MYL4

protein-coding

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

Gene summary

Myosin is a hexameric ATPase cellular motor protein. It is composed of two myosin heavy chains, two nonphosphorylatable myosin alkali light chains, and two phosphorylatable myosin regulatory light chains. This gene encodes a myosin alkali light chain that is found in embryonic muscle and adult atria. Two alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002476.2

Inheritance

ClinVar variants

P:16U:147B:57

Top phenotype

Atrial fibrillation, familial, 18

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr17:47,200,446-47,223,679

External References & Databases

Ensembl (ENSG00000198336)

Transcript & Mutation Effects

hg38 • Region Span ~23.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

atrial fibrillation, familial, 18STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0015001

Submitter: Labcorp Genetics (formerly Invitae)

familial atrial fibrillationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018054

Submitter: Orphanet

Clinical Genomic Database (CGD)

Atrial fibrillation, familial, 18AD

Manifestation: Cardiovascular

Intervention: Cardiovascular

Rationale: 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

Comments: Although only affected adults have been described, earlier surveillance is anticipated to reveal sequelae in children with variants

Refs: 25807286; 27066836

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYL4 variants in ClinVar

5 Conditions Cataloged

Atrial fibrillation, familial, 18Total: 268

not specifiedTotal: 54

not providedTotal: 38

MYL4-related disorderTotal: 13

Familial atrial fibrillationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002476.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	53 clinvar		54
missense	1 clinvar		141 clinvar	4 clinvar		146
nonsense	2 clinvar	1 clinvar	1 clinvar			4
start loss						0
frameshift	2 clinvar	1 clinvar				3
splice donor/acceptor (+/-2bp)		9 clinvar	4 clinvar			13
Total	5	11	147	57	0	220

Highest pathogenic variant AF is 0.000013136117

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 84 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002476.2	RefSeq	NP_002467.1	6	MANE Select
ENST00000393450.5	Ensembl	ENSP00000377096.1	6	MANE Select
NM_001002841.2	RefSeq	NP_001002841.1	6	Standard
ENST00000354968.5	Ensembl	ENSP00000347055.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

regulation of the force of heart contraction
muscle filament sliding
positive regulation of ATPase activity
cardiac muscle contraction

Molecular Function

actin monomer binding
calcium ion binding
myosin II heavy chain binding
actin filament binding

Cellular Component

cytosol
myosin complex
A band

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354968
Coding exons: 6
Length: 23234
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125745
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.377	109	121	0.903	0.00000694	1291
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.232

Intolerance Scores

LoFtool: 0.273
RVIS EVS: 0.04
RVIS percentile EVS: 56.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.283

Gene Damage Prediction

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