Emery-Dreifuss muscular dystrophy
diseaseOn this page
Also known as EDMDEmery Dreifuss Muscular DystrophyHumeroperoneal neuromuscular disease, (formerly)scapuloperoneal syndrome, X-linked (formerly)
Summary
Emery-Dreifuss muscular dystrophy (MONDO:0016830) is a disease with 9 cohort genes and 1 clinical trial. The dominant Reactome pathway is Meiotic synapsis (3 cohort genes).
At a glance
- Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
- Cohort genes: 9
- ClinVar variants: 1,200
- Phenotypes (HPO): 44
- Clinical trials: 1
Clinical features
Epidemiology
Prevalence records
1 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Point prevalence | 1-9 / 1 000 000 | 0.3 | Europe | Validated |
Signs & symptoms
Clinical features (HPO)
44 HPO clinical features (Orphanet curated; top 44 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000767 | Pectus excavatum | Very frequent (80-99%) |
| HP:0001315 | Reduced tendon reflexes | Very frequent (80-99%) |
| HP:0001387 | Joint stiffness | Very frequent (80-99%) |
| HP:0002486 | Myotonia | Very frequent (80-99%) |
| HP:0003198 | Myopathy | Very frequent (80-99%) |
| HP:0003236 | Elevated circulating creatine kinase concentration | Very frequent (80-99%) |
| HP:0006785 | Limb-girdle muscular dystrophy | Very frequent (80-99%) |
| HP:0000912 | Sprengel anomaly | Frequent (30-79%) |
| HP:0001288 | Gait disturbance | Frequent (30-79%) |
| HP:0001771 | Achilles tendon contracture | Frequent (30-79%) |
| HP:0002155 | Hypertriglyceridemia | Frequent (30-79%) |
| HP:0002515 | Waddling gait | Frequent (30-79%) |
| HP:0002987 | Elbow flexion contracture | Frequent (30-79%) |
| HP:0003141 | Increased LDL cholesterol concentration | Frequent (30-79%) |
| HP:0003306 | Spinal rigidity | Frequent (30-79%) |
| HP:0003418 | Back pain | Frequent (30-79%) |
| HP:0003458 | EMG: myopathic abnormalities | Frequent (30-79%) |
| HP:0003691 | Scapular winging | Frequent (30-79%) |
| HP:0003805 | Rimmed vacuoles | Frequent (30-79%) |
| HP:0004631 | Decreased cervical spine flexion due to contractures of posterior cervical muscles | Frequent (30-79%) |
| HP:0008948 | Proximal upper limb amyotrophy | Frequent (30-79%) |
| HP:0008956 | Proximal lower limb amyotrophy | Frequent (30-79%) |
| HP:0008994 | Proximal muscle weakness in lower limbs | Frequent (30-79%) |
| HP:0008997 | Proximal muscle weakness in upper limbs | Frequent (30-79%) |
| HP:0011807 | Type 1 muscle fiber atrophy | Frequent (30-79%) |
| HP:0030051 | Tip-toe gait | Frequent (30-79%) |
| HP:0030117 | Absent muscle fiber emerin | Frequent (30-79%) |
| HP:0000508 | Ptosis | Occasional (5-29%) |
| HP:0001252 | Hypotonia | Occasional (5-29%) |
| HP:0001513 | Obesity | Occasional (5-29%) |
| HP:0001644 | Dilated cardiomyopathy | Occasional (5-29%) |
| HP:0001678 | Atrioventricular block | Occasional (5-29%) |
| HP:0002650 | Scoliosis | Occasional (5-29%) |
| HP:0002808 | Kyphosis | Occasional (5-29%) |
| HP:0003307 | Hyperlordosis | Occasional (5-29%) |
| HP:0005115 | Supraventricular arrhythmia | Occasional (5-29%) |
| HP:0008064 | Ichthyosis | Occasional (5-29%) |
| HP:0009125 | Lipodystrophy | Occasional (5-29%) |
| HP:0001249 | Intellectual disability | Excluded (0%) |
| HP:0001605 | Vocal cord paralysis | Very rare (<1-4%) |
| HP:0001639 | Hypertrophic cardiomyopathy | Very rare (<1-4%) |
| HP:0001645 | Sudden cardiac death | Very rare (<1-4%) |
| HP:0002747 | Respiratory insufficiency due to muscle weakness | Very rare (<1-4%) |
| HP:0005155 | Ventricular escape rhythm | Very rare (<1-4%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Emery-Dreifuss muscular dystrophy |
| Mondo ID | MONDO:0016830 |
| MeSH | D020389 |
| OMIM | 310300 |
| Orphanet | 261 |
| DOID | DOID:11726 |
| ICD-11 | 749295636 |
| NCIT | C84685 |
| SNOMED CT | 111508004 |
| UMLS | C0410189 |
| MedGen | 96078 |
| GARD | 0006329 |
| NORD | 1084 |
| Is cancer (heuristic) | no |
Also known as: EDMD · Emery Dreifuss Muscular Dystrophy · Emery-Dreifuss muscular dystrophy · Humeroperoneal neuromuscular disease, (formerly) · scapuloperoneal syndrome, X-linked (formerly)
Data availability: 1,200 ClinVar variants · 5 cell lines.
Disease family
An umbrella term covering 4 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › muscular dystrophy › progressive muscular dystrophy › Emery-Dreifuss muscular dystrophy
Related subtypes (12): facioscapulohumeral muscular dystrophy, congenital fibrosis of extraocular muscles, Bethlem myopathy, oculopharyngeal muscular dystrophy, X-linked myopathy with excessive autophagy, myopathy, myofibrillar, 9, with early respiratory failure, progressive scapulohumeroperoneal distal myopathy, symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers, myotonic dystrophy, limb-girdle muscular dystrophy, childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome, oculopharyngodistal myopathy
Subtypes (4): scapuloperoneal myopathy, X-linked Emery-Dreifuss muscular dystrophy, Emery-Dreifuss muscular dystrophy 3, autosomal recessive, autosomal dominant Emery-Dreifuss muscular dystrophy
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:
290 uncertain significance, 234 likely benign, 36 benign, 31 conflicting classifications of pathogenicity, 4 benign/likely benign, 4 pathogenic, 1 uncertain significance/uncertain risk allele
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1453367 | NM_000117.3(EMD):c.399+1G>T | EMD | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 163403 | NM_000117.3(EMD):c.266-2A>G | EMD | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 2833998 | NM_000117.3(EMD):c.399+2T>C | EMD | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14525 | NM_170707.4(LMNA):c.1072G>A (p.Glu358Lys) | LMNA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 224680 | NM_170707.4(LMNA):c.985C>G (p.Arg329Gly) | LMNA | Uncertain significance/Uncertain risk allele | criteria provided, multiple submitters, no conflicts |
| 2424101 | NC_000022.10:g.(?37154355)(39148633_?)del | ANKRD54 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1066332 | NM_000117.3(EMD):c.104AGA[2] (p.Lys37del) | EMD | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 163404 | NM_000117.3(EMD):c.598T>C (p.Trp200Arg) | 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 |
| 201773 | NM_000117.3(EMD):c.449+5G>A | 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 |
| 201781 | NM_000117.3(EMD):c.545_547del (p.Tyr182_Pro183delinsSer) | EMD | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 227353 | NM_000117.3(EMD):c.400-9C>T | EMD | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 237013 | NM_000117.3(EMD):c.428C>T (p.Ser143Phe) | EMD | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 282181 | NM_000117.3(EMD):c.662G>T (p.Arg221Leu) | EMD | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 285164 | NM_000117.3(EMD):c.149C>A (p.Pro50His) | EMD | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1011860 | NM_015374.3(SUN2):c.1301C>T (p.Ser434Leu) | GTPBP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 178061 | NM_170707.4(LMNA):c.1488+14C>T | LMNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 199111 | NM_170707.4(LMNA):c.1551G>A (p.Gln517=) | LMNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 200934 | NM_170707.4(LMNA):c.398G>A (p.Arg133Gln) | LMNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 200936 | NM_170707.4(LMNA):c.471G>A (p.Thr157=) | LMNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 222694 | NM_170707.4(LMNA):c.937-8C>A | LMNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 245964 | NM_170707.4(LMNA):c.1487C>T (p.Thr496Met) | LMNA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1001133 | NM_001130965.3(SUN1):c.238G>A (p.Ala80Thr) | SUN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1002198 | NM_001130965.3(SUN1):c.900C>G (p.Phe300Leu) | SUN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1023177 | NM_001130965.3(SUN1):c.1921A>G (p.Met641Val) | SUN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1037447 | NM_001130965.3(SUN1):c.1390A>G (p.Ile464Val) | SUN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1356913 | NM_001130965.3(SUN1):c.1923G>A (p.Met641Ile) | SUN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1371425 | NM_001130965.3(SUN1):c.945T>A (p.Phe315Leu) | SUN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1376770 | NM_001130965.3(SUN1):c.1513G>A (p.Val505Ile) | SUN1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 32 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| DNAAF5 | Orphanet:244 | Primary ciliary dyskinesia |
| EMD | Orphanet:98863 | X-linked Emery-Dreifuss muscular dystrophy |
| FHL1 | Orphanet:178461 | X-linked myopathy with postural muscle atrophy |
| FHL1 | Orphanet:431272 | X-linked scapuloperoneal muscular dystrophy |
| FHL1 | Orphanet:97239 | Reducing body myopathy |
| FHL1 | Orphanet:98863 | X-linked Emery-Dreifuss muscular dystrophy |
| LMNA | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| LMNA | Orphanet:157973 | Congenital muscular dystrophy due to LMNA mutation |
| LMNA | Orphanet:1662 | Restrictive dermopathy |
| LMNA | Orphanet:168796 | Heart-hand syndrome, Slovenian type |
| LMNA | Orphanet:2229 | Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome |
| LMNA | Orphanet:2348 | Familial partial lipodystrophy, Dunnigan type |
| LMNA | Orphanet:280365 | Autosomal semi-dominant severe lipodystrophic laminopathy |
| LMNA | Orphanet:293888 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant |
| LMNA | Orphanet:293899 | Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant |
| LMNA | Orphanet:293910 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant |
| LMNA | Orphanet:300751 | Familial dilated cardiomyopathy with conduction defect due to LMNA mutation |
| LMNA | Orphanet:363618 | LMNA-related cardiocutaneous progeria syndrome |
| LMNA | Orphanet:54260 | Left ventricular noncompaction |
| LMNA | Orphanet:675396 | Epithelioid hemangioma |
| LMNA | Orphanet:740 | Hutchinson-Gilford progeria syndrome |
| LMNA | Orphanet:79084 | Familial partial lipodystrophy, Köbberling type |
| LMNA | Orphanet:79474 | Atypical Werner syndrome |
| LMNA | Orphanet:90153 | Mandibuloacral dysplasia with type A lipodystrophy |
| LMNA | Orphanet:98853 | Autosomal dominant Emery-Dreifuss muscular dystrophy |
| LMNA | Orphanet:98855 | Autosomal recessive Emery-Dreifuss muscular dystrophy |
| LMNA | Orphanet:98856 | Charcot-Marie-Tooth disease type 2B1 |
| LZTR1 | Orphanet:251576 | Gliosarcoma |
| LZTR1 | Orphanet:251579 | Giant cell glioblastoma |
| LZTR1 | Orphanet:2678 | Familial isolated café-au-lait macules |
| LZTR1 | Orphanet:648 | Noonan syndrome |
| LZTR1 | Orphanet:93921 | Full schwannomatosis |
Cohort genes → proteins
9 cohort genes, 9 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 9 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| SUN2 | HGNC:14210 | ENSG00000100242 | Q9UH99 | SUN domain-containing protein 2 | clinvar |
| SUN1 | HGNC:18587 | ENSG00000164828 | O94901 | SUN domain-containing protein 1 | clinvar |
| ANKRD54 | HGNC:25185 | ENSG00000100124 | Q6NXT1 | Ankyrin repeat domain-containing protein 54 | clinvar |
| DNAAF5 | HGNC:26013 | ENSG00000164818 | Q86Y56 | Dynein axonemal assembly factor 5 | clinvar |
| EMD | HGNC:3331 | ENSG00000102119 | P50402 | Emerin | clinvar |
| FHL1 | HGNC:3702 | ENSG00000022267 | Q13642 | Four and a half LIM domains protein 1 | clinvar |
| GTPBP1 | HGNC:4669 | ENSG00000100226 | O00178 | GTP-binding protein 1 | clinvar |
| LMNA | HGNC:6636 | ENSG00000160789 | P02545 | Prelamin-A/C | clinvar |
| LZTR1 | HGNC:6742 | ENSG00000099949 | Q8N653 | Leucine-zipper-like transcriptional regulator 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SUN2 | SUN domain-containing protein 2 | As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. |
| SUN1 | SUN domain-containing protein 1 | As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. |
| ANKRD54 | Ankyrin repeat domain-containing protein 54 | Plays an important role in regulating intracellular signaling events associated with erythroid terminal differentiation. |
| DNAAF5 | Dynein axonemal assembly factor 5 | Cytoplasmic protein involved in the delivery of the dynein machinery to the motile cilium. |
| EMD | Emerin | Stabilizes and promotes the formation of a nuclear actin cortical network. |
| FHL1 | Four and a half LIM domains protein 1 | May have an involvement in muscle development or hypertrophy. |
| GTPBP1 | GTP-binding protein 1 | GTPase that plays a role in the elongation phase of protein synthesis by forming ternary complexes with GTP and aminoacyl-transfer RNAs (aa-tRNAs), and delivering aa-tRNAs to the ribosomal A site in a GTP-dependent manner. |
| LMNA | Prelamin-A/C | Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane. |
| LZTR1 | Leucine-zipper-like transcriptional regulator 1 | Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates ubiquitination of Ras (K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS). |
Protein-family classification
Druggable: 0 · Difficult: 2 · Unknown: 7 · 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 | 7 | 1.4× | 0.484 |
| Scaffold/PPI | 1 | 1.9× | 0.623 |
| Transcription factor | 1 | 0.9× | 0.687 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| SUN2 | Other/Unknown | no | SUN_dom, Sun_CC2, SUN1-5 | |
| SUN1 | Other/Unknown | no | SUN_dom, SUN1_N, Sun_CC2 | |
| ANKRD54 | Scaffold/PPI | no | Ankyrin_rpt, Ankyrin_rpt-contain_sf | |
| DNAAF5 | Other/Unknown | no | HEAT, ARM-like, ARM-type_fold | |
| EMD | Other/Unknown | no | LEM_dom, LEM/LEM-like_dom_sf, LEM_emerin | |
| FHL1 | Transcription factor | no | Znf_LIM, Fhl1, LIM_FHL1/2/3/5_N | |
| GTPBP1 | Other/Unknown | no | T_Tr_GTP-bd_dom, EFTu-like_2, Transl_B-barrel_sf | |
| LMNA | Other/Unknown | no | Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf | |
| LZTR1 | Other/Unknown | no | BTB/POZ_dom, Kelch_1, SKP1/BTB/POZ_sf |
Expression context
Cohort genes with no expression data: 0.
9 cohort genes 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) | 9 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| mucosa of stomach | 4 |
| secondary oocyte | 2 |
| sural nerve | 2 |
| granulocyte | 1 |
| right coronary artery | 1 |
| oocyte | 1 |
| kidney epithelium | 1 |
| right testis | 1 |
| right uterine tube | 1 |
| bronchial epithelial cell | 1 |
| epithelium of bronchus | 1 |
| left ovary | 1 |
| left uterine tube | 1 |
| popliteal artery | 1 |
| biceps brachii | 1 |
| skeletal muscle tissue of biceps brachii | 1 |
| skeletal muscle tissue of rectus abdominis | 1 |
| ventricular zone | 1 |
| nipple | 1 |
| skin of abdomen | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SUN2 | 288 | ubiquitous | marker | granulocyte, mucosa of stomach, right coronary artery |
| SUN1 | 295 | ubiquitous | marker | secondary oocyte, oocyte, mucosa of stomach |
| ANKRD54 | 247 | ubiquitous | marker | right uterine tube, kidney epithelium, right testis |
| DNAAF5 | 280 | ubiquitous | marker | bronchial epithelial cell, secondary oocyte, epithelium of bronchus |
| EMD | 284 | ubiquitous | marker | left ovary, left uterine tube, popliteal artery |
| FHL1 | 291 | ubiquitous | marker | skeletal muscle tissue of rectus abdominis, biceps brachii, skeletal muscle tissue of biceps brachii |
| GTPBP1 | 269 | ubiquitous | marker | sural nerve, mucosa of stomach, ventricular zone |
| LMNA | 295 | ubiquitous | marker | nipple, mucosa of stomach, skin of abdomen |
| LZTR1 | 134 | ubiquitous | marker | sural nerve, pituitary gland, adenohypophysis |
Protein interactions among cohort
Intra-cohort edges: 7.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| LMNA | 7,173 |
| EMD | 3,503 |
| SUN2 | 2,123 |
| SUN1 | 1,844 |
| LZTR1 | 1,562 |
| FHL1 | 1,431 |
| GTPBP1 | 1,280 |
| ANKRD54 | 1,122 |
| DNAAF5 | 996 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| EMD | FHL1 | string_interaction |
| EMD | LMNA | intact, string_interaction |
| EMD | SUN1 | string_interaction |
| EMD | SUN2 | string_interaction |
| LMNA | SUN1 | string_interaction |
| LMNA | SUN2 | intact, string_interaction |
| SUN1 | SUN2 | string_interaction |
Structural data
PDB: 7 · AlphaFold-only: 2 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| LMNA | P02545 | 28 |
| SUN2 | Q9UH99 | 9 |
| SUN1 | O94901 | 8 |
| EMD | P50402 | 6 |
| GTPBP1 | O00178 | 6 |
| FHL1 | Q13642 | 4 |
| LZTR1 | Q8N653 | 3 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| DNAAF5 | Q86Y56 | 92.80 |
| ANKRD54 | Q6NXT1 | 68.74 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 9 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Meiotic synapsis | 3 | 105.7× | 3e-05 | SUN2, SUN1, LMNA |
| Depolymerization of the Nuclear Lamina | 2 | 380.7× | 1e-04 | EMD, LMNA |
| Initiation of Nuclear Envelope (NE) Reformation | 2 | 300.5× | 1e-04 | EMD, LMNA |
| Nuclear Envelope Breakdown | 2 | 228.4× | 2e-04 | EMD, LMNA |
| Meiosis | 2 | 142.8× | 4e-04 | SUN2, SUN1 |
| Reproduction | 2 | 95.2× | 7e-04 | SUN2, SUN1 |
| Breakdown of the nuclear lamina | 1 | 951.7× | 0.004 | LMNA |
| Cell Cycle | 2 | 18.0× | 0.014 | SUN2, SUN1 |
| IRE1alpha activates chaperones | 1 | 129.8× | 0.019 | LMNA |
| Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models | 1 | 129.8× | 0.019 | LMNA |
| Insertion of tail-anchored proteins into the endoplasmic reticulum membrane | 1 | 119.0× | 0.019 | EMD |
| Unfolded Protein Response (UPR) | 1 | 89.2× | 0.023 | LMNA |
| Dengue Virus Genome Translation and Replication | 1 | 79.3× | 0.024 | SUN2 |
| Oncogenic MAPK signaling | 1 | 62.1× | 0.029 | LMNA |
| XBP1(S) activates chaperone genes | 1 | 53.9× | 0.030 | LMNA |
| RHOD GTPase cycle | 1 | 51.0× | 0.030 | EMD |
| Signaling by BRAF and RAF1 fusions | 1 | 42.6× | 0.034 | LMNA |
| RHOG GTPase cycle | 1 | 37.1× | 0.037 | EMD |
| RAC2 GTPase cycle | 1 | 31.7× | 0.041 | EMD |
| RAC3 GTPase cycle | 1 | 29.7× | 0.042 | EMD |
| RAC1 GTPase cycle | 1 | 15.3× | 0.076 | EMD |
| Diseases of signal transduction by growth factor receptors and second messengers | 1 | 14.2× | 0.078 | LMNA |
| Cellular responses to stress | 1 | 9.2× | 0.113 | LMNA |
| Cellular responses to stimuli | 1 | 7.9× | 0.126 | LMNA |
| Disease | 1 | 3.3× | 0.273 | LMNA |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| nucleokinesis involved in cell motility in cerebral cortex radial glia guided migration | 2 | 1248.3× | 3e-05 | SUN2, SUN1 |
| nuclear matrix anchoring at nuclear membrane | 2 | 1248.3× | 3e-05 | SUN2, SUN1 |
| muscle organ development | 3 | 55.6× | 4e-04 | EMD, FHL1, LMNA |
| centrosome localization | 2 | 197.1× | 7e-04 | SUN2, SUN1 |
| nuclear migration | 2 | 162.8× | 9e-04 | SUN2, LMNA |
| nuclear migration along microfilament | 1 | 936.2× | 0.010 | SUN2 |
| RNA surveillance | 1 | 936.2× | 0.010 | GTPBP1 |
| DNA double-strand break attachment to nuclear envelope | 1 | 624.1× | 0.014 | LMNA |
| establishment or maintenance of microtubule cytoskeleton polarity | 1 | 468.1× | 0.016 | LMNA |
| nuclear pore localization | 1 | 374.5× | 0.016 | LMNA |
| meiotic attachment of telomere to nuclear envelope | 1 | 374.5× | 0.016 | SUN1 |
| negative regulation of mesenchymal cell proliferation | 1 | 312.1× | 0.018 | LMNA |
| nuclear membrane organization | 1 | 267.5× | 0.019 | EMD |
| protein localization to nuclear envelope | 1 | 234.1× | 0.019 | LMNA |
| regulation of protein localization to nucleus | 1 | 234.1× | 0.019 | LMNA |
| regulation of atrial cardiac muscle cell membrane depolarization | 1 | 208.1× | 0.019 | FHL1 |
| negative regulation of cardiac muscle hypertrophy in response to stress | 1 | 208.1× | 0.019 | LMNA |
| ventricular cardiac muscle cell development | 1 | 170.2× | 0.022 | LMNA |
| translational elongation | 1 | 133.8× | 0.025 | GTPBP1 |
| positive regulation of mRNA catabolic process | 1 | 133.8× | 0.025 | GTPBP1 |
| negative regulation of G2/M transition of mitotic cell cycle | 1 | 124.8× | 0.025 | FHL1 |
| GTP metabolic process | 1 | 124.8× | 0.025 | GTPBP1 |
| nuclear envelope organization | 1 | 110.1× | 0.026 | LMNA |
| positive regulation of potassium ion transmembrane transport | 1 | 110.1× | 0.026 | FHL1 |
| inner dynein arm assembly | 1 | 98.5× | 0.026 | DNAAF5 |
| regulation of intracellular signal transduction | 1 | 98.5× | 0.026 | ANKRD54 |
| regulation of telomere maintenance | 1 | 93.6× | 0.026 | LMNA |
| positive regulation of protein export from nucleus | 1 | 89.2× | 0.026 | EMD |
| negative regulation of release of cytochrome c from mitochondria | 1 | 89.2× | 0.026 | LMNA |
| outer dynein arm assembly | 1 | 81.4× | 0.028 | DNAAF5 |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 8
Druggability breadth: 4 of 9 evidence-associated genes (44%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| LMNA | BEPRIDIL |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| LMNA | 823 | 4 |
| SUN2 | 0 | 0 |
| SUN1 | 0 | 0 |
| ANKRD54 | 0 | 0 |
| DNAAF5 | 0 | 0 |
| EMD | 0 | 0 |
| FHL1 | 0 | 0 |
| GTPBP1 | 0 | 0 |
| LZTR1 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| BEPRIDIL | 4 | LMNA |
| PHENYLBUTAZONE | 4 | LMNA |
| CEFOTAXIME SODIUM | 4 | LMNA |
| DIENESTROL | 4 | LMNA |
| IFOSFAMIDE | 4 | LMNA |
| PROGESTERONE | 4 | LMNA |
| CLOTRIMAZOLE | 4 | LMNA |
| DAPSONE | 4 | LMNA |
| AMINOCAPROIC ACID | 4 | LMNA |
| FLUCONAZOLE | 4 | LMNA |
| COLCHICINE | 4 | LMNA |
| NABUMETONE | 4 | LMNA |
| OXAPROZIN | 4 | LMNA |
| BUMETANIDE | 4 | LMNA |
| GLIPIZIDE | 4 | LMNA |
| BROMFENAC | 4 | LMNA |
| ROPIVACAINE | 4 | LMNA |
| TIZANIDINE | 4 | LMNA |
| METAXALONE | 4 | LMNA |
| CARBAMAZEPINE | 4 | LMNA |
| SALMETEROL XINAFOATE | 4 | LMNA |
| AMIODARONE HYDROCHLORIDE | 4 | LMNA |
| METHYL SALICYLATE | 4 | LMNA |
| DIBUCAINE | 4 | LMNA |
| PHENELZINE | 4 | LMNA |
| HYDROCORTISONE ACETATE | 4 | LMNA |
| BRETYLIUM TOSYLATE | 4 | LMNA |
| IMIPRAMINE | 4 | LMNA |
| FURAZOLIDONE | 4 | LMNA |
| DROPERIDOL | 4 | LMNA |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| LMNA | 12 | Binding:9, Functional:3 |
| SUN2 | 1 | Binding:1 |
| ANKRD54 | 1 | Binding:1 |
| EMD | 1 | Binding:1 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
30 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.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| BEPRIDIL | 4 | LMNA |
| PHENYLBUTAZONE | 4 | LMNA |
| CEFOTAXIME SODIUM | 4 | LMNA |
| DIENESTROL | 4 | LMNA |
| IFOSFAMIDE | 4 | LMNA |
| PROGESTERONE | 4 | LMNA |
| CLOTRIMAZOLE | 4 | LMNA |
| DAPSONE | 4 | LMNA |
| AMINOCAPROIC ACID | 4 | LMNA |
| FLUCONAZOLE | 4 | LMNA |
| COLCHICINE | 4 | LMNA |
| NABUMETONE | 4 | LMNA |
| OXAPROZIN | 4 | LMNA |
| BUMETANIDE | 4 | LMNA |
| GLIPIZIDE | 4 | LMNA |
| BROMFENAC | 4 | LMNA |
| ROPIVACAINE | 4 | LMNA |
| TIZANIDINE | 4 | LMNA |
| METAXALONE | 4 | LMNA |
| CARBAMAZEPINE | 4 | LMNA |
| SALMETEROL XINAFOATE | 4 | LMNA |
| AMIODARONE HYDROCHLORIDE | 4 | LMNA |
| METHYL SALICYLATE | 4 | LMNA |
| DIBUCAINE | 4 | LMNA |
| PHENELZINE | 4 | LMNA |
| HYDROCORTISONE ACETATE | 4 | LMNA |
| BRETYLIUM TOSYLATE | 4 | LMNA |
| IMIPRAMINE | 4 | LMNA |
| FURAZOLIDONE | 4 | LMNA |
| DROPERIDOL | 4 | LMNA |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | LMNA |
| 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 | 8 | SUN2, SUN1, ANKRD54, DNAAF5, EMD, FHL1, GTPBP1, LZTR1 |
Undrugged target profiles
8 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| SUN2 | 1 | LMNA |
| SUN1 | 0 | LMNA |
| EMD | 1 | LMNA |
| ANKRD54 | 1 | — |
| DNAAF5 | 0 | — |
| FHL1 | 0 | — |
| GTPBP1 | 0 | — |
| LZTR1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 1.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT01403402 | Not specified | RECRUITING | Congenital Muscle Disease Study of Patient and Family Reported Medical Information |