MYLK2 Gene: Myosin Light Chain Kinase 2 - Function, Disease Associations, and Clinical Significance
A comprehensive biomedical overview of MYLK2, a cardiac-specific kinase implicated in hypertrophic cardiomyopathy and other myopathies.
Gene Information Card
| Symbol | MYLK2 |
|---|---|
| Full Name | myosin light chain kinase 2 |
| Gene Type | protein coding |
| Chromosomal Location | 20q13.31 |
| NCBI Gene ID | 85366 ncbi.nlm.nih.gov/gene/85366 |
| Ensembl ID | ENSG00000101384 |
| UniProt ID | Q9H1R3 |
| OMIM ID | 606566 |
| HGNC ID | 16211 |
| Aliases | MLCK2, skMLCK, KRP |
Description
MYLK2 encodes myosin light chain kinase 2, a calcium/calmodulin-dependent enzyme predominantly expressed in cardiac and skeletal muscle. It phosphorylates the regulatory light chain of myosin, modulating cardiac contractility. Mutations in MYLK2 are associated with hypertrophic cardiomyopathy (HCM) and other myopathies. The gene is located on chromosome 20q13.31 and is part of the immunoglobulin superfamily.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypertrophic Cardiomyopathy (HCM) | Missense mutations (e.g., p.His343Arg) impair kinase activity or calcium sensitivity, leading to altered myosin regulation and hypercontractility. | ClinVar: Pathogenic variants reported; OMIM 606566; PMID: 17503513 |
| Dilated Cardiomyopathy (DCM) | Rare variants may disrupt sarcomeric function, though evidence is limited. | ClinVar: Some variants of uncertain significance; PMID: 22538709 |
| Myopathy (general) | Expression in skeletal muscle suggests potential involvement in muscle disorders, but specific associations are not well established. | UniProt: Tissue expression; no direct disease link confirmed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | Not available | High expression (based on RNA-seq data from GTEx, but nTPM not provided) |
| Skeletal Muscle | Not available | High expression |
| Other tissues | Not available | Low or no expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes | Not available | Primary cell type expressing MYLK2 |
| Skeletal muscle cells | Not available | Expressed in mature muscle |
| Other cell lines | Not available | Not typically expressed in non-muscle lines |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.His343Arg (c.1028A>G) | Missense | Rare (found in HCM cohorts) | Reduced kinase activity; altered calcium sensitivity; pathogenic for HCM |
| p.Arg436Gln (c.1307G>A) | Missense | Rare | Uncertain significance; potential effect on substrate binding |
| p.Val261Ala (c.782T>C) | Missense | Rare | Uncertain significance; reported in HCM patients |
Mutation functional classification
Loss of Function (LOF)
Some MYLK2 mutations reduce kinase activity, impairing myosin light chain phosphorylation and affecting contractility.
Gain of Function (GOF)
Not well documented; some variants may increase activity but evidence is limited.
Dominant Negative (DN)
Mutant MYLK2 may interfere with normal kinase function in a dominant-negative manner, as seen in HCM.
View complete mutation data：
Gene Ontology (GO)
| • calmodulin binding | • protein kinase activity |
| • ATP binding | • myosin light chain kinase activity |
| • calcium ion binding | • muscle contraction |
| • cardiac muscle contraction | • regulation of cardiac muscle contraction |
Pathways
• Cardiac muscle contraction (KEGG hsa04260)
• Calcium signaling pathway (KEGG hsa04020)
• Regulation of actin cytoskeleton (KEGG hsa04810)
Protein Summary
MYLK2 encodes a 596-amino acid protein with a molecular mass of ~68 kDa. It contains an N-terminal immunoglobulin-like domain, a central kinase domain, and a calmodulin-binding region. The kinase phosphorylates the regulatory light chain of myosin (MYL2) at Ser15, enhancing actin-myosin interaction and contractile force. Expression is restricted to cardiac and skeletal muscle. Mutations in MYLK2 are linked to hypertrophic cardiomyopathy, with functional studies showing altered kinase activity and calcium sensitivity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MYLK2 Knockout HEK293 Cell Line | EDJ-KQ1435 | Human | 85366 | Details Get a Quote |
| MYLK2 Knockout HCT 116 Cell Line | EDJ-KQ20981 | Human | 85366 | Details Get a Quote |
| MYLK2 Knockout HeLa Cell Line | EDJ-KQ20982 | Human | 85366 | Details Get a Quote |
| MYLK2 Knockout A-549 Cell Line | EDJ-KQ66207 | Human | 85366 | Details Get a Quote |
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