MEF2A

protein-coding

myocyte enhancer factor 2A, the group of Myocyte enhancer factor 2 proteins|MADS box family

Gene summary

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]

MANE transcript

NM_001319206.4

Inheritance

ClinVar variants

P:2U:44B:11

Top phenotype

Coronary artery disease, autosomal dominant, 1

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr15:99,565,417-99,716,488

External References & Databases

Ensembl (ENSG00000068305)

Transcript & Mutation Effects

hg38 • Region Span ~151.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

coronary artery disease, autosomal dominant, 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012011

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MEF2A variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 37

not providedTotal: 14

Coronary artery disease, autosomal dominant, 1Total: 8

MEF2A-related disorderTotal: 4

Coronary artery disease/myocardial infarctionTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001319206.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	4 clinvar	2 clinvar	7
missense	2 clinvar		39 clinvar	5 clinvar		46
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	2	0	44	9	2	57

Highest pathogenic variant AF is 0.00097053853

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 333 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001319206.4	RefSeq	NP_001306135.1	10	MANE Select
ENST00000557942.6	Ensembl	ENSP00000453095.1	10	MANE Select
NM_001130926.5	RefSeq	NP_001124398.1	9	Standard
NM_001130927.5	RefSeq	NP_001124399.1	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mef2aa	Danio rerio	Structure: cardiac muscle cell Quality: disorganized abnormal

Gene / Model

Organism

Observed Phenotype

mef2aa

Danio rerio

Structure: cardiac muscle cell

Quality: disorganized

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Apelin signaling pathway - Homo sapiens (human)
Fluid shear stress and atherosclerosis - Homo sapiens (human)
cGMP-PKG signaling pathway - Homo sapiens (human)
EGF-Core
Energy Metabolism

Biological Process

mitochondrial genome maintenance
negative regulation of transcription by RNA polymerase II
MAPK cascade
transcription, DNA-templated
apoptotic process

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
RNA polymerase II transcription factor binding
DNA-binding transcription activator activity, RNA polymerase II-specific

Cellular Component

nuclear chromatin
nucleus
nucleoplasm
transcription factor complex
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354410
Coding exons: 9
Length: 239302
Individuals with no LoFs: 122180
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 122181
p: 0.00000409

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.54	205	277	0.739	0.0000146	3233
Missense (PolyPhen)		112	150.77	0.74285		1720
Synonymous	0.623	97	105	0.923	0.00000605	989
Loss of Function	3.95	2	22.0	0.0911	0.00000115	257

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000091	0.0000091	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle- specific genes. Also involved in the activation of numerous growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation. Associates with chromatin to the ZNF16 promoter. {ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15834131, ECO:0000269|PubMed:16371476, ECO:0000269|PubMed:16484498, ECO:0000269|PubMed:16563226, ECO:0000269|PubMed:21468593, ECO:0000269|PubMed:9858528}.;
Disease: DISEASE: Coronary artery disease, autosomal dominant, 1 (ADCAD1) [MIM:608320]: A common heart disease characterized by reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. Its most important complication is acute myocardial infarction. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.237

Intolerance Scores

LoFtool: 0.591
RVIS EVS: -0.31
RVIS percentile EVS: 31.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium