Bronchiectasis

Summary

Bronchiectasis (MONDO:0004822) is a disease with 3 cohort genes (6 GWAS associations across 20 studies) and 251 clinical trials. Top therapeutic interventions include theophylline anhydrous, sodium chloride, and mannitol.

At a glance

• Cohort genes: 3
• GWAS associations: 6
• ClinVar variants: 7
• Clinical trials: 251

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	bronchiectasis
Mondo ID	MONDO:0004822
MeSH	D001987
OMIM	211400
DOID	DOID:9563
ICD-10-CM	J47
ICD-11	1935524933
NCIT	C84475
SNOMED CT	12295008
UMLS	C0006267
MedGen	14234
Is cancer (heuristic)	no

Data availability: 7 ClinVar variants · 6 GWAS associations (20 studies).

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › lower respiratory tract disorder › bronchial disorder › bronchiectasis

Related subtypes (5): bronchial neoplasm, bronchitis, asthma, non-syndromic bridging bronchus, non-syndromic congenital bronchial atresia

Subtypes (1): idiopathic bronchiectasis

Genetics & variants

GWAS landscape

6 GWAS associations across 20 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs111991762	1e-12	EDEM3	G	3.15
rs183955695	3e-11	NCAPD3	C	2.54
rs3132948	7e-09	NOTCH4 - TSBP1-AS1	G	0.15
chr16:84352279	5e-08		G	24.04
rs762444653	2e-07	RUFY2	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90473715	UK Biobank Whole-Genome Sequencing Consortium	2025	6,822	451,618	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90080142	Backman JD	2021	3,053	384,169	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084128	Backman JD	2021	3,053	384,169	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90018801	Sakaue S	2021	2,888	440,263	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90436224	Zhou W	2018	1,882	375,505	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90478145	Verma A	2024	1,877	447,375	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90652027	Liu TY	2025	1,837	210,469	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90077677	Backman JD	2021	1,129	330,625	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081663	Backman JD	2021	1,129	330,625	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90077678	Backman JD	2021	1,030	328,022	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	5

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	2
unknown	2

Functional consequences

Consequence	Count
intron_variant	2
non_coding_transcript_exon_variant	1
intergenic_variant	1
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs111991762	1	184719108	G>A,C	0	intron_variant	EDEM3	1e-12	Tier 4: intronic/intergenic
rs183955695	11	134173524	C>T	0	non_coding_transcript_exon_variant	NCAPD3	3e-11	Tier 4: intronic/intergenic
rs3132948	6	32229442	T>A,G	0.05	intergenic_variant	NOTCH4 - TSBP1-AS1	7e-09	Tier 4: intronic/intergenic
chr16:84352279							5e-08	Tier 4: intronic/intergenic
rs762444653	10	68348523	A>G		intron_variant	RUFY2	2e-07	Tier 4: intronic/intergenic

ClinVar germline variants

7 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
982437	NM_033656.4(BRWD1):c.5573A>T (p.Gln1858Leu)	BRWD1	Likely pathogenic	no assertion criteria provided
635007	NC_000023.11:g.47242504G>A	USP11	Likely pathogenic	criteria provided, single submitter
982436	NM_033656.4(BRWD1):c.523C>T (p.His175Tyr)	BRWD1	Conflicting classifications of pathogenicity	no assertion criteria provided
982514	NM_033656.4(BRWD1):c.1016T>C (p.Leu339Ser)	BRWD1	Uncertain significance	no assertion criteria provided
982435	NM_033656.4(BRWD1):c.166G>A (p.Gly56Ser)	LOC130066680	Uncertain significance	no assertion criteria provided
997446	NM_006901.4(MYO9A):c.6656G>A (p.Arg2219His)	MYO9A	Uncertain significance	no assertion criteria provided
997447	NM_006901.4(MYO9A):c.2344C>A (p.Gln782Lys)	MYO9A	Uncertain significance	no assertion criteria provided

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
BRWD1	Orphanet:244	Primary ciliary dyskinesia
MYO9A	Orphanet:98914	Presynaptic congenital myasthenic syndromes

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
USP11	HGNC:12609	ENSG00000102226	P51784	Ubiquitin carboxyl-terminal hydrolase 11	clinvar
BRWD1	HGNC:12760	ENSG00000185658	Q9NSI6	Bromodomain and WD repeat-containing protein 1	clinvar
MYO9A	HGNC:7608	ENSG00000066933	B2RTY4	Unconventional myosin-IXa	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
USP11	Ubiquitin carboxyl-terminal hydrolase 11	Protease that can remove conjugated ubiquitin from target proteins and polyubiquitin chains.
BRWD1	Bromodomain and WD repeat-containing protein 1	May be a transcriptional activator.
MYO9A	Unconventional myosin-IXa	Myosins are actin-based motor molecules with ATPase activity.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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
Protease	1	12.2×	0.239
Scaffold/PPI	1	5.8×	0.246
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
USP11	Protease	yes		Peptidase_C19_UCH, Pept_C19_DUSP, USP_CS
BRWD1	Scaffold/PPI	no		Bromodomain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
MYO9A	Other/Unknown	no		IQ_motif_EF-hand-BS, RA_dom, RhoGAP_dom

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
middle temporal gyrus	1
pituitary gland	1
right frontal lobe	1
cortical plate	1
sural nerve	1
male germ cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
USP11	294	ubiquitous	marker	right frontal lobe, middle temporal gyrus, pituitary gland
BRWD1	266	ubiquitous	marker	cortical plate, sural nerve, calcaneal tendon
MYO9A	280	ubiquitous	marker	calcaneal tendon, male germ cell, sperm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
USP11	3,390
BRWD1	2,695
MYO9A	2,434

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
USP11	P51784	3
BRWD1	Q9NSI6	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYO9A	B2RTY4	58.07

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interleukin-7 signaling	1	105.7×	0.052	BRWD1
Association of TriC/CCT with target proteins during biosynthesis	1	97.6×	0.052	USP11
RHOV GTPase cycle	1	95.2×	0.052	MYO9A
RHOB GTPase cycle	1	51.4×	0.072	MYO9A
Chromatin organization	1	27.2×	0.082	BRWD1
RHOA GTPase cycle	1	24.9×	0.082	MYO9A
Chromatin modifying enzymes	1	24.1×	0.082	BRWD1
Signaling by Interleukins	1	21.4×	0.082	BRWD1
RHO GTPase cycle	1	20.0×	0.082	MYO9A
Ub-specific processing proteases	1	17.7×	0.083	USP11
Cytokine Signaling in Immune system	1	13.6×	0.098	BRWD1
Signaling by Rho GTPases	1	11.4×	0.100	MYO9A
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	11.2×	0.100	MYO9A
Immune System	1	4.3×	0.229	BRWD1
Signal Transduction	1	3.4×	0.267	MYO9A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of neuron projection arborization	1	936.2×	0.010	MYO9A
cell junction assembly	1	561.7×	0.010	MYO9A
establishment of epithelial cell apical/basal polarity	1	351.1×	0.010	MYO9A
protein deubiquitination	1	59.1×	0.038	USP11
regulation of small GTPase mediated signal transduction	1	48.0×	0.038	MYO9A
cytoskeleton organization	1	44.2×	0.038	BRWD1
regulation of cell shape	1	41.0×	0.038	BRWD1
visual perception	1	26.5×	0.051	MYO9A
intracellular signal transduction	1	12.7×	0.094	MYO9A
proteolysis	1	11.4×	0.094	USP11
regulation of transcription by RNA polymerase II	1	3.9×	0.236	BRWD1

Therapeutics

Drugs indicated for this disease

0 approved, 10 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Azithromycin	Phase 3 (in late-stage trials)
Beclomethasone Dipropionate	Phase 3 (in late-stage trials)
Brensocatib	Phase 3 (in late-stage trials)
Carbocysteine	Phase 3 (in late-stage trials)
Ciprofloxacin	Phase 3 (in late-stage trials)
Formoterol	Phase 3 (in late-stage trials)
Itraconazole	Phase 3 (in late-stage trials)
Mannitol	Phase 3 (in late-stage trials)
Roflumilast	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Melphalan, Tobramycin.

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
USP11	0	0
BRWD1	0	0
MYO9A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
BRWD1	37	Binding:37
USP11	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	USP11
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	BRWD1, MYO9A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
USP11	7	—
BRWD1	37	—
MYO9A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 251.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	167
PHASE4	25
PHASE2	22
PHASE3	19
PHASE1	9
PHASE1/PHASE2	6
EARLY_PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06242795	PHASE4	RECRUITING	Hypertonic Saline in NCFB
NCT06551337	PHASE4	RECRUITING	Vitamin D Replacement in Bronchiectasis
NCT07114120	PHASE4	RECRUITING	Clinical Study on the Treatment of Stable Bronchiectasis With Bailing Capsules Combined With Guben Kechuan Granules
NCT07283497	PHASE4	RECRUITING	Itraconazole Therapy In Bronchiectasis With Airway Mold
NCT07608328	PHASE4	NOT_YET_RECRUITING	Azithromycin to Modify Bronchiectasis Exacerbation Risk
NCT00749866	PHASE4	COMPLETED	Long Term Nebulised Gentamicin in Patients With Bronchiectasis
NCT00816309	PHASE4	COMPLETED	Is Regular Chest Physiotherapy an Effective Treatment in Severe, Non Cystic Fibrosis Bronchiectasis?
NCT00868075	PHASE4	COMPLETED	Pulmonary Rehabilitation in Non Cystic Fibrosis Bronchiectasis
NCT01299181	PHASE4	COMPLETED	A Trial of Atorvastatin as an Anti-Inflammatory Agent in Non-Cystic Fibrosis Bronchiectasis
NCT01299194	PHASE4	COMPLETED	Atorvastatin in Bronchiectasis in Patients With Pseudomonas Aeruginosa
NCT01677403	PHASE4	UNKNOWN	A Study to Access Safety and Efficacy of Nebulized Tobramycin in Patients With Bronchiectasis
NCT01684683	PHASE4	COMPLETED	The Effect of Theophylline in the Treatment of Bronchiectasis
NCT01769898	PHASE4	COMPLETED	The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis
NCT02047773	PHASE4	COMPLETED	Bacterial Load Guided Therapy for Severe Bronchiectasis Exacerbations
NCT02107274	PHASE4	COMPLETED	Efficacy of Azithromycin in Treatment of Bronchiectasis
NCT02507843	PHASE4	UNKNOWN	Vitamin D as an Adjunctive Treatment in Patients With Non-Cystic Fibrosis Bronchiectasis
NCT02509091	PHASE4	UNKNOWN	Therapy of Bronchoalveolar Lavage and Local Amikacin Injection in Patients With Acute Exacerbation of Bronchiectasis
NCT02546297	PHASE4	UNKNOWN	Comparisons of Inhaled LAMA or LAMA+LABA or ICS+LABA for COPD With Bronchiectasis
NCT02782312	PHASE4	COMPLETED	Salmeterol-Fluticasone Combined Inhaled Therapy for Non-cystic Fibrosis Bronchiectasis
NCT03147443	PHASE4	UNKNOWN	Evaluating the Effects of Traditional Chinese Medicine by N-of-1 Trials
NCT03262142	PHASE4	TERMINATED	Targeted AntiBiotics for Chronic Pulmonary Diseases
NCT03737617	PHASE4	WITHDRAWN	Immunoglobulin Replacement Therapy for Immunoglobulin G Subclass 2 Deficient Patients With Bronchiectasis
NCT04601792	PHASE4	UNKNOWN	A Series of N-of-1 Trials of Traditional Chinese Medicine Based on Bayesian Method
NCT04765033	PHASE4	COMPLETED	Trial on The Efficacy of Hypertonic Saline on Non-CF CSLD.
NCT06035055	PHASE4	UNKNOWN	Ceftolozane/Tazobactam Continuous Infusion for Infective Exacerbations of Cystic Fibrosis and Bronchiectasis
NCT06409299	PHASE3	NOT_YET_RECRUITING	Enhancing Lung Health in Kids With Structural Lung Damage and Malformations: Azithromycin (AZI) for Airway Infection Prevention
NCT06872892	PHASE3	RECRUITING	The AIRTIVITY™ Study: A Study to Find Out Whether BI 1291583 Helps People With Bronchiectasis
NCT07577804	PHASE3	NOT_YET_RECRUITING	A Study to Evaluate the Efficacy and Safety of CHF10196 Tablets (Florensocatib) Compared With Placebo in Male and Female Participants 12 to 85 Years of Age With Bronchiectasis
NCT00105183	PHASE3	COMPLETED	EZ-2053 in the Prophylaxis of Acute Pulmonary Allograft Rejection
NCT00277537	PHASE3	COMPLETED	Safety and Efficacy of Bronchitol in Bronchiectasis
NCT00415350	PHASE3	COMPLETED	Bronchiectasis and Long Term Azithromycin Treatment
NCT00484263	PHASE3	COMPLETED	The Long Term Effect of Inhaled Hypertonic Saline (6%) in Patients With Non Cystic Fibrosis Bronchiectasis
NCT00669331	PHASE3	COMPLETED	Inhaled Mannitol as a Mucoactive Therapy for Bronchiectasis
NCT01270074	PHASE3	COMPLETED	Prevention of Bronchiectasis in Infants With Cystic Fibrosis
NCT01313624	PHASE3	COMPLETED	Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis
NCT01314716	PHASE3	COMPLETED	Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis
NCT01480882	PHASE2/PHASE3	COMPLETED	Efficacy and Safety Study of a Percussion Device to Mobilise Sputum From Respiratory Passage
NCT01764841	PHASE3	COMPLETED	Ciprofloxacin Dry Powder for Inhalation in Non-cystic Fibrosis Bronchiectasis (Non-CF BE)
NCT02106832	PHASE3	COMPLETED	Ciprofloxacin Dry Powder for Inhalation (DPI) in Non-cystic Fibrosis Bronchiectasis (Non-CF BE)
NCT03443531	PHASE3	UNKNOWN	Effects of Traditional Chinese Medicine on Bronchiectasis Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
THEOPHYLLINE ANHYDROUS	4	6
SODIUM CHLORIDE	4	4
MANNITOL	4	3
SORBITOL	4	3
CIPROFLOXACIN	4	2
ITRACONAZOLE	4	2
ROFLUMILAST	4	2
TAZOBACTAM	4	2
TOBRAMYCIN	4	2
AZITHROMYCIN	4	1
BUDESONIDE	4	1
CEFTOLOZANE	4	1
COLISTIMETHATE SODIUM	4	1
ERYTHROMYCIN	4	1
GENTAMICIN	4	1
MEPOLIZUMAB	4	1
MEROPENEM	4	1
PIPERACILLIN	4	1
TIOTROPIUM BROMIDE	4	1
XENON XE-129, HYPERPOLARIZED	4	1
CARBOCYSTEINE	3	1
FLUTICASONE	3	1
ITEPEKIMAB	3	1
LACTOSE MONOHYDRATE	3	1
MOLGRAMOSTIM	3	1
MUREPAVADIN	3	1
OPELCONAZOLE	3	1
PROCALCITONIN	3	1
ZUCAPSAICIN	3	1
ADENOSINE TRIPHOSPHATE	2	1