MEF2C

Chr 5

myocyte enhancer factor 2C

Also known as: C5DELq14.3, DEL5q14.3, NEDHSIL

NCBI Gene: 4208ENSG00000081189UniProt: Q06413

This locus encodes a member of the MADS box transcription enhancer factor 2 (MEF2) family of proteins, which play a role in myogenesis. The encoded protein, MEF2 polypeptide C, has both trans-activating and DNA binding activities. This protein may play a role in maintaining the differentiated state of muscle cells. Mutations and deletions at this locus have been associated with severe cognitive disability, stereotypic movements, epilepsy, and cerebral malformation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2010]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language

Clinical highlights

Gene-disease validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
177
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.61
LOEUF
LOF*
Mechanism· G2P
📖
GeneReview available — MEF2C
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?
0.61LOEUF
pLI 0.017
Z-score 2.91
OE 0.32 (0.18–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
3.95Z-score
OE missense 0.34 (0.29–0.40)
96 obs / 283.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.32 (0.18–0.61)
0≤0.351.4
Missense OE?0.34 (0.29–0.40)
0≤0.61.4
Synonymous OE?0.84
0≤1.21.6
LoF obs/exp: 7 / 21.6Missense obs/exp: 96 / 283.2Syn Z: 1.37

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MEF2C · protein map & ClinVar variants

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

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