MEF2A

Chr 15AD

myocyte enhancer factor 2A

Also known as: ADCAD1, RSRFC4, RSRFC9, mef2

NCBI Gene: 4205ENSG00000068305UniProt: Q02078

The protein encoded by this gene is a DNA-binding transcription factor that activates many muscle-specific, growth factor-induced, and stress-induced genes. The encoded protein can act as a homodimer or as a heterodimer and is involved in several cellular processes, including muscle development, neuronal differentiation, cell growth control, and apoptosis. Defects in this gene could be a cause of autosomal dominant coronary artery disease 1 with myocardial infarction (ADCAD1). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

Primary Disease Associations & Inheritance

{Coronary artery disease, autosomal dominant, 1}MIM #608320
AD
160
ClinVar variants
84
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MEF2A
⚡
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.
📋
ClinVar Variants
84 Pathogenic / Likely Pathogenic· 48 VUS of 160 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.29LOEUF
pLI 0.987
Z-score 3.95
OE 0.09 (0.04–0.29)
Highly constrained

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

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.
1.54Z-score
OE missense 0.74 (0.66–0.83)
205 obs / 277.4 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.0.09 (0.04–0.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.66–0.83)
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.0.92
0≤1.21.6
LoF obs/exp: 2 / 22.0Missense obs/exp: 205 / 277.4Syn Z: 0.62

ClinVar Variant Classifications

160 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic77
Likely Pathogenic7
VUS48
Likely Benign13
Benign14
Conflicting1
77
Pathogenic
7
Likely Pathogenic
48
VUS
13
Likely Benign
14
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
75
0
77
Likely Pathogenic
0
0
7
0
7
VUS
0
34
14
0
48
Likely Benign
0
4
5
4
13
Benign
0
1
5
8
14
Conflicting
—1
Total04110612160

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Coronary artery disease, autosomal dominant, 1}

MIM #608320

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
AQP1 differentially orchestrates endothelial cell senescence.
Shabanian K et al.·Redox Biol
2024
Variants in exon 11 of MEF2A gene and coronary artery disease: evidence from a case-control study, systematic review, and meta-analysis.
Liu Y et al.·PLoS One
2012Meta-analysis
A Tiered Approach to Exome Sequencing Analysis in Early-Onset Primary Ovarian Insufficiency.
McGlacken-Byrne SM et al.·J Clin Endocrinol Metab
2025
Detection and functional characterization of a novel MEF2A variation responsible for familial dilated cardiomyopathy.
Qiao Q et al.·Clin Chem Lab Med
2020Functional
A Study of transcription factor MEF2A gene polymorphisms in patients with coronary artery disease.
Muhammad Sulaiman K·Cell Mol Biol (Noisy-le-grand)
2024Cohort
Mutation of MEF2A in an inherited disorder with features of coronary artery disease.
Wang L et al.·Science
2003
MEF2A is a transcription factor for circPVT1 and contributes to the malignancy of acute myeloid leukemia.
Wu K et al.·Int J Oncol
2024
MEF2A, MEF2C, and MEF2D as potential biomarkers of pancreatic cancer?
Zhai C et al.·BMC Cancer
2025
Myocyte enhancer factor 2A delays vascular endothelial cell senescence by activating the PI3K/p-Akt/SIRT1 pathway.
Liu B et al.·Aging (Albany NY)
2019
MEF2A transcriptionally upregulates the expression of ZEB2 and CTNNB1 in colorectal cancer to promote tumor progression.
Xiao Q et al.·Oncogene
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A novel role of Mef2a in mitochondrial homeostasis and muscle regeneration during sarcopenia.
Tao X et al.·Cells Dev
2025
USP4, Transcriptionally Activated by MEF2A, Protects Multiple Myeloma Cells From Endoplasmic Reticulum Stress-Mediated Apoptosis via Repressing NR4A1 Ubiquitination.
Lin J et al.·FASEB J
2025
Myxoid epithelioid smooth muscle tumor with a novel MEF2A::NCOA2 fusion arising in the rectum: case report and literature review.
Kunieda J et al.·Virchows Arch
2025Review
Inhibition of myocyte-specific enhancer factor 2A (MEF2A) attenuates cardiac fibrosis and improves heart function by regulating the Snail1/RhoA/α-SMA pathway.
Jiang Q et al.·J Bioenerg Biomembr
2025
N6-methyladenosine modification of MEF2A weakens cetuximab sensitivity in colorectal cancer via PD-L1/SOX12 axis.
Gao C et al.·Cell Death Discov
2025🔓 Open Access
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