MYH11

myosin heavy chain 11, the group of Myosin heavy chains, class II

Basic information

Region (hg38): 16:15703134-15857028

Links

ENSG00000133392 ∙ NCBI:4629 ∙ OMIM:160745 ∙ HGNC:7569 ∙ Uniprot:P35749 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• aortic aneurysm, familial thoracic 4 (Strong), mode of inheritance: AD
• megacystis-microcolon-intestinal hypoperistalsis syndrome (Supportive), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Supportive), mode of inheritance: AD
• megacystis-microcolon-intestinal hypoperistalsis syndrome 2 (Strong), mode of inheritance: AR
• aortic aneurysm, familial thoracic 4 (Strong), mode of inheritance: AD
• visceral myopathy 2 (Limited), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aortic aneurysm, familial thoracic 4; Visceral myopathy 2; Megacystis-microcolon-intestinal hypoperistalsis syndrome 2	AD/AR	Cardiovascular; Gastrointestinal; Renal	In Aortic aneurysm, familial thoracic 4, surveillance for aortic aneurysms and related anomalies (as well as PDA) can allow early detection and treatment, potentially decreasing morbidity and mortality; In Visceral myopathy 2, individuals have been described with a variety of gastrointestinal sequelae, some of which may benefit from medical and/or surgical interventions; Individuals with Megacystis-microcolon-intestinal hypoperistalsis syndrome may have anomalies such as intestinal and genitorenal anomalies, and awareness may allow prompt surgical and medical management	Cardiovascular; Gastrointestinal; Genitourinary; Renal	11249915; 14722581; 16444274; 17666408; 22415348; 22968129; 25407000; 29575632; 31389005; 31427716; 31944481

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYH11 gene.

• Familial thoracic aortic aneurysm and aortic dissection (1732 variants)
• Aortic aneurysm, familial thoracic 4 (1564 variants)
• not provided (782 variants)
• not specified (326 variants)
• Lissencephaly, Recessive (82 variants)
• Aortic aneurysm, familial thoracic 4;Visceral myopathy 2;Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 (77 variants)
• Lissencephaly 4 (72 variants)
• Cardiovascular phenotype (49 variants)
• Connective tissue disorder (44 variants)
• Inborn genetic diseases (35 variants)
• Visceral myopathy 2;Megacystis-microcolon-intestinal hypoperistalsis syndrome 2;Aortic aneurysm, familial thoracic 4 (33 variants)
• Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 (16 variants)
• MYH11-related condition (15 variants)
• Visceral myopathy 2 (13 variants)
• Familial aortopathy (9 variants)
• Isolated thoracic aortic aneurysm (7 variants)
• Megacystis-microcolon-intestinal hypoperistalsis syndrome 2;Visceral myopathy 2;Aortic aneurysm, familial thoracic 4 (6 variants)
• Visceral myopathy 2;Aortic aneurysm, familial thoracic 4;Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 (5 variants)
• Megacystis-microcolon-intestinal hypoperistalsis syndrome 2;Aortic aneurysm, familial thoracic 4;Visceral myopathy 2 (5 variants)
• Congenital aneurysm of ascending aorta (5 variants)
• Aortic aneurysm, familial thoracic 4;Megacystis-microcolon-intestinal hypoperistalsis syndrome 2;Visceral myopathy 2 (4 variants)
• Stroke disorder (3 variants)
• Marfan syndrome (2 variants)
• Aortic aneurysm, familial thoracic 6 (2 variants)
• Pulmonic stenosis (1 variants)
• Aortic aneurysm, familial thoracic 4;Congenital aneurysm of ascending aorta (1 variants)
• Altered myosin contractile function (1 variants)
• Chronic intestinal pseudoobstruction (1 variants)
• Aortic aneurysm (1 variants)
• See cases (1 variants)
• Ehlers-Danlos syndrome, classic type (1 variants)
• Megacystis-microcolon-intestinal hypoperistalsis syndrome 2;Familial thoracic aortic aneurysm and aortic dissection (1 variants)
• Aortic aneurysm, familial thoracic 4;Visceral myopathy 2 (1 variants)
• Aortic dilatation (1 variants)
• Abnormality of connective tissue (1 variants)
• Mitral regurgitation;Abnormal left ventricle morphology;Tricuspid regurgitation;Myopia;Aortic root aneurysm (1 variants)
• Loeys-Dietz syndrome (1 variants)
• Small cervical vertebral bodies (1 variants)
• Bicuspid aortic valve (1 variants)
• Wolff-Parkinson-White pattern (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYH11 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	691	8	705
missense		3	1129	23	2	1157
nonsense	9	7	11			27
start loss						0
frameshift	9	1	12	1		23
inframe indel			27			27
splice donor/acceptor (+/-2bp)	4	16	6			26
splice region			49	98	3	150
non coding			91	285	116	492
Total	22	27	1282	1000	126

Highest pathogenic variant AF is 0.00000658

Variants in MYH11

This is a list of pathogenic ClinVar variants found in the MYH11 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-15703187-G-A		Lissencephaly, Recessive • Familial thoracic aortic aneurysm and aortic dissection • Aortic aneurysm, familial thoracic 4	Uncertain significance (Jan 12, 2018)
16-15703227-C-T		Familial thoracic aortic aneurysm and aortic dissection • Lissencephaly, Recessive • Aortic aneurysm, familial thoracic 4	Uncertain significance (Jan 13, 2018)
16-15703279-GTC-G		Lissencephaly, Recessive	Uncertain significance (Jun 14, 2016)
16-15703329-C-A		Familial thoracic aortic aneurysm and aortic dissection • Lissencephaly, Recessive • Aortic aneurysm, familial thoracic 4	Uncertain significance (Jan 13, 2018)
16-15703350-G-T		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Jun 14, 2016)
16-15703360-G-A		Aortic aneurysm, familial thoracic 4	Likely benign (Jan 13, 2018)
16-15703381-C-T		Aortic aneurysm, familial thoracic 4	Likely benign (Jan 13, 2018)
16-15703382-G-A		Aortic aneurysm, familial thoracic 4	Uncertain significance (Apr 27, 2017)
16-15703384-C-T		Aortic aneurysm, familial thoracic 4	Uncertain significance (Jan 12, 2018)
16-15703391-C-A		Lissencephaly, Recessive • Aortic aneurysm, familial thoracic 4	Uncertain significance (Jan 12, 2018)
16-15703414-T-C		Lissencephaly, Recessive • Familial thoracic aortic aneurysm and aortic dissection • Aortic aneurysm, familial thoracic 4	Uncertain significance (Jan 13, 2018)
16-15703447-C-T		Familial thoracic aortic aneurysm and aortic dissection • Lissencephaly 4 • Aortic aneurysm, familial thoracic 4	Benign/Likely benign (Jan 13, 2018)
16-15703472-A-G		Familial thoracic aortic aneurysm and aortic dissection • Lissencephaly, Recessive • Aortic aneurysm, familial thoracic 4	Uncertain significance (Jan 13, 2018)
16-15703511-CTG-C		Familial thoracic aortic aneurysm and aortic dissection • Lissencephaly, Recessive	Uncertain significance (Jun 14, 2016)
16-15703553-A-G		Aortic aneurysm, familial thoracic 4	Uncertain significance (Jan 13, 2018)
16-15703571-G-C		Lissencephaly 4 • Familial thoracic aortic aneurysm and aortic dissection • Aortic aneurysm, familial thoracic 4	Benign/Likely benign (Jan 12, 2018)
16-15703602-G-C		Familial thoracic aortic aneurysm and aortic dissection • Lissencephaly, Recessive • Aortic aneurysm, familial thoracic 4	Uncertain significance (Jan 12, 2018)
16-15703617-G-C		Aortic aneurysm, familial thoracic 4	Uncertain significance (Jan 13, 2018)
16-15703687-G-A		Aortic aneurysm, familial thoracic 4	Uncertain significance (Jan 13, 2018)
16-15703763-A-G		Familial thoracic aortic aneurysm and aortic dissection • Lissencephaly, Recessive • Aortic aneurysm, familial thoracic 4	Uncertain significance (Jan 13, 2018)
16-15703925-GTTTTT-G		Lissencephaly, Recessive • Familial thoracic aortic aneurysm and aortic dissection	Benign/Likely benign (Jun 01, 2023)
16-15703925-G-GT			Benign (Aug 11, 2019)
16-15703930-T-G		Aortic aneurysm, familial thoracic 4	Uncertain significance (Jan 13, 2018)
16-15703954-G-T		Aortic aneurysm, familial thoracic 4	Likely benign (Nov 22, 2019)
16-15703972-C-T		not specified	Likely benign (Oct 12, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYH11	protein_coding	protein_coding	ENST00000396324	41	153862

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.773	0.227	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.44	985	1.12e+3	0.879	0.0000776	13102
Missense in Polyphen		343	494.75	0.69328		5974
Synonymous	-2.89	559	479	1.17	0.0000359	3639
Loss of Function	7.63	24	111	0.217	0.00000625	1275

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000274	0.000271
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000111	0.000109
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.000167	0.000167
Middle Eastern	0.000111	0.000109
South Asian	0.000558	0.000555
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Muscle contraction.
• Disease: DISEASE: Note=A chromosomal aberration involving MYH11 is found in acute myeloid leukemia of M4EO subtype. Pericentric inversion inv(16)(p13;q22). The inversion produces a fusion protein consisting of the 165 N-terminal residues of CBF-beta (PEPB2) and the tail region of MYH11.; DISEASE: Aortic aneurysm, familial thoracic 4 (AAT4) [MIM:132900]: A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. {ECO:0000269|PubMed:16444274}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tight junction - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Developmental Biology;Smooth Muscle Contraction;Signal Transduction;EPH-Ephrin signaling;EPHA-mediated growth cone collapse;RHO GTPases Activate ROCKs;RHO GTPases activate PAKs;RHO GTPases activate PKNs;RHO GTPases activate CIT;Muscle contraction;RHO GTPase Effectors;Signaling by Rho GTPases;Sema4D induced cell migration and growth-cone collapse;Sema4D in semaphorin signaling;Semaphorin interactions;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.400

Intolerance Scores

• loftool: 0.00613
• rvis_EVS: -3.1
• rvis_percentile_EVS: 0.47

Haploinsufficiency Scores

• pHI: 0.809
• hipred: Y
• hipred_score: 0.747
• ghis: 0.573

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.694

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Myh11
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; digestive/alimentary phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; renal/urinary system phenotype

Zebrafish Information Network

• Gene name: myh11a
• Affected structure: intestinal epithelial cell
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: muscle contraction;smooth muscle contraction;skeletal muscle myosin thick filament assembly;elastic fiber assembly;cardiac muscle fiber development
• Cellular component: cytosol;muscle myosin complex;myosin filament;melanosome;extracellular exosome
• Molecular function: motor activity;protein binding;calmodulin binding;ATP binding;structural constituent of muscle;actin filament binding