Multiple pterygium syndrome

Summary

Multiple pterygium syndrome (MONDO:0017415) 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	multiple pterygium syndrome
Mondo ID	MONDO:0017415
MeSH	C537377
Orphanet	294060
DOID	DOID:0080110
ICD-11	834369371
SNOMED CT	205819008
UMLS	C5848053
MedGen	1852087
GARD	0021177
NORD	1632
Is cancer (heuristic)	no

Also known as: pterygium syndrome · Pterygium Syndrome, Multiple

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › congenital limb malformation › arthrogryposis syndrome › multiple pterygium syndrome

Related subtypes (5): arthrogryposis multiplex congenita, popliteal pterygium syndrome, lethal congenital contracture syndrome, distal arthrogryposis, congenital amyoplasia

Subtypes (4): lethal multiple pterygium syndrome, autosomal recessive multiple pterygium syndrome, contractures, pterygia, and variable skeletal fusions syndrome, CHRNG-associated hypo-akinesia disorder of prenatal onset

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 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1326275	NM_005199.5(CHRNG):c.351-9T>C	CHRNG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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	clinvar

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: 0.