MYL3

myosin light chain 3, the group of Myosin light chains, class 1

Basic information

Region (hg38): 3:46835110-46882178

Links

ENSG00000160808

∙ NCBI:4634 ∙ OMIM:160790 ∙ HGNC:7584 ∙ Uniprot:P08590 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hypertrophic cardiomyopathy 8 (Strong), mode of inheritance: AD
hypertrophic cardiomyopathy 8 (Definitive), mode of inheritance: AD
dilated cardiomyopathy (Disputed Evidence), mode of inheritance: AD
arrhythmogenic right ventricular cardiomyopathy (Limited), mode of inheritance: AD
hypertrophic cardiomyopathy (Definitive), mode of inheritance: AD
hypertrophic cardiomyopathy 8 (Strong), mode of inheritance: AD
hypertrophic cardiomyopathy 8 (Strong), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial hypertrophic, 8	AD/AR	Cardiovascular	Early recognition may allow preventive measures and early medical management, which may ameliorate severe sequelae	Cardiovascular	6211078; 8673105; 12021217; 16267253; 21239446; 21896538

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYL3 gene.

Hypertrophic_cardiomyopathy (351 variants)
Cardiomyopathy (144 variants)
Cardiovascular_phenotype (133 variants)
not_provided (102 variants)
not_specified (60 variants)
Hypertrophic_cardiomyopathy_8 (46 variants)
Primary_familial_hypertrophic_cardiomyopathy (13 variants)
MYL3-related_disorder (11 variants)
Dilated_cardiomyopathy_1U (2 variants)
Amyloidosis,_hereditary_systemic_1 (1 variants)
Restrictive_cardiomyopathy (1 variants)
Long_QT_syndrome (1 variants)
Increased_left_ventricular_wall_thickness (1 variants)
Hypertrophic_cardiomyopathy_1 (1 variants)
Cardiomyopathy,_familial_restrictive,_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYL3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000258.3. 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			4 clinvar	81 clinvar	4 clinvar	89
missense	1 clinvar	15 clinvar	220 clinvar	6 clinvar		242
nonsense			2 clinvar			2
start loss		1	3			4
frameshift		2 clinvar	16 clinvar			18
splice donor/acceptor (+/-2bp)		1 clinvar	12 clinvar			13
Total	1	19	257	87	4

Highest pathogenic variant AF is 0.000051427

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYL3	protein_coding	protein_coding	ENST00000395869	6	24298

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0879	0.875	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.756	92	115	0.801	0.00000699	1300
Missense in Polyphen		24	38.5	0.62337		460
Synonymous	-0.959	51	43.0	1.19	0.00000269	364
Loss of Function	1.78	3	8.64	0.347	3.77e-7	115

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000353	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Regulatory light chain of myosin. Does not bind calcium.;
Disease: DISEASE: Cardiomyopathy, familial hypertrophic 8 (CMH8) [MIM:608751]: 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:12021217, ECO:0000269|PubMed:12707239, ECO:0000269|PubMed:23594557, ECO:0000269|PubMed:8673105}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Cardiac muscle contraction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Intracellular Signalling Through Prostacyclin Receptor and Prostacyclin;Striated Muscle Contraction;Regulation of Actin Cytoskeleton;Striated Muscle Contraction;Muscle contraction (Consensus)

Recessive Scores

pRec: 0.227

Intolerance Scores

loftool: 0.218
rvis_EVS: -0.38
rvis_percentile_EVS: 27.42

Haploinsufficiency Scores

pHI: 0.0778
hipred: Y
hipred_score: 0.875
ghis: 0.537

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.830

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Myl3
Phenotype

Gene ontology

Biological process: regulation of the force of heart contraction;regulation of striated muscle contraction;skeletal muscle tissue development;muscle filament sliding;positive regulation of ATPase activity;ventricular cardiac muscle tissue morphogenesis;cardiac muscle contraction
Cellular component: cytosol;muscle myosin complex;sarcomere;A band;I band
Molecular function: motor activity;actin monomer binding;calcium ion binding;structural constituent of muscle;myosin II heavy chain binding