MYOZ2
Chr 4ADmyozenin 2
Also known as: C4orf5, CMH16, CS-1, FATZ-2
MYOZ2 encodes myozenin-2, a sarcomeric protein that tethers calcineurin to alpha-actinin at the Z-line and modulates calcium-dependent signaling in cardiac and skeletal muscle. Mutations cause familial hypertrophic cardiomyopathy type 16 with autosomal dominant inheritance.
Primary Disease Associations & Inheritance
Disputed — evidence questions this relationship
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
343 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 20 | 0 | 20 |
Likely Pathogenic | 0 | 1 | 1 | 0 | 2 |
VUS | 9 | 155 | 35 | 0 | 199 |
Likely Benign | 0 | 4 | 27 | 52 | 83 |
Benign | 0 | 0 | 21 | 4 | 25 |
Conflicting | — | 12 | |||
| Total | 9 | 160 | 104 | 56 | 341 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MYOZ2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools