Emery-Dreifuss muscular dystrophy 2, autosomal dominant
diseaseOn this page
Also known as autosomal dominant limb-girdle muscular dystrophy caused by mutation in LMNAbenign scapuloperoneal muscular dystrophy with cardiomyopathyEDMD2EMD2Hauptmann-Thannhauser muscular dystrophyLGMD1Blimb-girdle muscular dystrophy due to lamin A/C deficiencylimb-girdle muscular dystrophy type 1BLMNA autosomal dominant limb-girdle muscular dystrophymuscular dystrophy, limb-girdle type 1Bmuscular dystrophy, limb-girdle, type 1Bmuscular dystrophy, proximal, type 1Bproximal muscular dystrophy type 1B
Summary
Emery-Dreifuss muscular dystrophy 2, autosomal dominant (MONDO:0021569) is a disease caused by LMNA (GenCC Definitive), with 3 cohort genes and 1 clinical trial.
At a glance
- Causal gene: LMNA (GenCC Definitive)
- Cohort genes: 3
- ClinVar variants: 280
- Clinical trials: 1
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Emery-Dreifuss muscular dystrophy 2, autosomal dominant |
| Mondo ID | MONDO:0021569 |
| MeSH | C535898 |
| OMIM | 159001, 181350 |
| Orphanet | 264 |
| DOID | DOID:0070247, DOID:0110301 |
| NCIT | C126745 |
| SNOMED CT | 240072005, 718178006 |
| UMLS | C0410190 |
| MedGen | 98048 |
| GARD | 0010230 |
| Is cancer (heuristic) | no |
Also known as: autosomal dominant limb-girdle muscular dystrophy caused by mutation in LMNA · benign scapuloperoneal muscular dystrophy with cardiomyopathy · EDMD2 · EMD2 · Emery-Dreifuss muscular dystrophy 2, autosomal dominant · Hauptmann-Thannhauser muscular dystrophy · LGMD1B · limb-girdle muscular dystrophy due to lamin A/C deficiency · limb-girdle muscular dystrophy type 1B · LMNA autosomal dominant limb-girdle muscular dystrophy · muscular dystrophy, limb-girdle type 1B · muscular dystrophy, limb-girdle, type 1B · muscular dystrophy, proximal, type 1B · proximal muscular dystrophy type 1B
Data availability: 280 ClinVar variants · 3 GenCC gene-disease records · 5 cell lines.
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 › muscular dystrophy, limb-girdle, autosomal dominant › Emery-Dreifuss muscular dystrophy 2, autosomal dominant
Related subtypes (7): autosomal dominant limb-girdle muscular dystrophy type 1F, autosomal dominant limb-girdle muscular dystrophy type 1G, myofibrillar myopathy 3, autosomal dominant limb-girdle muscular dystrophy type 1H, autosomal dominant limb-girdle muscular dystrophy type 1E (DES), autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6), muscular dystrophy, limb-girdle, autosomal dominant 4
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
280 retrieved; paginated sample, class counts are floors:
122 uncertain significance, 74 conflicting classifications of pathogenicity, 21 pathogenic, 19 pathogenic/likely pathogenic, 18 likely benign, 10 benign/likely benign, 8 likely pathogenic, 4 benign, 3 uncertain significance/uncertain risk allele, 1 not provided
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 14478 | NM_170707.4(LMNA):c.1357C>T (p.Arg453Trp) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 14481 | NM_170707.4(LMNA):c.1580G>C (p.Arg527Pro) | LMNA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14482 | NM_170707.4(LMNA):c.1589T>C (p.Leu530Pro) | LMNA | Pathogenic | no assertion criteria provided |
| 14489 | NM_170707.4(LMNA):c.1444C>T (p.Arg482Trp) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 14491 | NM_170707.4(LMNA):c.960del (p.Arg321fs) | LMNA | Pathogenic | criteria provided, single submitter |
| 14495 | NM_170707.4(LMNA):c.1130G>A (p.Arg377His) | LMNA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14511 | NM_170707.4(LMNA):c.777T>A (p.Tyr259Ter) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 14514 | NM_170707.4(LMNA):c.1477C>T (p.Gln493Ter) | LMNA | 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 |
| 1457399 | NM_170707.4(LMNA):c.822del (p.Arg275fs) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1691500 | NM_170707.4(LMNA):c.1549_1550del (p.Gln517fs) | LMNA | Pathogenic | no assertion criteria provided |
| 1695415 | NM_170707.4(LMNA):c.1381-2A>C | LMNA | Pathogenic | no assertion criteria provided |
| 200941 | NM_170707.4(LMNA):c.768G>A (p.Val256=) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 216958 | NM_170707.4(LMNA):c.810+1G>C | LMNA | Pathogenic | criteria provided, single submitter |
| 246077 | NM_170707.4(LMNA):c.1540T>C (p.Trp514Arg) | LMNA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 285468 | NM_170707.4(LMNA):c.83G>A (p.Arg28Gln) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3595598 | NM_170707.4(LMNA):c.5del (p.Glu2fs) | LMNA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 36473 | NM_170707.4(LMNA):c.1003C>T (p.Arg335Trp) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 48031 | NM_170707.4(LMNA):c.1129C>T (p.Arg377Cys) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 48070 | NM_170707.4(LMNA):c.607G>A (p.Glu203Lys) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 48074 | NM_170707.4(LMNA):c.673C>T (p.Arg225Ter) | LMNA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 48077 | NM_170707.4(LMNA):c.745C>G (p.Arg249Gly) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 48096 | NM_170707.4(LMNA):c.961C>T (p.Arg321Ter) | LMNA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 66762 | NM_170707.4(LMNA):c.1045C>T (p.Arg349Trp) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 66782 | NM_170707.4(LMNA):c.1157G>A (p.Arg386Lys) | LMNA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 66791 | NM_170707.4(LMNA):c.116A>G (p.Asn39Ser) | LMNA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 66800 | NM_170707.4(LMNA):c.1294C>T (p.Gln432Ter) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 66808 | NM_170707.4(LMNA):c.1358G>C (p.Arg453Pro) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 66817 | NM_170707.4(LMNA):c.1380+1G>A | LMNA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 66849 | NM_170707.4(LMNA):c.1583C>A (p.Thr528Lys) | LMNA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 40 · Orphanet: 26 · 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 |
|---|---|---|---|---|
| LMNA | Definitive | Semidominant | Emery-Dreifuss muscular dystrophy 2, autosomal dominant | 40 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| 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 |
| SYNE2 | Orphanet:98853 | Autosomal dominant Emery-Dreifuss muscular dystrophy |
| TMEM43 | Orphanet:293888 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant |
| TMEM43 | Orphanet:293899 | Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant |
| TMEM43 | Orphanet:293910 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant |
| TMEM43 | Orphanet:98853 | Autosomal dominant Emery-Dreifuss muscular dystrophy |
Cohort genes → proteins
3 cohort genes, 3 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 3 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| LMNA | HGNC:6636 | ENSG00000160789 | P02545 | Prelamin-A/C | gencc,clinvar |
| SYNE2 | HGNC:17084 | ENSG00000054654 | Q8WXH0 | Nesprin-2 | clinvar |
| TMEM43 | HGNC:28472 | ENSG00000170876 | Q9BTV4 | Transmembrane protein 43 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| 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. |
| SYNE2 | Nesprin-2 | Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. |
| TMEM43 | Transmembrane protein 43 | May have an important role in maintaining nuclear envelope structure by organizing protein complexes at the inner nuclear membrane. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 3 · 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 | 3 | 1.8× | 0.174 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| LMNA | Other/Unknown | no | Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf | |
| SYNE2 | Other/Unknown | no | Actinin_actin-bd_CS, CH_dom, Spectrin_repeat | |
| TMEM43 | Other/Unknown | no | TMEM43_fam |
Expression context
Cohort genes with no expression data: 0.
3 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) | 3 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| mucosa of stomach | 1 |
| nipple | 1 |
| skin of abdomen | 1 |
| ganglionic eminence | 1 |
| skeletal muscle tissue of biceps brachii | 1 |
| ventricular zone | 1 |
| ascending aorta | 1 |
| descending thoracic aorta | 1 |
| thoracic aorta | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| LMNA | 295 | ubiquitous | marker | nipple, mucosa of stomach, skin of abdomen |
| SYNE2 | 284 | ubiquitous | marker | ventricular zone, skeletal muscle tissue of biceps brachii, ganglionic eminence |
| TMEM43 | 287 | ubiquitous | marker | descending thoracic aorta, thoracic aorta, ascending aorta |
Protein interactions among cohort
Intra-cohort edges: 3.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| LMNA | 7,173 |
| SYNE2 | 2,276 |
| TMEM43 | 1,864 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| LMNA | SYNE2 | string_interaction |
| LMNA | TMEM43 | string_interaction |
| SYNE2 | TMEM43 | string_interaction |
Structural data
PDB: 2 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| LMNA | P02545 | 28 |
| SYNE2 | Q8WXH0 | 3 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| TMEM43 | Q9BTV4 | 89.92 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Meiotic synapsis | 2 | 141.0× | 9e-04 | LMNA, SYNE2 |
| Breakdown of the nuclear lamina | 1 | 1903.3× | 0.005 | LMNA |
| Depolymerization of the Nuclear Lamina | 1 | 380.7× | 0.011 | LMNA |
| Initiation of Nuclear Envelope (NE) Reformation | 1 | 300.5× | 0.011 | LMNA |
| IRE1alpha activates chaperones | 1 | 259.6× | 0.011 | LMNA |
| Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models | 1 | 259.6× | 0.011 | LMNA |
| Nuclear Envelope Breakdown | 1 | 228.4× | 0.011 | LMNA |
| Unfolded Protein Response (UPR) | 1 | 178.4× | 0.013 | LMNA |
| Meiosis | 1 | 142.8× | 0.014 | SYNE2 |
| Oncogenic MAPK signaling | 1 | 124.1× | 0.014 | LMNA |
| XBP1(S) activates chaperone genes | 1 | 107.7× | 0.015 | LMNA |
| Reproduction | 1 | 95.2× | 0.016 | SYNE2 |
| Signaling by BRAF and RAF1 fusions | 1 | 85.2× | 0.016 | LMNA |
| Diseases of signal transduction by growth factor receptors and second messengers | 1 | 28.4× | 0.045 | LMNA |
| Cellular responses to stress | 1 | 18.4× | 0.062 | LMNA |
| Cell Cycle | 1 | 18.0× | 0.062 | SYNE2 |
| Cellular responses to stimuli | 1 | 15.7× | 0.066 | LMNA |
| Disease | 1 | 6.5× | 0.147 | 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 3 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 | 2 | 488.5× | 2e-04 | LMNA, SYNE2 |
| positive regulation of cell communication by electrical coupling | 1 | 2808.7× | 0.004 | TMEM43 |
| nuclear migration along microfilament | 1 | 2808.7× | 0.004 | SYNE2 |
| nucleokinesis involved in cell motility in cerebral cortex radial glia guided migration | 1 | 1872.4× | 0.004 | SYNE2 |
| DNA double-strand break attachment to nuclear envelope | 1 | 1872.4× | 0.004 | LMNA |
| establishment or maintenance of microtubule cytoskeleton polarity | 1 | 1404.3× | 0.005 | LMNA |
| nuclear pore localization | 1 | 1123.5× | 0.005 | LMNA |
| negative regulation of mesenchymal cell proliferation | 1 | 936.2× | 0.005 | LMNA |
| nuclear membrane organization | 1 | 802.5× | 0.005 | TMEM43 |
| protein localization to nuclear envelope | 1 | 702.2× | 0.005 | LMNA |
| regulation of protein localization to nucleus | 1 | 702.2× | 0.005 | LMNA |
| metal ion transport | 1 | 624.1× | 0.005 | TMEM43 |
| negative regulation of cardiac muscle hypertrophy in response to stress | 1 | 624.1× | 0.005 | LMNA |
| ventricular cardiac muscle cell development | 1 | 510.7× | 0.005 | LMNA |
| nuclear envelope organization | 1 | 330.4× | 0.008 | LMNA |
| centrosome localization | 1 | 295.6× | 0.008 | SYNE2 |
| regulation of telomere maintenance | 1 | 280.9× | 0.008 | LMNA |
| negative regulation of release of cytochrome c from mitochondria | 1 | 267.5× | 0.008 | LMNA |
| regulation of cilium assembly | 1 | 200.6× | 0.010 | SYNE2 |
| double-strand break repair via nonhomologous end joining | 1 | 140.4× | 0.013 | LMNA |
| negative regulation of extrinsic apoptotic signaling pathway | 1 | 140.4× | 0.013 | LMNA |
| protein localization to nucleus | 1 | 117.0× | 0.015 | LMNA |
| cellular senescence | 1 | 98.5× | 0.017 | LMNA |
| sodium ion transport | 1 | 90.6× | 0.017 | TMEM43 |
| heterochromatin formation | 1 | 85.1× | 0.018 | LMNA |
| potassium ion transport | 1 | 63.8× | 0.023 | TMEM43 |
| memory | 1 | 61.1× | 0.023 | TMEM43 |
| muscle organ development | 1 | 55.6× | 0.024 | LMNA |
| regulation of cell migration | 1 | 52.5× | 0.025 | LMNA |
| protein import into nucleus | 1 | 48.0× | 0.026 | LMNA |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2
Druggability breadth: 2 of 3 evidence-associated genes (67%) 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 |
| SYNE2 | 0 | 0 |
| TMEM43 | 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 |
| TMEM43 | 1 | Binding:1 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 3; 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 | 2 | SYNE2, TMEM43 |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| SYNE2 | 0 | LMNA |
| TMEM43 | 1 | — |
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 |
|---|---|---|---|
| NCT05989620 | Not specified | RECRUITING | Long-Term Development of Muscular Dystrophy Outcome Assessments |