MYL3

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

Basic information

Region (hg38): 3:46835110-46882172

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 (227 variants)
• Cardiomyopathy (135 variants)
• not provided (89 variants)
• Cardiovascular phenotype (83 variants)
• not specified (61 variants)
• Hypertrophic cardiomyopathy 8 (45 variants)
• Primary familial hypertrophic cardiomyopathy (13 variants)
• Inborn genetic diseases (2 variants)
• MYL3-related condition (2 variants)
• Restrictive cardiomyopathy;Hypertrophic cardiomyopathy (1 variants)
• Hypertrophic cardiomyopathy 1 (1 variants)
• Cardiomyopathy, familial restrictive, 1 (1 variants)
• Increased left ventricular wall thickness (1 variants)
• Long QT syndrome (1 variants)
• Amyloidogenic transthyretin amyloidosis (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.

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			1	57	2	60
missense	1	2	154	1		158
nonsense			1			1
start loss			3			3
frameshift			5			5
inframe indel			1			1
splice donor/acceptor (+/-2bp)			8			8
splice region			11	9		20
non coding		1	8	30	13	52
Total	1	3	181	88	15

Variants in MYL3

This is a list of pathogenic ClinVar variants found in the MYL3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-46857910-G-T		Hypertrophic cardiomyopathy	Uncertain significance (Jun 14, 2016)
3-46857975-G-A		Hypertrophic cardiomyopathy 8	Uncertain significance (Jan 13, 2018)
3-46858003-G-T		Hypertrophic cardiomyopathy 8	Uncertain significance (Aug 09, 2021)
3-46858026-C-T		Hypertrophic cardiomyopathy 8	Benign (Jun 26, 2018)
3-46858088-C-T		not specified	Likely benign (May 24, 2016)
3-46858191-C-A			Benign (Mar 03, 2015)
3-46858226-C-G		Hypertrophic cardiomyopathy 8 • not specified • Cardiomyopathy	Likely benign (Aug 28, 2019)
3-46858231-C-T		Hypertrophic cardiomyopathy 8	Uncertain significance (Aug 20, 2021)
3-46858235-G-A		not specified • MYL3-related disorder	Benign/Likely benign (Aug 20, 2020)
3-46858238-C-T		Cardiomyopathy	Uncertain significance (Apr 25, 2023)
3-46858239-G-A		not specified • Hypertrophic cardiomyopathy 8 • Cardiomyopathy	Conflicting classifications of pathogenicity (Nov 20, 2019)
3-46858241-G-A		Cardiomyopathy • Hypertrophic cardiomyopathy	Benign (Nov 02, 2023)
3-46858243-T-G		Hypertrophic cardiomyopathy	Uncertain significance (Apr 10, 2023)
3-46858250-G-A		Cardiomyopathy	Likely benign (Mar 09, 2020)
3-46858252-AC-A		Hypertrophic cardiomyopathy	Uncertain significance (Mar 01, 2022)
3-46858253-C-T		Hypertrophic cardiomyopathy	Uncertain significance (Jul 03, 2019)
3-46858255-T-C		Cardiomyopathy • Hypertrophic cardiomyopathy	Uncertain significance (Dec 13, 2023)
3-46858256-G-GA		Hypertrophic cardiomyopathy • Cardiovascular phenotype	Uncertain significance (Feb 26, 2021)
3-46858257-A-T		Hypertrophic cardiomyopathy	Uncertain significance (Mar 03, 2022)
3-46858260-T-C		Hypertrophic cardiomyopathy	Uncertain significance (Dec 01, 2023)
3-46858260-T-G		Hypertrophic cardiomyopathy	Uncertain significance (Nov 18, 2023)
3-46858261-G-C		Primary familial hypertrophic cardiomyopathy	Uncertain significance (Sep 01, 2015)
3-46858264-T-C		Hypertrophic cardiomyopathy	Uncertain significance (Oct 23, 2023)
3-46858265-C-T		Cardiomyopathy	Likely benign (Dec 02, 2019)
3-46858265-C-CACAA		Hypertrophic cardiomyopathy	Uncertain significance (Dec 23, 2022)

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

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