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MYH11
myosin heavy chain 11
MYH11 encodes smooth muscle myosin heavy chain 11, a contractile protein essential for the function of blood vessels and the gastrointestinal tract. The MYH11 gene provides instructions for producing smooth muscle myosin heavy chain 11, a core component of the contractile machinery in smooth muscle tissue.
MYH11 is located on the short (p) arm of chromosome 16, at band 16p13.11. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 16 in the library →Overview
MYH11 encodes the heavy chain component of smooth muscle myosin, a motor protein responsible for generating force in the involuntary muscles that line blood vessels and internal organs. This gene is located on chromosome 16 and produces a protein of 1,972 amino acids that assembles into functional contractile units within smooth muscle cells.
Pathogenic variants in MYH11 follow an autosomal dominant inheritance pattern, meaning a single altered copy can cause disease. The gene is included in the ACMG Secondary Findings list (version 3.2) as a Tier 1 actionable gene, reflecting the clinical importance of identifying carriers for vascular surveillance and early intervention. MYH11-related conditions primarily affect the aorta and gastrointestinal system, with thoracic aortic aneurysm and dissection representing the most common and potentially life-threatening manifestation.
What the gene does
The MYH11 protein assembles into six-subunit myosin complexes found throughout smooth muscle tissue. Within each complex, two MYH11-encoded heavy chains pair with four regulatory light chains produced by different genes. The heavy chain's architecture divides into a globular head and elongated tail, each serving distinct mechanical roles.
Located at the head, the motor domain binds actin filaments and catalyses ATP breakdown. This enzymatic activity powers cyclic conformational shifts that pull actin along myosin, creating sliding between thick and thin filaments to produce contractile force. Meanwhile, the tail facilitates multi-protein assembly by linking with neighbouring myosin molecules, building the thick filament scaffolds essential for organised contraction.
Smooth muscle tissue containing MYH11 operates without conscious control, regulating vessel diameter to manage blood pressure, propelling digestive contents through rhythmic peristalsis, and governing numerous other automatic physiological processes. Unlike skeletal muscle that responds to voluntary commands, vascular and gastrointestinal smooth muscle depends on MYH11-mediated contraction for continuous involuntary function.
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Chromosome location
MYH11 is located on the short arm of chromosome 16 at position 13.11 (16p13.11). This chromosomal region contains multiple genes involved in smooth muscle development and function. The precise genomic context contributes to the gene's regulation and expression patterns in different smooth muscle tissues throughout development and adult life.
Protein structure
The MYH11 protein exhibits a characteristic myosin architecture with distinct functional regions. The N-terminal region contains a Myosin N-terminal SH3-like domain (amino acids 31-81) followed immediately by the Myosin motor domain (amino acids 85-783), which houses the catalytic machinery for ATP hydrolysis and force generation. Within the motor domain lie two actin-binding regions (amino acids 661-683 and 762-776) that mediate the protein's interaction with thin filaments during the contractile cycle.
Downstream of the motor sits an IQ domain (amino acids 786-815) that serves as the binding site for regulatory light chains, which modulate myosin activity in response to calcium signalling. The extended tail region features a lengthy coiled coil structure (amino acids 844-1934) enabling dimerisation and thick filament assembly. Three disordered regions (amino acids 858-882, 1744-1800, and 1866-1972) provide flexibility for protein-protein interactions. The C-terminal region (amino acids 1935-1972) completes the tail structure and contributes to higher-order filament organisation.
Key variants
Pathogenic variants in MYH11 typically cluster in the motor domain and coiled-coil regions, where they disrupt either the contractile mechanism or filament assembly. Missense changes predominate, altering single amino acids in critical structural or functional positions. These variants interfere with smooth muscle contraction, compromising the mechanical properties of blood vessel walls and gastrointestinal muscle layers. The spectrum of MYH11 variants demonstrates variable expressivity, with some families showing primarily vascular manifestations whilst others present with gastrointestinal features.
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.1033+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 |
c.1669C>T | p.Gln557Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Aortic aneurysm, familial thoracic 4 |
c.4578+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.4578+1G>C | - | Pathogenic/Likely pathogenic | ★★☆☆ | Aortic aneurysm, familial thoracic 4 |
c.5083-1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
g.(?_15703971)_(15838272_?)del | - | Pathogenic | ★☆☆☆ | Aortic aneurysm, familial thoracic 4 |
g.(?_15703981)_(15838262_?)del | - | Pathogenic | ★☆☆☆ | Aortic aneurysm, familial thoracic 4 |
g.(?_15823235)_(15838272_?)del | - | Pathogenic | ★☆☆☆ | Aortic aneurysm, familial thoracic 4 |
c.1024G>T | p.Glu342Ter | Pathogenic | ★☆☆☆ | Aortic aneurysm, familial thoracic 4 |
c.1116del | p.Met372fs | Pathogenic | ★☆☆☆ | Aortic aneurysm, familial thoracic 4 |
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 MYH11 variants cause familial thoracic aortic aneurysm and dissection, a life-threatening vascular condition in which the wall of the aorta weakens and may tear. Affected individuals face risk of aortic enlargement (aneurysm) and potentially catastrophic splitting of the vessel wall layers (dissection), often occurring at younger ages than in the general population.
MYH11 variants also underlie intestinal pseudo-obstruction and megacystis-microcolon-intestinal hypoperistalsis syndrome, conditions characterised by impaired gastrointestinal motility. These disorders result from defective smooth muscle contraction in the intestinal wall, leading to symptoms that mimic mechanical bowel obstruction despite the absence of physical blockage. Additionally, chromosomal rearrangements involving MYH11 have been identified in core binding factor acute myeloid leukaemia, though these acquired somatic changes differ from the germline variants that cause inherited vascular and gastrointestinal disease.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic MYH11 variants typically follow autosomal dominant inheritance.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
UK clinical status
MYH11 appears on multiple NHS Genomic Medicine Service gene panels, reflecting its clinical relevance across different specialties. The gene holds green (high evidence) classification on the Thoracic aortic aneurysm or dissection panel and the Thoracic aortic aneurysm or dissection (GMS) panel (R125), supporting its use in diagnostic testing for individuals with suspected inherited aortopathy. It also features on the Fetal anomalies panel (R21) and multiple gastrointestinal panels, including Gastrointestinal neuromuscular disorders, Paediatric disorders - additional genes, and Paediatric pseudo-obstruction syndrome (R438), enabling prenatal and paediatric diagnosis of smooth muscle dysfunction.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does autosomal dominant inheritance mean for MYH11?
Autosomal dominant inheritance means that inheriting one altered copy of MYH11 from either parent is sufficient to increase disease risk. Each child of an affected parent has a 50% chance of inheriting the variant, though not all carriers develop symptoms at the same age or severity.
Why is MYH11 on the ACMG Secondary Findings list?
MYH11 appears on this list because identifying pathogenic variants enables potentially life-saving interventions such as imaging surveillance for aortic enlargement and timely surgical repair before dissection occurs. Early detection allows carriers to benefit from monitoring protocols that can prevent catastrophic vascular events.
Do all MYH11 variant carriers develop aortic aneurysm?
Not all carriers develop clinically significant aortic disease, as these variants show variable expressivity and age-related penetrance. Some individuals may have mild aortic enlargement detected only through imaging, whilst others develop aneurysms requiring intervention. Regular cardiovascular monitoring helps identify those who need treatment.
References
- Eghtedar A, Borthakur G, Ravandi F. Characteristics of translocation (16;16)(p13;q22) acute myeloid leukemia. American journal of hematology. 2012. PMID: 22228403
- Goyama S, Mulloy JC. Molecular pathogenesis of core binding factor leukemia: current knowledge and future prospects. International journal of hematology. 2011. PMID: 21537931
- Shigesada K, van de Sluis B, Liu PP. Mechanism of leukemogenesis by the inv(16) chimeric gene CBFB/PEBP2B-MHY11. Oncogene. 2004. PMID: 15156186
- Durst KL, Lutterbach B, Kummalue T. The inv(16) fusion protein associates with corepressors via a smooth muscle myosin heavy-chain domain. Molecular and cellular biology. 2003. PMID: 12509458