Congenital myasthenic syndrome 4

Summary

Congenital myasthenic syndrome 4 (MONDO:1040021) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital myasthenic syndrome 4
Mondo ID	MONDO:1040021
GARD	0027234
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › postsynaptic congenital myasthenic syndrome › congenital myasthenic syndrome 4

Related subtypes (13): congenital myasthenic syndrome 10, congenital myasthenic syndrome 1A, congenital myasthenic syndrome 16, congenital myasthenic syndrome 8, congenital myasthenic syndrome 17, congenital myasthenic syndrome 2A, congenital myasthenic syndrome 2C, congenital myasthenic syndrome 3A, congenital myasthenic syndrome 3B, congenital myasthenic syndrome 3C, congenital myasthenic syndrome 9, congenital myasthenic syndrome 11, congenital myasthenic syndrome 19

Subtypes (3): congenital myasthenic syndrome 4A, congenital myasthenic syndrome 4C, congenital myasthenic syndrome 4B

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2170253	NM_000080.4(CHRNE):c.1192C>T (p.Gln398Ter)	CHRNE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHRNE	Orphanet:98913	Postsynaptic congenital myasthenic syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CHRNE	HGNC:1966	ENSG00000108556	Q04844	Acetylcholine receptor subunit epsilon	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHRNE	Acetylcholine receptor subunit epsilon	After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CHRNE	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	1
cardiac atrium	1
right atrium auricular region	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHRNE	162	broad	yes	right atrium auricular region, cardiac atrium, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHRNE	896

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHRNE	Q04844	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 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
Highly sodium permeable postsynaptic acetylcholine nicotinic receptors	1	1631.4×	0.002	CHRNE
Presynaptic nicotinic acetylcholine receptors	1	951.7×	0.002	CHRNE
Acetylcholine binding and downstream events	1	815.7×	0.002	CHRNE
Postsynaptic nicotinic acetylcholine receptors	1	815.7×	0.002	CHRNE
Neurotransmitter receptors and postsynaptic signal transmission	1	100.2×	0.014	CHRNE
Transmission across Chemical Synapses	1	76.1×	0.015	CHRNE
Neuronal System	1	44.3×	0.023	CHRNE

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
synaptic transmission, cholinergic	1	802.5×	0.004	CHRNE
acetylcholine receptor signaling pathway	1	624.1×	0.004	CHRNE
skeletal muscle contraction	1	510.7×	0.004	CHRNE
membrane depolarization	1	510.7×	0.004	CHRNE
muscle contraction	1	208.1×	0.006	CHRNE
monoatomic ion transmembrane transport	1	208.1×	0.006	CHRNE
chemical synaptic transmission	1	77.3×	0.015	CHRNE
signal transduction	1	16.1×	0.062	CHRNE

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
CHRNE	MECAMYLAMINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHRNE	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MECAMYLAMINE	4	CHRNE
NICOTINE	4	CHRNE
DONEPEZIL	4	CHRNE
TACRINE	4	CHRNE

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CHRNE	28	Binding:26, Functional:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

4 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)
MECAMYLAMINE	4	CHRNE
NICOTINE	4	CHRNE
DONEPEZIL	4	CHRNE
TACRINE	4	CHRNE

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CHRNE
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.