MYBPC3

Chr 11ADAR

myosin binding protein C3

Also known as: CMD1MM, CMH4, FHC, LVNC10, MYBP-C, cMyBP-C

NCBI Gene: 4607ENSG00000134571UniProt: Q14896OMIM: 600958

The protein regulates cardiac muscle contraction as a key component of the sarcomere's myosin-binding complex in heart muscle. Mutations cause hypertrophic cardiomyopathy, dilated cardiomyopathy, and left ventricular noncompaction through both autosomal dominant and autosomal recessive inheritance patterns. The pathogenic mechanism involves gain-of-function effects that disrupt normal cardiac contractility.

OMIMResearchSummary from RefSeq, OMIM, Mechanism
LOFmechanismAD/ARLOEUF 0.593 OMIM phenotypes
Clinical Summary— MYBPC3
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Gene-Disease Validity (ClinGen)
arrhythmogenic right ventricular cardiomyopathy · ADLimited

Limited evidence — not for standalone diagnostic reporting

5 total gene-disease associations curated

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.000
Z-score 4.32
OE 0.43 (0.32–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.45Z-score
OE missense 0.86 (0.80–0.91)
679 obs / 794.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.43 (0.32–0.59)
0≤0.351.4
Missense OE0.86 (0.80–0.91)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 29 / 67.3Missense obs/exp: 679 / 794.1Syn Z: -0.22
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedMYBPC3-related dilated cardiomyopathyOTHERAD
limitedMYBPC3-related arrhythmogenic right ventricular cardiomyopathyOTHERAD
definitiveMYBPC3-related hypertrophic cardiomyopathyLOFAD
DN
0.7132th %ile
GOF
0.6931th %ile
LOF
0.3649th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative, gain-of-function and loss-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.

DNprediction above median
GOFprediction above median
LOF1 literature citation

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.

Literature Evidence

LOFMutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathyPMID:7493025

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MYBPC3 · 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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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Generation of two induced pluripotent stem cell lines from hypertrophic cardiomyopathy patients carrying MYBPC3 mutations.
Wu CA et al.·Stem Cell Res
2026Cohort
MYBPC3 (c.194 C > T) mutation-mediated RyR2 dysfunction contributes to pathogenic phenotypes of DCM revealed by HiPSC modeling.
Xie M et al.·Cell Mol Life Sci
2026Open AccessFunctional
Case Report: Genomic and clinical insights into MYBPC3-related hypertrophic cardiomyopathy in Ecuadorian patients: implications for sudden cardiac death risk.
Paz-Cruz E et al.·Front Cardiovasc Med
2025Open AccessCohort
A case report of a Chinese patient with obstructive hypertrophic cardiomyopathy harboring rare variants in both the MYBPC3 and DSP genes.
Wu XY et al.·Front Cardiovasc Med
2025Open AccessCase report
Case Report: Lethal neonatal hypertrophic cardiomyopathy from compound heterozygous MYBPC3 variants.
Wang J et al.·Front Cardiovasc Med
2025Open AccessCase report
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients