MYLK3

Chr 16

myosin light chain kinase 3

Also known as: MLCK, MLCK2, caMLCK

NCBI Gene: 91807 ENSG00000140795 UniProt: Q32MK0 OMIM: 612147

MYLK3 encodes a kinase that phosphorylates cardiac myosin light chains and promotes sarcomere formation, thereby increasing cardiomyocyte contractility and potentiating cardiac muscle force generation. The gene shows tolerance to loss-of-function variants (LOEUF 0.72), but specific disease associations and inheritance patterns are not established in the provided data.

OMIM ResearchSummary from RefSeq, UniProt

Phosphorylation of cardiac myosin heavy chains (see MYH7B, MIM 609928) and light chains (see MYL2, MIM 160781) by a kinase, such as MYLK3, potentiates the force and rate of cross-bridge recruitment in cardiac myocytes (Chan et al., 2008 [PubMed 18202317]).[supplied by OMIM, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.72

Clinical Summary— MYLK3

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Gene-Disease Validity (ClinGen)

dilated cardiomyopathy · ADModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 657 VUS of 1054 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.000

Z-score 2.83

OE 0.47 (0.32–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.50Z-score

OE missense 0.94 (0.86–1.01)

447 obs / 477.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.32–0.72)

0≤0.351.4

Missense OE?0.94 (0.86–1.01)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 16 / 33.7Missense obs/exp: 447 / 477.9Syn Z: -0.51

This gene — mechanism propensity

0.7035th %ile

GOF

0.74top 25%

LOF

0.3355th %ile

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.

GOFprediction above median

DNprediction above median

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

1054 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS657

Likely Benign344

Benign21

Conflicting24

Likely Pathogenic

657

VUS

344

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	1	0	0	0	1
VUS	63	553	36	5	657
Likely Benign	0	8	101	235	344
Benign	0	4	7	10	21
Conflicting	—				24
Total	64	565	144	250	1,047

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap MYLK3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →