autosomal recessive limb-girdle muscular dystrophy type 2B

Summary

autosomal recessive limb-girdle muscular dystrophy type 2B (MONDO:0009676) is a disease caused by DYSF (GenCC Strong), with 3 cohort genes and 4 clinical trials. Top therapeutic interventions include deflazacort.

At a glance

• Prevalence: 1-9 / 1 000 000 (United Kingdom) [Orphanet-validated]
• Causal gene: DYSF (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 1,225
• Phenotypes (HPO): 29
• Clinical trials: 4

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.13	United Kingdom	Validated
Point prevalence	1-9 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0003236	Elevated circulating creatine kinase concentration	Very frequent (80-99%)
HP:0007340	Lower limb muscle weakness	Frequent (30-79%)
HP:0008994	Proximal muscle weakness in lower limbs	Frequent (30-79%)
HP:0001315	Reduced tendon reflexes	Occasional (5-29%)
HP:0001640	Cardiomegaly	Occasional (5-29%)
HP:0001667	Right ventricular hypertrophy	Occasional (5-29%)
HP:0001761	Pes cavus	Occasional (5-29%)
HP:0003115	Abnormal EKG	Occasional (5-29%)
HP:0003307	Hyperlordosis	Occasional (5-29%)
HP:0003551	Difficulty climbing stairs	Occasional (5-29%)
HP:0003691	Scapular winging	Occasional (5-29%)
HP:0003722	Neck flexor weakness	Occasional (5-29%)
HP:0008981	Calf muscle hypertrophy	Occasional (5-29%)
HP:0008997	Proximal muscle weakness in upper limbs	Occasional (5-29%)
HP:0009046	Difficulty running	Occasional (5-29%)
HP:0011712	Right bundle branch block	Occasional (5-29%)
HP:0012664	Reduced left ventricular ejection fraction	Occasional (5-29%)
HP:0100748	Muscular edema	Occasional (5-29%)
HP:0002015	Dysphagia	Very rare (<1-4%)
HP:0002072	Chorea	Very rare (<1-4%)
HP:0002540	Inability to walk	Very rare (<1-4%)
HP:0002996	Limited elbow movement	Very rare (<1-4%)
HP:0003306	Spinal rigidity	Very rare (<1-4%)
HP:0005085	Limited knee flexion/extension	Very rare (<1-4%)
HP:0008800	Limited hip movement	Very rare (<1-4%)
HP:0008959	Distal upper limb muscle weakness	Very rare (<1-4%)
HP:0030051	Tip-toe gait	Very rare (<1-4%)
HP:0045054	Brachial plexus neuropathy	Very rare (<1-4%)
HP:0100515	Pollakisuria	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive limb-girdle muscular dystrophy type 2B
Mondo ID	MONDO:0009676
MeSH	C535899
OMIM	253601
Orphanet	268
DOID	DOID:0110276
NCIT	C142080
SNOMED CT	718179003
UMLS	C1850889
MedGen	338149
GARD	0008574
Is cancer (heuristic)	no

Also known as: autosomal recessive limb-girdle muscular dystrophy caused by mutation in DYSF · DYSF autosomal recessive limb-girdle muscular dystrophy · LGMD2B · LGMD3 · limb-girdle muscular dystrophy due to dysferlin deficiency · limb-girdle muscular dystrophy type 2B · limb-girdle muscular dystrophy, type 2B · muscular dystrophy, limb-girdle, autosomal recessive 2 · muscular dystrophy, limb-girdle, type 2B

Data availability: 1,225 ClinVar variants · 2 GenCC gene-disease records · 28 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 recessive disease › autosomal recessive limb-girdle muscular dystrophy › autosomal recessive limb-girdle muscular dystrophy type 2B

Related subtypes (31): epidermolysis bullosa simplex 5B, with muscular dystrophy, autosomal recessive limb-girdle muscular dystrophy type 2A, autosomal recessive limb-girdle muscular dystrophy type 2C, autosomal recessive limb-girdle muscular dystrophy type 2H, autosomal recessive limb-girdle muscular dystrophy type 2F, autosomal recessive limb-girdle muscular dystrophy type 2G, autosomal recessive limb-girdle muscular dystrophy type 2E, autosomal recessive limb-girdle muscular dystrophy type 2I, autosomal recessive limb-girdle muscular dystrophy type 2D, autosomal recessive limb-girdle muscular dystrophy type 2J, autosomal recessive limb-girdle muscular dystrophy type 2K, autosomal recessive limb-girdle muscular dystrophy type 2L, autosomal recessive limb-girdle muscular dystrophy type 2M, autosomal recessive limb-girdle muscular dystrophy type 2O, autosomal recessive limb-girdle muscular dystrophy type 2N, autosomal recessive limb-girdle muscular dystrophy type 2Q, autosomal recessive limb-girdle muscular dystrophy type 2P, autosomal recessive limb-girdle muscular dystrophy type 2T, autosomal recessive limb-girdle muscular dystrophy type R18, autosomal recessive limb-girdle muscular dystrophy type 2U, limb-girdle muscular dystrophy due to POMK deficiency, autosomal recessive limb-girdle muscular dystrophy type 2X, autosomal recessive limb-girdle muscular dystrophy type 2W, autosomal recessive limb-girdle muscular dystrophy type 2Y, autosomal recessive limb-girdle muscular dystrophy type 2R1, muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8, muscular dystrophy, limb-girdle, autosomal recessive 23, muscular dystrophy, limb-girdle, autosomal recessive 26, muscular dystrophy, limb-girdle, autosomal recessive 27, muscular dystrophy, limb-girdle, autosomal recessive 28, muscular dystrophy, limb-girdle, autosomal recessive 29

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:

191 uncertain significance, 127 conflicting classifications of pathogenicity, 99 likely pathogenic, 90 pathogenic, 43 likely benign, 35 pathogenic/likely pathogenic, 11 benign, 4 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069667	NM_001130987.2(DYSF):c.4848del (p.Glu1616fs)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070532	NM_001130987.2(DYSF):c.1258del (p.Ala420fs)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072189	NM_001130987.2(DYSF):c.2624G>A (p.Trp875Ter)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072386	NM_001130987.2(DYSF):c.4954del (p.Ser1652fs)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075637	NM_001130987.2(DYSF):c.2605C>T (p.Gln869Ter)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180715	NM_001130987.2(DYSF):c.6236G>A (p.Trp2079Ter)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184483	NM_001130987.2(DYSF):c.5718C>G (p.Phe1906Leu)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1300185	NM_001130987.2(DYSF):c.4989del (p.Glu1663fs)	DYSF	Pathogenic	reviewed by expert panel
1321153	NM_001130987.2(DYSF):c.3931C>T (p.Gln1311Ter)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322811	NM_001130987.2(DYSF):c.1330A>T (p.Lys444Ter)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1350756	NM_001130987.2(DYSF):c.2697+5G>A	DYSF	Pathogenic	reviewed by expert panel
1381552	NM_001130987.2(DYSF):c.3113dup (p.Glu1039fs)	DYSF	Pathogenic	criteria provided, multiple submitters, no conflicts
1389207	NM_001130987.2(DYSF):c.5188C>T (p.Gln1730Ter)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1392298	NM_001130987.2(DYSF):c.3050G>A (p.Trp1017Ter)	DYSF	Pathogenic	criteria provided, multiple submitters, no conflicts
1402261	NM_001130987.2(DYSF):c.4254del (p.Ile1419fs)	DYSF	Pathogenic	criteria provided, multiple submitters, no conflicts
1433815	NM_001130987.2(DYSF):c.2266C>T (p.Gln756Ter)	DYSF	Pathogenic	reviewed by expert panel
1444196	NM_001130987.2(DYSF):c.6334A>G (p.Met2112Val)	DYSF	Pathogenic	reviewed by expert panel
1448346	NM_001130987.2(DYSF):c.2955dup (p.Met986fs)	DYSF	Pathogenic	criteria provided, multiple submitters, no conflicts
1455583	NM_001130987.2(DYSF):c.1117dup (p.Leu373fs)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1459445	NM_001130987.2(DYSF):c.5893C>T (p.Gln1965Ter)	DYSF	Pathogenic	criteria provided, multiple submitters, no conflicts
167021	NM_001130987.2(DYSF):c.2844G>C (p.Trp948Cys)	DYSF	Pathogenic	reviewed by expert panel
167025	NM_001130987.2(DYSF):c.3886C>T (p.Gln1296Ter)	DYSF	Pathogenic	reviewed by expert panel
167030	NM_001130987.2(DYSF):c.5642+1G>A	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1697322	NM_001130987.2(DYSF):c.5621del (p.Met1874fs)	DYSF	Pathogenic	criteria provided, single submitter
1708547	NM_001130987.2(DYSF):c.3702del (p.Val1235fs)	DYSF	Pathogenic	no assertion criteria provided
1708548	NM_001130987.2(DYSF):c.5096_5115delinsA (p.Gly1699fs)	DYSF	Pathogenic	no assertion criteria provided
1708550	NM_001130987.2(DYSF):c.5943C>A (p.Cys1981Ter)	DYSF	Pathogenic	no assertion criteria provided
1708551	NM_001130987.2(DYSF):c.2472C>A (p.Tyr824Ter)	DYSF	Pathogenic	criteria provided, single submitter
1708553	NM_001130987.2(DYSF):c.769C>T (p.Gln257Ter)	DYSF	Pathogenic	criteria provided, single submitter
1724499	NM_001130987.2(DYSF):c.4923C>A (p.Tyr1641Ter)	DYSF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 27 · 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
DYSF	Strong	Autosomal recessive	autosomal recessive limb-girdle muscular dystrophy type 2B	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DYSF	Orphanet:178400	Distal myopathy with anterior tibial onset
DYSF	Orphanet:199329	Congenital myopathy, Paradas type
DYSF	Orphanet:268	Dysferlin-related limb-girdle muscular dystrophy R2
DYSF	Orphanet:45448	Miyoshi myopathy
CAPN3	Orphanet:267	Calpain-3-related limb-girdle muscular dystrophy R1
CAPN3	Orphanet:565909	Calpain-3-related limb-girdle muscular dystrophy D4
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

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
DYSF	HGNC:3097	ENSG00000135636	O75923	Dysferlin	gencc,clinvar
CAPN3	HGNC:1480	ENSG00000092529	P20807	Calpain-3	clinvar
LMNA	HGNC:6636	ENSG00000160789	P02545	Prelamin-A/C	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DYSF	Dysferlin	Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion.
CAPN3	Calpain-3	Calcium-regulated non-lysosomal thiol-protease.
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.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Protease	1	12.2×	0.159
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DYSF	Other/Unknown	no		C2_dom, Peroxin/Ferlin, Ferlin_A-domain
CAPN3	Protease	yes	3.4.22.54	Pept_cys_AS, Peptidase_C2_calpain_cat, EF_hand_dom
LMNA	Other/Unknown	no		Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf

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
hindlimb stylopod muscle	2
blood	1
skeletal muscle tissue of rectus abdominis	1
C1 segment of cervical spinal cord	1
skeletal muscle tissue	1
mucosa of stomach	1
nipple	1
skin of abdomen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DYSF	257	ubiquitous	marker	blood, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis
CAPN3	134	broad	marker	hindlimb stylopod muscle, skeletal muscle tissue, C1 segment of cervical spinal cord
LMNA	295	ubiquitous	marker	nipple, mucosa of stomach, skin of abdomen

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMNA	7,173
CAPN3	1,977
DYSF	1,776

Intra-cohort edges

A	B	Sources
CAPN3	DYSF	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LMNA	P02545	28
DYSF	O75923	11
CAPN3	P20807	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Breakdown of the nuclear lamina	1	1268.9×	0.014	LMNA
Depolymerization of the Nuclear Lamina	1	253.8×	0.020	LMNA
Initiation of Nuclear Envelope (NE) Reformation	1	200.3×	0.020	LMNA
IRE1alpha activates chaperones	1	173.0×	0.020	LMNA
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models	1	173.0×	0.020	LMNA
Nuclear Envelope Breakdown	1	152.3×	0.020	LMNA
Unfolded Protein Response (UPR)	1	119.0×	0.022	LMNA
Smooth Muscle Contraction	1	88.5×	0.024	DYSF
Oncogenic MAPK signaling	1	82.8×	0.024	LMNA
XBP1(S) activates chaperone genes	1	71.8×	0.025	LMNA
Signaling by BRAF and RAF1 fusions	1	56.8×	0.029	LMNA
Meiotic synapsis	1	47.0×	0.032	LMNA
Degradation of the extracellular matrix	1	39.2×	0.035	CAPN3
Extracellular matrix organization	1	21.0×	0.060	CAPN3
Diseases of signal transduction by growth factor receptors and second messengers	1	18.9×	0.062	LMNA
Cellular responses to stress	1	12.3×	0.089	LMNA
Cellular responses to stimuli	1	10.5×	0.098	LMNA
Disease	1	4.4×	0.212	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
monocyte activation involved in immune response	1	5617.3×	0.003	DYSF
calcium-dependent self proteolysis	1	5617.3×	0.003	CAPN3
muscle organ development	2	111.2×	0.003	CAPN3, LMNA
positive regulation of satellite cell activation involved in skeletal muscle regeneration	1	2808.7×	0.005	CAPN3
DNA double-strand break attachment to nuclear envelope	1	1872.4×	0.006	LMNA
establishment or maintenance of microtubule cytoskeleton polarity	1	1404.3×	0.006	LMNA
cellular response to salt stress	1	1404.3×	0.006	CAPN3
nuclear pore localization	1	1123.5×	0.006	LMNA
G1 to G0 transition involved in cell differentiation	1	936.2×	0.006	CAPN3
negative regulation of mesenchymal cell proliferation	1	936.2×	0.006	LMNA
regulation of myoblast differentiation	1	802.5×	0.006	CAPN3
protein localization to nuclear envelope	1	702.2×	0.006	LMNA
regulation of protein localization to nucleus	1	702.2×	0.006	LMNA
negative regulation of cardiac muscle hypertrophy in response to stress	1	624.1×	0.006	LMNA
negative regulation of protein sumoylation	1	510.7×	0.006	CAPN3
ventricular cardiac muscle cell development	1	510.7×	0.006	LMNA
self proteolysis	1	510.7×	0.006	CAPN3
muscle structure development	1	468.1×	0.007	CAPN3
macrophage activation involved in immune response	1	374.5×	0.007	DYSF
myofibril assembly	1	374.5×	0.007	CAPN3
nuclear envelope organization	1	330.4×	0.008	LMNA
negative regulation of phagocytosis	1	330.4×	0.008	DYSF
regulation of telomere maintenance	1	280.9×	0.008	LMNA
positive regulation of proteolysis	1	267.5×	0.008	CAPN3
negative regulation of release of cytochrome c from mitochondria	1	267.5×	0.008	LMNA
regulation of neurotransmitter secretion	1	255.3×	0.008	DYSF
nuclear migration	1	244.2×	0.008	LMNA
muscle cell cellular homeostasis	1	216.1×	0.009	CAPN3
protein localization to membrane	1	200.6×	0.009	CAPN3
response to muscle activity	1	193.7×	0.009	CAPN3

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
DYSF	0	0
CAPN3	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): 1.

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

Symbol	Assays	Type breakdown
LMNA	12	Binding:9, Functional:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CAPN3	3.4.22.54, 3.4.22.56	calpain-3, caspase-3

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	1	CAPN3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DYSF

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)
DYSF	0	—
CAPN3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00527228	PHASE2/PHASE3	COMPLETED	Deflazacort in Dysferlinopathies
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments
NCT00893334	Not specified	COMPLETED	Evaluation of Limb-Girdle Muscular Dystrophy
NCT06507215	Not specified	COMPLETED	Dysferlinopathy Protein in Peripheral Blood Monocytes.

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DEFLAZACORT	4	1