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MYBPC3
myosin binding protein C3
The MYBPC3 gene provides instructions for cardiac myosin-binding protein C, a key component in heart muscle cells that helps regulate cardiac contraction. MYBPC3 encodes cardiac myosin-binding protein C (MyBP-C), which is integral to the function of sarcomeres, the contractile units within heart muscle.
MYBPC3 is located on the short (p) arm of chromosome 11, at band 11p11.2. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 11 in the library →Overview
The MYBPC3 gene, or myosin binding protein C3, is vital for proper heart function. It contains the genetic blueprint for cardiac myosin-binding protein C (MyBP-C), a protein specifically found in the muscle cells of the heart. This protein is a fundamental part of the sarcomere, which is the basic functional unit responsible for muscle contraction within the heart.
MyBP-C assists in orchestrating the complex interactions between different protein filaments within the sarcomere. Its precise regulation of these interactions is essential for the heart's ability to contract rhythmically and efficiently, thereby pumping blood throughout the body. Abnormalities in the MYBPC3 gene are commonly linked to inherited cardiac disorders.
What the gene does
The MYBPC3 gene directs the synthesis of cardiac myosin-binding protein C (MyBP-C), a protein critical to the contractile machinery of heart muscle cells. MyBP-C localises within the sarcomere, the fundamental unit of muscle contraction, where it associates with the thick protein filaments. Its primary role involves modulating the interaction between these thick filaments and the thin protein filaments that slide past them during contraction.
MyBP-C is thought to regulate the speed of this filament sliding through a process involving the binding and release of phosphate groups, thus fine-tuning the force and rhythm of cardiac muscle contraction. Beyond its direct role in contraction kinetics, MyBP-C also contributes to the structural integrity of muscle cells. It acts as a scaffold, providing a platform for the organisation of other proteins essential for maintaining muscle architecture. This dual function in regulating contraction and supporting structural organisation underscores its importance in healthy cardiac performance.
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Chromosome location
The MYBPC3 gene is situated on chromosome 11, specifically at position 11p11.2. This location refers to the short (p) arm of chromosome 11, within region 1, band 1, sub-band 2. The precise chromosomal address helps in mapping the gene's position within the human genome.
Protein structure
The MYBPC3 gene encodes a protein of 1274 amino acids, characterised by a complex modular structure. It features a notable Disordered region spanning amino acids 107-153. This is followed by a series of immunoglobulin-like C2-type domains, which are commonly involved in protein-protein interactions. These include Ig-like C2-type 1 (amino acids 153-256), Ig-like C2-type 2 (amino acids 362-452), Ig-like C2-type 3 (amino acids 453-543), Ig-like C2-type 4 (amino acids 544-633), Ig-like C2-type 5 (amino acids 645-771), Ig-like C2-type 6 (amino acids 971-1065), and Ig-like C2-type 7 (amino acids 1181-1274).
Interspersed with these Ig-like domains are fibronectin type-III domains, which also mediate protein interactions and structural roles. These are Fibronectin type-III 1 (amino acids 774-870), Fibronectin type-III 2 (amino acids 872-967), and Fibronectin type-III 3 (amino acids 1068-1163). This intricate domain arrangement facilitates the protein's multiple roles in muscle contraction and cellular organisation.
Key variants
Genetic changes, known as variants, in the MYBPC3 gene can alter the protein's normal function or production. These alterations can range from small changes in a single DNA building block to larger deletions or duplications of genetic material. Pathogenic variants can disrupt the protein's ability to regulate heart muscle contraction or maintain the structural integrity of cardiac cells. Understanding the specific type and location of these variants is crucial for assessing their potential clinical impact.
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.1505G>A | p.Arg502Gln | Pathogenic | ★★★☆ | Hypertrophic cardiomyopathy 4 |
g.47332110del | - | Pathogenic/Likely pathogenic | ★★☆☆ | Cardiomyopathy |
g.47332705G>C | - | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
g.47333203dup | - | Pathogenic | ★★☆☆ | not provided |
g.47333236del | - | Pathogenic | ★★☆☆ | Hypertrophic cardiomyopathy 4 |
g.47333332dup | - | Pathogenic | ★★☆☆ | Hypertrophic cardiomyopathy |
g.47333668delinsTT | - | Pathogenic | ★★☆☆ | not provided |
c.1352-2A>G | - | Pathogenic/Likely pathogenic | ★★☆☆ | Cardiovascular phenotype |
c.1358del | p.Pro453fs | Pathogenic | ★★☆☆ | Hypertrophic cardiomyopathy |
c.1377dup | p.Glu461fs | Pathogenic | ★★☆☆ | Cardiovascular phenotype |
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 MYBPC3 gene are a significant cause of inherited heart conditions. The most common condition associated with MYBPC3 variants is Hypertrophic cardiomyopathy, an autosomal dominant disorder characterised by thickening of the heart muscle. In some cases, MYBPC3 variants have also been linked to Left ventricular non-compaction (familial).
Inheritance pattern
Conditions caused by pathogenic MYBPC3 variants typically follow autosomal dominant inheritance.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
UK clinical status
The MYBPC3 gene is recognised within the NHS Genomic Medicine Service due to its association with several cardiac conditions. It is listed on multiple 'green' panels in PanelApp, indicating strong evidence for its role in these disorders and that variants in this gene are considered clinically actionable for diagnostic purposes. These panels include Hypertrophic cardiomyopathy (R131), Dilated and arrhythmogenic cardiomyopathy (R132), Dilated Cardiomyopathy and conduction defects, Left Ventricular Noncompaction Cardiomyopathy, and Paediatric or syndromic cardiomyopathy (R135).
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Diet & lifestyle considerations
Research suggests that certain lifestyle choices may influence the severity and progression of inherited heart conditions. For individuals with MYBPC3-associated conditions, maintaining a heart-healthy lifestyle is often recommended. This generally includes engaging in regular, moderate physical activity as advised by a healthcare professional, adopting a balanced diet rich in fruits, vegetables, and whole grains, and limiting intake of saturated fats, sodium, and processed foods. Avoiding smoking and excessive alcohol consumption are also widely recommended for overall cardiovascular health. It is important for individuals to discuss specific lifestyle modifications with their doctor.
Supplement considerations
Currently, there is no conclusive scientific evidence to suggest that specific supplements can prevent or treat conditions associated with MYBPC3 gene variants. Any individual considering taking supplements should discuss this with their healthcare provider. This is especially important for those with pre-existing heart conditions, as some supplements may interact with medications or have adverse effects.
Frequently asked questions
What is the MYBPC3 gene?
The MYBPC3 gene provides instructions for making cardiac myosin-binding protein C (MyBP-C), a protein found in heart muscle cells. It is essential for regulating heart muscle contraction.
What conditions are associated with MYBPC3 variants?
Pathogenic variants in the MYBPC3 gene are most commonly associated with Hypertrophic cardiomyopathy, a condition characterised by thickening of the heart muscle. Some variants may also be linked to Left ventricular non-compaction (familial).
How is MYBPC3-related hypertrophic cardiomyopathy inherited?
MYBPC3-related hypertrophic cardiomyopathy is typically inherited in an autosomal dominant manner. This means that inheriting just one copy of the altered gene is sufficient to increase the risk of developing the condition.
Is MYBPC3 covered by NHS genetic testing?
Yes, the MYBPC3 gene is included in several 'green' panels within the NHS Genomic Medicine Service, such as those for Hypertrophic cardiomyopathy and Dilated cardiomyopathy, indicating its clinical relevance for diagnostic testing.
Can lifestyle changes help manage MYBPC3-related conditions?
While lifestyle changes cannot alter the genetic cause, maintaining a heart-healthy lifestyle, including regular exercise and a balanced diet, is generally recommended. Any specific changes should be discussed with a healthcare professional.
References
- Marston S, Copeland O, Gehmlich K. How do MYBPC3 mutations cause hypertrophic cardiomyopathy? Journal of muscle research and cell motility. 2012. PMID: 22057632
- Previs MJ, Beck Previs S, Gulick J. Molecular mechanics of cardiac myosin-binding protein C in native thick filaments. Science (New York, N.Y.). 2012. PMID: 22923435
- Marston SB. How do mutations in contractile proteins cause the primary familial cardiomyopathies? Journal of cardiovascular translational research. 2011. PMID: 21424860
- Waldmüller S, Erdmann J, Binner P. Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure. European journal of heart failure. 2011. PMID: 21750094
- Hershberger RE, Norton N, Morales A. Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy. Circulation. Cardiovascular genetics. 2010. PMID: 20215591
- Møller DV, Andersen PS, Hedley P. The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy. European journal of human genetics : EJHG. 2009. PMID: 19293840
- Rodríguez JE, McCudden CR, Willis MS. Familial hypertrophic cardiomyopathy: basic concepts and future molecular diagnostics. Clinical biochemistry. 2009. PMID: 19318019
- Keren A, Syrris P, McKenna WJ. Hypertrophic cardiomyopathy: the genetic determinants of clinical disease expression. Nature clinical practice. Cardiovascular medicine. 2008. PMID: 18227814
- Kulikovskaya I, McClellan GB, Levine R. Multiple forms of cardiac myosin-binding protein C exist and can regulate thick filament stability. The Journal of general physiology. 2007. PMID: 17470661
- Bashyam MD, Savithri GR, Kumar MS. Molecular genetics of familial hypertrophic cardiomyopathy (FHC). Journal of human genetics. 2003. PMID: 12601548