MYH11

Chr 16ADAR

myosin heavy chain 11

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.303 OMIM phenotypes
Clinical SummaryMYH11
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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

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.
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ClinVar Variants
68 VUS of 100 total submissions
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Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.773
Z-score 7.63
OE 0.22 (0.160.30)
Highly constrained

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

Missense Constraint
1.44Z-score
OE missense 0.88 (0.830.93)
985 obs / 1120.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.160.30)
00.351.4
Missense OE0.88 (0.830.93)
00.61.4
Synonymous OE1.17
01.21.6
LoF obs/exp: 24 / 110.7Missense obs/exp: 985 / 1120.5Syn Z: -2.89
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedMYH11-related megacystis-microcolon-intestinal hypoperistalsis syndromeLOFAR

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

DN
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.PMID:31944481

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

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

VUS68
Likely Benign32
68
VUS
32
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
6
52
8
2
68
Likely Benign
0
0
10
22
32
Benign
0
0
0
0
0
Total6521824100

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

View in ClinVar →

Protein Context — Lollipop Plot

MYH11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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