MYLK2

myosin light chain kinase 2, the group of Myosin light chain kinase family

Basic information

Region (hg38): 20:31819307-31834689

Links

ENSG00000101306 ∙ NCBI:85366 ∙ OMIM:606566 ∙ HGNC:16243 ∙ Uniprot:Q9H1R3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy 1 (Limited), mode of inheritance: AD
• hypertrophic cardiomyopathy 1 (Limited), mode of inheritance: AD
• hypertrophic cardiomyopathy (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, hypertrophic	AD/Digenic	Cardiovascular	Surveillance for cardiomyopathy (eg, with echocardiography/electrocardiography) and early medical treatment may reduce morbidity	Cardiovascular	11733062
Digenic inheritance (with MYH7) has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYLK2 gene.

• Hypertrophic cardiomyopathy 1 (394 variants)
• Inborn genetic diseases (181 variants)
• not provided (131 variants)
• not specified (94 variants)
• Cardiomyopathy (39 variants)
• Hypertrophic cardiomyopathy (6 variants)
• Cardiomyopathy, hypertrophic, midventricular, digenic (2 variants)
• MYLK2-related condition (2 variants)
• Fabry disease (1 variants)
• Ventricular tachycardia (1 variants)
• Sudden unexplained death (1 variants)
• See cases (1 variants)
• Primary familial hypertrophic cardiomyopathy (1 variants)
• Long QT syndrome;Cardiomyopathy;Ventricular tachycardia (1 variants)
• Stroke disorder (1 variants)
• Left ventricular noncompaction cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYLK2 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			4	150	3	157
missense			237	10		247
nonsense			3			3
start loss						0
frameshift			8			8
inframe indel			5			5
splice donor/acceptor (+/-2bp)			3			3
splice region			3	19	1	23
non coding			7	63	22	92
Total	0	0	267	223	25

Variants in MYLK2

This is a list of pathogenic ClinVar variants found in the MYLK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-31819317-AC-A			Likely benign (Dec 24, 2019)
20-31819410-T-C		not specified	Benign (Nov 22, 2013)
20-31819415-C-T		not specified	Likely benign (Dec 18, 2017)
20-31819568-G-A		not specified	Uncertain significance (Aug 16, 2012)
20-31819578-C-T		Cardiomyopathy	Uncertain significance (Mar 11, 2020)
20-31819584-G-A		not specified • Cardiomyopathy;Long QT syndrome;Ventricular tachycardia • Hypertrophic cardiomyopathy 1 • Cardiomyopathy • MYLK2-related disorder	Conflicting classifications of pathogenicity (Jan 22, 2024)
20-31819585-C-T		Hypertrophic cardiomyopathy 1 • not specified	Uncertain significance (Jun 12, 2021)
20-31819586-G-A		Hypertrophic cardiomyopathy 1 • not specified	Benign/Likely benign (Dec 19, 2022)
20-31819588-C-T		not specified	Uncertain significance (Jan 29, 2024)
20-31819590-G-GA		Hypertrophic cardiomyopathy 1	Uncertain significance (Apr 30, 2022)
20-31819595-T-G		not specified	Uncertain significance (Oct 21, 2023)
20-31819596-G-A		not specified	Uncertain significance (May 28, 2014)
20-31819597-G-A		Hypertrophic cardiomyopathy 1	Uncertain significance (Nov 20, 2022)
20-31819601-A-G		not specified • Hypertrophic cardiomyopathy 1	Likely benign (Sep 27, 2023)
20-31819612-G-A		Hypertrophic cardiomyopathy 1	Uncertain significance (Feb 16, 2023)
20-31819630-C-A		not specified • Hypertrophic cardiomyopathy 1	Conflicting classifications of pathogenicity (Sep 21, 2023)
20-31819630-C-T		Hypertrophic cardiomyopathy 1	Uncertain significance (Dec 22, 2020)
20-31819640-G-A		Hypertrophic cardiomyopathy 1	Likely benign (Sep 06, 2023)
20-31819641-C-A		Hypertrophic cardiomyopathy 1	Likely benign (Jun 23, 2022)
20-31819643-G-A		Hypertrophic cardiomyopathy 1	Likely benign (Oct 17, 2022)
20-31819645-G-C		Hypertrophic cardiomyopathy 1	Likely benign (Aug 17, 2023)
20-31819646-G-T		Hypertrophic cardiomyopathy 1	Uncertain significance (Jun 23, 2022)
20-31819651-A-G		Hypertrophic cardiomyopathy 1	Likely benign (Apr 06, 2023)
20-31819651-A-T		Hypertrophic cardiomyopathy 1	Uncertain significance (Oct 17, 2023)
20-31819896-G-A			Benign (Jun 19, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYLK2	protein_coding	protein_coding	ENST00000375994	12	15382

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.233	0.767	125724	1	23	125748	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.225	325	337	0.965	0.0000195	3914
Missense in Polyphen		101	117.16	0.86206		1428
Synonymous	-0.342	144	139	1.04	0.00000935	1166
Loss of Function	3.50	6	24.8	0.242	0.00000117	319

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000244	0.000239
Ashkenazi Jewish	0.00	0.00
East Asian	0.000275	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.0000812	0.0000791
Middle Eastern	0.000275	0.000272
South Asian	0.000131	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Implicated in the level of global muscle contraction and cardiac function. Phosphorylates a specific serine in the N- terminus of a myosin light chain. {ECO:0000269|PubMed:11733062}.
• Pathway: Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Integrin-mediated Cell Adhesion;Myometrial Relaxation and Contraction Pathways;Focal Adhesion (Consensus)

Recessive Scores

• pRec: 0.150

Intolerance Scores

• loftool: 0.498
• rvis_EVS: -0.24
• rvis_percentile_EVS: 36.23

Haploinsufficiency Scores

• pHI: 0.349
• hipred: Y
• hipred_score: 0.578
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.947

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mylk2
• Phenotype: muscle phenotype

Gene ontology

• Biological process: striated muscle contraction;neuromuscular synaptic transmission;positive regulation of gene expression;skeletal muscle satellite cell differentiation;peptidyl-threonine phosphorylation;regulation of muscle filament sliding;skeletal muscle cell differentiation;protein autophosphorylation;cardiac muscle tissue morphogenesis;cardiac muscle contraction
• Cellular component: nucleus;cytoplasm;sarcomere
• Molecular function: calmodulin-dependent protein kinase activity;myosin light chain kinase activity;protein binding;calmodulin binding;ATP binding;myosin light chain binding