MYH4

Chr 17

myosin heavy chain 4

Also known as: MYH2B, MyHC-2B, MyHC-IIb

NCBI Gene: 4622ENSG00000264424UniProt: Q9Y623

Enables double-stranded RNA binding activity. Involved in muscle contraction. Located in myofibril. [provided by Alliance of Genome Resources, Jul 2025]

330
ClinVar variants
12
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— MYH4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 302 VUS of 330 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
1.04LOEUF
pLI 0.000
Z-score 1.18
OE 0.88 (0.74–1.04)
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.
0.11Z-score
OE missense 0.99 (0.94–1.04)
1020 obs / 1030.0 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.0.88 (0.74–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.94–1.04)
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.1.00
0≤1.21.6
LoF obs/exp: 92 / 105.1Missense obs/exp: 1020 / 1030.0Syn Z: 0.02

ClinVar Variant Classifications

330 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
VUS302
Likely Benign7
Benign8
Conflicting1
12
Pathogenic
302
VUS
7
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
0
0
0
VUS
0
287
15
0
302
Likely Benign
0
5
0
2
7
Benign
0
5
0
3
8
Conflicting
—1
Total0297275330

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

View in ClinVar →

Protein Context — Lollipop Plot

MYH4 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The class II myosin MYH4 safeguards genome integrity and suppresses tumor progression.
Thatte J et al.·J Clin Invest
2025
Expression of the myosin heavy chain IIB gene in porcine skeletal muscle: the role of the CArG-Box promoter response element.
Brown DM et al.·PLoS One
2014
The Novel MuRF2 Target SNX5 Regulates PKA Activity Through Stabilization of RI-α and Controls Myogenic Differentiation.
Li N et al.·J Cachexia Sarcopenia Muscle
2025
A bioinformatics approach to identify a disulfidptosis-related gene signature for prognostic implication in colon adenocarcinoma.
Hu G et al.·Sci Rep
2023
Identification of potential biomarkers for cerebral palsy and the development of prediction models.
Zheng H et al.·Exp Biol Med (Maywood)
2024Functional
Muscle wasting and function after muscle activation and early protocol-based physiotherapy: an explorative trial.
Wollersheim T et al.·J Cachexia Sarcopenia Muscle
2019
Basal bioenergetic abnormalities in skeletal muscle from ryanodine receptor malignant hyperthermia-susceptible R163C knock-in mice.
Giulivi C et al.·J Biol Chem
2011
Myofibrillar myopathy caused by a mutation in the motor domain of mouse MyHC IIb.
Kurapati R et al.·Hum Mol Genet
2012Functional
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
Spastic Cerebral Palsy

3D-Microscopic Muscle Architecture in Cerebral Palsy

RECRUITING
NCT06584851Universitaire Ziekenhuizen KU LeuvenStarted 2019-05-02

External Resources

Links to major genomics databases and tools