants detected by whole exome sequencing. In one patient, a 1 bp deletion in exon 17 was predicted to result in premature termination. In a second patient, a single base pair insertion in exon 5 was also predicted to result in premature termination, and in a third patient, a stop-gain variant was found. All three mutations are predicted to result in haploinsufficiency. The phenotypes of the patients is similar: dysmorphic features including a bulbous nasal tip with depressed nasal bridge, short mouth and straight eyebrows; developmental delay, motor delay, and intellectual disability.
  • PUBMED: 25106414
    Asadollahi et al (2013) report two individuals with de novo intragenic deletions and one individual with a 1 Mb triplication of the whole gene plus MAP1LC3B2. The deletion patients showed hypotonia, moderate intellectual disability, conotruncal heart defects, and facial anomalies. Patient 1 had a 17 kb deletion of exon 2. In silico studies showed the deletion to be out of frame. Patient 2 had a 115 kb deletion of exons 3 and 4, which was de novo by qPCR.
  • PUBMED: 29959045
    Tørring et al. describe 8 patients with de novo MED13L variants and intellectual disability, speech and motor delay, and dysmorphic facial features. 5 had loss-of-function variants including c.2071C>T p.(Gln691*), c.5861_5890+1del p.(Glu1954Metfs*15), c.5173C>T p.(Gln1725*), c.6274dup p.(Gln2092Profs*16), and c.5681G>A p.(Trp1894*). All 5 LoF variants are predicted to undergo nonsense mediated decay. Additionally, microdeletions were seen in 2 individuals including exon 2 deletion and exon 3-4 deletion.
  • PUBMED: 33930262
    Dawudziuk et al describes a single patient with developmental delay and behavioral abnormalities who has a de novo loss-of-function MED13L variant c.5941C>T, p.(Gln1981*). The variant is predicted to undergo nonsense mediated decay.
HI Evidence Comments:
Individuals with pathogenic heterozygous MED13L variants have delayed development, intellectual disability, limited speech, distinctive dysmorphic facial features including frontal bossing, upslanting palpebral fissures, depressed nasal bridge with bulbous tip, and macrostomia. Some individuals may have cardiac malformations (adapted from https://omim.org/entry/616789).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Published Evidence:
  • PUBMED: 25106414
    Asadollahi et al (2013) report two individuals with de novo intragenic deletions (described above) and one individual (Pt 3) with a 1 Mb triplication of the whole MED13L gene plus MAP1LC3B2. Patient 3 showed a milder phenotype, with neonatal hypotonia, delayed walking and toilet training. Microarray using Affymetrix 6.0 platform showed a de novo 1 Mb triplication of all of MED13L and flanking gene, MAP1LC3B2. Because of the involvement of the other gene, this information does not contribute to the triplosensitivity score.

Genomic View

Select assembly: (NC_000012.11) (NC_000012.12)