MYL11

Chr 16ADAR

myosin light chain 11

Also known as: DA1C, HUMMLC2B, MLC2B, MRLC2, MYLPF

NCBI Gene: 29895 ENSG00000180209 UniProt: Q96A32 OMIM: 617378

The protein is a myosin regulatory subunit that maintains muscle integrity during early development and facilitates muscle contraction through calcium ion binding. Mutations cause distal arthrogryposis type 1C, a congenital condition affecting the hands and feet with joint contractures present from birth. The gene shows high constraint against loss-of-function variants and demonstrates both autosomal dominant and autosomal recessive inheritance patterns.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable calcium ion binding activity. Predicted to be a structural constituent of muscle. Involved in muscle contraction. Located in lysosomal membrane. Implicated in distal arthrogryposis type 1C. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismAD/ARLOEUF 0.521 OMIM phenotype

Clinical Summary— MYL11

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.76) — some intolerance to loss-of-function variants.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.760

Z-score 2.48

OE 0.11 (0.04–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.65Z-score

OE missense 0.82 (0.69–0.98)

88 obs / 106.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.52)

0≤0.351.4

Missense OE?0.82 (0.69–0.98)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 1 / 9.1Missense obs/exp: 88 / 106.9Syn Z: 0.64

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedMYL11-related arthrogryposis, distalOTHERAD

strongMYL11-related arthrogryposis, distalOTHERAR

This gene — mechanism propensity

0.79top 25%

GOF

0.72top 25%

LOF

0.2971th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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.