MEF2A

Chr 15AD

myocyte enhancer factor 2A

Also known as: ADCAD1, RSRFC4, RSRFC9, mef2

NCBI Gene: 4205 ENSG00000068305 UniProt: Q02078 OMIM: 600660

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Coronary artery disease, autosomal dominant, 1}MIM #608320

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.29

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

1.54Z-score

OE missense 0.74 (0.66–0.83)

205 obs / 277.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.29)

0≤0.351.4

Missense OE?0.74 (0.66–0.83)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 2 / 22.0Missense obs/exp: 205 / 277.4Syn Z: 0.62

Background carrier burden — how many people carry a rare variant somewhere in MEF2A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

622 rare PASS variants

Rare truncating (LoF)

1 in 1,100

77 rare PASS variants

Rare synonymous (reference)

1 in 170

281 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MEF2A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 1,500
South Asian	~43k	1 in 79	1 in 1,300
Remaining (unassigned)	~30k	1 in 92	1 in 760
European (Finnish)	~27k	1 in 350	1 in 2,600
Admixed American	~22k	1 in 170	1 in 940
African / African American	~21k	1 in 150	1 in 690
East Asian	~20k	1 in 110	1 in 930
Ashkenazi Jewish	~13k	1 in 330	≈ 1 in 6,200
Middle Eastern	~2,884	1 in 120	1 in 220

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 10 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 10.? see exons ↓