Congenital myasthenic syndrome 6

Summary

Congenital myasthenic syndrome 6 (MONDO:0009689) is a disease caused by CHAT (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: CHAT (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 937

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital myasthenic syndrome 6
Mondo ID	MONDO:0009689
MeSH	C535759
OMIM	254210
DOID	DOID:0110671
NCIT	C132292
SNOMED CT	230670003
UMLS	C0393929
MedGen	140751
GARD	0009689
Is cancer (heuristic)	no

Also known as: CHAT congenital myasthenic syndrome · Cms Ia2 · CMS Ia2, formerly · CMS w/episodic apnea · CMS-ea · CMS1A · CMS1A2, formerly · CMS6 · CMSEA · congenital myasthenic syndrome 6 · congenital myasthenic syndrome caused by mutation in CHAT · congenital myasthenic syndrome type 1a · congenital myasthenic syndrome type 6 · congenital myasthenic syndrome type Ia · congenital myasthenic syndrome type Ia2, formerly · congenital myasthenic syndrome with episodic apnea · FIM · FIM, formerly · FIMG2 (formerly) · FIMG2, formerly (+11 more)

Data availability: 937 ClinVar variants · 2 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital myasthenic syndrome 6

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, 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 muscular dystrophy, 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

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

329 likely benign, 163 uncertain significance, 28 pathogenic, 22 likely pathogenic, 17 benign, 16 pathogenic/likely pathogenic, 14 conflicting classifications of pathogenicity, 11 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069123	NM_020549.5(CHAT):c.472C>T (p.Gln158Ter)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073040	NM_020549.5(CHAT):c.951del (p.Val318fs)	CHAT	Pathogenic	criteria provided, single submitter
1073926	NM_020549.5(CHAT):c.1909G>T (p.Glu637Ter)	CHAT	Pathogenic	criteria provided, single submitter
1322074	NM_020549.5(CHAT):c.1408C>T (p.Arg470Ter)	CHAT	Pathogenic	criteria provided, multiple submitters, no conflicts
1324064	NM_020549.5(CHAT):c.1663G>T (p.Glu555Ter)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451989	NM_020549.5(CHAT):c.1620dup (p.Leu541fs)	CHAT	Pathogenic	criteria provided, single submitter
1452196	NM_020549.5(CHAT):c.1510C>T (p.Arg504Ter)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452884	NM_020549.5(CHAT):c.1681C>T (p.Arg561Ter)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1460078	NC_000010.10:g.(?50821083)(50874150_?)del	CHAT	Pathogenic	criteria provided, single submitter
1487028	NM_020549.5(CHAT):c.1896_1918del (p.Ala633fs)	CHAT	Pathogenic	criteria provided, single submitter
17506	NM_020549.5(CHAT):c.631C>G (p.Pro211Ala)	CHAT	Pathogenic	criteria provided, multiple submitters, no conflicts
17507	NM_020549.5(CHAT):c.1321G>A (p.Glu441Lys)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17510	NM_020549.5(CHAT):c.1679G>A (p.Arg560His)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17513	NM_020549.5(CHAT):c.914T>C (p.Ile305Thr)	CHAT	Pathogenic	no assertion criteria provided
17515	NM_020549.5(CHAT):c.1007T>C (p.Ile336Thr)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1804816	NM_020549.5(CHAT):c.451C>T (p.Arg151Ter)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1805033	NM_020549.5(CHAT):c.1444dup (p.Arg482fs)	CHAT	Pathogenic	criteria provided, single submitter
196498	NM_020549.5(CHAT):c.418C>T (p.Gln140Ter)	CHAT	Pathogenic	criteria provided, multiple submitters, no conflicts
1991517	NM_020549.5(CHAT):c.1387C>T (p.Gln463Ter)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2136861	NM_020549.5(CHAT):c.1262G>C (p.Trp421Ser)	CHAT	Pathogenic	criteria provided, single submitter
2136862	NM_020549.5(CHAT):c.1891G>A (p.Ala631Thr)	CHAT	Pathogenic	criteria provided, single submitter
2198081	NM_020549.5(CHAT):c.1850_1851del (p.Gly617fs)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2426565	NC_000010.10:g.(?50856533)(50857702_?)del	CHAT	Pathogenic	criteria provided, single submitter
2680729	NM_020549.5(CHAT):c.1441dup (p.Arg481fs)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680731	NM_020549.5(CHAT):c.593G>A (p.Trp198Ter)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680736	NM_020549.5(CHAT):c.1231G>T (p.Gly411Ter)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2694017	NM_020549.5(CHAT):c.1027G>T (p.Glu343Ter)	CHAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2728783	NM_020549.5(CHAT):c.619del (p.Arg207fs)	CHAT	Pathogenic	criteria provided, single submitter
2733909	NM_020549.5(CHAT):c.1455G>A (p.Trp485Ter)	CHAT	Pathogenic	criteria provided, single submitter
2760853	NM_020549.5(CHAT):c.1058_1061dup (p.Ser355fs)	CHAT	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 3 · 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
CHAT	Strong	Autosomal recessive	congenital myasthenic syndrome 6	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHAT	Orphanet:98914	Presynaptic congenital myasthenic syndromes
SLC18A3	Orphanet:98914	Presynaptic congenital myasthenic syndromes
SLC18A3	Orphanet:994	Fetal akinesia deformation sequence

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CHAT	HGNC:1912	ENSG00000070748	P28329	Choline O-acetyltransferase	gencc,clinvar
SLC18A3	HGNC:10936	ENSG00000187714	Q16572	Vesicular acetylcholine transporter	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHAT	Choline O-acetyltransferase	Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses.
SLC18A3	Vesicular acetylcholine transporter	Electrogenic antiporter that exchanges one cholinergic neurotransmitter, acetylcholine or choline, with two intravesicular protons across the membrane of synaptic vesicles.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Transporter	1	38.9×	0.051
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CHAT	Enzyme (other)	yes	2.3.1.6	Carn_acyl_trans, CAT-like_dom_sf, Cho/carn_acyl_trans_1_2
SLC18A3	Transporter	yes		MFS, MFS_dom, MFS_trans_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
primordial germ cell in gonad	2
putamen	2
male germ line stem cell (sensu Vertebrata) in testis	1
endometrium epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHAT	68	tissue_specific	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, putamen
SLC18A3	60	tissue_specific	yes	primordial germ cell in gonad, endometrium epithelium, putamen

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHAT	1,743
SLC18A3	1,568

Intra-cohort edges

A	B	Sources
CHAT	SLC18A3	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC18A3	Q16572	11
CHAT	P28329	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Acetylcholine Neurotransmitter Release Cycle	2	671.8×	8e-06	CHAT, SLC18A3
Synthesis of PC	1	203.9×	0.010	CHAT
Cargo recognition for clathrin-mediated endocytosis	1	52.4×	0.023	SLC18A3
Clathrin-mediated endocytosis	1	42.6×	0.023	SLC18A3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
neurotransmitter transport	2	421.3×	5e-05	CHAT, SLC18A3
acetylcholine uptake	1	4213.0×	7e-04	SLC18A3
positive regulation of neuromuscular junction development	1	4213.0×	7e-04	SLC18A3
acetylcholine biosynthetic process	1	2808.7×	7e-04	CHAT
positive regulation of acetylcholine secretion, neurotransmission	1	2808.7×	7e-04	SLC18A3
serotonin uptake	1	766.0×	0.002	SLC18A3
phosphatidylcholine biosynthetic process	1	401.2×	0.004	CHAT
positive regulation of long-term synaptic potentiation	1	337.0×	0.004	SLC18A3
neuromuscular synaptic transmission	1	300.9×	0.004	CHAT
chemical synaptic transmission	1	38.6×	0.026	SLC18A3

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHAT	1	3
SLC18A3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COENZYME_A	3	CHAT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
SLC18A3	17	Binding:17
CHAT	7	Binding:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CHAT	2.3.1.6	choline O-acetyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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)
COENZYME_A	3	CHAT

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	CHAT
C	Druggable family + PDB, no drug	1	SLC18A3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC18A3	17	CHAT

Clinical trials & evidence

Clinical trials

Clinical trials: 0.