MYL2
myosin light chain 2, the group of Myosin light chains, class 2
Basic information
Region (hg38): 12:110909996-111052434
Links
Phenotypes
GenCC
Source:
- hypertrophic cardiomyopathy 10 (Strong), mode of inheritance: AD
- congenital fiber-type disproportion myopathy (Supportive), mode of inheritance: AD
- hypertrophic cardiomyopathy 10 (Strong), mode of inheritance: AD
- myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy (Moderate), mode of inheritance: AR
- hypertrophic cardiomyopathy 10 (Definitive), mode of inheritance: AD
- hypertrophic cardiomyopathy 10 (Definitive), mode of inheritance: AD
- hypertrophic cardiomyopathy (Definitive), mode of inheritance: AD
- dilated cardiomyopathy (Limited), mode of inheritance: AD
- arrhythmogenic right ventricular cardiomyopathy (No Known Disease Relationship), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cardiomyopathy, familial hypertrophic, 10 | AD | Cardiovascular | Medical/surgical (ICD) management may ameliorate/prevent severe sequelae | Cardiovascular; Musculoskeletal | 8673105; 9535554; 12404107; 21896538; 23365102 |
ClinVar
This is a list of variants' phenotypes submitted to
- Hypertrophic_cardiomyopathy_10 (396 variants)
- Cardiomyopathy (174 variants)
- Hypertrophic_cardiomyopathy (168 variants)
- Cardiovascular_phenotype (153 variants)
- not_provided (131 variants)
- not_specified (76 variants)
- Myopathy,_myofibrillar,_12,_infantile-onset,_with_cardiomyopathy (21 variants)
- MYL2-related_disorder (11 variants)
- Primary_familial_hypertrophic_cardiomyopathy (10 variants)
- Primary_dilated_cardiomyopathy (4 variants)
- Congenital_heart_disease (2 variants)
- Congenital_myopathy_with_fiber_type_disproportion (2 variants)
- Hypertrophic_cardiomyopathy_1 (2 variants)
- Premature_ventricular_contraction (1 variants)
- Congestive_heart_failure (1 variants)
- Familial_isolated_restrictive_cardiomyopathy (1 variants)
- Death_in_infancy (1 variants)
- Cardiomyopathy,_dilated,_and_heart_failure (1 variants)
- Death_in_early_adulthood (1 variants)
- Dilated_cardiomyopathy_1S (1 variants)
- Arrhythmogenic_right_ventricular_cardiomyopathy (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYL2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000432.4. 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 | 82 | 83 | ||||
| missense | 19 | 229 | 257 | |||
| nonsense | 10 | 12 | ||||
| start loss | 1 | 1 | 2 | |||
| frameshift | 26 | 31 | ||||
| splice donor/acceptor (+/-2bp) | 11 | 18 | ||||
| Total | 3 | 34 | 278 | 88 | 0 |
Highest pathogenic variant AF is 0.0000311304
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MYL2 | protein_coding | protein_coding | ENST00000228841 | 7 | 9904 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 2.73e-8 | 0.0899 | 125702 | 0 | 46 | 125748 | 0.000183 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.396 | 86 | 97.0 | 0.887 | 0.00000581 | 1123 |
| Missense in Polyphen | 27 | 29.855 | 0.90437 | 398 | ||
| Synonymous | -0.797 | 44 | 37.8 | 1.16 | 0.00000294 | 281 |
| Loss of Function | -0.315 | 11 | 9.93 | 1.11 | 5.17e-7 | 114 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000206 | 0.000206 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000218 | 0.000217 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.000249 | 0.000246 |
| Middle Eastern | 0.000218 | 0.000217 |
| South Asian | 0.000229 | 0.000229 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Contractile protein that plays a role in heart development and function (By similarity). Following phosphorylation, plays a role in cross-bridge cycling kinetics and cardiac muscle contraction by increasing myosin lever arm stiffness and promoting myosin head diffusion; as a consequence of the increase in maximum contraction force and calcium sensitivity of contraction force. These events altogether slow down myosin kinetics and prolong duty cycle resulting in accumulated myosins being cooperatively recruited to actin binding sites to sustain thin filament activation as a means to fine-tune myofilament calcium sensitivity to force (By similarity). During cardiogenesis plays an early role in cardiac contractility by promoting cardiac myofibril assembly (By similarity). {ECO:0000250|UniProtKB:P08733, ECO:0000250|UniProtKB:P51667}.;
- Disease
- DISEASE: Cardiomyopathy, familial hypertrophic 10 (CMH10) [MIM:608758]: 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. Rarely, patients present a variant of familial hypertrophic cardiomyopathy, characterized by mid-left ventricular chamber thickening. {ECO:0000269|PubMed:11102452, ECO:0000269|PubMed:12404107, ECO:0000269|PubMed:12707239, ECO:0000269|PubMed:12818575, ECO:0000269|PubMed:8673105, ECO:0000269|PubMed:9535554}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Focal adhesion - Homo sapiens (human);Cardiac muscle contraction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Tight junction - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Cardiac Progenitor Differentiation;Myometrial Relaxation and Contraction Pathways;Focal Adhesion;Striated Muscle Contraction;VEGFA-VEGFR2 Signaling Pathway;ccr3 signaling in eosinophils;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;alk in cardiac myocytes;rho cell motility signaling pathway;nfat and hypertrophy of the heart ;rac1 cell motility signaling pathway;Striated Muscle Contraction;Muscle contraction;Stabilization and expansion of the E-cadherin adherens junction;PAR4-mediated thrombin signaling events;PAR1-mediated thrombin signaling events;CDC42 signaling events;N-cadherin signaling events;RhoA signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.273
Intolerance Scores
- loftool
- 0.606
- rvis_EVS
- -0.27
- rvis_percentile_EVS
- 33.97
Haploinsufficiency Scores
- pHI
- 0.249
- hipred
- Y
- hipred_score
- 0.573
- ghis
- 0.556
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.809
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Myl2
- Phenotype
- pigmentation 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); hematopoietic system phenotype; normal phenotype; 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); liver/biliary system phenotype; respiratory system phenotype; embryo phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- myl2b
- Affected structure
- heart
- Phenotype tag
- abnormal
- Phenotype quality
- increased size
Gene ontology
- Biological process
- regulation of the force of heart contraction;regulation of striated muscle contraction;heart development;post-embryonic development;muscle filament sliding;negative regulation of cell growth;muscle cell fate specification;muscle fiber development;cardiac myofibril assembly;ventricular cardiac muscle tissue morphogenesis;heart contraction;cardiac muscle contraction;positive regulation of the force of heart contraction
- Cellular component
- cytosol;cytoskeleton;actin cytoskeleton;myosin complex;myofibril;sarcomere;A band;cardiac myofibril
- Molecular function
- actin monomer binding;calcium ion binding;protein binding;structural constituent of muscle;myosin heavy chain binding