MEF2A

Chr 15AD

myocyte enhancer factor 2A

Also known as: ADCAD1, RSRFC4, RSRFC9, mef2

MEF2A encodes a DNA-binding transcription factor that activates muscle-specific, growth factor-induced, and stress-induced genes, and plays critical roles in muscle development, neuronal differentiation, cell growth control, and apoptosis. Mutations cause autosomal dominant coronary artery disease with myocardial infarction, primarily affecting the cardiovascular system. This gene is highly constrained against loss-of-function variants (pLI 0.99), indicating that such mutations are likely to have severe consequences.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.291 OMIM phenotype
Clinical SummaryMEF2A
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.987
Z-score 3.95
OE 0.09 (0.040.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.54Z-score
OE missense 0.74 (0.660.83)
205 obs / 277.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.040.29)
00.351.4
Missense OE0.74 (0.660.83)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 2 / 22.0Missense obs/exp: 205 / 277.4Syn Z: 0.62
DN
0.5082th %ile
GOF
0.2995th %ile
LOF
0.80top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.29
DN1 literature citation

Literature Evidence

DNWe recently discovered that a seven-amino acid deletion in MEF2A, a transcription factor with a high level of expression in the endothelium of coronary arteries, co-segregates with CAD/MI in one family, and it suppresses transcription activation activity of MEF2A by a dominant-negative mechanism.PMID:15496429

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MEF2A · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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