MYH6

myosin heavy chain 6, the group of Myosin heavy chains, class II|MicroRNA protein coding host genes

Basic information

Region (hg38): 14:23381982-23408273

Links

ENSG00000197616 ∙ NCBI:4624 ∙ OMIM:160710 ∙ HGNC:7576 ∙ Uniprot:P13533 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy 14 (Limited), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• Keppen-Lubinsky syndrome (Moderate), mode of inheritance: AD
• atrial septal defect 3 (Limited), mode of inheritance: AD
• hypertrophic cardiomyopathy 14 (Strong), mode of inheritance: AD
• hypertrophic cardiomyopathy (Limited), mode of inheritance: AD
• dilated cardiomyopathy (Limited), mode of inheritance: AD
• hypertrophic cardiomyopathy 14 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 1EE; Cardiomyopathy, familial hypertrophic 14; Atrial septal defect 3	AD	Cardiovascular	In Cardiomyopathy, permanent cardiac pacing is the only effective treatment for symptomatic/irreversible sinus node dysfunction; Sick sinus syndrome is the most common indication for permanent pacemaker implantation; In Atrial septal defect, individuals may require surgical and other interventions, and diagnosis may allow prompt management	Cardiovascular	11815426; 15998695; 15735645; 21378987; 22194935

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYH6 gene.

• Hypertrophic cardiomyopathy 14 (2 variants)
• Heart, malformation of (1 variants)
• Primary familial dilated cardiomyopathy (1 variants)
• Inborn genetic diseases (1 variants)
• Hypertrophic cardiomyopathy 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYH6 gene is commonly pathogenic or not. These statistics are base on transcript: . 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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	553	21	582
missense	2	3	1205	19	7	1236
nonsense		1	27			28
start loss						0
frameshift	2		45			47
splice donor/acceptor (+/-2bp)	1	2	37		1	41
Total	5	6	1322	572	29

Highest pathogenic variant AF is 0.00000656832

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYH6	protein_coding	protein_coding	ENST00000405093	37	26288

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.60e-32	0.708	125589	0	159	125748	0.000632

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.858	1040	1.12e+3	0.928	0.0000809	12829
Missense in Polyphen		438	475.06	0.92199		5314
Synonymous	-2.30	533	470	1.14	0.0000338	3618
Loss of Function	2.72	65	93.3	0.697	0.00000459	1176

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00237	0.00237
Ashkenazi Jewish	0.00120	0.00119
East Asian	0.00116	0.00109
Finnish	0.0000495	0.0000462
European (Non-Finnish)	0.000477	0.000475
Middle Eastern	0.00116	0.00109
South Asian	0.000589	0.000588
Other	0.00114	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Muscle contraction.
• Disease: DISEASE: Atrial septal defect 3 (ASD3) [MIM:614089]: A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. {ECO:0000269|PubMed:15735645}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial hypertrophic 14 (CMH14) [MIM:613251]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:11815426, ECO:0000269|PubMed:15998695}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated 1EE (CMD1EE) [MIM:613252]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:15998695}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Sick sinus syndrome 3 (SSS3) [MIM:614090]: The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. {ECO:0000269|PubMed:21378987}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. The lifetime risk of being diagnosed with sick sinus syndrome is higher for carriers of variant p.Arg721Trp than for non-carriers. {ECO:0000269|PubMed:21378987}.
• Pathway: Cardiac muscle contraction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Cardiac Progenitor Differentiation;Striated Muscle Contraction;Striated Muscle Contraction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.116

Intolerance Scores

• loftool: 0.0684
• rvis_EVS: -2.78
• rvis_percentile_EVS: 0.66

Haploinsufficiency Scores

• pHI: 0.846
• hipred: N
• hipred_score: 0.495
• ghis: 0.465

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.793

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myh6
• Phenotype: immune system 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; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: myh6
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• Biological process: in utero embryonic development;regulation of the force of heart contraction;regulation of heart rate;protein dephosphorylation;muscle contraction;striated muscle contraction;adult heart development;visceral muscle development;regulation of heart contraction;regulation of blood pressure;cardiac muscle hypertrophy in response to stress;muscle filament sliding;myofibril assembly;BMP signaling pathway;regulation of ATPase activity;sarcomere organization;ATP metabolic process;cardiac muscle fiber development;atrial cardiac muscle tissue morphogenesis;ventricular cardiac muscle tissue morphogenesis;cardiac muscle contraction;canonical Wnt signaling pathway;regulation of heart growth
• Cellular component: stress fiber;cytosol;muscle myosin complex;myosin complex;myofibril;sarcomere;Z disc;myosin filament
• Molecular function: microfilament motor activity;calmodulin binding;ATP binding;ATPase activity;myosin phosphatase activity;protein kinase binding;actin-dependent ATPase activity;actin filament binding