MYL4

myosin light chain 4, the group of Myosin light chains, class 1

Basic information

Region (hg38): 17:47200446-47223679

Links

ENSG00000198336

∙ NCBI:4635 ∙ OMIM:160770 ∙ HGNC:7585 ∙ Uniprot:P12829 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

familial atrial fibrillation (Supportive), mode of inheritance: AD
atrial fibrillation, familial, 18 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Atrial fibrillation, familial, 18	AD	Cardiovascular	The condition involves conduction disease with atrial fibrillation and reduced left atrial function, and early recognition may allow preventive measures and early medical and surgical management, which may ameliorate severe sequelae	Cardiovascular	25807286; 27066836
Although only affected adults have been described, earlier surveillance is anticipated to reveal sequelae in children with variants

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYL4 gene.

Atrial_fibrillation,_familial,_18 (231 variants)
not_specified (29 variants)
not_provided (26 variants)
MYL4-related_disorder (8 variants)
Familial_atrial_fibrillation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYL4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002476.2. 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			1 clinvar	45 clinvar		46
missense	1 clinvar		117 clinvar	2 clinvar	1 clinvar	121
nonsense	2 clinvar	1 clinvar	1 clinvar			4
start loss						0
frameshift	2 clinvar	1 clinvar	1 clinvar			4
splice donor/acceptor (+/-2bp)		8 clinvar	2 clinvar			10
Total	5	10	122	47	1

Highest pathogenic variant AF is 0.000013136117

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYL4	protein_coding	protein_coding	ENST00000354968	6	23234

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000120	0.632	125727	0	18	125745	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.377	109	121	0.903	0.00000694	1291
Missense in Polyphen		34	39.723	0.85593		427
Synonymous	1.04	38	47.1	0.807	0.00000280	388
Loss of Function	0.754	7	9.51	0.736	3.99e-7	125

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000291	0.0000291
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.0000795	0.0000791
Middle Eastern	0.000272	0.000272
South Asian	0.0000653	0.0000653
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Regulatory light chain of myosin. Does not bind calcium.;
Disease: DISEASE: Atrial fibrillation, familial, 18 (ATFB18) [MIM:617280]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:27066836}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Cardiac muscle contraction - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Myometrial Relaxation and Contraction Pathways;Striated Muscle Contraction;Striated Muscle Contraction;Muscle contraction (Consensus)

Recessive Scores

pRec: 0.232

Intolerance Scores

loftool: 0.273
rvis_EVS: 0.04
rvis_percentile_EVS: 56.92

Haploinsufficiency Scores

pHI: 0.896
hipred: Y
hipred_score: 0.507
ghis: 0.452

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.283

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Myl4
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype;

Gene ontology

Biological process: regulation of the force of heart contraction;muscle filament sliding;positive regulation of ATPase activity;cardiac muscle contraction
Cellular component: cytosol;myosin complex;A band
Molecular function: actin monomer binding;calcium ion binding;myosin II heavy chain binding;actin filament binding