MEF2C

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

Basic information

Region (hg38): 5:88717116-88904257

Links

ENSG00000081189 ∙ NCBI:4208 ∙ OMIM:600662 ∙ HGNC:6996 ∙ Uniprot:Q06413 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 20 (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 20 (Moderate), mode of inheritance: AD
• intellectual disability, autosomal dominant 20 (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 20 (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	19876902; 19592390; 20412115; 20513142; 23001426

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MEF2C gene.

• Intellectual disability, autosomal dominant 20 (300 variants)
• not provided (126 variants)
• not specified (42 variants)
• Inborn genetic diseases (33 variants)
• Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations (18 variants)
• Autism spectrum disorder (4 variants)
• Intellectual disability (3 variants)
• MEF2C-related condition (3 variants)
• MEF2C-Related Disorder (2 variants)
• Neurodevelopmental disorder (2 variants)
• Seizure (2 variants)
• Frontotemporal dementia (2 variants)
• 5q14.3 microdeletion syndrome (1 variants)
• MEF2C-related complex neurodevelopmental disorder (1 variants)
• MEF2C Haploinsufficiency Syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MEF2C gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	97		100
missense	4	20	102	9	8	143
nonsense	5	3	3	1		12
start loss		1				1
frameshift	22	3	3			28
inframe indel	1		2			3
splice donor/acceptor (+/-2bp)	11	8		1		20
splice region		2	9	11	4	26
non coding	2	2	14	54	24	96
Total	45	37	127	162	32

Highest pathogenic variant AF is 0.00000657

Variants in MEF2C

This is a list of pathogenic ClinVar variants found in the MEF2C region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-88719217-T-A		Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations	Uncertain significance (Jun 14, 2016)
5-88719558-C-T		Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations	Benign/Likely benign (Jun 01, 2022)
5-88719559-G-A		Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations	Uncertain significance (Jun 14, 2016)
5-88719725-T-TCA		Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations	Uncertain significance (Jun 14, 2016)
5-88720336-AT-A		Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations	Uncertain significance (Jun 14, 2016)
5-88720336-A-AT		Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations	Benign (Jun 14, 2016)
5-88720336-A-ATT		Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations	Uncertain significance (Jun 14, 2016)
5-88722488-CT-C		Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations	Uncertain significance (Jun 14, 2016)
5-88722548-TATAGC-T		Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations	Uncertain significance (Jun 14, 2016)
5-88722571-GA-G			Benign (Aug 20, 2019)
5-88722571-GAA-G		Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations	Uncertain significance (Jun 14, 2016)
5-88722588-G-C		not specified	Benign (Jul 08, 2014)
5-88722606-A-T		Intellectual disability	Likely pathogenic (Apr 20, 2020)
5-88722610-T-C		Intellectual disability, autosomal dominant 20	Likely benign (Nov 01, 2021)
5-88722611-G-T			Uncertain significance (Apr 01, 2018)
5-88722613-C-T			Uncertain significance (Jul 29, 2022)
5-88722614-C-T		Autosomal dominant epilepsy	Likely pathogenic (Mar 23, 2023)
5-88722623-G-A		Intellectual disability, autosomal dominant 20	Uncertain significance (Feb 08, 2013)
5-88722625-A-C		Intellectual disability, autosomal dominant 20	Likely benign (Feb 21, 2020)
5-88722628-T-C		Intellectual disability, autosomal dominant 20	Likely benign (Feb 21, 2020)
5-88722630-G-T		Intellectual disability, autosomal dominant 20	Likely benign (Jan 11, 2023)
5-88722634-G-A		not specified	Likely benign (May 11, 2017)
5-88722641-A-G		Intellectual disability, autosomal dominant 20	Benign (Oct 25, 2022)
5-88722643-T-A		Intellectual disability, autosomal dominant 20	Likely benign (Feb 21, 2020)
5-88722644-G-T		Intellectual disability, autosomal dominant 20	Uncertain significance (Feb 21, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MEF2C	protein_coding	protein_coding	ENST00000340208	10	185948

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0173	0.982	124637	0	17	124654	0.0000682

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.95	96	283	0.339	0.0000165	3144
Missense in Polyphen		36	151.56	0.23753		1720
Synonymous	1.37	95	114	0.837	0.00000757	952
Loss of Function	2.91	7	21.6	0.324	0.00000124	260

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000994	0.0000993
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000802	0.0000796
Middle Eastern	0.00	0.00
South Asian	0.000203	0.000196
Other	0.000166	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle- specific genes. Controls cardiac morphogenesis and myogenesis, and is also involved in vascular development. Plays an essential role in hippocampal-dependent learning and memory by suppressing the number of excitatory synapses and thus regulating basal and evoked synaptic transmission. Crucial for normal neuronal development, distribution, and electrical activity in the neocortex. Necessary for proper development of megakaryocytes and platelets and for bone marrow B-lymphopoiesis. Required for B-cell survival and proliferation in response to BCR stimulation, efficient IgG1 antibody responses to T-cell-dependent antigens and for normal induction of germinal center B-cells. May also be involved in neurogenesis and in the development of cortical architecture (By similarity). Isoform 3 and isoform 4, which lack the repressor domain, are more active than isoform 1 and isoform 2. {ECO:0000250|UniProtKB:Q8CFN5, ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:15340086, ECO:0000269|PubMed:15831463, ECO:0000269|PubMed:15834131, ECO:0000269|PubMed:9069290, ECO:0000269|PubMed:9384584}.
• Disease: DISEASE: Mental retardation, autosomal dominant 20 (MRD20) [MIM:613443]: A disorder characterized by severe mental retardation, absent speech, hypotonia, poor eye contact and stereotypic movements. Dysmorphic features include high broad forehead with variable small chin, short nose with anteverted nares, large open mouth, upslanted palpebral fissures and prominent eyebrows. Some patients have seizures. {ECO:0000269|PubMed:19592390}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Oxytocin signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);EGF-Core;Energy Metabolism;Heart Development;SRF and miRs in Smooth Muscle Differentiation and Proliferation;miRs in Muscle Cell Differentiation;Cell Differentiation - Index expanded;Cell Differentiation - Index;B Cell Receptor Signaling Pathway;Adipogenesis;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Cardiac Progenitor Differentiation;MECP2 and Associated Rett Syndrome;TGF-beta Signaling Pathway;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Prion disease pathway;EGF-EGFR Signaling Pathway;Endochondral Ossification;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Developmental Biology;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Signal Transduction;Signaling by Interleukins;role of erk5 in neuronal survival pathway;regulation of pgc-1a;p38 mapk signaling pathway;angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling;signal dependent regulation of myogenesis by corepressor mitr;alk in cardiac myocytes;nfat and hypertrophy of the heart ;carm1 and regulation of the estrogen receptor;mapkinase signaling pathway;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;Innate Immune System;Immune System;Nuclear Events (kinase and transcription factor activation);CDO in myogenesis;Myogenesis;Signaling by NTRK1 (TRKA);TGF_beta_Receptor;control of skeletal myogenesis by hdac and calcium/calmodulin-dependent kinase (camk);Signaling by NTRKs;ERK/MAPK targets;MAPK targets/ Nuclear events mediated by MAP kinases;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;Signaling events mediated by HDAC Class II;ErbB1 downstream signaling;MyD88 dependent cascade initiated on endosome;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Signaling by Receptor Tyrosine Kinases;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;Signaling mediated by p38-alpha and p38-beta;Regulation of retinoblastoma protein;Trk receptor signaling mediated by the MAPK pathway;Regulation of nuclear SMAD2/3 signaling (Consensus)

Recessive Scores

• pRec: 0.0941

Intolerance Scores

• loftool: 0.391
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58

Haploinsufficiency Scores

• pHI: 0.978
• hipred: Y
• hipred_score: 0.790
• ghis: 0.602

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mef2c
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; muscle phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: mef2ca
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: undifferentiated

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;MAPK cascade;blood vessel development;osteoblast differentiation;neuron migration;B cell homeostasis;heart looping;endochondral ossification;blood vessel remodeling;chondrocyte differentiation;germinal center formation;regulation of germinal center formation;primary heart field specification;secondary heart field specification;outflow tract morphogenesis;sinoatrial valve morphogenesis;cardiac ventricle formation;regulation of transcription, DNA-templated;transcription by RNA polymerase II;apoptotic process;humoral immune response;nervous system development;heart development;muscle organ development;skeletal muscle tissue development;muscle cell fate determination;learning or memory;positive regulation of gene expression;negative regulation of gene expression;positive regulation of alkaline phosphatase activity;neural crest cell differentiation;cardiac muscle hypertrophy in response to stress;myotube differentiation;neuron differentiation;platelet formation;monocyte differentiation;negative regulation of ossification;melanocyte differentiation;positive regulation of bone mineralization;positive regulation of B cell proliferation;cellular response to drug;skeletal muscle cell differentiation;cellular response to trichostatin A;B cell proliferation;regulation of neuron apoptotic process;negative regulation of neuron apoptotic process;negative regulation of blood vessel endothelial cell migration;regulation of megakaryocyte differentiation;positive regulation of myoblast differentiation;positive regulation of neuron differentiation;positive regulation of osteoblast differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of neurotransmitter secretion;regulation of synaptic plasticity;positive regulation of skeletal muscle tissue development;neuron development;cell morphogenesis involved in neuron differentiation;embryonic viscerocranium morphogenesis;B cell receptor signaling pathway;smooth muscle cell differentiation;positive regulation of muscle cell differentiation;regulation of synapse assembly;regulation of synaptic transmission, glutamatergic;ventricular cardiac muscle cell differentiation;roof of mouth development;regulation of synaptic activity;positive regulation of cardiac muscle cell proliferation;excitatory postsynaptic potential;regulation of sarcomere organization;cartilage morphogenesis;regulation of dendritic spine development;renal tubule morphogenesis;cellular response to lipopolysaccharide;cellular response to calcium ion;cellular response to parathyroid hormone stimulus;cellular response to fluid shear stress;cellular response to transforming growth factor beta stimulus;positive regulation of cell proliferation in bone marrow;glomerulus morphogenesis;nephron tubule epithelial cell differentiation;positive regulation of protein homodimerization activity;negative regulation of vascular smooth muscle cell proliferation;negative regulation of vascular associated smooth muscle cell migration;negative regulation of vascular endothelial cell proliferation;positive regulation of macrophage apoptotic process;regulation of NMDA receptor activity;regulation of AMPA receptor activity;positive regulation of cardiac muscle cell differentiation;positive regulation of behavioral fear response;epithelial cell proliferation involved in renal tubule morphogenesis;positive regulation of skeletal muscle cell differentiation
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;cytoplasm;sarcoplasm;nuclear speck;protein-containing complex;intracellular membrane-bounded organelle;postsynapse
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;AT DNA binding;chromatin binding;DNA-binding transcription factor activity;protein binding;RNA polymerase II general transcription initiation factor activity;activating transcription factor binding;histone deacetylase binding;transcription regulatory region DNA binding;protein heterodimerization activity;HMG box domain binding