Idiopathic bronchiectasis

Summary

Idiopathic bronchiectasis (MONDO:0018956) is a disease with 1 cohort gene and 5 clinical trials.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 19
• Clinical trials: 5

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	29	Europe	Validated
Annual incidence	1-9 / 100 000	1.8	Finland	Validated
Prevalence at birth	1-5 / 10 000	29	Finland	Validated

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0002110	Bronchiectasis	Obligate (100%)
HP:0002795	Abnormal respiratory system physiology	Very frequent (80-99%)
HP:0011947	Respiratory tract infection	Very frequent (80-99%)
HP:0031245	Productive cough	Very frequent (80-99%)
HP:0002094	Dyspnea	Frequent (30-79%)
HP:0002105	Hemoptysis	Frequent (30-79%)
HP:0002783	Recurrent lower respiratory tract infections	Frequent (30-79%)
HP:0005376	Recurrent Haemophilus influenzae infections	Frequent (30-79%)
HP:0030828	Wheezing	Frequent (30-79%)
HP:0030830	Crackles	Frequent (30-79%)
HP:0030877	Reduced FEV1/FVC ratio	Frequent (30-79%)
HP:0100749	Chest pain	Frequent (30-79%)
HP:0001658	Myocardial infarction	Occasional (5-29%)
HP:0001945	Fever	Occasional (5-29%)
HP:0002097	Emphysema	Occasional (5-29%)
HP:0004326	Cachexia	Occasional (5-29%)
HP:0011949	Acute infectious pneumonia	Occasional (5-29%)
HP:0100812	Halitosis	Occasional (5-29%)
HP:0001217	Clubbing	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	idiopathic bronchiectasis
Mondo ID	MONDO:0018956
Orphanet	60033
SNOMED CT	233629001
UMLS	C0339985
MedGen	573462
GARD	0016664
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 › respiratory system disorder › lower respiratory tract disorder › bronchial disorder › bronchiectasis › idiopathic bronchiectasis

Subtypes (3): bronchiectasis with or without elevated sweat chloride 1, bronchiectasis with or without elevated sweat chloride 2, bronchiectasis with or without elevated sweat chloride 3

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 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
504974	NM_001038.6(SCNN1A):c.942del (p.Asn315fs)	SCNN1A	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCNN1A	Orphanet:130	Brugada syndrome
SCNN1A	Orphanet:171876	Generalized pseudohypoaldosteronism type 1
SCNN1A	Orphanet:526	Liddle syndrome
SCNN1A	Orphanet:60033	Idiopathic bronchiectasis

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
SCNN1A	HGNC:10599	ENSG00000111319	P37088	Epithelial sodium channel subunit alpha	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCNN1A	Epithelial sodium channel subunit alpha	This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis.

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)
SCNN1A	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS

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
metanephros cortex	1
nasal cavity epithelium	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCNN1A	283	broad	marker	nasal cavity epithelium, metanephros cortex, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCNN1A	1,300

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCNN1A	P37088	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Sensory perception of salty taste	1	1903.3×	0.003	SCNN1A
Sensory perception of taste	1	335.9×	0.009	SCNN1A
Stimuli-sensing channels	1	135.9×	0.013	SCNN1A
Ion channel transport	1	96.0×	0.013	SCNN1A
Sensory Perception	1	95.2×	0.013	SCNN1A
Transport of small molecules	1	25.1×	0.040	SCNN1A

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
sensory perception of salty taste	1	4213.0×	0.001	SCNN1A
cellular response to aldosterone	1	2407.4×	0.001	SCNN1A
cellular response to vasopressin	1	2106.5×	0.001	SCNN1A
multicellular organismal-level water homeostasis	1	1685.2×	0.001	SCNN1A
sensory perception of sour taste	1	1685.2×	0.001	SCNN1A
sodium ion homeostasis	1	936.2×	0.002	SCNN1A
intracellular sodium ion homeostasis	1	766.0×	0.002	SCNN1A
cellular response to acidic pH	1	732.7×	0.002	SCNN1A
sodium ion import across plasma membrane	1	624.1×	0.002	SCNN1A
regulation of blood pressure	1	221.7×	0.005	SCNN1A
sodium ion transmembrane transport	1	203.0×	0.005	SCNN1A

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
SCNN1A	AMILORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCNN1A	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMILORIDE	4	SCNN1A
552-02 FREE BASE	2	SCNN1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SCNN1A	6	Binding:4, ADMET:1, Functional:1

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

2 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)
AMILORIDE	4	SCNN1A
552-02 FREE BASE	2	SCNN1A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SCNN1A
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: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07566611	Not specified	NOT_YET_RECRUITING	Primary Ciliary Dyskinesia in Adult Bronchiectasis
NCT02061852	Not specified	TERMINATED	Evaluation of the Safety of the Medical Device Simeox®
NCT03750734	Not specified	COMPLETED	Target Validation and Discovery in Idiopathic Bronchiectasis
NCT03809091	Not specified	UNKNOWN	WGS of Korean Idiopathic Bronchiectasis
NCT04417777	Not specified	COMPLETED	Genetic Study of the Dilatations of the Idiopathic Bronchi in French Polynesia