Emery-Dreifuss muscular dystrophy 1, X-linked

Summary

Emery-Dreifuss muscular dystrophy 1, X-linked (MONDO:0100531) is a disease caused by EMD (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: EMD (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 48

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Emery-Dreifuss muscular dystrophy 1, X-linked
Mondo ID	MONDO:0100531
OMIM	310300
DOID	DOID:0070246
NCIT	C168730
UMLS	C5243475
MedGen	1720295
GARD	0026265
Is cancer (heuristic)	no

Also known as: EDMD1 · EMD1 · Emery-Dreifuss muscular dystrophy 1, X-linked · Humeroperoneal neuromuscular disease

Data availability: 48 ClinVar variants · 1 GenCC gene-disease record · 7 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › X-linked disease › X-linked Emery-Dreifuss muscular dystrophy › Emery-Dreifuss muscular dystrophy 1, X-linked

Related subtypes (2): X-linked myopathy with postural muscle atrophy, Emery-Dreifuss muscular dystrophy 6, X-linked

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

48 retrieved; paginated sample, class counts are floors:

14 conflicting classifications of pathogenicity, 13 uncertain significance, 7 pathogenic, 5 pathogenic/likely pathogenic, 5 likely pathogenic, 2 benign/likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1074960	NM_000117.3(EMD):c.153del (p.Ser52fs)	EMD	Pathogenic	criteria provided, multiple submitters, no conflicts
179133	NM_000117.3(EMD):c.650_654dup (p.Gln219fs)	EMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2032371	NM_000117.3(EMD):c.674del (p.Leu225fs)	EMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2584927	NM_000117.3(EMD):c.282C>G (p.Tyr94Ter)	EMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280697	NM_000117.3(EMD):c.60del (p.Asn20fs)	EMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
289486	NM_000117.3(EMD):c.251_255del (p.Leu84fs)	EMD	Pathogenic	criteria provided, multiple submitters, no conflicts
3234967	NM_000117.3(EMD):c.512C>G (p.Ser171Ter)	EMD	Pathogenic	criteria provided, single submitter
3254765	NM_000117.3(EMD):c.428_430del (p.Ser143_Glu144delinsTer)	EMD	Pathogenic	criteria provided, single submitter
3366307	NM_000117.3(EMD):c.178del (p.Ser60fs)	EMD	Pathogenic	criteria provided, single submitter
4279045	NM_000117.3(EMD):c.2T>C (p.Met1Thr)	EMD	Pathogenic	criteria provided, single submitter
585847	NM_000117.3(EMD):c.116_143del (p.Phe39fs)	EMD	Pathogenic	criteria provided, multiple submitters, no conflicts
92441	NM_000117.3(EMD):c.450-2A>G	EMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2627908	NM_000117.3(EMD):c.441C>A (p.Cys147Ter)	EMD	Likely pathogenic	criteria provided, single submitter
3069158	NM_000117.3(EMD):c.662_663insT (p.Gln222fs)	EMD	Likely pathogenic	criteria provided, single submitter
3241393	NM_000117.3(EMD):c.450-1G>A	EMD	Likely pathogenic	criteria provided, single submitter
3896858	NM_000117.3(EMD):c.359C>A (p.Ser120Ter)	EMD	Likely pathogenic	criteria provided, single submitter
4731943	NM_000117.3(EMD):c.265+1G>A	EMD	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066332	NM_000117.3(EMD):c.104AGA[2] (p.Lys37del)	EMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1495732	NM_000117.3(EMD):c.422C>T (p.Ser141Phe)	EMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1563917	NM_000117.3(EMD):c.403C>T (p.His135Tyr)	EMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179659	NM_000117.3(EMD):c.77T>C (p.Val26Ala)	EMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198043	NM_000117.3(EMD):c.454C>T (p.Arg152Cys)	EMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
201777	NM_000117.3(EMD):c.671C>T (p.Pro224Leu)	EMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2675026	NM_000117.3(EMD):c.161C>T (p.Ser54Phe)	EMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
286452	NM_000117.3(EMD):c.610C>G (p.Arg204Gly)	EMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
36030	NM_000117.3(EMD):c.470G>A (p.Arg157Gln)	EMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
42277	NM_000117.3(EMD):c.571A>G (p.Met191Val)	EMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
42278	NM_000117.3(EMD):c.646G>A (p.Gly216Arg)	EMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
444835	NM_000117.3(EMD):c.400G>A (p.Val134Met)	EMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
531733	NM_000117.3(EMD):c.353G>A (p.Arg118His)	EMD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
EMD	Definitive	X-linked	X-linked Emery-Dreifuss muscular dystrophy	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EMD	Orphanet:98863	X-linked Emery-Dreifuss muscular dystrophy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EMD	HGNC:3331	ENSG00000102119	P50402	Emerin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EMD	Emerin	Stabilizes and promotes the formation of a nuclear actin cortical network.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EMD	Other/Unknown	no		LEM_dom, LEM/LEM-like_dom_sf, LEM_emerin

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ovary	1
left uterine tube	1
popliteal artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EMD	284	ubiquitous	marker	left ovary, left uterine tube, popliteal artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EMD	3,503

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EMD	P50402	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Depolymerization of the Nuclear Lamina	1	761.3×	0.005	EMD
Initiation of Nuclear Envelope (NE) Reformation	1	601.0×	0.005	EMD
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	1	475.8×	0.005	EMD
Nuclear Envelope Breakdown	1	456.8×	0.005	EMD
RHOD GTPase cycle	1	203.9×	0.009	EMD
RHOG GTPase cycle	1	148.3×	0.009	EMD
RAC2 GTPase cycle	1	126.9×	0.009	EMD
RAC3 GTPase cycle	1	119.0×	0.009	EMD
RAC1 GTPase cycle	1	61.1×	0.016	EMD

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
nuclear membrane organization	1	2407.4×	0.004	EMD
positive regulation of protein export from nucleus	1	802.5×	0.004	EMD
amyloid fibril formation	1	601.9×	0.004	EMD
regulation of canonical Wnt signaling pathway	1	543.6×	0.004	EMD
negative regulation of fibroblast proliferation	1	495.6×	0.004	EMD
skeletal muscle cell differentiation	1	343.9×	0.004	EMD
cellular response to growth factor stimulus	1	318.0×	0.004	EMD
muscle contraction	1	208.1×	0.006	EMD
muscle organ development	1	166.8×	0.007	EMD
negative regulation of canonical Wnt signaling pathway	1	117.8×	0.008	EMD

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EMD	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
EMD	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	EMD

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
EMD	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.