EMD
emerin, the group of LEM domain containing
Basic information
Region (hg38): X:154379272-154381574
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- X-linked Emery-Dreifuss muscular dystrophy (386 variants)
- not provided (120 variants)
- Cardiovascular phenotype (89 variants)
- Emery-Dreifuss muscular dystrophy (55 variants)
- not specified (48 variants)
- Emery-Dreifuss muscular dystrophy 1, X-linked (25 variants)
- Cardiomyopathy (15 variants)
- Neuromuscular disease (3 variants)
- EMD-related condition (1 variants)
- Primary dilated cardiomyopathy (1 variants)
- Primary familial dilated cardiomyopathy (1 variants)
- See cases (1 variants)
- Myopathy;Flexion contracture;Failure to thrive (1 variants)
- Primary familial hypertrophic cardiomyopathy (1 variants)
- Hypertrophic cardiomyopathy (1 variants)
- Charcot-Marie-Tooth disease type 2 (1 variants)
- Dilated cardiomyopathy 1A (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 | 105 | 111 | ||||
| missense | 134 | 146 | ||||
| nonsense | 18 | 22 | ||||
| start loss | 3 | |||||
| frameshift | 28 | 38 | ||||
| inframe indel | 6 | |||||
| splice donor/acceptor (+/-2bp) | 12 | |||||
| splice region ? | 1 | 9 | 13 | 1 | 24 | |
| non coding ? | 42 | 49 | ||||
| Total | 57 | 19 | 146 | 156 | 9 |
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 (Jun 26, 2023) | ||
| 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 • Cardiomyopathy • EMD-related disorder | 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 | Likely 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:
| 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:
- 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
- loftool
- 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