Pneumothorax

Summary

Pneumothorax (MONDO:0002076) is a disease (an umbrella term covering 5 Mondo subtypes) with 1 cohort gene (4 GWAS associations across 17 studies) and 119 clinical trials. Top therapeutic interventions include diclofenac.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 4
• ClinVar variants: 2
• Clinical trials: 119

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pneumothorax
Mondo ID	MONDO:0002076
MeSH	D011030
DOID	DOID:1673
ICD-11	1946559257
NCIT	C38006
SNOMED CT	36118008
UMLS	C0032326
MedGen	19365
Is cancer (heuristic)	no

Also known as: pneumothorax · pneumothorax (disease)

Data availability: 2 ClinVar variants · 4 GWAS associations (17 studies) · 1 HPO phenotype.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › lower respiratory tract disorder › pleural disorder › pneumothorax

Related subtypes (4): pleurisy, congenital chylothorax, pleural empyema, pleural neoplasm

Subtypes (5): spontaneous tension pneumothorax, tuberculous pneumothorax, hemopneumothorax, familial spontaneous pneumothorax, catamenial pneumothorax

Genetics & variants

GWAS landscape

4 GWAS associations across 17 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs113993960	3e-12	CFTR	?	1.97
rs55916589	1e-08	CWH43 - SNX18P23	T	0.26
rs931794	4e-08	HYKK	A	0.17
chr5:14821889	3e-07		?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90478161	Verma A	2024	4,202	442,977	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473736	UK Biobank Whole-Genome Sequencing Consortium	2025	3,584	454,856	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90080158	Backman JD	2021	3,065	384,755	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084144	Backman JD	2021	3,065	384,755	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90018902	Sakaue S	2021	1,747	475,987	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90080153	Backman JD	2021	1,190	386,185	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084139	Backman JD	2021	1,190	386,185	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90436234	Zhou W	2018	1,174	397,411	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90478160	Verma A	2024	880	120,270	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481075	Verma A	2024	880	120,270	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	3
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
inframe_insertion	1
intergenic_variant	1
3_prime_UTR_variant	1
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs113993960	7	117559591	ATCT>A,ATCTTCT	0.05	inframe_insertion	CFTR	3e-12	Tier 1: coding
rs55916589	4	49107097	A>G,T	0.05	intergenic_variant	CWH43 - SNX18P23	1e-08	Tier 4: intronic/intergenic
rs931794	15	78533838	G>A,C	0.05	3_prime_UTR_variant	HYKK	4e-08	Tier 2: splice/UTR
chr5:14821889							3e-07	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
523328	NM_000093.5(COL5A1):c.608G>T (p.Gly203Val)	COL5A1	Likely pathogenic	criteria provided, single submitter
267893	46;XY;t(20;22)(q13.3;q11.2)		Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL5A1	Orphanet:287	Classical Ehlers-Danlos 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
COL5A1	HGNC:2209	ENSG00000130635	P20908	Collagen alpha-1(V) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL5A1	Collagen alpha-1(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).

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)
COL5A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen

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
periodontal ligament	1
stromal cell of endometrium	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL5A1	248	ubiquitous	marker	stromal cell of endometrium, periodontal ligament, tendon of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL5A1	2,600

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL5A1	P20908	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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
Fibronectin matrix formation	1	571.0×	0.007	COL5A1
Attachment of bacteria to epithelial cells	1	496.5×	0.007	COL5A1
Syndecan interactions	1	423.0×	0.007	COL5A1
MET activates PTK2 signaling	1	380.7×	0.007	COL5A1
Collagen chain trimerization	1	259.6×	0.007	COL5A1
Signaling by PDGF	1	253.8×	0.007	COL5A1
NCAM1 interactions	1	248.3×	0.007	COL5A1
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.007	COL5A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL5A1
Collagen degradation	1	175.7×	0.007	COL5A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL5A1
Non-integrin membrane-ECM interactions	1	154.3×	0.007	COL5A1
ECM proteoglycans	1	150.3×	0.007	COL5A1
Integrin cell surface interactions	1	134.3×	0.007	COL5A1

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
integrin biosynthetic process	1	16852.0×	8e-04	COL5A1
negative regulation of endodermal cell differentiation	1	8426.0×	8e-04	COL5A1
tendon development	1	4213.0×	8e-04	COL5A1
eye morphogenesis	1	4213.0×	8e-04	COL5A1
collagen biosynthetic process	1	1053.2×	0.002	COL5A1
wound healing, spreading of epidermal cells	1	1053.2×	0.002	COL5A1
supramolecular fiber organization	1	1053.2×	0.002	COL5A1
skin development	1	443.5×	0.003	COL5A1
blood vessel development	1	374.5×	0.003	COL5A1
heart morphogenesis	1	374.5×	0.003	COL5A1
collagen fibril organization	1	224.7×	0.005	COL5A1
cell migration	1	61.5×	0.018	COL5A1
cell adhesion	1	37.5×	0.027	COL5A1

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Minocycline	Phase 3 (in late-stage trials)

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL5A1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	COL5A1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COL5A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 119.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	104
PHASE3	7
PHASE4	3
PHASE2/PHASE3	3
PHASE1/PHASE2	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01329432	PHASE4	UNKNOWN	Surfactant Administration During Spontaneous Breathing
NCT01463553	PHASE4	UNKNOWN	Improving Primary Spontaneous Pneumothorax (PSP) Treatment Techniques in VATS
NCT05121233	PHASE4	UNKNOWN	Local Anesthesia Versus Combined Local Anesthesia With Single Dose Analgesia on Pain Control During Thoracic Ultrasound Guided Procedures
NCT00154895	PHASE3	UNKNOWN	Additional Minocycline Pleurodesis After Thoracoscopic Procedures for Primary Spontaneous Pneumothorax
NCT00270751	PHASE2/PHASE3	UNKNOWN	Pleural Abrasion Plus Minocycline Versus Apical Pleurectomy for Primary Spontaneous Pneumothorax
NCT00418392	PHASE3	UNKNOWN	Intrapleural Minocycline After Simple Aspiration for the Prevention of Primary Spontaneous Pneumothorax
NCT00562302	PHASE3	COMPLETED	Bio-Seal Biopsy Track Plug for Reducing Pneumothorax Rates Post Lung Biopsy Procedure
NCT00563641	PHASE3	COMPLETED	Very Early Surfactant and NCPAP for Premature Infants With RDS
NCT00713362	PHASE2/PHASE3	UNKNOWN	Chest Tube Drainage or Thoracoscopic Surgery for Failed Aspiration of Spontaneous Pneumothorax
NCT01127880	PHASE2/PHASE3	COMPLETED	Role of Antibiotics to Reduce Infectious Complications in Tube Thoracotomy Management of Traumatic Hemopneumothorax
NCT01522885	PHASE3	COMPLETED	KatGuide Method Versus Conventional Method at Insertion of Chest Tube
NCT02558608	PHASE3	UNKNOWN	Effect of Dissecting of The Inferior Pulmonary Ligament on Postoperative Pulmonary Reexpansion and Recurrence
NCT03734471	PHASE3	UNKNOWN	Reactor Thoracostomy
NCT06731647	PHASE2	RECRUITING	Non-steroidal Anti-inflammatory Drugs in Pleurodesis
NCT04130451	PHASE1/PHASE2	UNKNOWN	Efficacy, Safety and Re-occurrence of Pneumothorax and Hydro-pneumothorax With Talc and Pyodine Pleurodesis
NCT00001465	Not specified	RECRUITING	Study of the Disease Process of Lymphangioleiomyomatosis
NCT00033137	Not specified	RECRUITING	Genetic Analysis of Birt Hogg-Dube Syndrome and Characterization of Predisposition to Kidney Cancer
NCT06022081	Not specified	ACTIVE_NOT_RECRUITING	Lung Ultrasound Versus Chest Radiography for Detection of Pneumothorax
NCT06340178	Not specified	RECRUITING	CT-guided Lung Biopsy Risk Optimization Method
NCT06515015	Not specified	RECRUITING	Evaluation of the Feasibility, Safety, and Efficacy of Single-use Endobronchial Silicon Spigots for the Treatment of Refractory Pneumothorax
NCT06538376	Not specified	RECRUITING	Clinical Utility of Portable Dynamic Chest X Ray (DDR) in the ICU
NCT06548386	Not specified	RECRUITING	Feasibility and Accuracy of a Novel Pleural Drain Gas Analyzer in Detecting Air Leaks
NCT06686251	Not specified	RECRUITING	Evaluation of the Efficacy of Diagnostic Support Algorithms in Chest X-rays- LuAna Trial
NCT06842043	Not specified	NOT_YET_RECRUITING	AI-Assisted Chest X-Ray for Misplaced Endotracheal and Nasogastric Tubes and Pneumothorax in Emergency and Critical Care Settings
NCT06958848	Not specified	RECRUITING	16F vs 24F Chest Drain After Minimally Invasive Lobectomy and/or Segmentectomy
NCT06983366	Not specified	RECRUITING	Validation and Clinical Utility of the Lung Sliding Index (LSI) for Differentiating Pulmonary Diseases
NCT07018856	Not specified	RECRUITING	Feasibility Study of Novice-Performed Lung Ultrasound for Pneumothorax Detection After Cardiac Surgery
NCT07186933	Not specified	RECRUITING	Driving Pressure During Surgeries With High Risk for Postoperative Pulmonary Complications
NCT07206940	Not specified	ACTIVE_NOT_RECRUITING	Study of the Benefits of Virtual Reality Headsets for Reducing Anxiety in Patients Treated for Pleural Effusion or Pneumothorax Using Small-bore Chest Drainage Tubes
NCT07211529	Not specified	RECRUITING	Intraoperative Paravertebral Block and Postoperative Complications
NCT07319572	Not specified	NOT_YET_RECRUITING	Comparison of Chest Tube Wound Closure: Comparison Between Purse String Method and Plug Method.
NCT07344714	Not specified	RECRUITING	Predicting the Need for Prolonged Respiratory Support in Neonates Delivered in a Lower-Level NICU Setting
NCT07395349	Not specified	NOT_YET_RECRUITING	Safety And Recovery Of Tubeless Strategy In Uniportal VATS Wedge Resection
NCT00520221	Not specified	COMPLETED	Intrapleural Minocycline Following Simple Aspiration for Primary Spontaneous Pneumothorax
NCT00530725	Not specified	COMPLETED	Management of Occult Pneumothoraces in Mechanically Ventilated Patients
NCT00544479	Not specified	COMPLETED	No Routine CXR After Bronchoscopy
NCT00556335	Not specified	COMPLETED	Pneumothorax Therapy: Manual Aspiration Versus Conventional Chest Tube Drainage
NCT00575198	Not specified	COMPLETED	Drainage Amount for Removal of Thoracostomy Tube
NCT00767962	Not specified	COMPLETED	A Prospective Randomised Study of Efficacy, Safety and Costs of Talc Pleurodesis Under Medical Thoracoscopy and Pleurodesis Under Video-assisted Thoracoscopy Surgery for Recurrent Primary Spontaneous Pneumothorax
NCT00839553	Not specified	UNKNOWN	Intrapleural Minocycline After Aspiration of Spontaneous Pneumothorax

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DICLOFENAC	4	1