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MED13L
mediator complex subunit 13L
The MED13L gene provides instructions for a protein that is a critical component of the mediator complex, influencing gene transcription and various aspects of early development. The MED13L gene encodes the Mediator complex subunit 13-like protein, which plays a key role in regulating gene expression by connecting gene-activating proteins to the transcription machinery.
MED13L is located on the long (q) arm of chromosome 12, at band 12q24.21. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 12 in the library →Overview
The MED13L gene provides the blueprint for a protein that serves as a subunit within the mediator complex, a crucial protein assembly responsible for regulating gene activity, specifically transcription. This gene's product is involved in the initial step where genetic information from DNA is converted into proteins. The MED13L protein's function within this complex is integral to various developmental processes during early life.
The mediator complex, through components like the MED13L protein, forms a physical link between proteins that initiate gene transcription (transcription factors) and the enzyme RNA polymerase II, which carries out the transcription process. This connection is fundamental for initiating gene expression. Dysfunction of the MED13L gene can therefore have widespread effects on development and cellular function.
What the gene does
The MED13L protein is an integral part of the mediator complex, a large multi-protein structure that acts as a transcriptional co-regulator. Its primary function involves mediating interactions between DNA-binding transcription factors and RNA polymerase II, thereby regulating the rate at which genes are transcribed into RNA. This regulatory role is vital for controlling the expression of specific genes at appropriate times during development and in response to cellular signals.
Beyond its core role in transcription, the MED13L protein, as part of the mediator complex, is thought to influence numerous aspects of early development. This includes the formation and maturation of cardiac tissues, the development of neurons in the brain, and the proper formation of facial structures. The mediator complex and its subunits, including MED13L, are also implicated in cellular signalling pathways that govern processes such as cell growth, cell migration, and cellular differentiation, where cells acquire specialised functions.
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Chromosome location
The MED13L gene is located on chromosome 12, specifically at position 12q24.21. This chromosomal address indicates its precise location on the long (q) arm of chromosome 12. The gene's position is important for understanding its genetic context and how chromosomal abnormalities in this region might affect its function.
Protein structure
The MED13L protein is approximately 2210 amino acids in length and exhibits a complex domain organisation. It features several intrinsically disordered regions, specifically at amino acids 391-414, 435-489, 519-582, 736-770, 1016-1096, 1530-1656, and 2045-2080. These disordered regions often play a role in protein-protein interactions and signalling. Additionally, the protein contains two LXXLL motifs, located at amino acids 669-673 and 1225-1229, which are typically involved in nuclear receptor binding. A Leucine-zipper region is also present between amino acids 1380-1401, suggesting potential roles in protein dimerisation.
Key variants
Variants in the MED13L gene can alter the function of the Mediator complex subunit 13-like protein, leading to disrupted gene regulation and developmental processes. These genetic changes can range from single base-pair alterations to larger deletions or duplications within the gene. Understanding the nature and impact of these variants is crucial for clinical assessment, though specific variants are not discussed here.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1135C>T | p.Arg379Ter | Pathogenic | ★★☆☆ | Global developmental delay |
c.1708_1709del | p.Ser570fs | Pathogenic | ★★☆☆ | Cardiac anomalies - developmental delay - facial dysmorphism syndrome |
c.1994_1997del | p.Glu665fs | Pathogenic | ★★☆☆ | not provided |
c.2065C>T | p.Gln689Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Cardiac anomalies - developmental delay - facial dysmorphism syndrome |
c.2071C>T | p.Gln691Ter | Pathogenic | ★★☆☆ | Neurodevelopmental disorder |
c.2579A>G | p.Asp860Gly | Pathogenic/Likely pathogenic | ★★☆☆ | Cardiac anomalies - developmental delay - facial dysmorphism syndrome |
c.2597C>T | p.Pro866Leu | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.2606C>T | p.Pro869Leu | Pathogenic/Likely pathogenic | ★★☆☆ | Cardiac anomalies - developmental delay - facial dysmorphism syndrome |
c.263G>A | p.Trp88Ter | Pathogenic | ★★☆☆ | Dextro-looped transposition of the great arteries |
c.2996+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Cardiac anomalies - developmental delay - facial dysmorphism syndrome |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the MED13L gene are primarily associated with MED13L syndrome, a neurodevelopmental disorder. Individuals with MED13L syndrome typically present with developmental delay, intellectual disability, and characteristic facial features. In some cases, MED13L syndrome can also involve other clinical manifestations such as recurrent seizures (epilepsy) or congenital heart defects, including critical congenital heart disease.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic MED13L variants typically follow autosomal dominant inheritance.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
UK clinical status
The MED13L gene is included in several UK NHS national genomic testing panels, indicating its recognised clinical significance within the UK healthcare system. It is listed as 'green' on the DDG2P panel, the Foetal anomalies panel (R21), and the Intellectual disability panel. This signifies that there is strong evidence for a gene-disease association and that testing for MED13L variants is routinely offered for these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the function of the MED13L gene?
The MED13L gene provides instructions for a protein that is a subunit of the mediator complex. This complex regulates gene activity by linking transcription factors to RNA polymerase II, which is essential for initiating gene transcription and plays a role in early development.
What conditions are associated with MED13L gene variants?
Variants in the MED13L gene are primarily associated with MED13L syndrome. This condition is characterised by developmental delay, intellectual disability, specific facial features, and can sometimes include seizures or congenital heart defects.
How does the MED13L gene affect development?
As part of the mediator complex, the MED13L protein influences gene expression that is critical for the proper development of various organs and systems. This includes the heart, neurons in the brain, and structures in the face during early developmental stages.
References
- Smol T, Petit F, Piton A. MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype. Neurogenetics. 2018. PMID: 29511999
- Asadollahi R, Zweier M, Gogoll L. Genotype-phenotype evaluation of MED13L defects in the light of a novel truncating and a recurrent missense mutation. European journal of medical genetics. 2017. PMID: 28645799
- van Haelst MM, Monroe GR, Duran K. Further confirmation of the MED13L haploinsufficiency syndrome. European journal of human genetics : EJHG. 2015. PMID: 24781760
- Cafiero C, Marangi G, Orteschi D. Novel de novo heterozygous loss-of-function variants in MED13L and further delineation of the MED13L haploinsufficiency syndrome. European journal of human genetics : EJHG. 2015. PMID: 25712080
- Asadollahi R, Oneda B, Sheth F. Dosage changes of MED13L further delineate its role in congenital heart defects and intellectual disability. European journal of human genetics : EJHG. 2013. PMID: 23403903