Transient neonatal myasthenia gravis

Summary

Transient neonatal myasthenia gravis (MONDO:0018326) is a disease caused by CHRNG (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: CHRNG (GenCC Strong)
• Cohort genes: 1
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	transient neonatal myasthenia gravis
Mondo ID	MONDO:0018326
Orphanet	391504
ICD-10-CM	P94.0
ICD-11	2096990223
NCIT	C117308
UMLS	C0495465
MedGen	96918
GARD	0021625
Is cancer (heuristic)	no

Also known as: neonatal myasthenia gravis · NMG · transient neonatal acquired myasthenia · transient neonatal autoimmune myasthenia gravis

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › autoimmune disorder of the nervous system › autoimmune disorder of peripheral nervous system › myasthenia gravis › transient neonatal myasthenia gravis

Related subtypes (5): neonatal myasthenia gravis, myasthenia, limb-girdle, autoimmune, myasthenia gravis with thymus hyperplasia, adult-onset myasthenia gravis, juvenile myasthenia gravis

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
CHRNG	Strong	Autosomal recessive	transient neonatal myasthenia gravis	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHRNG	Orphanet:2990	Autosomal recessive multiple pterygium syndrome
CHRNG	Orphanet:33108	Lethal multiple pterygium 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
CHRNG	HGNC:1967	ENSG00000196811	P07510	Acetylcholine receptor subunit gamma	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHRNG	Acetylcholine receptor subunit gamma	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)
CHRNG	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	1
muscle of leg	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHRNG	54	tissue_specific	marker	pancreatic ductal cell, gastrocnemius, muscle of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHRNG	778

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CHRNG	P07510	81.91

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	CHRNG
Presynaptic nicotinic acetylcholine receptors	1	951.7×	0.002	CHRNG
Acetylcholine binding and downstream events	1	815.7×	0.002	CHRNG
Postsynaptic nicotinic acetylcholine receptors	1	815.7×	0.002	CHRNG
Neurotransmitter receptors and postsynaptic signal transmission	1	100.2×	0.014	CHRNG
Transmission across Chemical Synapses	1	76.1×	0.015	CHRNG
Neuronal System	1	44.3×	0.023	CHRNG

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
acetylcholine receptor signaling pathway	1	624.1×	0.005	CHRNG
skeletal muscle contraction	1	510.7×	0.005	CHRNG
membrane depolarization	1	510.7×	0.005	CHRNG
muscle contraction	1	208.1×	0.007	CHRNG
monoatomic ion transmembrane transport	1	208.1×	0.007	CHRNG
chemical synaptic transmission	1	77.3×	0.015	CHRNG
signal transduction	1	16.1×	0.062	CHRNG

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
CHRNG	VARENICLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHRNG	10	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VARENICLINE	4	CHRNG
NICOTINE	4	CHRNG
TROPISETRON	4	CHRNG
BUPROPION	4	CHRNG
MECAMYLAMINE	4	CHRNG
DEXMECAMYLAMINE	3	CHRNG
CYTISINICLINE	3	CHRNG
RADAFAXINE	2	CHRNG
GTS-21	2	CHRNG
TC-2216	1	CHRNG

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CHRNG	67	Binding:36, Functional:31

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

10 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)
VARENICLINE	4	CHRNG
NICOTINE	4	CHRNG
TROPISETRON	4	CHRNG
BUPROPION	4	CHRNG
MECAMYLAMINE	4	CHRNG
DEXMECAMYLAMINE	3	CHRNG
CYTISINICLINE	3	CHRNG
RADAFAXINE	2	CHRNG
GTS-21	2	CHRNG
TC-2216	1	CHRNG

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CHRNG
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: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford