Congenital myasthenic syndrome 18

Summary

Congenital myasthenic syndrome 18 (MONDO:0014590) is a disease caused by SNAP25 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: SNAP25 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 183

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital myasthenic syndrome 18
Mondo ID	MONDO:0014590
OMIM	616330
DOID	DOID:0110683
UMLS	C4225364
MedGen	906793
GARD	0016091
Is cancer (heuristic)	no

Also known as: CMS18 · congenital myasthenic syndrome caused by mutation in SNAP25 · congenital myasthenic syndrome type 18 · myasthenic syndrome, congenital, 18 · myasthenic syndrome, congenital, 18, with intellectual disability and ataxia · myasthenic syndrome, congenital, type 18 · SNAP25 congenital myasthenic syndrome · SNAP25-DEE

Data availability: 183 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital myasthenic syndrome 18

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, 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

183 retrieved; paginated sample, class counts are floors:

93 likely benign, 56 uncertain significance, 11 likely pathogenic, 9 benign, 5 conflicting classifications of pathogenicity, 4 benign/likely benign, 3 pathogenic/likely pathogenic, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1285516	NM_130811.4(SNAP25):c.127G>C (p.Gly43Arg)	SNAP25	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1285521	NM_130811.4(SNAP25):c.212T>C (p.Met71Thr)	SNAP25	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1712269	NM_130811.4(SNAP25):c.529C>T (p.Gln177Ter)	SNAP25	Pathogenic	criteria provided, single submitter
253030	NM_130811.4(SNAP25):c.200T>A (p.Ile67Asn)	SNAP25	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3899925	SNAP25, VAL48PHE	SNAP25	Pathogenic	no assertion criteria provided
3338444	GRCh37/hg19 20p12.3-12.1(chr20:5454270-13610745)x1	ANKEF1	Likely pathogenic	no assertion criteria provided
1066155	NM_130811.4(SNAP25):c.593G>C (p.Arg198Pro)	SNAP25	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1285522	NM_130811.4(SNAP25):c.496G>T (p.Asp166Tyr)	SNAP25	Likely pathogenic	criteria provided, single submitter
1285529	NM_130811.4(SNAP25):c.520C>T (p.Gln174Ter)	SNAP25	Likely pathogenic	criteria provided, single submitter
1685449	NM_130811.4(SNAP25):c.170T>C (p.Leu57Pro)	SNAP25	Likely pathogenic	criteria provided, single submitter
2107892	NM_130811.4(SNAP25):c.74C>T (p.Ser25Leu)	SNAP25	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2814496	NM_130811.4(SNAP25):c.542T>A (p.Ile181Asn)	SNAP25	Likely pathogenic	criteria provided, single submitter
2834612	NM_130811.4(SNAP25):c.508_528dup (p.Arg176_Gln177insGluIleAspThrGlnAsnArg)	SNAP25	Likely pathogenic	criteria provided, single submitter
3235704	NM_130811.4(SNAP25):c.550_552del (p.Lys184del)	SNAP25	Likely pathogenic	criteria provided, single submitter
803598	NM_130811.4(SNAP25):c.553G>C (p.Ala185Pro)	SNAP25	Likely pathogenic	criteria provided, single submitter
986340	NM_130811.4(SNAP25):c.589C>T (p.Gln197Ter)	SNAP25	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1025754	NM_130811.4(SNAP25):c.89G>A (p.Arg30His)	SNAP25	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1065446	NM_130811.4(SNAP25):c.596C>T (p.Ala199Val)	SNAP25	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1392766	NM_130811.4(SNAP25):c.514G>A (p.Asp172Asn)	SNAP25	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1394489	NM_130811.4(SNAP25):c.296A>T (p.Asp99Val)	SNAP25	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2754201	NM_130811.4(SNAP25):c.488T>G (p.Met163Arg)	SNAP25	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1042738	NM_130811.4(SNAP25):c.591A>C (p.Gln197His)	SNAP25	Uncertain significance	criteria provided, multiple submitters, no conflicts
1062961	NM_130811.4(SNAP25):c.552+6C>T	SNAP25	Uncertain significance	criteria provided, single submitter
1285530	NM_130811.4(SNAP25):c.92G>A (p.Arg31His)	SNAP25	Uncertain significance	criteria provided, multiple submitters, no conflicts
1285532	NM_130811.4(SNAP25):c.404G>A (p.Arg135His)	SNAP25	Uncertain significance	criteria provided, multiple submitters, no conflicts
1347052	NM_130811.4(SNAP25):c.487A>G (p.Met163Val)	SNAP25	Uncertain significance	criteria provided, single submitter
1355693	NM_130811.4(SNAP25):c.503G>T (p.Gly168Val)	SNAP25	Uncertain significance	criteria provided, single submitter
1360397	NM_130811.4(SNAP25):c.23G>A (p.Arg8His)	SNAP25	Uncertain significance	criteria provided, multiple submitters, no conflicts
1367384	NM_130811.4(SNAP25):c.408-3C>T	SNAP25	Uncertain significance	criteria provided, single submitter
1379054	NM_130811.4(SNAP25):c.356G>A (p.Arg119His)	SNAP25	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
SNAP25	Strong	Autosomal dominant	congenital myasthenic syndrome 18	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SNAP25	Orphanet:98914	Presynaptic congenital myasthenic syndromes

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
SNAP25	HGNC:11132	ENSG00000132639	P60880	Synaptosomal-associated protein 25	gencc,clinvar
ANKEF1	HGNC:15803	ENSG00000132623	Q9NU02	Ankyrin repeat and EF-hand domain-containing protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SNAP25	Synaptosomal-associated protein 25	t-SNARE involved in the molecular regulation of neurotransmitter release.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.0

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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SNAP25	Other/Unknown	no		T_SNARE_dom, SNAP-25_dom, SNAP-25_N_SNARE_chord
ANKEF1	Scaffold/PPI	no		EF_hand_dom, Ankyrin_rpt, EF-hand-dom_pair

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellum	1
pons	1
left testis	1
male germ cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SNAP25	220	broad	marker	pons, cerebellar cortex, cerebellum
ANKEF1	209	ubiquitous	marker	sperm, male germ cell, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANKEF1	861
SNAP25	163

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SNAP25	P60880	14

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANKEF1	Q9NU02	80.95

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. Enrichment computed across 2 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Toxicity of botulinum toxin type C (botC)	1	3806.7×	0.003	SNAP25
Toxicity of botulinum toxin type E (botE)	1	3806.7×	0.003	SNAP25
Toxicity of botulinum toxin type A (botA)	1	2855.0×	0.003	SNAP25
Neurotoxicity of clostridium toxins	1	1427.5×	0.005	SNAP25
Uptake and actions of bacterial toxins	1	815.7×	0.005	SNAP25
Acetylcholine Neurotransmitter Release Cycle	1	671.8×	0.005	SNAP25
Serotonin Neurotransmitter Release Cycle	1	634.4×	0.005	SNAP25
Norepinephrine Neurotransmitter Release Cycle	1	634.4×	0.005	SNAP25
GABA synthesis, release, reuptake and degradation	1	634.4×	0.005	SNAP25
Dopamine Neurotransmitter Release Cycle	1	496.5×	0.005	SNAP25
Other interleukin signaling	1	475.8×	0.005	SNAP25
Glutamate Neurotransmitter Release Cycle	1	456.8×	0.005	SNAP25
Neurotransmitter release cycle	1	439.2×	0.005	SNAP25
Bacterial Infection Pathways	1	335.9×	0.006	SNAP25
Sensory processing of sound	1	308.6×	0.006	SNAP25
Regulation of insulin secretion	1	219.6×	0.008	SNAP25
Integration of energy metabolism	1	175.7×	0.010	SNAP25
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.010	SNAP25
Sensory Perception	1	95.2×	0.016	SNAP25
Transmission across Chemical Synapses	1	76.1×	0.019	SNAP25
Signaling by Interleukins	1	64.2×	0.022	SNAP25
Neuronal System	1	44.3×	0.030	SNAP25
Cytokine Signaling in Immune system	1	40.8×	0.031	SNAP25
Innate Immune System	1	25.5×	0.047	SNAP25
Infectious disease	1	24.8×	0.047	SNAP25
Neutrophil degranulation	1	23.1×	0.048	SNAP25
Disease	1	13.1×	0.080	SNAP25
Immune System	1	13.0×	0.080	SNAP25
Metabolism	1	11.6×	0.086	SNAP25

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
presynaptic dense core vesicle exocytosis	1	4213.0×	0.003	SNAP25
synaptic vesicle fusion to presynaptic active zone membrane	1	1685.2×	0.003	SNAP25
neurotransmitter uptake	1	1404.3×	0.003	SNAP25
obsolete synaptic vesicle docking	1	1296.3×	0.003	SNAP25
synaptic vesicle priming	1	802.5×	0.003	SNAP25
synaptic vesicle exocytosis	1	766.0×	0.003	SNAP25
associative learning	1	481.5×	0.004	SNAP25
regulation of neuron projection development	1	432.1×	0.004	SNAP25
regulation of insulin secretion	1	391.9×	0.004	SNAP25
long-term synaptic potentiation	1	280.9×	0.005	SNAP25
locomotory behavior	1	179.3×	0.007	SNAP25
exocytosis	1	151.8×	0.007	SNAP25
chemical synaptic transmission	1	77.3×	0.013	SNAP25

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SNAP25	0	0
ANKEF1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	SNAP25, ANKEF1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SNAP25	0	—
ANKEF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.