MYL4

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

Basic information

Region (hg38): 17:47200445-47223679

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 (164 variants)
• not provided (26 variants)
• Inborn genetic diseases (8 variants)
• MYL4-related condition (2 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.

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				28		28
missense	1		81	1	1	84
nonsense	2		1			3
start loss						0
frameshift	1					1
inframe indel			6			6
splice donor/acceptor (+/-2bp)		6	1			7
splice region			5	8	3	16
non coding			1	20	17	38
Total	4	6	90	49	18

Highest pathogenic variant AF is 0.0000197

Variants in MYL4

This is a list of pathogenic ClinVar variants found in the MYL4 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-47209428-T-C		Atrial fibrillation, familial, 18	Likely benign (Sep 03, 2022)
17-47209433-A-G		Atrial fibrillation, familial, 18	Uncertain significance (Feb 03, 2022)
17-47209436-A-G		Atrial fibrillation, familial, 18	Uncertain significance (Aug 03, 2021)
17-47209441-G-A		Atrial fibrillation, familial, 18	Uncertain significance (Mar 27, 2022)
17-47209444-C-G		Atrial fibrillation, familial, 18 • not specified	Uncertain significance (Dec 08, 2023)
17-47209445-C-T		Atrial fibrillation, familial, 18	Uncertain significance (Aug 06, 2017)
17-47209447-A-G		not specified	Uncertain significance (Aug 29, 2023)
17-47209452-G-C		Atrial fibrillation, familial, 18	Uncertain significance (Dec 27, 2022)
17-47209453-G-A		Familial atrial fibrillation • Atrial fibrillation, familial, 18	Pathogenic (Sep 07, 2022)
17-47209460-C-T		Atrial fibrillation, familial, 18	Uncertain significance (Jul 16, 2023)
17-47209464-GCCAGCT-G		Atrial fibrillation, familial, 18	Uncertain significance (Nov 15, 2023)
17-47209464-GCCAGCTCCAGCT-G		Atrial fibrillation, familial, 18	Uncertain significance (May 27, 2022)
17-47209464-G-GCCAGCT		Atrial fibrillation, familial, 18	Uncertain significance (Dec 13, 2023)
17-47209479-A-G		Atrial fibrillation, familial, 18	Likely benign (May 21, 2023)
17-47209479-AGCTCCAGCCCCT-A		Atrial fibrillation, familial, 18	Uncertain significance (Apr 30, 2023)
17-47209488-C-T		Atrial fibrillation, familial, 18	Likely benign (Dec 05, 2023)
17-47209490-C-T		Atrial fibrillation, familial, 18	Uncertain significance (Oct 07, 2020)
17-47209492-G-T		Atrial fibrillation, familial, 18	Uncertain significance (Oct 15, 2023)
17-47209494-A-C		Atrial fibrillation, familial, 18	Likely benign (Jul 12, 2022)
17-47209494-A-G		Atrial fibrillation, familial, 18	Likely benign (Dec 11, 2023)
17-47209494-A-ACCAGCCCCTGCC		Atrial fibrillation, familial, 18	Uncertain significance (May 03, 2022)
17-47209504-G-A		Atrial fibrillation, familial, 18	Uncertain significance (Apr 02, 2022)
17-47209521-T-TCCC		Atrial fibrillation, familial, 18	Uncertain significance (Oct 28, 2023)
17-47209524-C-T		Atrial fibrillation, familial, 18	Likely benign (Jul 22, 2022)
17-47209525-A-G		Atrial fibrillation, familial, 18	Uncertain significance (May 21, 2022)

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