congenital myasthenic syndrome 3C

Summary

congenital myasthenic syndrome 3C (MONDO:0014585) is a disease caused by CHRND (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CHRND (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital myasthenic syndrome 3C
Mondo ID	MONDO:0014585
OMIM	616323
DOID	DOID:0110664
UMLS	C4225370
MedGen	903088
GARD	0016086
Is cancer (heuristic)	no

Also known as: CMS3C · congenital myasthenic syndrome type 3C · myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency

Data availability: 17 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 › postsynaptic congenital myasthenic syndrome › congenital myasthenic syndrome 3C

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 9, congenital myasthenic syndrome 11, congenital myasthenic syndrome 19, congenital myasthenic syndrome 4

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

17 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 4 conflicting classifications of pathogenicity, 2 likely pathogenic, 2 pathogenic, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
18368	NM_000751.3(CHRND):c.234G>A (p.Trp78Ter)	CHRND	Pathogenic	criteria provided, multiple submitters, no conflicts
189818	NM_000751.3(CHRND):c.901_1048-282del	CHRND	Pathogenic	no assertion criteria provided
645129	NM_000751.3(CHRND):c.821-2A>C	CHRND	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18364	NM_000751.3(CHRND):c.812C>A (p.Pro271Gln)	CHRND	Likely pathogenic	criteria provided, single submitter
3899381	NM_000751.3(CHRND):c.166_172del (p.Leu56fs)	CHRND	Likely pathogenic	criteria provided, single submitter
189817	NM_000751.3(CHRND):c.1204G>A (p.Glu402Lys)	CHRND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
281423	NM_000751.3(CHRND):c.919C>T (p.Pro307Ser)	CHRND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
283138	NM_000751.3(CHRND):c.727C>T (p.Arg243Cys)	CHRND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
840118	NM_000751.3(CHRND):c.823G>A (p.Gly275Ser)	CHRND	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1378317	NM_000751.3(CHRND):c.601G>A (p.Asp201Asn)	CHRND	Uncertain significance	criteria provided, multiple submitters, no conflicts
286380	NM_000751.3(CHRND):c.1220G>A (p.Arg407Gln)	CHRND	Uncertain significance	criteria provided, multiple submitters, no conflicts
3896802	NM_000751.3(CHRND):c.756C>A (p.Asn252Lys)	CHRND	Uncertain significance	criteria provided, single submitter
3896803	NM_000751.3(CHRND):c.887C>T (p.Ser296Phe)	CHRND	Uncertain significance	criteria provided, single submitter
4845292	NM_000751.3(CHRND):c.638T>G (p.Ile213Arg)	CHRND	Uncertain significance	criteria provided, single submitter
548627	NM_000751.3(CHRND):c.1181A>C (p.Lys394Thr)	CHRND	Uncertain significance	criteria provided, single submitter
953201	NM_000751.3(CHRND):c.1334T>C (p.Ile445Thr)	CHRND	Uncertain significance	criteria provided, multiple submitters, no conflicts
767409	NM_000751.3(CHRND):c.132C>G (p.Pro44=)	CHRND	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
CHRND	Strong	Autosomal dominant	congenital myasthenic syndrome 3A	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHRND	Orphanet:33108	Lethal multiple pterygium syndrome
CHRND	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
CHRND	HGNC:1965	ENSG00000135902	Q07001	Acetylcholine receptor subunit delta	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHRND	Acetylcholine receptor subunit delta	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)
CHRND	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
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHRND	86	tissue_specific	yes	gastrocnemius, muscle of leg, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHRND	1,041

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHRND	Q07001	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	CHRND
Presynaptic nicotinic acetylcholine receptors	1	951.7×	0.002	CHRND
Acetylcholine binding and downstream events	1	815.7×	0.002	CHRND
Postsynaptic nicotinic acetylcholine receptors	1	815.7×	0.002	CHRND
Neurotransmitter receptors and postsynaptic signal transmission	1	100.2×	0.014	CHRND
Transmission across Chemical Synapses	1	76.1×	0.015	CHRND
Neuronal System	1	44.3×	0.023	CHRND

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
skeletal muscle tissue growth	1	2808.7×	0.002	CHRND
musculoskeletal movement	1	2808.7×	0.002	CHRND
acetylcholine receptor signaling pathway	1	624.1×	0.003	CHRND
neuromuscular process	1	526.6×	0.003	CHRND
skeletal muscle contraction	1	510.7×	0.003	CHRND
membrane depolarization	1	510.7×	0.003	CHRND
muscle contraction	1	208.1×	0.006	CHRND
monoatomic ion transmembrane transport	1	208.1×	0.006	CHRND
chemical synaptic transmission	1	77.3×	0.014	CHRND
signal transduction	1	16.1×	0.062	CHRND

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
CHRND	VARENICLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHRND	10	4

Drugs targeting cohort genes (top 30)

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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CHRND	75	Binding:44, 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	CHRND
NICOTINE	4	CHRND
TROPISETRON	4	CHRND
BUPROPION	4	CHRND
MECAMYLAMINE	4	CHRND
DEXMECAMYLAMINE	3	CHRND
CYTISINICLINE	3	CHRND
RADAFAXINE	2	CHRND
GTS-21	2	CHRND
TC-2216	1	CHRND

Druggability pyramid

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

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