MYH11

Chr 16ADAR

myosin heavy chain 11

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

NCBI Gene: 4629ENSG00000133392UniProt: P35749

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]

Primary Disease Associations & Inheritance

Aortic aneurysm, familial thoracic 4MIM #132900
AD
Megacystis-microcolon-intestinal hypoperistalsis syndrome 2MIM #619351
AR
Visceral myopathy 2MIM #619350
AD
564
ClinVar variants
17
Pathogenic / LP
0.77
pLI score
5
Active trials
Clinical Summary— MYH11
🧬
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.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 335 VUS of 564 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.44Z-score
OE missense 0.88 (0.83–0.93)
985 obs / 1120.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.22 (0.16–0.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.83–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 24 / 110.7Missense obs/exp: 985 / 1120.5Syn Z: -2.89

ClinVar Variant Classifications

564 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic6
VUS335
Likely Benign211
Conflicting1
11
Pathogenic
6
Likely Pathogenic
335
VUS
211
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
7
0
11
Likely Pathogenic
6
0
0
0
6
VUS
7
278
46
4
335
Likely Benign
0
0
93
118
211
Benign
0
0
0
0
0
Conflicting
—1
Total17278146122564

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.

Gene2Phenotype Curations

MYH11-related megacystis-microcolon-intestinal hypoperistalsis syndrome

limited
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Aortic aneurysm, familial thoracic 4

MIM #132900

Molecular basis of disorder known

Autosomal dominant

Megacystis-microcolon-intestinal hypoperistalsis syndrome 2

MIM #619351

Molecular basis of disorder known

Autosomal recessive

Visceral myopathy 2

MIM #619350

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — MYH11
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Loeys-Dietz Syndrome.
Velchev JD et al.·Adv Exp Med Biol
2021
16p13.11 microduplication in 45 new patients: refined clinical significance and genotype-phenotype correlations.
Allach El Khattabi L et al.·J Med Genet
2020Cohort
Macrophage-Derived 25-Hydroxycholesterol Promotes Vascular Inflammation, Atherogenesis, and Lesion Remodeling.
Canfrán-Duque A et al.·Circulation
2023Functional
Deciphering the tumor immune microenvironment: single-cell and spatial transcriptomic insights into cervical cancer fibroblasts.
Lin Z et al.·J Exp Clin Cancer Res
2025
Autozygome and high throughput confirmation of disease genes candidacy.
Maddirevula S et al.·Genet Med
2019
Inactivation of RhoA for Hypertension Treatment Through the TRPV4-RhoA-RhoGDI1 Axis.
Wang J et al.·Circulation
2025
Transcriptome-based molecular subtypes and differentiation hierarchies improve the classification framework of acute myeloid leukemia.
Cheng WY et al.·Proc Natl Acad Sci U S A
2022
Single-cell RNA sequencing reveals the vascular smooth muscle cell phenotypic landscape in aortic aneurysm.
Cao G et al.·Cell Commun Signal
2023
Expanding the phenotypic spectrum of Chromosome 16p13.11 microduplication: A multicentric analysis of 206 patients.
Hamad A et al.·Eur J Med Genet
2023Cohort
A multi-omics pipeline integrating machine learning and spatial-cellular analysis identifies SASH1 as a prognostic biomarker and therapeutic target in head and neck squamous cell carcinoma.
Dai Z et al.·Int J Surg
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Acute Myeloid Leukemia

Interferon-alpha As Maintenance Therapy for Favorable-risk Acute Myeloid Leukemia

RECRUITING
NCT06802718Phase PHASE3Peking University People's HospitalStarted 2023-01-01
Interferon
AML, ChildhoodAcute Myeloid Leukemia

Clinical Study of Induction Therapy Options Based on Molecular Subtyping and MRD in Children and Adolescents With AML

RECRUITING
NCT06221683Phase PHASE2Children's Hospital of Soochow UniversityStarted 2024-01-01
HomoharringtonineCytarabineEtoposide
Acute Myeloid Leukemia With T(8;21)(Q22;Q22)Acute Myeloid Leukemia With T(16;16)(P13;Q22)KIT Gene Mutation

A New Treatment of Newly Diagnosed KIT Mutation CBF-Acute Myeloid Leukemia

RECRUITING
NCT07028073Phase PHASE1, PHASE2The First Affiliated Hospital of Soochow UniversityStarted 2025-05-15
Group A (FIT): Avapritinib + IA regimenGroup B (UNFIT): Avapritinib + VA regimen
Aortic Aneurysm and Dissection

MITAORTA - Role of Mitochondrial Dynamic in Aneurysm and Dissection of Ascending Thoracic Aorta

ACTIVE NOT RECRUITING
NCT05434481Phase NAUniversity Hospital, AngersStarted 2022-09-07
Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases
Acute Myeloid Leukemia

Study of A Venetoclax-based, Anthracycline-free Regimen in Newly Diagnosed CBFβ::MYH11(+) AML

RECRUITING
NCT06429098Phase PHASE2The First Affiliated Hospital of Soochow UniversityStarted 2024-01-01
Venetoclaxazacitidinedecitabine

External Resources

Links to major genomics databases and tools