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EMD
emerin
The EMD gene provides instructions for emerin, a protein crucial for the structural integrity and function of the nuclear envelope, particularly in muscle cells. The EMD gene encodes the emerin protein, which is an important component of the nuclear envelope, the membrane surrounding the cell's nucleus.
EMD is located on the long (q) arm of chromosome X, at band Xq28. Arm ratio per GRCh38 - banding schematic.
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Overview
The EMD gene is responsible for producing a protein called emerin, which is vital for the normal function of various tissues, especially skeletal and cardiac muscles. Emerin is located within the nuclear envelope, a double membrane that encloses the cell's nucleus and regulates the movement of molecules in and out of it.
Emerin interacts with other proteins on the inner surface of the nuclear envelope, contributing to gene regulation, cell division, and cellular signalling. It also helps maintain the structural stability of the nucleus and participates in its assembly during cell division.
What the gene does
The emerin protein, encoded by the EMD gene, is integral to the nuclear envelope, where it performs several critical functions. It is involved in regulating the activity of specific genes, which is essential for proper cell function and development. Emerin also plays a role in controlling cell division and facilitating chemical signalling pathways within the cell.
Through its interactions with other proteins, emerin helps to maintain the structural integrity and stability of the nucleus. This includes contributing to the assembly of the nuclear envelope during cell division, ensuring that the genetic material is properly enclosed and protected. While emerin is found in many tissues, its role in skeletal and cardiac muscle function appears to be particularly important.
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Chromosome location
The EMD gene is situated on the X chromosome at position Xq28. This specific location indicates that the gene is found on the long arm of the X chromosome. The gene provides instructions for a protein that is 254 amino acids long.
Protein structure
The emerin protein comprises several distinct functional regions. It features an N-terminal LEM domain, spanning amino acids 1 to 45. This domain is known for its role in interactions with chromatin and other nuclear proteins. Further along the protein, a region from amino acids 46 to 222 is involved in interaction with F-actin, linking the nuclear envelope to the cytoskeleton. Additionally, a specific region between amino acids 168 and 186 facilitates interaction with CTNNB1 (beta-catenin), which is important for signal transduction pathways.
Key variants
Variants in the EMD gene can affect the structure and function of the emerin protein, leading to various health consequences. Over 100 different pathogenic variants within the EMD gene have been identified. These changes can result in a dysfunctional or absent emerin protein, disrupting the normal processes that depend on it within the nuclear envelope.
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.116_143del | p.Phe39fs | Pathogenic | ★★☆☆ | Emery-Dreifuss muscular dystrophy 1, X-linked |
c.135dup | p.Arg46fs | Pathogenic/Likely pathogenic | ★★☆☆ | Emery-Dreifuss muscular dystrophy |
c.153del | p.Ser52fs | Pathogenic | ★★☆☆ | X-linked Emery-Dreifuss muscular dystrophy |
c.187+1G>A | - | Pathogenic | ★★☆☆ | X-linked Emery-Dreifuss muscular dystrophy |
c.282C>G | p.Tyr94Ter | Pathogenic/Likely pathogenic | ★★☆☆ | X-linked Emery-Dreifuss muscular dystrophy |
c.359_362del | p.Gln119_Ser120insTer | Pathogenic/Likely pathogenic | ★★☆☆ | X-linked Emery-Dreifuss muscular dystrophy |
c.399+1G>T | - | Pathogenic | ★★☆☆ | Emery-Dreifuss muscular dystrophy |
c.399+2T>C | - | Pathogenic | ★★☆☆ | X-linked Emery-Dreifuss muscular dystrophy |
c.650_654del | p.Leu217fs | Pathogenic | ★★☆☆ | Cardiovascular phenotype |
c.674del | p.Leu225fs | Pathogenic/Likely pathogenic | ★★☆☆ | X-linked Emery-Dreifuss muscular dystrophy |
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 EMD gene are primarily associated with Emery-Dreifuss muscular dystrophy, an X-linked inherited condition. This disorder affects both skeletal muscles, which are used for movement, and the heart muscle. Individuals with Emery-Dreifuss muscular dystrophy typically experience joint contractures, progressive muscle weakness and wasting, and significant heart problems, including a heightened risk of sudden cardiac events.
Inheritance pattern
Conditions caused by pathogenic EMD variants typically follow x-linked inheritance.
X-linked recessive: sons of a carrier mother have a 50% chance of being affected. Daughters have a 50% chance of being carriers.
UK clinical status
The EMD gene is recognised within the UK's NHS Genomic Medicine Service due to its clinical significance. It is included on several PanelApp panels, indicating its relevance in diagnosing specific conditions. These panels include 'Congenital muscular dystrophy', 'Dilated and arrhythmogenic cardiomyopathy', 'Foetal anomalies', 'Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies', 'Paediatric or syndromic cardiomyopathy', and 'Progressive cardiac conduction disease'. The 'green' status for these panels signifies strong evidence for the gene's association with these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the emerin protein?
The emerin protein, encoded by the EMD gene, is a component of the nuclear envelope. It helps maintain the structural stability of the nucleus, regulates gene activity, and is involved in cell division and signalling pathways.
What condition is primarily associated with EMD gene variants?
Pathogenic variants in the EMD gene are primarily associated with X-linked Emery-Dreifuss muscular dystrophy. This condition affects skeletal and cardiac muscles, leading to joint contractures, muscle weakness, and heart issues.
How is Emery-Dreifuss muscular dystrophy inherited?
Emery-Dreifuss muscular dystrophy linked to EMD gene variants has an X-linked inheritance pattern. This means the gene is located on the X chromosome, and males are typically more severely affected due to having only one X chromosome.
References
- Koch AJ, Holaska JM. Emerin in health and disease. Seminars in cell & developmental biology. 2014. PMID: 24365856
- Berk JM, Tifft KE, Wilson KL. The nuclear envelope LEM-domain protein emerin. Nucleus (Austin, Tex.). 2013. PMID: 23873439
- Wilson KL, Holaska JM, Montes de Oca R. Nuclear membrane protein emerin: roles in gene regulation, actin dynamics and human disease. Novartis Foundation symposium. 2005. PMID: 15773747
- Bengtsson L, Wilson KL. Multiple and surprising new functions for emerin, a nuclear membrane protein. Current opinion in cell biology. 2004. PMID: 15037308
- Fairley EA, Kendrick-Jones J, Ellis JA. The Emery-Dreifuss muscular dystrophy phenotype arises from aberrant targeting and binding of emerin at the inner nuclear membrane. Journal of cell science. 1999. PMID: 10393813
- Adam MP, Bick S, Mirzaa GM. Emery-Dreifuss Muscular Dystrophy. 1993. PMID: 20301609