MEF2D

Chr 1

myocyte enhancer factor 2D

NCBI Gene: 4209 ENSG00000116604 UniProt: Q14814 OMIM: 600663

This gene is a member of the myocyte-specific enhancer factor 2 (MEF2) family of transcription factors. Members of this family are involved in control of muscle and neuronal cell differentiation and development, and are regulated by class II histone deacetylases. Fusions of the encoded protein with Deleted in Azoospermia-Associated Protein 1 (DAZAP1) due to a translocation have been found in an acute lymphoblastic leukemia cell line, suggesting a role in leukemogenesis. The encoded protein may also be involved in Parkinson disease and myotonic dystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.24

Clinical Summary— MEF2D

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

33 VUS of 50 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.24LOEUF

pLI 0.997

Z-score 4.36

OE 0.08 (0.03–0.24)

Highly constrained

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

Missense Constraint?

2.25Z-score

OE missense 0.65 (0.58–0.73)

211 obs / 325.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.24)

0≤0.351.4

Missense OE?0.65 (0.58–0.73)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 2 / 25.9Missense obs/exp: 211 / 325.2Syn Z: -0.31

This gene — mechanism propensity

0.3594th %ile

GOF

0.2398th %ile

LOF

0.86top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.24

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

50 submitted variants in ClinVar

ClinVar

Classification Summary

VUS33

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	32	33
Likely Benign	0	0	0
Benign	0	0	0
Total	1	32	33

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap MEF2D — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →