Arthrogryposis syndrome

Summary

Arthrogryposis syndrome (MONDO:0015225) is a disease (an umbrella term covering 6 Mondo subtypes) with 8 cohort genes. The dominant Reactome pathway is Striated Muscle Contraction (3 cohort genes).

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 8
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	arthrogryposis syndrome
Mondo ID	MONDO:0015225
Orphanet	109007
ICD-11	1692487835
GARD	0019870
Is cancer (heuristic)	no

Also known as: arthrogryposis syndrome

Data availability: 13 ClinVar variants · 2 GenCC gene-disease records · 2 cell lines.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › congenital limb malformation › arthrogryposis syndrome

Related subtypes (106): Adams-Oliver syndrome, ADULT syndrome, Hypoglossia-hypodactyly syndrome, ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, Cooks syndrome, Townes-Brocks syndrome, brachydactyly-arterial hypertension syndrome, brachydactyly-preaxial hallux varus syndrome, fibular aplasia-ectrodactyly syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, femoral-facial syndrome, laurin-Sandrow syndrome, Emery-Nelson syndrome, hand-foot-genital syndrome, IVIC syndrome, Leri pleonosteosis, OSLAM syndrome, pelvis-shoulder dysplasia, phocomelia-ectrodactyly-deafness-sinus arrhythmia syndrome, Poland syndrome, crossed polysyndactyly, postaxial tetramelic oligodactyly, radio-renal syndrome, scalp defects-postaxial polydactyly syndrome, splenogonadal fusion-limb defects-micrognathia syndrome, Karsch-Neugebauer syndrome, symphalangism with multiple anomalies of hands and feet, proximal symphalangism, tarsal-carpal coalition syndrome, extensor tendons of finger anomalies, tetramelic monodactyly, thumb stiffness-brachydactyly-intellectual disability syndrome, tibia, hypoplasia or aplasia of, with polydactyly, Say-field-Coldwell syndrome, triphalangeal thumbs-brachyectrodactyly syndrome, humerus trochlea aplasia, Aphalangy-hemivertebrae-urogenital-intestinal dysgenesis syndrome, camptodactyly syndrome, Guadalajara type 2, Cenani-Lenz syndactyly syndrome, split hand-foot malformation 1 with sensorineural hearing loss, EEM syndrome, ectrodactyly-polydactyly syndrome, lethal faciocardiomelic dysplasia, femur-fibula-ulna complex, Gollop-Wolfgang complex, acromesomelic dysplasia 2B, Fuhrmann syndrome, hallux varus-preaxial polysyndactyly syndrome, Keutel syndrome, absence deformity of leg-cataract syndrome, intellectual disability-spasticity-ectrodactyly syndrome, fibular aplasia, tibial campomelia, and oligosyndactyly syndrome, pelviscapular dysplasia, radioulnar synostosis-developmental delay-hypotonia syndrome, rapadilino syndrome, EEC syndrome, Sugarman brachydactyly, tetraamelia-multiple malformations syndrome, thrombocytopenia-absent radius syndrome, phocomelia, Schinzel type, ulna hypoplasia-intellectual disability syndrome, syndactyly-telecanthus-anogenital and renal malformations syndrome, Mononen-Karnes-Senac syndrome, absent radius-anogenital anomalies syndrome, ulnar hypoplasia-split foot syndrome, aphalangy-syndactyly-microcephaly syndrome, 2q37 microdeletion syndrome, absent tibia-polydactyly-arachnoid cyst syndrome, skeletal dysplasia-epilepsy-short stature syndrome, autosomal recessive amelia, temtamy preaxial brachydactyly syndrome, radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome, acropectoral syndrome, familial digital arthropathy-brachydactyly, Duane-radial ray syndrome, ulnar/fibula ray defect-brachydactyly syndrome, intellectual disability-brachydactyly-Pierre Robin syndrome, Al-Gazali syndrome, cocoon syndrome, mammary-digital-nail syndrome, syndactyly-camptodactyly and clinodactyly of fifth fingers-bifid toes syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, split-foot malformation-mesoaxial polydactyly syndrome, TELO2-related intellectual disability-neurodevelopmental disorder, radial deficiency-tibial hypoplasia syndrome, camptodactyly-taurinuria syndrome, fibular dimelia-diplopodia syndrome, shoulder and thorax deformity-congenital heart disease syndrome, Cornelia de Lange syndrome, familial clubfoot with or without associated lower limb anomalies, heart-hand syndrome, hyperphosphatasia-intellectual disability syndrome, limb transversal defect-cardiac anomaly syndrome, triphalangeal thumb-polysyndactyly syndrome, multiple synostoses syndrome, hereditary thrombocytosis with transverse limb defect, thalidomide embryopathy, tibial aplasia-ectrodactyly syndrome, microcephaly-brachydactyly-kyphoscoliosis syndrome, acrofacial dysostosis, caudal regression-sirenomelia spectrum, Rubinstein-Taybi syndrome, acrocephalosyndactyly, congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome, omphalocele-diaphragmatic hernia-cardiovascular anomalies-radial ray defect syndrome

Subtypes (6): arthrogryposis multiplex congenita, multiple pterygium syndrome, popliteal pterygium syndrome, lethal congenital contracture syndrome, distal arthrogryposis, congenital amyoplasia

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

13 retrieved; paginated sample, class counts are floors:

7 conflicting classifications of pathogenicity, 4 uncertain significance, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
208584	NM_000158.4(GBE1):c.691+2T>C	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
254646	NM_052867.4(NALCN):c.1733A>G (p.Tyr578Cys)	NALCN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1341390	NM_000158.4(GBE1):c.1063C>T (p.Arg355Cys)	GBE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
346793	NM_000158.4(GBE1):c.721A>G (p.Met241Val)	GBE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
238813	NM_001267550.2(TTN):c.59402G>A (p.Gly19801Asp)	LOC126806424	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197940	NM_182961.4(SYNE1):c.7976C>A (p.Thr2659Asn)	SYNE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178169	NM_001267550.2(TTN):c.92696T>C (p.Ile30899Thr)	TTN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
179334	NM_001267550.2(TTN):c.86729AAG[1] (p.Glu28911del)	TTN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
202582	NM_001267550.2(TTN):c.1066G>C (p.Glu356Gln)	TTN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4074922	NM_001457.4(FLNB):c.5252T>C (p.Ile1751Thr)	FLNB	Uncertain significance	criteria provided, single submitter
3377247	NM_002470.4(MYH3):c.2083C>T (p.Arg695Trp)	MYH3	Uncertain significance	criteria provided, single submitter
4075151	NM_182961.4(SYNE1):c.9530A>T (p.Asp3177Val)	SYNE1	Uncertain significance	criteria provided, single submitter
4072188	NM_001267550.2(TTN):c.13084G>C (p.Glu4362Gln)	TTN	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 44 · 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
ACTC1	Strong	Autosomal dominant	distal arthrogryposis	12
MYO9A	Limited	Unknown	arthrogryposis syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACTC1	Orphanet:154	Familial isolated dilated cardiomyopathy
ACTC1	Orphanet:54260	Left ventricular noncompaction
ACTC1	Orphanet:99103	Atrial septal defect, ostium secundum type
MYO9A	Orphanet:98914	Presynaptic congenital myasthenic syndromes
TTN	Orphanet:140922	Titin-related limb-girdle muscular dystrophy R10
TTN	Orphanet:154	Familial isolated dilated cardiomyopathy
TTN	Orphanet:169186	Autosomal recessive centronuclear myopathy
TTN	Orphanet:178464	Hereditary myopathy with early respiratory failure
TTN	Orphanet:289377	Early-onset myopathy with fatal cardiomyopathy
TTN	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
TTN	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
TTN	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
TTN	Orphanet:324604	Classic multiminicore myopathy
TTN	Orphanet:334	Hereditary atrial fibrillation
TTN	Orphanet:466921	Childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndrome
TTN	Orphanet:609	Tibial muscular dystrophy
TTN	Orphanet:707983	Early-onset autosomal recessive TTN-related distal myopathy
SYNE1	Orphanet:319332	Autosomal recessive myogenic arthrogryposis multiplex congenita
SYNE1	Orphanet:88644	Autosomal recessive ataxia, Beauce type
SYNE1	Orphanet:98853	Autosomal dominant Emery-Dreifuss muscular dystrophy
NALCN	Orphanet:1146	Distal arthrogryposis type 1
NALCN	Orphanet:1147	Sheldon-Hall syndrome
NALCN	Orphanet:2053	Freeman-Sheldon syndrome
NALCN	Orphanet:562528	Congenital limbs-face contractures-hypotonia-developmental delay syndrome
NALCN	Orphanet:700336	Hypotonia-speech impairment-severe cognitive delay syndrome due to NALCN deficiency
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
GBE1	Orphanet:206583	Adult polyglucosan body disease
GBE1	Orphanet:308621	Glycogen storage disease due to glycogen branching enzyme deficiency, progressive hepatic form
GBE1	Orphanet:308638	Glycogen storage disease due to glycogen branching enzyme deficiency, non progressive hepatic form
GBE1	Orphanet:308655	Glycogen storage disease due to glycogen branching enzyme deficiency, fatal perinatal neuromuscular form
GBE1	Orphanet:308670	Glycogen storage disease due to glycogen branching enzyme deficiency, congenital neuromuscular form
GBE1	Orphanet:308684	Glycogen storage disease due to glycogen branching enzyme deficiency, childhood combined hepatic and myopathic form
GBE1	Orphanet:308698	Glycogen storage disease due to glycogen branching enzyme deficiency, childhood neuromuscular form
GBE1	Orphanet:308712	Glycogen storage disease due to glycogen branching enzyme deficiency, adult neuromuscular form
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

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ACTC1	HGNC:143	ENSG00000159251	P68032	Actin, alpha cardiac muscle 1	gencc
MYO9A	HGNC:7608	ENSG00000066933	B2RTY4	Unconventional myosin-IXa	gencc
TTN	HGNC:12403	ENSG00000155657	Q8WZ42	Titin	clinvar
SYNE1	HGNC:17089	ENSG00000131018	Q8NF91	Nesprin-1	clinvar
NALCN	HGNC:19082	ENSG00000102452	Q8IZF0	Sodium leak channel NALCN	clinvar
FLNB	HGNC:3755	ENSG00000136068	O75369	Filamin-B	clinvar
GBE1	HGNC:4180	ENSG00000114480	Q04446	1,4-alpha-glucan-branching enzyme	clinvar
MYH3	HGNC:7573	ENSG00000109063	P11055	Myosin-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
MYO9A	Unconventional myosin-IXa	Myosins are actin-based motor molecules with ATPase activity.
TTN	Titin	Key component in the assembly and functioning of vertebrate striated muscles.
SYNE1	Nesprin-1	Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization.
NALCN	Sodium leak channel NALCN	Voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability.
FLNB	Filamin-B	Connects cell membrane constituents to the actin cytoskeleton.
GBE1	1,4-alpha-glucan-branching enzyme	Glycogen-branching enzyme participates in the glycogen biosynthetic process along with glycogenin and glycogen synthase.
MYH3	Myosin-3	Muscle contraction.

Protein-family classification

Druggable: 4 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.5

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	7.3×	0.143
Ion channel	1	13.9×	0.174
Kinase	1	3.5×	0.424
Scaffold/PPI	1	2.2×	0.474
Other/Unknown	3	0.7×	0.919

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ACTC1	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
MYO9A	Other/Unknown	no		IQ_motif_EF-hand-BS, RA_dom, RhoGAP_dom
TTN	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ig_sub2, Ig_sub
SYNE1	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
NALCN	Ion channel	yes		Ion_trans_dom, Volt_channel_dom_sf, NALCN
FLNB	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
GBE1	Antibody/Immunoglobulin	yes		Glyco_hydro_13_N, GH13_cat_dom, A-amylase/branching_C
MYH3	Scaffold/PPI	no		Myosin_head_motor_dom-like, Myosin_tail, SH3_Myosin

Expression context

Cohort genes with no expression data: 0.

7 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
biceps brachii	2
gluteal muscle	2
heart right ventricle	1
left ventricle myocardium	1
myocardium	1
male germ cell	1
sperm	1
skeletal muscle tissue of biceps brachii	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
Brodmann (1909) area 23	1
corpus callosum	1
middle temporal gyrus	1
mucosa of transverse colon	1
tibial nerve	1
transverse colon	1
tibialis anterior	1
left testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACTC1	224	broad	marker	left ventricle myocardium, heart right ventricle, myocardium
MYO9A	280	ubiquitous	marker	calcaneal tendon, male germ cell, sperm
TTN	223	broad	marker	biceps brachii, gluteal muscle, skeletal muscle tissue of biceps brachii
SYNE1	275	ubiquitous	marker	cerebellar hemisphere, right hemisphere of cerebellum, calcaneal tendon
NALCN	201	ubiquitous	marker	middle temporal gyrus, Brodmann (1909) area 23, corpus callosum
FLNB	290	ubiquitous	marker	mucosa of transverse colon, tibial nerve, transverse colon
GBE1	293	ubiquitous	marker	gluteal muscle, tibialis anterior, biceps brachii
MYH3	203	tissue_specific	yes	left testis, right testis, testis

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TTN	4,237
GBE1	3,402
FLNB	2,927
SYNE1	2,886
MYO9A	2,434
NALCN	1,860
MYH3	1,795
ACTC1	996

Intra-cohort edges

A	B	Sources
SYNE1	TTN	string_interaction

Structural data

PDB: 6 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTN	Q8WZ42	64
FLNB	O75369	23
ACTC1	P68032	16
NALCN	Q8IZF0	5
SYNE1	Q8NF91	3
GBE1	Q04446	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYH3	P11055	74.35
MYO9A	B2RTY4	58.07

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 8 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	3	115.7×	4e-05	TTN, ACTC1, MYH3
RHOB GTPase cycle	2	38.6×	0.014	ACTC1, MYO9A
Glycogen storage disease type IV (GBE1)	1	475.8×	0.018	GBE1
Muscle contraction	2	19.3×	0.024	ACTC1, MYH3
RHOA GTPase cycle	2	18.7×	0.024	ACTC1, MYO9A
Regulation of CDH1 Function	1	119.0×	0.030	ACTC1
RHO GTPase cycle	2	15.0×	0.030	ACTC1, MYO9A
Glycogen synthesis	1	102.0×	0.031	GBE1
Formation of the dystrophin-glycoprotein complex (DGC)	1	38.6×	0.053	ACTC1
Meiosis	1	35.7×	0.053	SYNE1
RHOV GTPase cycle	1	35.7×	0.053	MYO9A
Signaling by Rho GTPases	2	8.6×	0.053	ACTC1, MYO9A
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	2	8.4×	0.053	ACTC1, MYO9A
Reproduction	1	23.8×	0.074	SYNE1
Activation of STAT3 by cadherin engagement	1	20.4×	0.075	ACTC1
Non-integrin membrane-ECM interactions	1	19.3×	0.075	ACTC1
ISG15 antiviral mechanism	1	18.8×	0.075	FLNB
Meiotic synapsis	1	17.6×	0.075	SYNE1
Stimuli-sensing channels	1	17.0×	0.075	NALCN
Ion channel transport	1	12.0×	0.101	NALCN
Platelet degranulation	1	11.0×	0.104	TTN
Extracellular matrix organization	1	7.9×	0.136	ACTC1
Signal Transduction	2	2.5×	0.198	ACTC1, MYO9A
Cell Cycle	1	4.5×	0.210	SYNE1
Transport of small molecules	1	3.1×	0.277	NALCN

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
skeletal muscle thin filament assembly	2	702.2×	2e-04	TTN, ACTC1
cardiac muscle tissue morphogenesis	2	351.1×	3e-04	TTN, ACTC1
cardiac myofibril assembly	2	324.1×	3e-04	TTN, ACTC1
muscle filament sliding	2	263.3×	4e-04	TTN, MYH3
actin filament-based movement	2	200.6×	5e-04	ACTC1, MYH3
skeletal muscle contraction	2	127.7×	0.001	TTN, MYH3
cardiac muscle contraction	2	100.3×	0.001	TTN, ACTC1
sarcomere organization	2	95.8×	0.001	TTN, MYH3
muscle contraction	2	52.0×	0.004	TTN, MYH3
actin-myosin filament sliding	1	1053.2×	0.006	ACTC1
skeletal muscle myosin thick filament assembly	1	702.2×	0.007	TTN
sarcomerogenesis	1	702.2×	0.007	TTN
nuclear matrix anchoring at nuclear membrane	1	702.2×	0.007	SYNE1
positive regulation of synaptic transmission, cholinergic	1	421.3×	0.009	NALCN
cytoplasmic actin-based contraction involved in cell motility	1	421.3×	0.009	ACTC1
mesenchyme migration	1	421.3×	0.009	ACTC1
regulation of neuron projection arborization	1	351.1×	0.010	MYO9A
detection of muscle stretch	1	300.9×	0.011	TTN
cardiac muscle hypertrophy	1	210.7×	0.014	TTN
cell junction assembly	1	210.7×	0.014	MYO9A
keratinocyte development	1	191.5×	0.015	FLNB
obsolete protein kinase A signaling	1	175.5×	0.016	TTN
regulation of resting membrane potential	1	162.0×	0.016	NALCN
establishment of epithelial cell apical/basal polarity	1	131.7×	0.019	MYO9A
mitotic chromosome condensation	1	123.9×	0.019	TTN
positive regulation of synaptic transmission, GABAergic	1	123.9×	0.019	NALCN
epithelial cell morphogenesis	1	117.0×	0.019	FLNB
glycogen biosynthetic process	1	117.0×	0.019	GBE1
striated muscle contraction	1	105.3×	0.019	TTN
muscle cell differentiation	1	105.3×	0.019	SYNE1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 8

Druggability breadth: 3 of 8 evidence-associated genes (38%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ACTC1	0	0
MYO9A	0	0
TTN	0	0
SYNE1	0	0
NALCN	0	0
FLNB	0	0
GBE1	0	0
MYH3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ACTC1	6	Binding:6
FLNB	2	Binding:2
TTN	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TTN	2.7.11.1	non-specific serine/threonine protein kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

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	0
C	Druggable family + PDB, no drug	4	TTN, NALCN, FLNB, GBE1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	ACTC1, MYO9A, SYNE1, MYH3

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)
ACTC1	6	—
MYO9A	0	—
TTN	1	—
SYNE1	0	—
NALCN	0	—
FLNB	2	—
GBE1	0	—
MYH3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.