MYH11

Chr 16ADAR

myosin heavy chain 11

Also known as: AAT4, FAA4, SMHC, SMMHC, SMMS-1, VSCM2

NCBI Gene: 4629 ENSG00000133392 UniProt: P35749 OMIM: 160745

MYH11 encodes smooth muscle myosin heavy chain, which converts chemical energy to mechanical energy through ATP hydrolysis to enable smooth muscle contraction. Mutations cause autosomal dominant familial thoracic aortic aneurysm or autosomal recessive visceral myopathy and megacystis-microcolon-intestinal hypoperistalsis syndrome, affecting vascular and gastrointestinal smooth muscle function. The gene is highly constrained against loss-of-function variants (LOEUF 0.305), reflecting its essential role in smooth muscle contractility.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a smooth muscle myosin belonging to the myosin heavy chain family. The gene product is a subunit of a hexameric protein that consists of two heavy chain subunits and two pairs of non-identical light chain subunits. It functions as a major contractile protein, converting chemical energy into mechanical energy through the hydrolysis of ATP. A chromosomal rearrangement involving this gene is associated with acute myeloid leukemia of the M4Eo subtype. Mutations in this gene are associated with visceral myopathy, megacystis-microcolon-intestinal hypoperistalsis syndrome 2, and familial thoracic aortic aneurysm 4. [provided by RefSeq, May 2022]

OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.303 OMIM phenotypes

Clinical Summary— MYH11

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Gene-Disease Validity (ClinGen)

congenital heart disease · ADLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.

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Clinical Trials

4 active or recruiting trials — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.773

Z-score 7.63

OE 0.22 (0.16–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.44Z-score

OE missense 0.88 (0.83–0.93)

985 obs / 1120.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.16–0.30)

0≤0.351.4

Missense OE?0.88 (0.83–0.93)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 24 / 110.7Missense obs/exp: 985 / 1120.5Syn Z: -2.89

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateMYH11-related megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS)LOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.74top 25%

GOF

0.5268th %ile

LOF

0.4039th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNHeterozygous dominant negative MYH11 pathogenic variants have been associated with thoracic aortic aneurysm and dissection while biallelic null alleles have been associated with megacystis microcolon intestinal hypoperistalsis syndrome.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References