MYLK2
Chr 20ADDigenic dominantmyosin light chain kinase 2
Also known as: KMLC, MLCK, MLCK2, skMLCK
This gene encodes a calcium/calmodulin-dependent myosin light chain kinase that phosphorylates myosin light chains to regulate muscle contraction and cardiac function, with exclusive expression in adult skeletal muscle. Mutations cause hypertrophic cardiomyopathy through digenic inheritance, meaning pathogenic variants in this gene work together with variants in another gene to cause disease. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.477), and there is a GeneReviews entry available for additional clinical guidance.
Primary Disease Associations & Inheritance
Disputed — evidence questions this relationship
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
501 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 6 | 0 | 6 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 14 | 226 | 23 | 2 | 265 |
Likely Benign | 0 | 8 | 73 | 106 | 187 |
Benign | 0 | 0 | 7 | 3 | 10 |
Conflicting | — | 23 | |||
| Total | 14 | 234 | 112 | 111 | 494 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MYLK2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools