EMD

emerin, the group of LEM domain containing

Basic information

Region (hg38): X:154379273-154381574

Links

ENSG00000102119 ∙ NCBI:2010 ∙ OMIM:300384 ∙ HGNC:3331 ∙ Uniprot:P50402 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• heart conduction disease (Strong), mode of inheritance: XL
• X-linked Emery-Dreifuss muscular dystrophy (Definitive), mode of inheritance: XL
• X-linked Emery-Dreifuss muscular dystrophy (Supportive), mode of inheritance: XL
• X-linked Emery-Dreifuss muscular dystrophy (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Emery-Dreifuss muscular dystrophy 1, X-linked	XL	Cardiovascular	Surveillance for and treatment of cardiac disease (eg, with EKG), including pacemaker implantation, may be beneficial	Cardiovascular; Musculoskeletal	4567289; 3319295; 2685312; 7894480; 9195226; 10377322; 10323252; 10382910; 20301609; 21496632; 21697856
Individuals, including females, can have serious cardiac conduction defects

ClinVar

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

• X-linked Emery-Dreifuss muscular dystrophy (49 variants)
• not provided (20 variants)
• Emery-Dreifuss muscular dystrophy 1, X-linked (3 variants)
• Cardiovascular phenotype (3 variants)
• Emery-Dreifuss muscular dystrophy (1 variants)
• EMD-related disorder (1 variants)
• Neuromuscular disease (1 variants)
• Myopathy;Flexion contracture;Failure to thrive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EMD 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			4	116	1	121
missense	1	1	142	11	2	157
nonsense	19	4				23
start loss	3					3
frameshift	30	10	2			42
inframe indel		1	7			8
splice donor/acceptor (+/-2bp)	9	6				15
splice region		1	10	17	1	29
non coding			1	71	7	79
Total	62	22	156	198	10

Highest pathogenic variant AF is 0.00000887

Variants in EMD

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

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

Position	Type	Phenotype	Significance	ClinVar
X-154379314-CGTGACGCGACAACGATTCGGCT-C		X-linked Emery-Dreifuss muscular dystrophy • EMD-related disorder	Likely benign (Nov 17, 2022)
X-154379351-A-G			Likely benign (Jul 09, 2018)
X-154379368-G-A		EMD-related disorder	Likely benign (May 05, 2021)
X-154379461-C-T		not specified	Likely benign (Mar 13, 2017)
X-154379478-A-C			Uncertain significance (Jan 24, 2017)
X-154379485-A-G		X-linked Emery-Dreifuss muscular dystrophy	Pathogenic (Jun 19, 2019)
X-154379486-T-G		X-linked Emery-Dreifuss muscular dystrophy	Pathogenic (Oct 02, 2020)
X-154379487-G-A		X-linked Emery-Dreifuss muscular dystrophy	Pathogenic (Jul 05, 2022)
X-154379493-C-T		X-linked Emery-Dreifuss muscular dystrophy	Likely benign (Mar 06, 2022)
X-154379496-C-A		X-linked Emery-Dreifuss muscular dystrophy	Pathogenic (May 28, 2019)
X-154379496-C-G		X-linked Emery-Dreifuss muscular dystrophy	Pathogenic (Jul 09, 2019)
X-154379496-C-T		X-linked Emery-Dreifuss muscular dystrophy • Emery-Dreifuss muscular dystrophy • Cardiovascular phenotype • EMD-related disorder • Cardiomyopathy	Conflicting classifications of pathogenicity (Jan 05, 2024)
X-154379499-A-G		X-linked Emery-Dreifuss muscular dystrophy	Likely benign (Apr 12, 2022)
X-154379499-AG-A		X-linked Emery-Dreifuss muscular dystrophy	Likely pathogenic (Oct 08, 2018)
X-154379502-T-A		Cardiovascular phenotype	Uncertain significance (Mar 08, 2022)
X-154379503-C-T		Dilated cardiomyopathy 1A	Uncertain significance (Oct 21, 2019)
X-154379503-CT-C		X-linked myopathy with postural muscle atrophy	Pathogenic (Feb 13, 2024)
X-154379504-T-A		X-linked Emery-Dreifuss muscular dystrophy	Uncertain significance (Nov 03, 2021)
X-154379507-C-G		Primary dilated cardiomyopathy • X-linked Emery-Dreifuss muscular dystrophy	Uncertain significance (Jul 24, 2023)
X-154379507-C-T		X-linked Emery-Dreifuss muscular dystrophy	Uncertain significance (Nov 03, 2021)
X-154379514-C-G		X-linked Emery-Dreifuss muscular dystrophy • Cardiovascular phenotype	Likely benign (Sep 23, 2023)
X-154379514-C-T		X-linked Emery-Dreifuss muscular dystrophy	Likely benign (Apr 24, 2022)
X-154379515-G-A		X-linked Emery-Dreifuss muscular dystrophy	Uncertain significance (Jun 25, 2022)
X-154379516-A-G		X-linked Emery-Dreifuss muscular dystrophy	Uncertain significance (Jun 15, 2022)
X-154379517-G-A		X-linked Emery-Dreifuss muscular dystrophy • Cardiovascular phenotype	Likely benign (Dec 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EMD	protein_coding	protein_coding	ENST00000369842	6	2327

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.932	0.0679	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.165	115	110	1.04	0.00000886	1642
Missense in Polyphen		32	37.278	0.85842		558
Synonymous	-2.42	64	43.7	1.47	0.00000335	511
Loss of Function	2.71	0	8.55	0.00	5.43e-7	152

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-catenin activity by preventing its accumulation in the nucleus. Acts by influencing the nuclear accumulation of beta- catenin through a CRM1-dependent export pathway. Links centrosomes to the nuclear envelope via a microtubule association. EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD. Required for proper localization of non-farnesylated prelamin-A/C. {ECO:0000269|PubMed:15328537, ECO:0000269|PubMed:16680152, ECO:0000269|PubMed:16858403, ECO:0000269|PubMed:17785515, ECO:0000269|PubMed:19323649}.
• Disease: DISEASE: Emery-Dreifuss muscular dystrophy 1, X-linked (EDMD1) [MIM:310300]: A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. {ECO:0000269|PubMed:10323252, ECO:0000269|PubMed:11587540, ECO:0000269|PubMed:15009215, ECO:0000269|PubMed:15328537}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Dilated cardiomyopathy (DCM) - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy;Clearance of Nuclear Envelope Membranes from Chromatin;Nuclear Envelope Breakdown;Mitotic Prophase;Initiation of Nuclear Envelope Reformation;Nuclear Envelope Reassembly;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.537

Intolerance Scores

• rvis_EVS: -0.05
• rvis_percentile_EVS: 49.76

Haploinsufficiency Scores

• pHI: 0.0626
• hipred: Y
• hipred_score: 0.701
• ghis: 0.462

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.493

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Emd
• Phenotype: homeostasis/metabolism phenotype; muscle 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: muscle contraction;mitotic nuclear envelope reassembly;muscle organ development;skeletal muscle cell differentiation;positive regulation of protein export from nucleus;negative regulation of fibroblast proliferation;regulation of canonical Wnt signaling pathway;cellular response to growth factor stimulus;negative regulation of canonical Wnt signaling pathway
• Cellular component: nuclear envelope;nuclear inner membrane;nuclear outer membrane;nucleoplasm;cytoplasm;endoplasmic reticulum;spindle;microtubule;membrane;integral component of membrane;spindle pole centrosome;nuclear membrane;cortical endoplasmic reticulum
• Molecular function: actin binding;protein binding;cadherin binding;beta-tubulin binding