Congenital muscular dystrophy

Summary

Congenital muscular dystrophy (MONDO:0019950) is a disease (an umbrella term covering 23 Mondo subtypes) with 9 cohort genes and 8 clinical trials. Top therapeutic interventions include omigapil.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Umbrella term: 23 Mondo subtypes
• Cohort genes: 9
• ClinVar variants: 24
• Clinical trials: 8

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Europe	Validated
Point prevalence	1-9 / 1 000 000	0.563	Italy	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital muscular dystrophy
Mondo ID	MONDO:0019950
Orphanet	97242
DOID	DOID:0050557
ICD-11	396687076
SNOMED CT	240059009
UMLS	C0699743
MedGen	147063
GARD	0009138
Is cancer (heuristic)	no

Also known as: CMD · congenital MD · MDC

Data availability: 24 ClinVar variants.

Disease family

An umbrella term covering 23 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital muscular dystrophy

Related subtypes (216): polymicrogyria, congenital myasthenic syndrome with tubular aggregates, prenatal-onset spinal muscular atrophy with congenital bone fractures, anencephaly, cerebral cavernous malformation, meningocele, progressive external ophthalmoplegia, congenital nystagmus, congenital toxoplasmosis, congenital contractural arachnodactyly, congenital trigeminal anesthesia, familial congenital palsy of trochlear nerve, Myhre syndrome, Aase-Smith syndrome, KBG syndrome, autosomal dominant primary microcephaly, Mobius syndrome, MYH7-related skeletal myopathy, congenital stationary night blindness autosomal dominant 2, Prader-Willi syndrome, congenital myopathy 7A, myosin storage, autosomal dominant, Smith-Magenis syndrome, spina bifida, Freeman-Sheldon syndrome, isolated cerebellar hypoplasia/agenesis, Chediak-Higashi syndrome, Cohen syndrome, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, diastematomyelia, EEM syndrome, Mowat-Wilson syndrome, Johanson-Blizzard syndrome, intellectual disability, Buenos-Aires type, myasthenia, congenital, refractory to acetylcholinesterase inhibitors, congenital myasthenic syndrome 6, Bailey-Bloch congenital myopathy, congenital stationary night blindness 1B, radioulnar synostosis-developmental delay-hypotonia syndrome, Schinzel-Giedion syndrome, schizencephaly, intellectual disability, Wolff type, X-linked intellectual disability-plagiocephaly syndrome, X-linked adrenal hypoplasia congenita, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, blepharophimosis - intellectual disability syndrome, MKB type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, infantile-onset X-linked spinal muscular atrophy, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, X-linked intellectual disability with marfanoid habitus, Wieacker-Wolff syndrome, MERRF syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, intellectual disability-sparse hair-brachydactyly syndrome, myofibrillar myopathy 1, isolated hereditary congenital facial paralysis, fibrosis of extraocular muscles, congenital, 2, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, developmental malformations-deafness-dystonia syndrome, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, AICA-ribosiduria, myofibrillar myopathy 3, fibrosis of extraocular muscles, congenital, 3c, myofibrillar myopathy 4, myofibrillar myopathy 5, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, intellectual disability, autosomal recessive 12, progressive myoclonic epilepsy type 3, chromosome 15q13.3 microdeletion syndrome, combined pituitary hormone deficiencies, genetic form, congenital stationary night blindness 1D, DYRK1A-related intellectual disability syndrome, Pitt-Hopkins-like syndrome 2, developmental and epileptic encephalopathy, 15, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, developmental and epileptic encephalopathy, 18, CTCF-related neurodevelopmental disorder, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Bardet-Biedl syndrome 11, cerebellar-facial-dental syndrome, fibrosis of extraocular muscles, congenital, 5, congenital myasthenic syndrome 15, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, congenital myasthenic syndrome 18, autosomal recessive spinocerebellar ataxia 20, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, congenital stationary night blindness 1G, hypomyelinating leukodystrophy 10, developmental and epileptic encephalopathy, 50, congenital insensitivity to pain-hypohidrosis syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, intellectual disability, autosomal recessive 53, TELO2-related intellectual disability-neurodevelopmental disorder, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, autosomal recessive limb-girdle muscular dystrophy type 2Y, myofibrillar myopathy 7, short stature-brachydactyly-obesity-global developmental delay syndrome, autosomal recessive limb-girdle muscular dystrophy type 2R1, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, congenital laryngeal palsy, congenital or early infantile CACH syndrome, congenital epulis, severe congenital nemaline myopathy, intermediate nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, holoprosencephaly, congenital insensitivity to pain with hyperhidrosis, congenital hydrocephalus, familial congenital mirror movements, macrocephaly-short stature-paraplegia syndrome, cephalocele, mitochondrial neurogastrointestinal encephalomyopathy, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, 7p22.1 microduplication syndrome, congenital achiasma, congenital retinal arteriovenous communication, 3q27.3 microdeletion syndrome, Prader-Willi-like syndrome, 9q31.1q31.3 microdeletion syndrome, congenital oculomotor nerve palsy, congenital abducens nerve palsy, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, lissencephaly spectrum disorders, hyaline body myopathy, 22q11.2 deletion syndrome, craniorachischisis, Leber congenital amaurosis, Ritscher-Schinzel syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, congenital vitreoretinal dysplasia, periventricular nodular heterotopia, postsynaptic congenital myasthenic syndrome, subcortical band heterotopia, congenital fibrosis of extraocular muscles type 1, Al Gazali Khidr Prem Chandran syndrome, distal arthrogryposis Moore weaver type, congenital myotonic dystrophy, myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic, developmental and epileptic encephalopathy, 77, night blindness, congenital stationary, type1i, neuropathy, congenital hypomelinating, congenital axonal neuropathy with encephalopathy, developmental and epileptic encephalopathy, 73, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, isolated exencephaly, myasthenic syndrome, congenital, 22, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, X-linked congenital stationary night blindness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, FOXG1 disorder, alpha-actinopathy, TPM3-related myopathy, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, myopathy caused by variation in POMGNT1, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, segmental spinal dysgenesis, myopathy, myofibrillar, 13, with rimmed vacuoles, congenital neuronal ceroid lipofuscinosis 10

Subtypes (23): Ullrich congenital muscular dystrophy, Bethlem myopathy, arthrogryposis due to muscular dystrophy, congenital muscular dystrophy-infantile cataract-hypogonadism syndrome, muscular dystrophy, congenital, with rapid progression, congenital myasthenic syndrome 10, megaconial type congenital muscular dystrophy, congenital muscular dystrophy 1B, congenital merosin-deficient muscular dystrophy 1A, congenital muscular dystrophy due to integrin alpha-7 deficiency, congenital muscular dystrophy due to LMNA mutation, congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome, congenital myopathy, Paradas type, autosomal recessive myogenic arthrogryposis multiplex congenita, muscular dystrophy-dystroglycanopathy, congenital muscular dystrophy with hyperlaxity, muscle-eye-brain disease, rigid spine syndrome, congenital muscular dystrophy with cataracts and intellectual disability, SNUPN-related muscular dystrophy with or without multi-system involvement, congenital muscular dystrophy caused by variation in POMGNT2, collagen 6-related congenital muscular dystrophy, congenital muscular dystrophy without intellectual disability

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

24 retrieved; paginated sample, class counts are floors:

6 likely pathogenic, 5 conflicting classifications of pathogenicity, 4 uncertain significance, 4 pathogenic/likely pathogenic, 3 benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
17621	NM_000070.3(CAPN3):c.550del (p.Thr184fs)	CAPN3	Pathogenic	reviewed by expert panel
279809	NM_017946.4(FKBP14):c.362dup (p.Glu122fs)	FKBP14	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1183973	NM_000426.4(LAMA2):c.2834del (p.Gly945fs)	LAMA2	Pathogenic	no assertion criteria provided
66860	NM_170707.4(LMNA):c.1622G>A (p.Arg541His)	LMNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66931	NM_170707.4(LMNA):c.746G>A (p.Arg249Gln)	LMNA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3636001	NM_000257.4(MYH7):c.5000T>C (p.Leu1667Pro)	LOC126861897	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
424831	NM_001267550.2(TTN):c.[39547+3A>G];[42151+1G>C]		Likely pathogenic	criteria provided, single submitter
424832	NM_001267550.2(TTN):c.[42315_42318delGAAA];[67349-2A>C]		Likely pathogenic	criteria provided, single submitter
424833	NM_001267550.2(TTN):c.[106531+2T>A];[107867delT]		Likely pathogenic	criteria provided, single submitter
560376	NM_000426.4(LAMA2):c.5460del (p.Val1821fs)	LAMA2	Likely pathogenic	no assertion criteria provided
3233370	NM_170707.4(LMNA):c.1560G>C (p.Trp520Cys)	LMNA	Likely pathogenic	criteria provided, single submitter
374199	NM_000540.3(RYR1):c.1186G>A (p.Glu396Lys)	RYR1	Likely pathogenic	criteria provided, single submitter
417777	NM_016532.4(INPP5K):c.149T>C (p.Ile50Thr)	INPP5K	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
161291	NM_170707.4(LMNA):c.1931G>A (p.Arg644His)	LMNA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
374201	NM_170707.4(LMNA):c.130G>T (p.Val44Phe)	LMNA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194453	NM_001164508.2(NEB):c.25367C>T (p.Thr8456Met)	NEB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
374200	NM_000540.3(RYR1):c.844C>T (p.Arg282Trp)	RYR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
689371	NM_001849.4(COL6A2):c.3044_3047delinsACCA (p.Ile1015_Arg1016delinsAsnHis)	COL6A2	Uncertain significance	criteria provided, single submitter
374050	NM_001164508.2(NEB):c.7362C>G (p.Asn2454Lys)	NEB	Uncertain significance	criteria provided, single submitter
162593	NM_001077365.2(POMT1):c.1503_1508dup (p.500_501RE[4])	POMT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
374142	NM_000540.3(RYR1):c.14713C>A (p.Pro4905Thr)	RYR1	Uncertain significance	criteria provided, single submitter
162596	NM_013382.7(POMT2):c.-47_-44del	LOC130056177	Benign	criteria provided, single submitter
95453	NM_001077365.2(POMT1):c.123-5dup	POMT1	Benign	criteria provided, multiple submitters, no conflicts
93252	NM_000540.3(RYR1):c.13513G>C (p.Asp4505His)	RYR1	Benign	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 56 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RYR1	Orphanet:169186	Autosomal recessive centronuclear myopathy
RYR1	Orphanet:169189	Autosomal dominant centronuclear myopathy
RYR1	Orphanet:178145	Moderate multiminicore disease with hand involvement
RYR1	Orphanet:324581	Benign Samaritan congenital myopathy
RYR1	Orphanet:33108	Lethal multiple pterygium syndrome
RYR1	Orphanet:423	Malignant hyperthermia of anesthesia
RYR1	Orphanet:424107	Congenital myopathy with myasthenic-like onset
RYR1	Orphanet:466650	Exercise-induced malignant hyperthermia
RYR1	Orphanet:597	Central core disease
RYR1	Orphanet:700188	Calf-predominant weakness-gastrocnemius medialis atrophy-distal myopathy
RYR1	Orphanet:98905	Congenital multicore myopathy with external ophthalmoplegia
RYR1	Orphanet:99741	King-Denborough syndrome
CAPN3	Orphanet:267	Calpain-3-related limb-girdle muscular dystrophy R1
CAPN3	Orphanet:565909	Calpain-3-related limb-girdle muscular dystrophy D4
FKBP14	Orphanet:300179	Kyphoscoliotic Ehlers-Danlos syndrome due to FKBP22 deficiency
COL6A2	Orphanet:289380	Myosclerosis
COL6A2	Orphanet:610	Bethlem muscular dystrophy
COL6A2	Orphanet:646113	Intermediate collagen VI-related muscular dystrophy
COL6A2	Orphanet:75840	Ullrich congenital muscular dystrophy
INPP5K	Orphanet:662184	Congenital muscular dystrophy-cataract-intellectual disability syndrome
LAMA2	Orphanet:258	Laminin subunit alpha 2-related congenital muscular dystrophy
LAMA2	Orphanet:565837	Laminin subunit alpha 2-related limb-girdle muscular dystrophy R23
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
NEB	Orphanet:171430	Severe congenital nemaline myopathy
NEB	Orphanet:171433	Intermediate nemaline myopathy
NEB	Orphanet:171436	Typical nemaline myopathy
NEB	Orphanet:171439	Childhood-onset nemaline myopathy
NEB	Orphanet:33108	Lethal multiple pterygium syndrome
NEB	Orphanet:399103	Autosomal recessive distal nebulin myopathy
NEB	Orphanet:708123	Autosomal dominant distal nebulin myopathy

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
RYR1	HGNC:10483	ENSG00000196218	P21817	Ryanodine receptor 1	clinvar
CAPN3	HGNC:1480	ENSG00000092529	P20807	Calpain-3	clinvar
FKBP14	HGNC:18625	ENSG00000106080	Q9NWM8	Peptidyl-prolyl cis-trans isomerase FKBP14	clinvar
COL6A2	HGNC:2212	ENSG00000142173	P12110	Collagen alpha-2(VI) chain	clinvar
INPP5K	HGNC:33882	ENSG00000132376	Q9BT40	Inositol polyphosphate 5-phosphatase K	clinvar
LAMA2	HGNC:6482	ENSG00000196569	P24043	Laminin subunit alpha-2	clinvar
LMNA	HGNC:6636	ENSG00000160789	P02545	Prelamin-A/C	clinvar
NEB	HGNC:7720	ENSG00000183091	P20929	Nebulin	clinvar
POMT1	HGNC:9202	ENSG00000130714	Q9Y6A1	Protein O-mannosyl-transferase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RYR1	Ryanodine receptor 1	Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules.
CAPN3	Calpain-3	Calcium-regulated non-lysosomal thiol-protease.
FKBP14	Peptidyl-prolyl cis-trans isomerase FKBP14	PPIase which accelerates the folding of proteins during protein synthesis.
COL6A2	Collagen alpha-2(VI) chain	Collagen VI acts as a cell-binding protein.
INPP5K	Inositol polyphosphate 5-phosphatase K	Inositol 5-phosphatase which acts on inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate.
LAMA2	Laminin subunit alpha-2	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
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.
NEB	Nebulin	This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils.
POMT1	Protein O-mannosyl-transferase 1	Transfers mannosyl residues to the hydroxyl group of serine or threonine residues.

Protein-family classification

Druggable: 5 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.56

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
Enzyme (other)	3	4.0×	0.166
Ion channel	1	12.4×	0.195
Protease	1	4.1×	0.368
Scaffold/PPI	1	1.9×	0.519
Other/Unknown	3	0.6×	0.955

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RYR1	Ion channel	yes		RIH_dom, B30.2/SPRY, Ryanodine_rcpt
CAPN3	Protease	yes	3.4.22.54	Pept_cys_AS, Peptidase_C2_calpain_cat, EF_hand_dom
FKBP14	Enzyme (other)	yes	5.2.1.8	PPIase_FKBP_dom, EF_hand_dom, EF-hand-dom_pair
COL6A2	Other/Unknown	no		VWF_A, Collagen, vWFA_dom_sf
INPP5K	Enzyme (other)	yes	3.1.3.56	IPPc, Endo/exonu/phosph_ase_sf, SKICH
LAMA2	Other/Unknown	no		Laminin_IV, EGF, Laminin_G
LMNA	Other/Unknown	no		Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf
NEB	Scaffold/PPI	no		Nebulin_repeat, SH3_domain, Nebulin-like
POMT1	Enzyme (other)	yes	2.4.1.109	ArnT-like_N, MIR_motif, PMT-like

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
gluteal muscle	2
hindlimb stylopod muscle	2
mucosa of stomach	2
gastrocnemius	1
C1 segment of cervical spinal cord	1
skeletal muscle tissue	1
cartilage tissue	1
corpus epididymis	1
tibia	1
descending thoracic aorta	1
right coronary artery	1
stromal cell of endometrium	1
pigmented layer of retina	1
right lobe of thyroid gland	1
right lung	1
calcaneal tendon	1
right ovary	1
nipple	1
skin of abdomen	1
biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RYR1	214	broad	marker	gluteal muscle, gastrocnemius, hindlimb stylopod muscle
CAPN3	134	broad	marker	hindlimb stylopod muscle, skeletal muscle tissue, C1 segment of cervical spinal cord
FKBP14	260	ubiquitous	marker	tibia, corpus epididymis, cartilage tissue
COL6A2	263	ubiquitous	marker	stromal cell of endometrium, right coronary artery, descending thoracic aorta
INPP5K	283	ubiquitous	marker	pigmented layer of retina, right lung, right lobe of thyroid gland
LAMA2	272	ubiquitous	marker	mucosa of stomach, calcaneal tendon, right ovary
LMNA	295	ubiquitous	marker	nipple, mucosa of stomach, skin of abdomen
NEB	204	tissue_specific	marker	gluteal muscle, tibialis anterior, biceps brachii
POMT1	264	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMNA	7,173
COL6A2	2,786
LAMA2	2,688
FKBP14	2,296
RYR1	2,177
CAPN3	1,977
POMT1	1,475
NEB	1,402
INPP5K	1,300

Intra-cohort edges

A	B	Sources
LAMA2	POMT1	string_interaction

Structural data

PDB: 8 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LMNA	P02545	28
CAPN3	P20807	5
NEB	P20929	3
RYR1	P21817	2
FKBP14	Q9NWM8	2
LAMA2	P24043	2
COL6A2	P12110	1
INPP5K	Q9BT40	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
POMT1	Q9Y6A1	88.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 56. Enrichment computed across 9 evidence-associated genes (9 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 9 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	423.0×	0.026	LMNA
Defective POMT2 causes MDDGA2, MDDGB2 and MDDGC2	1	423.0×	0.026	POMT1
Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1	1	423.0×	0.026	POMT1
XBP1(S) activates chaperone genes	2	47.9×	0.026	FKBP14, LMNA
ECM proteoglycans	2	33.4×	0.026	COL6A2, LAMA2
DAG1 core M1 glycosylations	1	317.2×	0.029	POMT1
DAG1 core M2 glycosylations	1	253.8×	0.031	POMT1
DAG1 core M3 glycosylations	1	211.5×	0.033	POMT1
Muscle contraction	2	17.1×	0.035	RYR1, NEB
Extracellular matrix organization	2	14.0×	0.047	CAPN3, LAMA2
Depolymerization of the Nuclear Lamina	1	84.6×	0.060	LMNA
Initiation of Nuclear Envelope (NE) Reformation	1	66.8×	0.062	LMNA
MET promotes cell motility	1	66.8×	0.062	LAMA2
IRE1alpha activates chaperones	1	57.7×	0.062	LMNA
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models	1	57.7×	0.062	LMNA
Attachment of bacteria to epithelial cells	1	55.2×	0.062	LAMA2
Nuclear Envelope Breakdown	1	50.8×	0.062	LMNA
Laminin interactions	1	42.3×	0.062	LAMA2
MET activates PTK2 signaling	1	42.3×	0.062	LAMA2
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	40.9×	0.062	LAMA2
PI Metabolism	1	39.6×	0.062	INPP5K
Unfolded Protein Response (UPR)	1	39.6×	0.062	LMNA
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	37.3×	0.062	POMT1
Signaling by MET	1	35.2×	0.062	LAMA2
Striated Muscle Contraction	1	34.3×	0.062	NEB
Formation of the dystrophin-glycoprotein complex (DGC)	1	34.3×	0.062	LAMA2
Collagen chain trimerization	1	28.8×	0.067	COL6A2
Signaling by PDGF	1	28.2×	0.067	COL6A2
NCAM1 interactions	1	27.6×	0.067	COL6A2
Oncogenic MAPK signaling	1	27.6×	0.067	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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
muscle organ development	4	83.4×	9e-06	CAPN3, LAMA2, LMNA, NEB
calcium-dependent self proteolysis	1	2106.5×	0.016	CAPN3
positive regulation of renal water transport	1	2106.5×	0.016	INPP5K
positive regulation of satellite cell activation involved in skeletal muscle regeneration	1	1053.2×	0.016	CAPN3
cardiac muscle thin filament assembly	1	702.2×	0.016	NEB
DNA double-strand break attachment to nuclear envelope	1	702.2×	0.016	LMNA
somatic muscle development	1	526.6×	0.016	NEB
regulation of actin filament length	1	526.6×	0.016	NEB
establishment or maintenance of microtubule cytoskeleton polarity	1	526.6×	0.016	LMNA
negative regulation of dephosphorylation	1	526.6×	0.016	INPP5K
cellular response to salt stress	1	526.6×	0.016	CAPN3
negative regulation of D-glucose transmembrane transport	1	421.3×	0.016	INPP5K
positive regulation of synaptic transmission, cholinergic	1	421.3×	0.016	LAMA2
nuclear pore localization	1	421.3×	0.016	LMNA
G1 to G0 transition involved in cell differentiation	1	351.1×	0.016	CAPN3
negative regulation of mesenchymal cell proliferation	1	351.1×	0.016	LMNA
negative regulation of protein targeting to membrane	1	351.1×	0.016	INPP5K
regulation of basement membrane organization	1	351.1×	0.016	LAMA2
cellular response to calcium ion	2	50.1×	0.016	RYR1, CAPN3
regulation of cell migration	2	39.4×	0.016	LAMA2, LMNA
Schwann cell differentiation	1	300.9×	0.016	LAMA2
response to caffeine	1	300.9×	0.016	RYR1
regulation of myoblast differentiation	1	300.9×	0.016	CAPN3
negative regulation of glycogen biosynthetic process	1	263.3×	0.016	INPP5K
protein localization to nuclear envelope	1	263.3×	0.016	LMNA
regulation of protein localization to nucleus	1	263.3×	0.016	LMNA
regulation of glycogen biosynthetic process	1	234.1×	0.017	INPP5K
negative regulation of cardiac muscle hypertrophy in response to stress	1	234.1×	0.017	LMNA
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	210.7×	0.017	RYR1
negative regulation of calcium ion transport	1	210.7×	0.017	INPP5K

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 7

Druggability breadth: 5 of 9 evidence-associated genes (56%) 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
FKBP14	1	2
RYR1	0	0
CAPN3	0	0
COL6A2	0	0
INPP5K	0	0
LAMA2	0	0
NEB	0	0
POMT1	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): 4.

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

Symbol	Assays	Type breakdown
RYR1	16	Binding:13, Functional:3
LMNA	12	Binding:9, Functional:3
FKBP14	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CAPN3	3.4.22.54, 3.4.22.56	calpain-3, caspase-3
FKBP14	5.2.1.8	peptidylprolyl isomerase
INPP5K	3.1.3.56	inositol-polyphosphate 5-phosphatase
POMT1	2.4.1.109	dolichyl-phosphate-mannose-protein mannosyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
RYR1	1

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	1	FKBP14
C	Druggable family + PDB, no drug	3	RYR1, CAPN3, INPP5K
D	Druggable family + AlphaFold only, no drug	1	POMT1
E	Difficult family or no structure, no drug	3	COL6A2, LAMA2, NEB

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RYR1	16	—
CAPN3	0	—
COL6A2	0	—
INPP5K	0	—
LAMA2	0	—
NEB	0	—
POMT1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 8.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE4	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01422200	PHASE4	COMPLETED	Flu Vaccine Study in Neuromuscular Patients 2011
NCT01805024	PHASE1	COMPLETED	Congenital Muscular Dystrophy Ascending Multiple Dose Cohort Study Analyzing Pharmacokinetics at Three Dose Levels In Children and Adolescents With Assessment of Safety and Tolerability of Omigapil (CALLISTO)
NCT05102916	Not specified	RECRUITING	Swiss Registry for Neuromuscular Disorders
NCT05982119	Not specified	RECRUITING	Assessments in Patients With Muscular Pathology and in Control Subjects : The ActiLiège Next Study
NCT06529848	Not specified	RECRUITING	Impact of Exercise Training on Ischemia With Non-Obstructive Coronary Arteries (INOCA): The ExINOCA Study
NCT07138963	Not specified	RECRUITING	Phenotype - Genotype Correlation in a Sample of Egyptian Patients With Congenital Myopathies and Congenital Muscular Dystrophies
NCT01836627	Not specified	COMPLETED	A Study to Test Lung Stretch Therapy (Hyperinsufflation) in Children With Collagen VI Muscular Dystrophy
NCT04001595	Not specified	UNKNOWN	Global FKRP Registry

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
OMIGAPIL	2	1