MYH8

Chr 17AD

myosin heavy chain 8

Also known as: DA7, MyHC-peri, MyHC-pn, gtMHC-F

NCBI Gene: 4626ENSG00000133020UniProt: P13535

Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is predominantly expressed in fetal skeletal muscle. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in trismus-pseudocamptodactyly syndrome. [provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

Carney complex variantMIM #608837
Trismus-pseudocamptodactyly syndromeMIM #158300
AD
UniProtArthrogryposis, distal, 7
339
ClinVar variants
11
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MYH8
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 227 VUS of 339 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.03LOEUF
pLI 0.000
Z-score 1.30
OE 0.86 (0.72–1.03)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.35Z-score
OE missense 0.97 (0.92–1.02)
965 obs / 996.0 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.0.86 (0.72–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.92–1.02)
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.1.04
0≤1.21.6
LoF obs/exp: 86 / 100.0Missense obs/exp: 965 / 996.0Syn Z: -0.68

ClinVar Variant Classifications

339 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS227
Likely Benign40
Benign41
Conflicting20
10
Pathogenic
1
Likely Pathogenic
227
VUS
40
Likely Benign
41
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
9
0
10
Likely Pathogenic
0
0
1
0
1
VUS
8
180
33
6
227
Likely Benign
0
12
14
14
40
Benign
0
4
24
13
41
Conflicting
—20
Total81978133339

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

View in ClinVar →

Protein Context — Lollipop Plot

MYH8 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MYH8-related Carney complex variant

refuted
ADUndeterminedDecreased Gene Product Level
Dev. DisordersSkin
G2P ↗
stop gained NMD triggeringframeshift variant NMD triggering

MYH8-related Trismus-pseudocamptodactyly syndrome

strong
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersSkin
G2P ↗
missense variant

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Carney complex variant

MIM #608837

Molecular basis of disorder known

Trismus-pseudocamptodactyly syndrome

MIM #158300

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Hereditary myosin myopathies.
Oldfors A·Neuromuscul Disord
2007Review
Thick filament diseases.
Oldfors A et al.·Adv Exp Med Biol
2008Review
Myosinopathies: pathology and mechanisms.
Tajsharghi H et al.·Acta Neuropathol
2013Review
Novel MYH8 mutations in 152 Han Chinese samples with ovarian endometriosis.
Lou J et al.·Gynecol Endocrinol
2020
Genetic Factors Involved in Mandibular Prognathism.
Doraczynska-Kowalik A et al.·J Craniofac Surg
2017Review
Screening of hub genes and immunocytes related to tendon injury based on bioinformatics and machine learning models.
Sun S et al.·Sci Rep
2025Functional
Clinical phenotypes and molecular genetic mechanisms of Carney complex.
Wilkes D et al.·Lancet Oncol
2005Review
Caution in interpretation of disease causality for heterozygous loss-of-function variants in the MYH8 gene associated with autosomal dominant disorder.
Dai Z et al.·Eur J Med Genet
2017
Phenotypic variation in trismus-pseudocamptodactyly syndrome caused by a recurrent MYH8 mutation.
Minzer-Conzetti K et al.·Clin Dysmorphol
2008
Biochemical and functional characterization of skeletal muscle cells differentiated from tonsil-derived mesenchymal stem cells.
Choi Y et al.·Muscle Nerve
2023Functional
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools