X-linked Emery-Dreifuss muscular dystrophy

Summary

X-linked Emery-Dreifuss muscular dystrophy (MONDO:0010680) is a disease caused by EMD (GenCC Definitive), with 7 cohort genes and 1 clinical trial.

At a glance

• Prevalence: 1-9 / 1 000 000 (United Kingdom) [Orphanet-validated]
• Causal gene: EMD (GenCC Definitive)
• Cohort genes: 7
• ClinVar variants: 570
• Phenotypes (HPO): 44
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

3 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 / 100 000	1	Worldwide	Not yet validated
Prevalence at birth	1-9 / 100 000	1	Worldwide	Not yet 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:0000470	Short neck	Frequent (30-79%)
HP:0000912	Sprengel anomaly	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0001639	Hypertrophic cardiomyopathy	Frequent (30-79%)
HP:0002155	Hypertriglyceridemia	Frequent (30-79%)
HP:0002515	Waddling gait	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:0001678	Atrioventricular block	Occasional (5-29%)
HP:0001771	Achilles tendon contracture	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002808	Kyphosis	Occasional (5-29%)
HP:0002987	Elbow flexion contracture	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: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	X-linked Emery-Dreifuss muscular dystrophy
Mondo ID	MONDO:0010680
MeSH	D000083143
Orphanet	98863
ICD-11	516501338
UMLS	C0751337
MedGen	148284
GARD	0002102
Is cancer (heuristic)	no

Also known as: Emerinopathy · Emery-Dreifuss muscular dystrophy, X-linked · muscular dystrophy, tardive Emery-Dreifuss type, with contractures · X-linked Emery-Dreifuss muscular dystrophy

Data availability: 570 ClinVar variants · 4 GenCC gene-disease records · 7 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

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

Related subtypes (49): X-linked Opitz G/BBB syndrome, X-linked immunoneurologic disorder, X-linked adrenal hypoplasia congenita, X-linked lissencephaly with abnormal genitalia, X-linked severe congenital neutropenia, X-linked distal spinal muscular atrophy type 3, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders, Aland island eye disease, X-linked erythropoietic protoporphyria, X-linked central congenital hypothyroidism with late-onset testicular enlargement, X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome, X-linked acrogigantism due to Xq26 microduplication, Wiskott-Aldrich syndrome, X-linked Alport syndrome, X-linked mandibulofacial dysostosis, X-linked chondrodysplasia punctata, choroideremia, cone dystrophy, X-linked, with tapetal-like sheen, diabetes insipidus, nephrogenic, X-linked, Dyggve-Melchior-Clausen syndrome, X-linked, dyskeratosis congenita, X-linked, X-linked hypohidrotic ectodermal dysplasia, X-linked Ehlers-Danlos syndrome, epidermodysplasia verruciformis, X-linked, exudative vitreoretinopathy 2, X-linked, Aarskog-Scott syndrome, X-linked, hemophilia A, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius, hyper-IgM syndrome type 1, X-linked lymphoproliferative syndrome, macular dystrophy, X-linked, X-linked myotubular myopathy, X-linked lethal multiple pterygium syndrome, X-linked retinoschisis, spondyloepiphyseal dysplasia tarda, X-linked, X-linked cerebellar ataxia, adrenoleukodystrophy, Charcot-Marie-Tooth disease type X, X-linked dominant disease, X-linked recessive disease, X-linked hypophosphatemic rickets, X-linked sideroblastic anemia 1, X-linked deafness, X-linked cone-rod dystrophy, X-linked congenital stationary night blindness, X-linked congenital hemolytic anemia, X-linked complex neurodevelopmental disorder, X-linked intellectual disability, leukemia, acute, X-linked

Subtypes (3): X-linked myopathy with postural muscle atrophy, Emery-Dreifuss muscular dystrophy 1, X-linked, 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

570 retrieved; paginated sample, class counts are floors:

222 likely benign, 183 uncertain significance, 73 pathogenic, 53 conflicting classifications of pathogenicity, 13 benign/likely benign, 13 pathogenic/likely pathogenic, 8 benign, 5 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2422157	NC_000023.10:g.(?152014869)(155171615_?)del	ABCD1	Pathogenic	criteria provided, single submitter
3243728	NC_000023.10:g.(?152954030)(154005142_?)del	ABCD1	Pathogenic	criteria provided, single submitter
665050	NC_000023.10:g.(?152990712)(153650075_?)del	ARHGAP4	Pathogenic	criteria provided, single submitter
1048786	NM_000117.3(EMD):c.631del (p.Arg211fs)	EMD	Pathogenic	criteria provided, single submitter
1048787	NM_000117.3(EMD):c.449+1G>A	EMD	Pathogenic	criteria provided, single submitter
1070850	NC_000023.10:g.(?153607835)(153609567_?)del	EMD	Pathogenic	criteria provided, single submitter
1071626	NM_000117.3(EMD):c.483C>G (p.Tyr161Ter)	EMD	Pathogenic	criteria provided, single submitter
1072810	NM_000117.3(EMD):c.570dup (p.Met191fs)	EMD	Pathogenic	criteria provided, single submitter
1074346	NM_000117.3(EMD):c.643_653dup (p.Gln219fs)	EMD	Pathogenic	criteria provided, single submitter
1074958	NM_000117.3(EMD):c.2T>G (p.Met1Arg)	EMD	Pathogenic	criteria provided, single submitter
1074959	NM_000117.3(EMD):c.102C>G (p.Tyr34Ter)	EMD	Pathogenic	criteria provided, single submitter
1074960	NM_000117.3(EMD):c.153del (p.Ser52fs)	EMD	Pathogenic	criteria provided, multiple submitters, no conflicts
1075797	NM_000117.3(EMD):c.650_654del (p.Leu217fs)	EMD	Pathogenic	criteria provided, single submitter
11171	NM_000117.3(EMD):c.506_507del (p.Pro169fs)	EMD	Pathogenic	criteria provided, single submitter
11172	NM_000117.3(EMD):c.1A>G (p.Met1Val)	EMD	Pathogenic	criteria provided, multiple submitters, no conflicts
11173	NM_000117.3:c.55_83del	EMD	Pathogenic	no assertion criteria provided
11174	NM_000117.3(EMD):c.139_140dup (p.Leu48fs)	EMD	Pathogenic	no assertion criteria provided
11176	NM_000117.3(EMD):c.130C>T (p.Gln44Ter)	EMD	Pathogenic	criteria provided, multiple submitters, no conflicts
11177	NM_000117.3(EMD):c.615del (p.Ile206fs)	EMD	Pathogenic	no assertion criteria provided
11178	NM_000117.3(EMD):c.548C>A (p.Pro183His)	EMD	Pathogenic	criteria provided, single submitter
11179	NM_000117.3(EMD):c.547C>A (p.Pro183Thr)	EMD	Pathogenic	no assertion criteria provided
1184471	NM_000117.3(EMD):c.125del (p.Glu42fs)	EMD	Pathogenic	no assertion criteria provided
1330855	NM_000117.3(EMD):c.187+1G>A	EMD	Pathogenic	criteria provided, multiple submitters, no conflicts
1374482	NM_000117.3(EMD):c.266-3A>G	EMD	Pathogenic	criteria provided, single submitter
1451449	NM_000117.3(EMD):c.561_567dup (p.Phe190fs)	EMD	Pathogenic	criteria provided, single submitter
1453367	NM_000117.3(EMD):c.399+1G>T	EMD	Pathogenic	criteria provided, multiple submitters, no conflicts
1456997	NM_000117.3(EMD):c.570del (p.Phe190fs)	EMD	Pathogenic	criteria provided, single submitter
163403	NM_000117.3(EMD):c.266-2A>G	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
179496	NM_000117.3(EMD):c.83-2A>G	EMD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 20 · 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
FHL1	Definitive	X-linked	X-linked myopathy with postural muscle atrophy	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
FLNA	Orphanet:1826	Frontometaphyseal dysplasia
FLNA	Orphanet:2301	Congenital short bowel syndrome
FLNA	Orphanet:2484	Melnick-Needles syndrome
FLNA	Orphanet:482606	X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome
FLNA	Orphanet:555877	FLNA-related X-linked myxomatous valvular dysplasia
FLNA	Orphanet:75497	X-linked Ehlers-Danlos syndrome
FLNA	Orphanet:88630	Terminal osseous dysplasia-pigmentary defects syndrome
FLNA	Orphanet:90650	Otopalatodigital syndrome type 1
FLNA	Orphanet:90652	Otopalatodigital syndrome type 2
FLNA	Orphanet:98892	Periventricular nodular heterotopia
FLNA	Orphanet:99811	Neuronal intestinal pseudoobstruction
ABCD1	Orphanet:139396	X-linked cerebral adrenoleukodystrophy
ABCD1	Orphanet:139399	Adrenomyeloneuropathy
ABCD1	Orphanet:369942	CADDS
ABCD1	Orphanet:388	Hirschsprung disease

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EMD	HGNC:3331	ENSG00000102119	P50402	Emerin	gencc,clinvar
FHL1	HGNC:3702	ENSG00000022267	Q13642	Four and a half LIM domains protein 1	gencc
TEX28	HGNC:2563	ENSG00000278057	O15482	Testis-specific protein TEX28	clinvar
DNASE1L1	HGNC:2957	ENSG00000013563	P49184	Deoxyribonuclease-1-like 1	clinvar
FLNA	HGNC:3754	ENSG00000196924	P21333	Filamin-A	clinvar
ABCD1	HGNC:61	ENSG00000101986	P33897	ATP-binding cassette sub-family D member 1	clinvar
ARHGAP4	HGNC:674	ENSG00000089820	P98171	Rho GTPase-activating protein 4	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.
FHL1	Four and a half LIM domains protein 1	May have an involvement in muscle development or hypertrophy.
FLNA	Filamin-A	Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins.
ABCD1	ATP-binding cassette sub-family D member 1	ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen.
ARHGAP4	Rho GTPase-activating protein 4	Inhibitory effect on stress fiber organization.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.43

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
Phosphatase	1	12.0×	0.260
Transporter	1	11.1×	0.260
Antibody/Immunoglobulin	1	4.2×	0.433
Scaffold/PPI	1	2.5×	0.512
Transcription factor	1	1.2×	0.714
Other/Unknown	2	0.5×	0.968

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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
TEX28	Other/Unknown	no		Testis-specific_TEX28, TEX28/TMCC
DNASE1L1	Phosphatase	yes		Endo/exonuclease/phosphatase, DNase_I, Deoxyribonuclease-1_AS
FLNA	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
ABCD1	Transporter	yes	7.6.2.4	ABC_transporter-like_ATP-bd, AAA+_ATPase, FA_transporter
ARHGAP4	Scaffold/PPI	no		RhoGAP_dom, FCH_dom, SH3_domain

Expression context

Cohort genes with no expression data: 0.

6 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)	1
broad (>20)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
popliteal artery	2
left ovary	1
left uterine tube	1
biceps brachii	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
gastrocnemius	1
gluteal muscle	1
hindlimb stylopod muscle	1
right coronary artery	1
tibial artery	1
ileal mucosa	1
left adrenal gland	1
left adrenal gland cortex	1
granulocyte	1
monocyte	1
spleen	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
FHL1	291	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, skeletal muscle tissue of biceps brachii
TEX28	19	tissue_specific	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, left testis
DNASE1L1	283	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, gluteal muscle
FLNA	285	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery
ABCD1	201	ubiquitous	marker	ileal mucosa, left adrenal gland cortex, left adrenal gland
ARHGAP4	229	broad	marker	granulocyte, spleen, monocyte

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FLNA	5,321
EMD	3,503
FHL1	1,431
ABCD1	1,181
ARHGAP4	1,088
DNASE1L1	1,012
TEX28	407

Intra-cohort edges

A	B	Sources
EMD	FHL1	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FLNA	P21333	26
ABCD1	P33897	14
EMD	P50402	6
FHL1	Q13642	4
ARHGAP4	P98171	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DNASE1L1	P49184	90.83
TEX28	O15482	75.02

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 34. Enrichment computed across 7 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective ABCD1 causes ALD	1	1142.0×	0.021	ABCD1
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	1	380.7×	0.021	ABCD1
OAS antiviral response	1	253.8×	0.021	FLNA
Linoleic acid (LA) metabolism	1	228.4×	0.021	ABCD1
GP1b-IX-V activation signalling	1	190.3×	0.021	FLNA
Beta-oxidation of very long chain fatty acids	1	175.7×	0.021	ABCD1
Depolymerization of the Nuclear Lamina	1	152.3×	0.021	EMD
alpha-linolenic acid (ALA) metabolism	1	142.8×	0.021	ABCD1
Peroxisomal lipid metabolism	1	134.3×	0.021	ABCD1
Cell-extracellular matrix interactions	1	134.3×	0.021	FLNA
ABC transporters in lipid homeostasis	1	120.2×	0.021	ABCD1
Initiation of Nuclear Envelope (NE) Reformation	1	120.2×	0.021	EMD
RHO GTPases activate PAKs	1	108.8×	0.021	FLNA
Class I peroxisomal membrane protein import	1	103.8×	0.021	ABCD1
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	1	95.2×	0.021	EMD
Nuclear Envelope Breakdown	1	91.4×	0.021	EMD
ABC transporter disorders	1	87.8×	0.021	ABCD1
RAC1 GTPase cycle	2	24.4×	0.021	EMD, ARHGAP4
RHOD GTPase cycle	1	40.8×	0.043	EMD
Protein localization	1	38.1×	0.044	ABCD1
RHOG GTPase cycle	1	29.7×	0.054	EMD
Disorders of transmembrane transporters	1	27.9×	0.054	ABCD1
Fatty acid metabolism	1	26.2×	0.054	ABCD1
RAC2 GTPase cycle	1	25.4×	0.054	EMD
ABC-family protein mediated transport	1	24.3×	0.054	ABCD1
RAC3 GTPase cycle	1	23.8×	0.054	EMD
Platelet degranulation	1	17.6×	0.070	FLNA
RHOA GTPase cycle	1	14.9×	0.079	ARHGAP4
CDC42 GTPase cycle	1	14.5×	0.079	ARHGAP4
Metabolism of lipids	1	6.3×	0.169	ABCD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of potassium ion transmembrane transport	2	330.4×	0.001	FHL1, FLNA
regulation of membrane repolarization during atrial cardiac muscle cell action potential	1	2808.7×	0.010	FLNA
regulation of membrane repolarization during cardiac muscle cell action potential	1	2808.7×	0.010	FLNA
peroxisomal membrane transport	1	1404.3×	0.010	ABCD1
very long-chain fatty-acyl-CoA catabolic process	1	1404.3×	0.010	ABCD1
tubulin deacetylation	1	936.2×	0.010	FLNA
positive regulation of unsaturated fatty acid biosynthetic process	1	936.2×	0.010	ABCD1
formation of radial glial scaffolds	1	702.2×	0.010	FLNA
sterol homeostasis	1	702.2×	0.010	ABCD1
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1	561.7×	0.010	FLNA
long-chain fatty acid import into peroxisome	1	561.7×	0.010	ABCD1
establishment of Sertoli cell barrier	1	561.7×	0.010	FLNA
regulation of fatty acid beta-oxidation	1	468.1×	0.010	ABCD1
long-chain fatty acid catabolic process	1	468.1×	0.010	ABCD1
myelin maintenance	1	468.1×	0.010	ABCD1
regulation of mitochondrial depolarization	1	468.1×	0.010	ABCD1
protein localization to bicellular tight junction	1	468.1×	0.010	FLNA
negative regulation of transcription by RNA polymerase I	1	401.2×	0.010	FLNA
fatty acid elongation	1	401.2×	0.010	ABCD1
very long-chain fatty acid catabolic process	1	401.2×	0.010	ABCD1
nuclear membrane organization	1	401.2×	0.010	EMD
muscle organ development	2	55.6×	0.010	EMD, FHL1
blood coagulation, intrinsic pathway	1	351.1×	0.011	FLNA
regulation of atrial cardiac muscle cell membrane depolarization	1	312.1×	0.012	FHL1
negative regulation of fibroblast migration	1	255.3×	0.013	ARHGAP4
positive regulation of fatty acid beta-oxidation	1	255.3×	0.013	ABCD1
fatty acid derivative biosynthetic process	1	255.3×	0.013	ABCD1
positive regulation of platelet activation	1	216.1×	0.013	FLNA
regulation of cellular response to oxidative stress	1	216.1×	0.013	ABCD1
positive regulation of integrin-mediated signaling pathway	1	216.1×	0.013	FLNA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 6

Druggability breadth: 2 of 7 evidence-associated genes (29%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FLNA	1	2
EMD	0	0
FHL1	0	0
TEX28	0	0
DNASE1L1	0	0
ABCD1	0	0
ARHGAP4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	FLNA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FLNA	7	Binding:7
EMD	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABCD1	7.6.2.4	ABC-type fatty-acyl-CoA transporter

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
MOLIBRESIB	2	FLNA

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	1	FLNA
C	Druggable family + PDB, no drug	1	ABCD1
D	Druggable family + AlphaFold only, no drug	1	DNASE1L1
E	Difficult family or no structure, no drug	4	EMD, FHL1, TEX28, ARHGAP4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
EMD	1	—
FHL1	0	—
TEX28	0	—
DNASE1L1	0	—
ABCD1	0	—
ARHGAP4	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
NCT03058185	Not specified	RECRUITING	Observatoire Des Patients Atteints de Laminopathies et Emerinopathies (Observatory for PAtients With Laminopathies and Emerinopathies)