Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Summary

Emery-Dreifuss muscular dystrophy 5, autosomal dominant (MONDO:0013072) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3,954

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Emery-Dreifuss muscular dystrophy 5, autosomal dominant
Mondo ID	MONDO:0013072
OMIM	612999
DOID	DOID:0070250
UMLS	C2751805
MedGen	414111
GARD	0018207
Is cancer (heuristic)	no

Also known as: autosomal dominant Emery-Dreifuss muscular dystrophy caused by mutation in SYNE2 · EDMD5 · Emery-Dreifuss muscular dystrophy 5, autosomal dominant · SYNE2 autosomal dominant Emery-Dreifuss muscular dystrophy

Data availability: 3,954 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant Emery-Dreifuss muscular dystrophy › Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Related subtypes (3): Emery-Dreifuss muscular dystrophy 4, autosomal dominant, Emery-Dreifuss muscular dystrophy 7, autosomal dominant, Emery-Dreifuss muscular dystrophy 2, autosomal dominant

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

600 retrieved; paginated sample, class counts are floors:

318 uncertain significance, 163 likely benign, 84 benign, 27 conflicting classifications of pathogenicity, 6 benign/likely benign, 1 pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1027485	NM_182914.3(SYNE2):c.2970C>A (p.Tyr990Ter)	SYNE2	Pathogenic	criteria provided, single submitter
1006912	NM_182914.3(SYNE2):c.8861C>T (p.Ala2954Val)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1027463	NM_182914.3(SYNE2):c.15142C>G (p.Gln5048Glu)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030386	NM_182914.3(SYNE2):c.9778C>T (p.Arg3260Cys)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1039825	NM_182914.3(SYNE2):c.14239A>G (p.Met4747Val)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1044193	NM_182914.3(SYNE2):c.16602C>G (p.Phe5534Leu)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1045035	NM_182914.3(SYNE2):c.19625G>A (p.Gly6542Glu)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1049337	NM_182914.3(SYNE2):c.17723G>A (p.Arg5908His)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1056431	NM_182914.3(SYNE2):c.11528C>T (p.Ser3843Leu)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1094345	NM_182914.3(SYNE2):c.14681G>A (p.Arg4894Gln)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1096599	NM_182914.3(SYNE2):c.16619C>G (p.Ala5540Gly)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1100676	NM_182914.3(SYNE2):c.20551C>G (p.Leu6851Val)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1139936	NM_182914.3(SYNE2):c.9303A>G (p.Ile3101Met)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1146903	NM_182914.3(SYNE2):c.1598C>T (p.Ala533Val)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1153593	NM_182914.3(SYNE2):c.18550C>T (p.Arg6184Trp)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1169434	NM_182914.3(SYNE2):c.12346G>A (p.Glu4116Lys)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1256347	NM_182914.3(SYNE2):c.10348T>C (p.Trp3450Arg)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1256350	NM_182914.3(SYNE2):c.2296A>G (p.Met766Val)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
130472	NM_182914.3(SYNE2):c.13417C>T (p.Pro4473Ser)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1335148	NM_182914.3(SYNE2):c.15316A>G (p.Met5106Val)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1337296	NM_182914.3(SYNE2):c.19726T>C (p.Leu6576=)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1353999	NM_182914.3(SYNE2):c.14063G>A (p.Arg4688Gln)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1368888	NM_182914.3(SYNE2):c.4768G>T (p.Val1590Phe)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1376229	NM_182914.3(SYNE2):c.16117A>G (p.Ile5373Val)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1389212	NM_182914.3(SYNE2):c.10070A>G (p.Tyr3357Cys)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1424305	NM_182914.3(SYNE2):c.2663C>T (p.Ser888Phe)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1425328	NM_182914.3(SYNE2):c.15776G>A (p.Ser5259Asn)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1441564	NM_182914.3(SYNE2):c.7481T>C (p.Ile2494Thr)	SYNE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000295	NM_182914.3(SYNE2):c.14962A>G (p.Ile4988Val)	SYNE2	Uncertain significance	criteria provided, single submitter
1000604	NM_182914.3(SYNE2):c.16514G>A (p.Arg5505Gln)	SYNE2	Uncertain significance	criteria provided, single submitter

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
SYNE2	Supportive	Autosomal dominant	autosomal dominant Emery-Dreifuss muscular dystrophy	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SYNE2	Orphanet:98853	Autosomal dominant 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
SYNE2	HGNC:17084	ENSG00000054654	Q8WXH0	Nesprin-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SYNE2	Nesprin-2	Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization.

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)
SYNE2	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat

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
ganglionic eminence	1
skeletal muscle tissue of biceps brachii	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SYNE2	284	ubiquitous	marker	ventricular zone, skeletal muscle tissue of biceps brachii, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SYNE2	2,276

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SYNE2	Q8WXH0	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Meiosis	1	285.5×	0.009	SYNE2
Reproduction	1	190.3×	0.009	SYNE2
Meiotic synapsis	1	141.0×	0.009	SYNE2
Cell Cycle	1	36.0×	0.028	SYNE2

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 migration along microfilament	1	8426.0×	5e-04	SYNE2
nucleokinesis involved in cell motility in cerebral cortex radial glia guided migration	1	5617.3×	5e-04	SYNE2
centrosome localization	1	887.0×	0.002	SYNE2
nuclear migration	1	732.7×	0.002	SYNE2
regulation of cilium assembly	1	601.9×	0.002	SYNE2
positive regulation of cell migration	1	61.7×	0.016	SYNE2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SYNE2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	SYNE2

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)
SYNE2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.