MYBPC3
myosin binding protein C3, the group of I-set domain containing|Myosin binding proteins
Basic information
Region (hg38): 11:47331406-47352702
Previous symbols: [ "CMH4" ]
Links
Phenotypes
GenCC
Source:
- left ventricular noncompaction 10 (Definitive), mode of inheritance: AD
- hypertrophic cardiomyopathy 4 (Definitive), mode of inheritance: AD
- left ventricular noncompaction 10 (Moderate), mode of inheritance: AD
- familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
- hypertrophic cardiomyopathy 4 (Definitive), mode of inheritance: AD
- hypertrophic cardiomyopathy 4 (Strong), mode of inheritance: AD
- arrhythmogenic right ventricular cardiomyopathy (Limited), mode of inheritance: AD
- dilated cardiomyopathy (Limited), mode of inheritance: AD
- hypertrophic cardiomyopathy (Definitive), mode of inheritance: AD
- hypertrophic cardiomyopathy 4 (Strong), mode of inheritance: AR
- left ventricular noncompaction 10 (Limited), mode of inheritance: AR
- atrial fibrillation (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cardiomyopathy, familial hypertrophic, 4; Cardiomyopathy, dilated, 1MM; Left ventricular noncompaction 10 | AD/AR | Cardiovascular | Surveillance in order to allow early diagnosis and treatment of cardiomyopathy can be beneficial; Cardiac transplantation has been described | Cardiovascular | 7493026; 7493025; 9241277; 9562578; 10424815; 12788380; 15519027; 16199542; 16679492; 17655857; 17937428; 18337725; 19858127; 21839045; 22021246; 22314326; 22455086 |
ClinVar
This is a list of variants' phenotypes submitted to
- Hypertrophic_cardiomyopathy (3222 variants)
- Cardiovascular_phenotype (1462 variants)
- Cardiomyopathy (1441 variants)
- not_provided (1173 variants)
- Hypertrophic_cardiomyopathy_4 (634 variants)
- not_specified (534 variants)
- Left_ventricular_noncompaction_10 (325 variants)
- Primary_familial_hypertrophic_cardiomyopathy (153 variants)
- MYBPC3-related_disorder (121 variants)
- Primary_dilated_cardiomyopathy (30 variants)
- Left_ventricular_noncompaction_cardiomyopathy (26 variants)
- Hypertrophic_cardiomyopathy_1 (24 variants)
- Dilated_Cardiomyopathy,_Dominant (20 variants)
- Long_QT_syndrome (10 variants)
- See_cases (6 variants)
- Dilated_cardiomyopathy_1A (5 variants)
- Cardiomyopathy,_dilated,_1MM (4 variants)
- Left_ventricular_noncompaction (4 variants)
- Left_ventricular_noncompaction_1 (4 variants)
- Asymmetric_septal_hypertrophy (3 variants)
- Brugada_syndrome (3 variants)
- Wolff-Parkinson-White_pattern (3 variants)
- Premature_ventricular_contraction (2 variants)
- Paroxysmal_atrial_fibrillation (2 variants)
- Left_ventricular_hypertrophy (2 variants)
- Catecholaminergic_polymorphic_ventricular_tachycardia_1 (2 variants)
- Primary_familial_dilated_cardiomyopathy (2 variants)
- Mitochondrial_disease (2 variants)
- SUDDEN_INFANT_DEATH_SYNDROME (2 variants)
- Peripheral_neuropathy (1 variants)
- Concentric_hypertrophic_cardiomyopathy (1 variants)
- Dilated_cardiomyopathy_1I (1 variants)
- Inborn_genetic_diseases (1 variants)
- Noncompaction_cardiomyopathy (1 variants)
- Abnormality_of_the_cardiovascular_system (1 variants)
- MYBPC3-related_cardiomyopathies (1 variants)
- Cardiac_arrest (1 variants)
- Catecholaminergic_polymorphic_ventricular_tachycardia (1 variants)
- Heart_block (1 variants)
- Amyloidosis,_hereditary_systemic_1 (1 variants)
- Sudden_unexplained_death (1 variants)
- Intellectual_disability (1 variants)
- Dyspnea (1 variants)
- Prolonged_QT_interval (1 variants)
- Aganglionic_megacolon (1 variants)
- Arrhythmogenic_right_ventricular_cardiomyopathy (1 variants)
- hyprtrophic_cardiomyopathy (1 variants)
- Isolated_Noncompaction_of_the_Ventricular_Myocardium (1 variants)
- Heart_failure (1 variants)
- Tachycardia (1 variants)
- Arrhythmogenic_right_ventricular_dysplasia_1 (1 variants)
- Cardiomyopathy,_familial_hypertrophic,_4,_susceptibility_to (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYBPC3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000256.3. 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 | 36 | 660 | 14 | 715 | ||
| missense | 22 | 96 | 1583 | 97 | 1806 | |
| nonsense | 147 | 65 | 212 | |||
| start loss | 3 | 3 | ||||
| frameshift | 398 | 163 | 564 | |||
| splice donor/acceptor (+/-2bp) | 68 | 132 | 208 | |||
| Total | 638 | 461 | 1630 | 757 | 22 |
Highest pathogenic variant AF is 0.00014437114
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MYBPC3 | protein_coding | protein_coding | ENST00000545968 | 34 | 21297 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 8.01e-11 | 1.00 | 124677 | 0 | 79 | 124756 | 0.000317 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.45 | 679 | 794 | 0.855 | 0.0000538 | 8148 |
| Missense in Polyphen | 261 | 349.89 | 0.74595 | 3556 | ||
| Synonymous | -0.219 | 335 | 330 | 1.02 | 0.0000238 | 2519 |
| Loss of Function | 4.32 | 29 | 67.3 | 0.431 | 0.00000329 | 793 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000874 | 0.000827 |
| Ashkenazi Jewish | 0.0000997 | 0.0000994 |
| East Asian | 0.000414 | 0.000389 |
| Finnish | 0.000337 | 0.000278 |
| European (Non-Finnish) | 0.000264 | 0.000256 |
| Middle Eastern | 0.000414 | 0.000389 |
| South Asian | 0.000445 | 0.000392 |
| Other | 0.000334 | 0.000330 |
dbNSFP
Source:
- Function
- FUNCTION: Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role.;
- Disease
- DISEASE: Cardiomyopathy, familial hypertrophic 4 (CMH4) [MIM:115197]: 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:11499718, ECO:0000269|PubMed:11499719, ECO:0000269|PubMed:11815426, ECO:0000269|PubMed:12379228, ECO:0000269|PubMed:12628722, ECO:0000269|PubMed:12707239, ECO:0000269|PubMed:12818575, ECO:0000269|PubMed:12951062, ECO:0000269|PubMed:12974739, ECO:0000269|PubMed:14563344, ECO:0000269|PubMed:15114369, ECO:0000269|PubMed:15519027, ECO:0000269|PubMed:15563892, ECO:0000269|PubMed:16004897, ECO:0000269|PubMed:16199542, ECO:0000269|PubMed:18403758, ECO:0000269|PubMed:18929575, ECO:0000269|PubMed:18957093, ECO:0000269|PubMed:23840593, ECO:0000269|PubMed:28265379, ECO:0000269|PubMed:7744002, ECO:0000269|PubMed:9048664, ECO:0000269|PubMed:9541104, ECO:0000269|PubMed:9541115, ECO:0000269|PubMed:9562578}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated 1MM (CMD1MM) [MIM:615396]: 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:20215591}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=MYBPC3 mutations may be involved in restrictive cardiomyopathy (RCM), a rare non-ischemic myocardial disease. RCM is characterized by restrictive ventricular-filling physiology in the presence of normal or reduced diastolic and/or systolic volumes (of 1 or both ventricles), biatrial enlargement, and normal ventricular wall thickness. {ECO:0000269|PubMed:26163040}.; DISEASE: Left ventricular non-compaction 10 (LVNC10) [MIM:615396]: A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC10 is an autosomal dominant condition. {ECO:0000269|PubMed:21551322}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Dilated cardiomyopathy (DCM) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Striated Muscle Contraction;Striated Muscle Contraction;Muscle contraction
(Consensus)
Recessive Scores
- pRec
- 0.214
Intolerance Scores
- loftool
- 0.498
- rvis_EVS
- -0.53
- rvis_percentile_EVS
- 20.54
Haploinsufficiency Scores
- pHI
- 0.492
- hipred
- N
- hipred_score
- 0.492
- ghis
- 0.510
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.918
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mybpc3
- Phenotype
- homeostasis/metabolism phenotype; muscle 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- mybpc3
- Affected structure
- atrium
- Phenotype tag
- abnormal
- Phenotype quality
- increased size
Gene ontology
- Biological process
- heart morphogenesis;muscle contraction;regulation of striated muscle contraction;cell adhesion;muscle filament sliding;skeletal muscle thin filament assembly;skeletal muscle myosin thick filament assembly;positive regulation of ATPase activity;regulation of muscle filament sliding;sarcomere organization;cardiac muscle fiber development;cardiac myofibril assembly;cardiac muscle tissue morphogenesis;ventricular cardiac muscle tissue morphogenesis;cardiac muscle contraction;striated muscle myosin thick filament assembly
- Cellular component
- cytosol;striated muscle myosin thick filament;striated muscle thin filament;C zone;sarcomere;Z disc;M band;A band;cardiac myofibril
- Molecular function
- ATPase activator activity;protein binding;structural constituent of muscle;myosin binding;titin binding;myosin heavy chain binding;identical protein binding;metal ion binding;actin filament binding;muscle alpha-actinin binding