Arthrogryposis

Summary

Arthrogryposis (MONDO:0008779) is a disease (an umbrella term covering 5 Mondo subtypes) caused by variants in MYBPC1 and MYH3, with 9 cohort genes and 9 clinical trials. The dominant Reactome pathway is Striated Muscle Contraction (5 cohort genes).

At a glance

• Causal genes: MYBPC1 (GenCC Strong), MYH3 (GenCC Strong)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 9
• ClinVar variants: 5
• Clinical trials: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	arthrogryposis
Mondo ID	MONDO:0008779
EFO	EFO:0003857
MeSH	D001176
NCIT	C84572
UMLS	C0003886
MedGen	2455
Is cancer (heuristic)	no

Also known as: Arthrogryposes, congenital multiple · congenital multiple Arthrogryposes · congenital multiple arthrogryposis

Data availability: 5 ClinVar variants · 4 GenCC gene-disease records · 2 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › arthrogryposis

Related subtypes (53): cerebellar ataxia, chronic tic disorder, choreatic disease, extrapyramidal and movement disease, benign shuddering attacks, transient tic disorder, essential tremor, lingual-facial-buccal dyskinesia, kuru, inherited Creutzfeldt-Jakob disease, Tourette syndrome, clonic hemifacial spasm, Huntington disease, multiple system atrophy, spinal muscular atrophy-progressive myoclonic epilepsy syndrome, benign paroxysmal tonic upgaze of childhood with ataxia, hereditary geniospasm, tremor-nystagmus-duodenal ulcer syndrome, Lafora disease, Unverricht-Lundborg syndrome, neuronal intranuclear inclusion disease, Huntington disease-like 3, brain-lung-thyroid syndrome, myoclonus, familial, proximal myopathy with extrapyramidal signs, progressive myoclonic epilepsy type 7, progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome, progressive non-fluent aphasia, opsoclonus-myoclonus syndrome, isolated facial myokymia, primary orthostatic tremor, familial congenital mirror movements, neuroacanthocytosis, behavioral variant of frontotemporal dementia, frontotemporal dementia with motor neuron disease, hyperekplexia, intellectual disability-hyperkinetic movement-truncal ataxia syndrome, neurodegeneration with brain iron accumulation, Huntington disease-like syndrome due to C9ORF72 expansions, variably protease-sensitive prionopathy, corticobasal syndrome, sensorineural hearing loss-early graying-essential tremor syndrome, progressive supranuclear palsy, Sandifer syndrome, psychogenic movement disorders, epilepsy with myoclonic absences, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, childhood-onset benign chorea with striatal involvement, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, PRRT2-associated paroxysmal movement disorder, SLC6A3-related dopamine transporter deficiency syndrome, dyskinesia with orofacial involvement, autosomal dominant, complex movement disorder with or without neurodevelopmental features

Subtypes (5): congenital contractural arachnodactyly, Freeman-Sheldon syndrome, boylan dew greco syndrome, distal arthrogryposis Moore weaver type, massa casaer ceulemans syndrome

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

5 retrieved; paginated sample, class counts are floors:

4 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
12463	NM_003289.4(TPM2):c.397C>T (p.Arg133Trp)	TPM2	Pathogenic	criteria provided, multiple submitters, no conflicts
2579718	NM_005159.5(ACTC1):c.1121G>A (p.Arg374His)	ACTC1	Likely pathogenic	criteria provided, single submitter
1324108	NM_198721.4(COL25A1):c.382C>T (p.Arg128Ter)	COL25A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3384057	NM_004826.4(ECEL1):c.1184+1G>T	ECEL1	Likely pathogenic	criteria provided, single submitter
4820580	NM_001457.4(FLNB):c.623G>T (p.Trp208Leu)	FLNB	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 46 · Orphanet: 34 · 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
MYBPC1	Strong	Autosomal dominant	arthrogryposis, distal, type 1B	11
MYH3	Strong	Autosomal dominant	distal arthrogryposis type 2B1	14
SCN1A	Moderate	Autosomal dominant	arthrogryposis	20
TNNI1	Moderate	Autosomal dominant	arthrogryposis

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCN1A	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SCN1A	Orphanet:2382	Lennox-Gastaut syndrome
SCN1A	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
SCN1A	Orphanet:33069	Dravet syndrome
SCN1A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN1A	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SCN1A	Orphanet:569	Familial or sporadic hemiplegic migraine
MYBPC1	Orphanet:1146	Distal arthrogryposis type 1
MYBPC1	Orphanet:137783	Lethal congenital contracture syndrome type 3
MYBPC1	Orphanet:498693	MYBPC1-related autosomal recessive non-lethal arthrogryposis multiplex congenita syndrome
MYH3	Orphanet:1146	Distal arthrogryposis type 1
MYH3	Orphanet:1147	Sheldon-Hall syndrome
MYH3	Orphanet:2053	Freeman-Sheldon syndrome
MYH3	Orphanet:2990	Autosomal recessive multiple pterygium syndrome
MYH3	Orphanet:3275	Spondylocarpotarsal synostosis
MYH3	Orphanet:65743	Autosomal dominant multiple pterygium syndrome
TPM2	Orphanet:1146	Distal arthrogryposis type 1
TPM2	Orphanet:1147	Sheldon-Hall syndrome
TPM2	Orphanet:171436	Typical nemaline myopathy
TPM2	Orphanet:171439	Childhood-onset nemaline myopathy
TPM2	Orphanet:171881	Cap myopathy
TPM2	Orphanet:2020	Congenital fiber-type disproportion myopathy
ACTC1	Orphanet:154	Familial isolated dilated cardiomyopathy
ACTC1	Orphanet:54260	Left ventricular noncompaction
ACTC1	Orphanet:99103	Atrial septal defect, ostium secundum type
COL25A1	Orphanet:1143	Neurogenic arthrogryposis multiplex congenita
COL25A1	Orphanet:45358	Congenital fibrosis of extraocular muscles
COL25A1	Orphanet:91411	Congenital ptosis
ECEL1	Orphanet:329457	Distal arthrogryposis type 5D
FLNB	Orphanet:1190	Atelosteogenesis type I
FLNB	Orphanet:1263	Boomerang dysplasia
FLNB	Orphanet:3275	Spondylocarpotarsal synostosis
FLNB	Orphanet:503	Larsen syndrome
FLNB	Orphanet:56305	Atelosteogenesis type III

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
SCN1A	HGNC:10585	ENSG00000144285	P35498	Sodium channel protein type 1 subunit alpha	gencc
TNNI1	HGNC:11945	ENSG00000159173	P19237	Troponin I, slow skeletal muscle	gencc
MYBPC1	HGNC:7549	ENSG00000196091	Q00872	Myosin-binding protein C, slow-type	gencc
MYH3	HGNC:7573	ENSG00000109063	P11055	Myosin-3	gencc
TPM2	HGNC:12011	ENSG00000198467	P07951	Tropomyosin beta chain	clinvar
ACTC1	HGNC:143	ENSG00000159251	P68032	Actin, alpha cardiac muscle 1	clinvar
COL25A1	HGNC:18603	ENSG00000188517	Q9BXS0	Collagen alpha-1(XXV) chain	clinvar
ECEL1	HGNC:3147	ENSG00000171551	O95672	Endothelin-converting enzyme-like 1	clinvar
FLNB	HGNC:3755	ENSG00000136068	O75369	Filamin-B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCN1A	Sodium channel protein type 1 subunit alpha	Pore-forming subunit of Nav1.1, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes.
TNNI1	Troponin I, slow skeletal muscle	Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
MYBPC1	Myosin-binding protein C, slow-type	Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands.
MYH3	Myosin-3	Muscle contraction.
TPM2	Tropomyosin beta chain	Binds to actin filaments in muscle and non-muscle cells.
ACTC1	Actin, alpha cardiac muscle 1	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
COL25A1	Collagen alpha-1(XXV) chain	Inhibits fibrillization of amyloid-beta peptide during the elongation phase.
ECEL1	Endothelin-converting enzyme-like 1	May contribute to the degradation of peptide hormones and be involved in the inactivation of neuronal peptides.
FLNB	Filamin-B	Connects cell membrane constituents to the actin cytoskeleton.

Protein-family classification

Druggable: 4 · Difficult: 1 · Unknown: 4 · Druggable fraction: 0.44

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
Antibody/Immunoglobulin	2	6.5×	0.180
Ion channel	1	12.4×	0.195
Protease	1	4.1×	0.368
Scaffold/PPI	1	1.9×	0.519
Other/Unknown	4	0.8×	0.847

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCN1A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_channel_a1su
TNNI1	Other/Unknown	no		Troponin, Troponin_sf, Troponin_I
MYBPC1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
MYH3	Scaffold/PPI	no		Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin
TPM2	Other/Unknown	no		Tropomyosin
ACTC1	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
COL25A1	Other/Unknown	no		Collagen, Collagen_Structural_Proteins
ECEL1	Protease	yes		Peptidase_M13, Peptidase_M13_N, Peptidase_M13_C
FLNB	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom

Expression context

Cohort genes with no expression data: 0.

8 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
skeletal muscle tissue of biceps brachii	2
skeletal muscle tissue of rectus abdominis	2
left testis	2
right testis	2
Brodmann (1909) area 23	1
lateral nuclear group of thalamus	1
primary visual cortex	1
diaphragm	1
biceps brachii	1
testis	1
blood vessel layer	1
popliteal artery	1
saphenous vein	1
heart right ventricle	1
left ventricle myocardium	1
myocardium	1
sperm	1
adenohypophysis	1
left ovary	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCN1A	154	tissue_specific	marker	Brodmann (1909) area 23, lateral nuclear group of thalamus, primary visual cortex
TNNI1	183	broad	marker	skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, diaphragm
MYBPC1	225	broad	marker	biceps brachii, skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii
MYH3	203	tissue_specific	yes	left testis, right testis, testis
TPM2	283	ubiquitous	marker	saphenous vein, popliteal artery, blood vessel layer
ACTC1	224	broad	marker	left ventricle myocardium, heart right ventricle, myocardium
COL25A1	163	broad	marker	sperm, left testis, right testis
ECEL1	152	broad	marker	left ovary, right ovary, adenohypophysis
FLNB	290	ubiquitous	marker	mucosa of transverse colon, tibial nerve, transverse colon

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FLNB	2,927
SCN1A	2,287
MYBPC1	1,816
MYH3	1,795
TNNI1	1,367
ECEL1	1,194
COL25A1	1,104
ACTC1	996
TPM2	357

Intra-cohort edges

A	B	Sources
MYBPC1	MYH3	string_interaction
MYH3	TNNI1	biogrid_interaction
MYH3	TPM2	biogrid_interaction
TNNI1	TPM2	biogrid_interaction

Structural data

PDB: 4 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FLNB	O75369	23
ACTC1	P68032	16
MYBPC1	Q00872	8
SCN1A	P35498	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TPM2	P07951	91.51
ECEL1	O95672	88.62
TNNI1	P19237	78.44
MYH3	P11055	74.35
COL25A1	Q9BXS0	57.23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 9 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Striated Muscle Contraction	5	192.9×	4e-10	TNNI1, TPM2, ACTC1, MYBPC1, MYH3
Muscle contraction	4	38.6×	2e-05	SCN1A, ACTC1, MYBPC1, MYH3
Regulation of CDH1 Function	1	119.0×	0.070	ACTC1
Interaction between L1 and Ankyrins	1	46.0×	0.093	SCN1A
Phase 0 - rapid depolarisation	1	43.3×	0.093	SCN1A
Formation of the dystrophin-glycoprotein complex (DGC)	1	38.6×	0.093	ACTC1
Smooth Muscle Contraction	1	33.2×	0.093	TPM2
Collagen chain trimerization	1	32.4×	0.093	COL25A1
Collagen degradation	1	22.0×	0.093	COL25A1
Collagen biosynthesis and modifying enzymes	1	21.3×	0.093	COL25A1
Activation of STAT3 by cadherin engagement	1	20.4×	0.093	ACTC1
Non-integrin membrane-ECM interactions	1	19.3×	0.093	ACTC1
RHOB GTPase cycle	1	19.3×	0.093	ACTC1
ISG15 antiviral mechanism	1	18.8×	0.093	FLNB
L1CAM interactions	1	15.0×	0.108	SCN1A
Cardiac conduction	1	13.6×	0.111	SCN1A
RHOA GTPase cycle	1	9.3×	0.150	ACTC1
Extracellular matrix organization	1	7.9×	0.165	ACTC1
RHO GTPase cycle	1	7.5×	0.165	ACTC1
Axon guidance	1	5.6×	0.205	SCN1A
Nervous system development	1	5.4×	0.205	SCN1A
Signaling by Rho GTPases	1	4.3×	0.234	ACTC1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	4.2×	0.234	ACTC1
Developmental Biology	1	1.8×	0.455	SCN1A
Signal Transduction	1	1.3×	0.563	ACTC1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
actin filament-based movement	2	178.3×	0.003	ACTC1, MYH3
skeletal muscle contraction	2	113.5×	0.003	TNNI1, MYH3
cardiac muscle contraction	2	89.2×	0.003	TNNI1, ACTC1
sarcomere organization	2	85.1×	0.003	MYBPC1, MYH3
actin-myosin filament sliding	1	936.2×	0.008	ACTC1
regulation of ATP-dependent activity	1	936.2×	0.008	TPM2
muscle contraction	2	46.2×	0.008	TPM2, MYH3
cytoplasmic actin-based contraction involved in cell motility	1	374.5×	0.013	ACTC1
mesenchyme migration	1	374.5×	0.013	ACTC1
actin filament organization	2	26.4×	0.013	TPM2, ACTC1
skeletal muscle thin filament assembly	1	312.1×	0.015	ACTC1
transition between fast and slow fiber	1	267.5×	0.016	TNNI1
regulation of striated muscle contraction	1	234.1×	0.016	TNNI1
axonogenesis involved in innervation	1	187.2×	0.018	COL25A1
membrane depolarization during action potential	1	187.2×	0.018	SCN1A
keratinocyte development	1	170.2×	0.018	FLNB
neuronal action potential propagation	1	156.0×	0.018	SCN1A
cardiac muscle tissue morphogenesis	1	156.0×	0.018	ACTC1
cardiac myofibril assembly	1	144.0×	0.018	ACTC1
detection of mechanical stimulus involved in sensory perception of pain	1	124.8×	0.019	SCN1A
muscle filament sliding	1	117.0×	0.019	MYH3
neuromuscular process controlling posture	1	117.0×	0.019	SCN1A
respiratory system process	1	104.0×	0.019	ECEL1
epithelial cell morphogenesis	1	104.0×	0.019	FLNB
nerve development	1	104.0×	0.019	SCN1A
heart contraction	1	85.1×	0.022	ACTC1
ventricular cardiac muscle tissue morphogenesis	1	78.0×	0.023	TNNI1
cardiac muscle cell action potential involved in contraction	1	78.0×	0.023	SCN1A
actomyosin structure organization	1	62.4×	0.027	ACTC1
adult walking behavior	1	55.1×	0.029	SCN1A

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 8

Druggability breadth: 3 of 9 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
SCN1A	MEXILETINE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN1A	94	4
TNNI1	0	0
MYBPC1	0	0
MYH3	0	0
TPM2	0	0
ACTC1	0	0
COL25A1	0	0
ECEL1	0	0
FLNB	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MEXILETINE HYDROCHLORIDE	4	SCN1A
BEPRIDIL	4	SCN1A
DIBUCAINE	4	SCN1A
ARTICAINE	4	SCN1A
BUPIVACAINE	4	SCN1A
IMIPRAMINE	4	SCN1A
DROPERIDOL	4	SCN1A
DICYCLOMINE	4	SCN1A
TETRABENAZINE	4	SCN1A
PHENIRAMINE	4	SCN1A
PRILOCAINE	4	SCN1A
PROPOXYCAINE	4	SCN1A
PROPARACAINE	4	SCN1A
HEXYLCAINE	4	SCN1A
PRAMOXINE	4	SCN1A
BENOXINATE	4	SCN1A
QUINIDINE	4	SCN1A
FELODIPINE	4	SCN1A
PHENYTOIN	4	SCN1A
QUININE	4	SCN1A
NISOLDIPINE	4	SCN1A
NIFEDIPINE	4	SCN1A
PRAZOSIN	4	SCN1A
DILTIAZEM	4	SCN1A
PRENYLAMINE	4	SCN1A
COCAINE	4	SCN1A
TRIFLUOPERAZINE	4	SCN1A
CINNARIZINE	4	SCN1A
THIORIDAZINE	4	SCN1A
ETIDOCAINE	4	SCN1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SCN1A	149	Binding:115, Functional:18, ADMET:14, Toxicity:2
ACTC1	6	Binding:6
FLNB	2	Binding:2

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SCN1A	149

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MEXILETINE HYDROCHLORIDE	4	SCN1A
BEPRIDIL	4	SCN1A
DIBUCAINE	4	SCN1A
ARTICAINE	4	SCN1A
BUPIVACAINE	4	SCN1A
IMIPRAMINE	4	SCN1A
DROPERIDOL	4	SCN1A
DICYCLOMINE	4	SCN1A
TETRABENAZINE	4	SCN1A
PHENIRAMINE	4	SCN1A
PRILOCAINE	4	SCN1A
PROPOXYCAINE	4	SCN1A
PROPARACAINE	4	SCN1A
HEXYLCAINE	4	SCN1A
PRAMOXINE	4	SCN1A
BENOXINATE	4	SCN1A
QUINIDINE	4	SCN1A
FELODIPINE	4	SCN1A
PHENYTOIN	4	SCN1A
QUININE	4	SCN1A
NISOLDIPINE	4	SCN1A
NIFEDIPINE	4	SCN1A
PRAZOSIN	4	SCN1A
DILTIAZEM	4	SCN1A
PRENYLAMINE	4	SCN1A
COCAINE	4	SCN1A
TRIFLUOPERAZINE	4	SCN1A
CINNARIZINE	4	SCN1A
THIORIDAZINE	4	SCN1A
ETIDOCAINE	4	SCN1A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SCN1A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	MYBPC1, FLNB
D	Druggable family + AlphaFold only, no drug	1	ECEL1
E	Difficult family or no structure, no drug	5	TNNI1, MYH3, TPM2, ACTC1, COL25A1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TNNI1	0	—
MYBPC1	0	—
MYH3	0	—
TPM2	0	—
ACTC1	6	—
COL25A1	0	—
ECEL1	0	—
FLNB	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01028833	PHASE2	COMPLETED	Effects of Power Mobility on Young Children With Severe Motor Impairments
NCT04798378	Not specified	ACTIVE_NOT_RECRUITING	NuroSleeve Powered Brace & Stimulation System to Restore Arm Function
NCT06192134	Not specified	NOT_YET_RECRUITING	Continuous Passive Motion Device for Children With Arthrogryposis
NCT07429188	Not specified	RECRUITING	Impact Study on Users of Upper Limb Assistive Devices
NCT01144741	Not specified	TERMINATED	Survey Study and Records Review of Treatment Outcomes in Freeman-Sheldon Syndrome
NCT01306994	Not specified	WITHDRAWN	Study of Resting and Exercising Body Functioning in Freeman-Sheldon Syndrome and Related Conditions
NCT01307475	Not specified	TERMINATED	Study of Quality of Life in Freeman-Sheldon Syndrome and Related Conditions
NCT02218593	Not specified	COMPLETED	WREX Outcome Study
NCT04789746	Not specified	UNKNOWN	Ready, Set, Go! A Physical Fitness Intervention for Children With Mobility Challenges