MYH11
myosin heavy chain 11, the group of Myosin heavy chains, class II
Basic information
Region (hg38): 16:15703135-15858438
Links
Phenotypes
GenCC
Source:
- 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
- visceral myopathy 2 (Limited), mode of inheritance: AR
- megacystis-microcolon-intestinal hypoperistalsis syndrome 2 (Limited), mode of inheritance: AR
Clinical Genomic Database
Source:
| 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
- Familial_thoracic_aortic_aneurysm_and_aortic_dissection (2583 variants)
- Aortic_aneurysm,_familial_thoracic_4 (2106 variants)
- not_provided (847 variants)
- not_specified (370 variants)
- Megacystis-microcolon-intestinal_hypoperistalsis_syndrome_2 (158 variants)
- Visceral_myopathy_2 (143 variants)
- MYH11-related_disorder (93 variants)
- Lissencephaly,_Recessive (56 variants)
- Lissencephaly_4 (54 variants)
- Connective_tissue_disorder (44 variants)
- Cardiovascular_phenotype (27 variants)
- Inborn_genetic_diseases (9 variants)
- Familial_aortopathy (7 variants)
- Isolated_thoracic_aortic_aneurysm (7 variants)
- Congenital_aneurysm_of_ascending_aorta (6 variants)
- See_cases (5 variants)
- Aortic_aneurysm,_familial_thoracic_6 (2 variants)
- Visceral_myopathy_1 (2 variants)
- Marfan_syndrome (2 variants)
- NDE1-related_disorder (2 variants)
- Myopia (1 variants)
- Mitral_regurgitation (1 variants)
- Megacystis,_microcolon,_hypoperistalsis_syndrome (1 variants)
- Aortic_dilatation (1 variants)
- Bicuspid_aortic_valve (1 variants)
- Altered_myosin_contractile_function (1 variants)
- Thoracic_aortic_aneurysm_or_dissection (1 variants)
- Loeys-Dietz_syndrome (1 variants)
- Wolff-Parkinson-White_pattern (1 variants)
- Aortic_aneurysm (1 variants)
- Abnormal_left_ventricle_morphology (1 variants)
- Pulmonic_stenosis (1 variants)
- Ehlers-Danlos_syndrome,_classic_type (1 variants)
- Aortic_root_aneurysm (1 variants)
- Esophageal_and_colonic_dysmotility (1 variants)
- Joint_hypermobility (1 variants)
- Tricuspid_regurgitation (1 variants)
- Chronic_intestinal_pseudoobstruction (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. These statistics are base on transcript: NM_000002474.3. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 17 | 957 | 17 | 991 | ||
| missense | 1685 | 81 | 10 | 1783 | ||
| nonsense | 12 | 13 | 20 | 45 | ||
| start loss | 1 | 1 | ||||
| frameshift | 15 | 22 | 43 | |||
| splice donor/acceptor (+/-2bp) | 24 | 13 | 41 | |||
| Total | 31 | 51 | 1757 | 1038 | 27 |
Highest pathogenic variant AF is 0.000034716195
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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