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MYH7
myosin heavy chain 7
The MYH7 gene provides instructions for producing myosin heavy chain-7, a protein essential for muscle contraction in both cardiac and skeletal muscles. The MYH7 gene is fundamental for proper muscle function, guiding the synthesis of a key protein involved in generating the mechanical force for muscle contraction.
MYH7 is located on the long (q) arm of chromosome 14, at band 14q11.2. Arm ratio per GRCh38 - banding schematic.
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The MYH7 gene encodes the myosin heavy chain-7 protein, a vital component found in cardiac muscle and specific types of skeletal muscle. This protein is particularly abundant in type I, or "slow-twitch," skeletal muscle fibres, which are known for their endurance and resistance to fatigue, such as those involved in maintaining posture. The primary role of myosin heavy chain-7 is to generate the mechanical force necessary for muscle contraction.
Disruptions in the MYH7 gene's normal function can lead to a range of inherited conditions, predominantly affecting the heart and skeletal muscles. These conditions can manifest as various forms of cardiomyopathy, where the heart muscle is abnormal, or myopathies, which involve skeletal muscle weakness. Understanding the genetic basis of these disorders, particularly the role of MYH7, is critical for diagnosis and management in clinical practice.
What the gene does
The myosin heavy chain-7 protein, encoded by the MYH7 gene, plays a central role in the mechanics of muscle contraction. It functions as a motor protein, converting chemical energy into mechanical force. Within muscle cells, myosin heavy chain-7 combines with other proteins to form thick filaments, which are fundamental structures within sarcomeres. Sarcomeres are the basic contractile units of muscle tissue, characterised by their organised arrangement of overlapping thick (myosin) and thin (actin) protein filaments.
Muscle contraction occurs through a cyclical process where the thick and thin filaments interact. The myosin heads, part of the myosin heavy chain-7 protein, attach to the actin filaments, pivot, and then detach. This cyclic attachment, power stroke, and release allow the thin filaments to slide past the thick filaments, causing the sarcomere to shorten. This shortening ultimately leads to muscle contraction.
In cardiac muscle, this coordinated contraction is responsible for pumping blood efficiently throughout the body. In skeletal muscles, particularly in slow-twitch fibres, the sustained contraction and relaxation facilitated by myosin heavy chain-7 enable movement and maintenance of posture without rapid fatigue. Pathogenic variants in MYH7 can impair the function of the myosin heavy chain-7 protein, leading to inefficient or abnormal muscle contraction, which underlies the development of various cardiac and skeletal muscle conditions.
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Chromosome location
The MYH7 gene is situated on chromosome 14, specifically at position 14q11.2. This genomic location refers to the long (q) arm of chromosome 14, within region 1, band 1, and sub-band 2. The gene's position is consistent across individuals and is a critical identifier for genetic mapping and diagnostic purposes.
Protein structure
The myosin heavy chain-7 protein, comprising 1935 amino acids, exhibits a complex structure integral to its motor function. It features several distinct domains and regions. The Myosin N-terminal SH3-like domain is located at amino acids 32-81, followed by the extensive Myosin motor domain spanning amino acids 85-778, which is crucial for its ATPase activity and interaction with actin. Within the motor domain, two distinct Actin-binding regions are identified: one from amino acids 655-677 and another from amino acids 757-771, both mediating the protein's attachment to actin filaments. Further along the protein, an IQ domain is found at amino acids 781-810, involved in light chain binding. The majority of the protein, from amino acids 839-1935, forms a Coiled coil structure, facilitating dimerisation. Finally, a Disordered region is present at amino acids 1907-1935, which may play a role in regulatory interactions.
Key variants
Variants within the MYH7 gene can significantly impact the structure and function of the myosin heavy chain-7 protein, leading to a spectrum of inherited disorders. These genetic changes can range from single amino acid substitutions to larger deletions or insertions, all capable of disrupting the protein's ability to participate effectively in muscle contraction. Pathogenic variants in MYH7 are typically inherited in an autosomal dominant pattern, meaning a single altered copy of the gene is sufficient to cause the condition.
The clinical consequences of MYH7 variants are diverse, with some leading to severe cardiac dysfunction while others primarily affect skeletal muscles. The specific location and nature of a variant often influence the resulting phenotype, contributing to the variability observed in associated conditions. Genetic testing can identify these variants, aiding in diagnosis and informing family planning decisions.
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.1207C>T | p.Arg403Trp | Pathogenic | ★★★☆ | Hypertrophic cardiomyopathy 1 |
c.1208G>A | p.Arg403Gln | Pathogenic | ★★★☆ | Hypertrophic cardiomyopathy 1 |
c.1357C>A | p.Arg453Ser | Pathogenic | ★★★☆ | Hypertrophic cardiomyopathy 1 |
c.1357C>T | p.Arg453Cys | Pathogenic | ★★★☆ | Hypertrophic cardiomyopathy 1 |
c.1358G>A | p.Arg453His | Pathogenic | ★★★☆ | not provided |
c.1594T>C | p.Ser532Pro | Pathogenic | ★★★☆ | Dilated cardiomyopathy 1S |
c.1750G>C | p.Gly584Arg | Pathogenic | ★★★☆ | Hypertrophic cardiomyopathy 1 |
c.1988G>A | p.Arg663His | Pathogenic | ★★★☆ | Primary familial hypertrophic cardiomyopathy |
c.2146G>A | p.Gly716Arg | Pathogenic | ★★★☆ | Hypertrophic cardiomyopathy 1 |
c.2155C>T | p.Arg719Trp | Pathogenic | ★★★☆ | Hypertrophic cardiomyopathy 1 |
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
Variants in the MYH7 gene are associated with several inherited conditions, primarily affecting cardiac and skeletal muscle. These include Hypertrophic cardiomyopathy, a common cardiac condition characterised by thickening of the heart muscle, and Familial dilated cardiomyopathy (all), where the heart's pumping chambers become enlarged and weakened. Other conditions linked to MYH7 variants are Left ventricular non-compaction (familial), a rare disorder affecting the heart muscle structure, and various myopathies impacting skeletal muscle function, such as Laing distal myopathy and myosin storage myopathy.
Inheritance pattern
Conditions caused by pathogenic MYH7 variants typically follow autosomal dominant inheritance.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
UK clinical status
In the UK, the MYH7 gene is recognised within the NHS Genomic Medicine Service due to its association with several inherited conditions. It is included on multiple R-number panels for diagnostic testing, indicating its clinical significance. These panels encompass a range of cardiac and muscular disorders, such as Congenital myopathy, Dilated and arrhythmogenic cardiomyopathy, Hypertrophic cardiomyopathy, and Left Ventricular Noncompaction Cardiomyopathy. MYH7 is also relevant for Foetal anomalies and Paediatric disorders, reflecting its broad impact on muscle development and function from an early age.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Diet & lifestyle considerations
While genetic predispositions like those associated with MYH7 variants are not directly modifiable through lifestyle, adopting a healthy lifestyle can generally support overall cardiovascular health and muscle function. For individuals with MYH7-related conditions, lifestyle recommendations are often tailored to manage symptoms and reduce the risk of complications. For example, maintaining a balanced diet, engaging in regular, appropriate physical activity, and avoiding excessive alcohol consumption are general recommendations that may support heart health. However, specific exercise limitations or dietary adjustments should always be discussed with a healthcare professional, as recommendations can vary significantly based on the individual's condition severity and specific diagnosis. Research suggests that a heart-healthy lifestyle, including managing blood pressure and cholesterol, may contribute to better outcomes for individuals with certain cardiac conditions, but it does not prevent the genetic condition itself.
Supplement considerations
For individuals with MYH7-related conditions, there is no conclusive scientific evidence that specific dietary supplements can prevent, treat, or cure these inherited disorders. While some supplements, such as Coenzyme Q10 or L-carnitine, are sometimes discussed in the context of muscle and heart health, their efficacy in treating MYH7-associated conditions specifically has not been definitively established through rigorous clinical trials. Any decision to take supplements should be carefully considered and discussed with a healthcare professional, especially given potential interactions with prescribed medications or underlying health conditions. It is important to rely on evidence-based treatments and medical advice rather than unproven remedies.
Frequently asked questions
What is the primary function of the MYH7 gene?
The MYH7 gene provides instructions for making myosin heavy chain-7, a protein vital for muscle contraction in both cardiac and specific skeletal muscles. It generates the mechanical force needed for muscles to contract by forming thick filaments within sarcomeres.
What conditions are associated with variants in the MYH7 gene?
Variants in the MYH7 gene are linked to several inherited conditions, including Hypertrophic cardiomyopathy, Familial dilated cardiomyopathy, Left ventricular non-compaction, Laing distal myopathy, and myosin storage myopathy.
How are MYH7-related conditions typically inherited?
MYH7-related conditions are generally inherited in an autosomal dominant pattern. This means that an individual needs to inherit only one altered copy of the MYH7 gene from a parent to be affected by the condition.
Is the MYH7 gene part of NHS genetic testing in the UK?
Yes, the MYH7 gene is included in several NHS Genomic Medicine Service R-number panels for diagnostic testing in the UK, covering various cardiac and muscular disorders like hypertrophic cardiomyopathy and congenital myopathy.
Can lifestyle changes prevent MYH7-related conditions?
While lifestyle changes cannot prevent genetically determined MYH7-related conditions, a healthy lifestyle can generally support cardiovascular health and muscle function. Any specific dietary or exercise recommendations should be discussed with a healthcare professional.
Are there specific supplements recommended for MYH7-related conditions?
There is no conclusive scientific evidence that specific dietary supplements can prevent or treat MYH7-related conditions. It is crucial to consult with a healthcare professional before taking any supplements, as they may interact with medications or not be beneficial.
References
- Dong X, Fan P, Tian T. Recent advancements in the molecular genetics of left ventricular noncompaction cardiomyopathy. Clinica chimica acta; international journal of clinical chemistry. 2017. PMID: 27989498
- Finsterer J, Stöllberger C, Towbin JA. Left ventricular noncompaction cardiomyopathy: cardiac, neuromuscular, and genetic factors. Nature reviews. Cardiology. 2017. PMID: 28079110
- Meredith C, Herrmann R, Parry C. Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onset distal myopathy (MPD1). American journal of human genetics. 2004. PMID: 15322983
- Van Driest SL, Jaeger MA, Ommen SR. Comprehensive analysis of the beta-myosin heavy chain gene in 389 unrelated patients with hypertrophic cardiomyopathy. Journal of the American College of Cardiology. 2004. PMID: 15358028
- Tajsharghi H, Thornell LE, Lindberg C. Myosin storage myopathy associated with a heterozygous missense mutation in MYH7. Annals of neurology. 2003. PMID: 14520662