Chronic obstructive pulmonary disease

Summary

Chronic obstructive pulmonary disease (MONDO:0005002) is a disease (an umbrella term covering 5 Mondo subtypes) with 75 cohort genes (1,266 GWAS associations across 119 studies) and 3,782 clinical trials. The dominant Reactome pathway is Highly calcium permeable nicotinic acetylcholine receptors (4 cohort genes). Top therapeutic interventions include formoterol, glycopyrronium, and tiotropium.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 1,266
• ClinVar variants: 40
• Clinical trials: 3,782

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	chronic obstructive pulmonary disease
Mondo ID	MONDO:0005002
EFO	EFO:0000341
MeSH	D029424
OMIM	606963
DOID	DOID:3083
ICD-11	133207228
NCIT	C3199
SNOMED CT	13645005
UMLS	C0024117
MedGen	9818
Is cancer (heuristic)	no

Also known as: chronic obstructive airways disease · chronic obstructive lung disease · chronic obstructive pulmonary disease (COPD) · chronic obstructive pulmonary disease, (COPD) · COLD · cold · cold (chronic obstructive lung disease) · COPD · COPD, chronic obstructive pulmonary disease · disease (COPD), chronic obstructive · obstructive lung disease, chronic · obstructive pulmonary disease (COPD), chronic · pulmonary disease (COPD), chronic obstructive

Data availability: 40 ClinVar variants · 1,266 GWAS associations (119 studies) · 1 GenCC gene-disease record · 5 cell lines.

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 › lung disorder › obstructive lung disease › chronic obstructive pulmonary disease

Subtypes (5): bronchiectasis, pulmonary emphysema, chronic bronchitis, diffuse panbronchiolitis, COPD, severe early onset

Genetics & variants

GWAS landscape

1,266 GWAS associations across 119 studies. Top hits map to 38 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs34712979	6e-161	NPNT	G	0.06
rs10037493	1e-117	HTR4	C	0.05
rs7753012	3e-110	ADGRG6	T	0.05
rs6828540	7e-101	GUSBP5 - KRT18P51	G	0.05
rs2165489	2e-97	THSD4	C	0.05
rs9391855	3e-83	AGER	C	0.08
rs2001546	7e-83	CDC123	A	0.04
rs13140176	4e-59	GUSBP5 - KRT18P51	A	1.18
rs62191107	1e-55	LINC01940 - HDAC4	T	0.04
rs7162542	4e-54	ADAMTSL3	C	0.03
rs2798641	3e-51	ARMC2	C	0.04
rs1990950	2e-50	ADAM19	G	0.03
rs4888415	5e-48	CFDP1	C	0.03
rs633185	2e-47	ARHGAP42	?
rs62202378	5e-47	LINC01807	T	0.05
rs55884799	1e-42	KCNS3	T	0.04
rs13141641	9e-41	KRT18P51 - HHIP-AS1	T	1.22
rs9399401	2e-40	ADGRG6	T	1.16
rs6537293	5e-40	GUSBP5 - KRT18P51	G
rs10123811	1e-38	GLIS3	C	0.03
rs9788721	4e-38	HYKK	T	0.15
rs2464523	4e-37	FAM13A	C	0.03
rs2955133	5e-37	EEFSEC	T	0.04
rs631126	2e-35	MTCL1	T	0.03
rs146059675	2e-35	TSHZ3	C	0.04
rs7424080	1e-34	LINC01876	T	0.04
rs10059996	5e-34	FGF18 - SMIM23	T	0.03
rs1441358	7e-33	THSD4	G	1.13
rs879394	8e-32	LINC02082 - LINC01997	G	0.03
rs17058639	1e-31	SLMAP	C	0.03

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST007692	Sakornsakolpat P	2019	35,735	222,076	Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.
GCST011766	Moll M	2021	31,465	203,688	A Systematic Analysis of Protein-altering Exonic Variants in Chronic Obstructive Pulmonary Disease.
GCST90016585	Kim W	2020	21,077	179,689	Genome-wide Gene-by-smoking Interaction Study of Chronic Obstructive Pulmonary Disease.
GCST90016586	Kim W	2020	21,077	179,689	Genome-wide Gene-by-smoking Interaction Study of Chronic Obstructive Pulmonary Disease.
GCST90016587	Kim W	2020	21,077	179,689	Genome-wide Gene-by-smoking Interaction Study of Chronic Obstructive Pulmonary Disease.
GCST90016590	Kim W	2020	21,077	179,689	Genome-wide Gene-by-smoking Interaction Study of Chronic Obstructive Pulmonary Disease.
GCST90016591	Kim W	2020	21,077	179,689	Genome-wide Gene-by-smoking Interaction Study of Chronic Obstructive Pulmonary Disease.
GCST90016592	Kim W	2020	21,077	179,689	Genome-wide Gene-by-smoking Interaction Study of Chronic Obstructive Pulmonary Disease.
GCST90016594	Kim W	2020	16,488	169,688	Genome-wide Gene-by-smoking Interaction Study of Chronic Obstructive Pulmonary Disease.
GCST90018807	Sakaue S	2021	13,530	454,945	A cross-population atlas of genetic associations for 220 human phenotypes.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	5
Tier 3: regulatory	0
Tier 4: intronic/intergenic	43

MAF distribution

Bucket	Variants
common (>=0.05)	46
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	3

Functional consequences

Consequence	Count
intron_variant	36
intergenic_variant	5
splice_region_variant	2
3_prime_UTR_variant	2
missense_variant	2
unknown	2
5_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs34712979	4	105897896	G>A,T	0.05	splice_region_variant	NPNT	6e-161	Tier 2: splice/UTR
rs10037493	5	148475407	C>A,G,T	0.05	intron_variant	HTR4	1e-117	Tier 4: intronic/intergenic
rs7753012	6	142424746	T>A,C,G	0.05	intron_variant	ADGRG6	3e-110	Tier 4: intronic/intergenic
rs6828540	4	144542079	G>A,C	0.05	intron_variant	GUSBP5 - KRT18P51	7e-101	Tier 4: intronic/intergenic
rs2165489	15	71381439	C>G,T	0.05	intron_variant	THSD4	2e-97	Tier 4: intronic/intergenic
rs9391855	6	32182024	C>T	0.05	intron_variant	AGER	3e-83	Tier 4: intronic/intergenic
rs2001546	10	12243736	A>T	0.05	intron_variant	CDC123	7e-83	Tier 4: intronic/intergenic
rs13140176	4	144567946	A>G,T	0.39	intron_variant	GUSBP5 - KRT18P51	4e-59	Tier 4: intronic/intergenic
rs62191107	2	238954831	T>C	0.05	intergenic_variant	LINC01940 - HDAC4	1e-55	Tier 4: intronic/intergenic
rs7162542	15	83845538	C>A,G,T	0.05	intron_variant	ADAMTSL3	4e-54	Tier 4: intronic/intergenic
rs2798641	6	108946847	C>T	0.05	intron_variant	ARMC2	3e-51	Tier 4: intronic/intergenic
rs1990950	5	157493748	G>C,T	0.05	intron_variant	ADAM19	2e-50	Tier 4: intronic/intergenic
rs4888415	16	75415023	C>G,T	0.05	intron_variant	CFDP1	5e-48	Tier 4: intronic/intergenic
rs633185	11	100722807	G>A,C	0.05	intron_variant	ARHGAP42	2e-47	Tier 4: intronic/intergenic
rs62202378	2	228697179	T>A,G	0.05	intron_variant	LINC01807	5e-47	Tier 4: intronic/intergenic
rs55884799	2	18106357	T>C	0.05	intergenic_variant	KCNS3	1e-42	Tier 4: intronic/intergenic
rs13141641	4	144585304	T>A,C	0.41	intron_variant	KRT18P51 - HHIP-AS1	9e-41	Tier 4: intronic/intergenic
rs9399401	6	142347764	T>A,C	0.28	intron_variant	ADGRG6	2e-40	Tier 4: intronic/intergenic
rs6537293	4	144558609	A>G	0.39	intron_variant	GUSBP5 - KRT18P51	5e-40	Tier 4: intronic/intergenic
rs10123811	9	4143735	C>G,T	0.05	intron_variant	GLIS3	1e-38	Tier 4: intronic/intergenic
rs9788721	15	78510527	C>A,G,T	0.05	intron_variant	HYKK	4e-38	Tier 4: intronic/intergenic
rs2464523	4	88939696	C>G,T	0.05	intron_variant	FAM13A	4e-37	Tier 4: intronic/intergenic
rs2955133	3	128226479	T>A,C	0.05	intron_variant	EEFSEC	5e-37	Tier 4: intronic/intergenic
rs631126	18	8800725	T>A,C,G	0.05	intron_variant	MTCL1	2e-35	Tier 4: intronic/intergenic
rs146059675	19	31338847	CT>C,CTT,CTTT	0.05	intron_variant	TSHZ3	2e-35	Tier 4: intronic/intergenic
rs7424080	2	156141090	T>C	0.05	intron_variant	LINC01876	1e-34	Tier 4: intronic/intergenic
rs10059996	5	171474459	T>G	0.05	intron_variant	FGF18 - SMIM23	5e-34	Tier 4: intronic/intergenic
rs1441358	15	71320175	T>C,G	0.34	intron_variant	THSD4	7e-33	Tier 4: intronic/intergenic
rs879394	3	168992055	G>C,T	0.05	intergenic_variant	LINC02082 - LINC01997	8e-32	Tier 4: intronic/intergenic
rs17058639	3	57896874	C>T	0.05	splice_region_variant	SLMAP	1e-31	Tier 2: splice/UTR

ClinVar germline variants

40 retrieved; paginated sample, class counts are floors:

14 association, 11 likely pathogenic, 4 benign, 2 uncertain significance; association, 2 uncertain significance, 2 conflicting classifications of pathogenicity, 2 pathogenic, 1 established risk allele; association, 1 conflicting classifications of pathogenicity; risk factor, 1 pathogenic/pathogenic, low penetrance; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
3336651	NM_000750.5(CHRNB4):c.1411G>C (p.Val471Leu)	CHRNB4	Pathogenic	no assertion criteria provided
3242552	NM_000583.4(GC):c.1366A>T (p.Asn456Tyr)	GC	Pathogenic	no assertion criteria provided
17969	NM_001127701.1(SERPINA1):c.863A>T (p.Glu288Val)	SERPINA1	Pathogenic/Pathogenic, low penetrance; other	criteria provided, multiple submitters, no conflicts
3336641	NM_000583.4(GC):c.1368C>A (p.Asn456Lys)	GC	Likely pathogenic	no assertion criteria provided
3336642	NM_000583.4(GC):c.1322_1323insTG (p.Val442fs)	GC	Likely pathogenic	no assertion criteria provided
3336643	NM_000583.4(GC):c.1328del (p.Asn443fs)	GC	Likely pathogenic	no assertion criteria provided
3336644	NM_000583.4(GC):c.1349C>G (p.Ser450Cys)	GC	Likely pathogenic	no assertion criteria provided
3336646	NM_000583.4(GC):c.1364T>C (p.Ile455Thr)	GC	Likely pathogenic	no assertion criteria provided
3336647	NM_000583.4(GC):c.1330A>T (p.Lys444Ter)	GC	Likely pathogenic	no assertion criteria provided
3336648	NM_000583.4(GC):c.1324dup (p.Val442fs)	GC	Likely pathogenic	no assertion criteria provided
3336649	NM_000583.4(GC):c.1327_1328insT (p.Asn443fs)	GC	Likely pathogenic	no assertion criteria provided
4796619	NM_002133.3(HMOX1):c.546C>A (p.Tyr182Ter)	HMOX1	Likely pathogenic	criteria provided, single submitter
3336640	NM_001013619.4(HYKK):c.337+256T>C	HYKK	Likely pathogenic	no assertion criteria provided
3336650	NC_000012.12:g.47906043T>C	VDR	Likely pathogenic	no assertion criteria provided
1027621	NM_003357.5(SCGB1A1):c.-26G>A	SCGB1A1	Established risk allele; association	no assertion criteria provided
1318566	NM_002133.3(HMOX1):c.287G>A (p.Trp96Ter)	HMOX1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
17967	NM_001127701.1(SERPINA1):c.1096G>A (p.Glu366Lys)	SERPINA1	Conflicting classifications of pathogenicity; risk factor	criteria provided, conflicting classifications
410674	NM_198253.3(TERT):c.1931C>T (p.Thr644Met)	TERT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1027620	NC_000011.10:g.34788896T>C		association	no assertion criteria provided
1027622	NC_000011.10:g.34758731G>A		association	no assertion criteria provided
1027617	NM_014883.4(FAM13A):c.605+25827G>A	FAM13A	association	no assertion criteria provided
1027619	NC_000004.12:g.88448181T>C	FAM13A	association	no assertion criteria provided
1162779	NM_014883.4(FAM13A):c.843+16335C>A	FAM13A	Uncertain significance; association	no assertion criteria provided
3336645	NM_000583.4(GC):c.1375_1376insG (p.Pro459fs)	GC	Uncertain significance	no assertion criteria provided
870129	NC_000004.12:g.144539078A>G	HHIP	association	no assertion criteria provided
870130	NC_000004.12:g.144565237A>G	HHIP	association	no assertion criteria provided
870131	NC_000004.12:g.144559628A>G	HHIP	association	no assertion criteria provided
694514	NM_005345.6(HSPA1A):c.330G>C (p.Glu110Asp)	HSPA1A	association	no assertion criteria provided
694515	NC_000006.12:g.31815431A>C	HSPA1A	association	no assertion criteria provided
694516	NM_005345.6(HSPA1A):c.-27G>C	HSPA1A	association	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 62 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 6

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
SCGB1A1	SCGB1A1	GWAS
HHIP	HHIP	GWAS
FAM13A	FAM13A	GWAS, Orphanet
CHRNB4	CHRNB4	GWAS
DSP	DSP	GWAS, Orphanet
HYKK	HYKK	GWAS

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
HMOX1	Limited	Unknown	chronic obstructive pulmonary disease	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FAM13A	Orphanet:2032	Idiopathic pulmonary fibrosis
DSP	Orphanet:154	Familial isolated dilated cardiomyopathy
DSP	Orphanet:158687	Lethal acantholytic erosive disorder
DSP	Orphanet:2032	Idiopathic pulmonary fibrosis
DSP	Orphanet:293165	Skin fragility-woolly hair-palmoplantar keratoderma syndrome
DSP	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
DSP	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
DSP	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
DSP	Orphanet:369992	Severe dermatitis-multiple allergies-metabolic wasting syndrome
DSP	Orphanet:476096	Erythrokeratodermia-cardiomyopathy syndrome
DSP	Orphanet:50942	Striate palmoplantar keratoderma
DSP	Orphanet:65282	Carvajal syndrome
HMOX1	Orphanet:562509	Heme oxygenase-1 deficiency
HMOX1	Orphanet:586	Cystic fibrosis
RREB1	Orphanet:567	22q11.2 deletion syndrome
SEC24C	Orphanet:567	22q11.2 deletion syndrome
BMP6	Orphanet:465508	Symptomatic form of HFE-related hemochromatosis
SIX5	Orphanet:107	BOR syndrome
ARID1A	Orphanet:1465	Coffin-Siris syndrome
SOX9	Orphanet:140	Campomelic dysplasia
SOX9	Orphanet:2138	46,XX ovotesticular difference of sex development
SOX9	Orphanet:242	46,XY complete gonadal dysgenesis
SOX9	Orphanet:251510	46,XY partial gonadal dysgenesis
SOX9	Orphanet:393	46,XX testicular difference of sex development
SOX9	Orphanet:718	Isolated Pierre Robin sequence
SYNGAP1	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SYNGAP1	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
SYNGAP1	Orphanet:544254	SYNGAP1-related developmental and epileptic encephalopathy
HNF1A	Orphanet:319303	Chromophobe renal cell carcinoma
HNF1A	Orphanet:324575	Hyperinsulinism due to HNF1A deficiency
HNF1A	Orphanet:404511	Clear cell papillary renal cell carcinoma
HNF1A	Orphanet:552	MODY
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic anemia
TGFB2	Orphanet:60030	Loeys-Dietz syndrome
TGFB2	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
THRA	Orphanet:566231	Resistance to thyroid hormone due to a mutation in thyroid hormone receptor alpha
TNFSF15	Orphanet:186	Primary biliary cholangitis
TNRC6A	Orphanet:86814	Familial adult myoclonic epilepsy
TOP2B	Orphanet:567502	B-cell immunodeficiency-limb anomaly-urogenital malformation syndrome
VDR	Orphanet:93160	Hypocalcemic vitamin D-resistant rickets
WNT7A	Orphanet:2854	Fuhrmann syndrome
WNT7A	Orphanet:2879	Phocomelia, Schinzel type

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	66
gwas_and_clinvar	6
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCGB1A1	HGNC:12523	ENSG00000149021	P11684	Uteroglobin	gwas,clinvar
HHIP	HGNC:14866	ENSG00000164161	Q96QV1	Hedgehog-interacting protein	gwas,clinvar
FAM13A	HGNC:19367	ENSG00000138640	O94988	Protein FAM13A	gwas,clinvar
CHRNB4	HGNC:1964	ENSG00000117971	P30926	Neuronal acetylcholine receptor subunit beta-4	gwas,clinvar
DSP	HGNC:3052	ENSG00000096696	P15924	Desmoplakin	gwas,clinvar
HYKK	HGNC:34403	ENSG00000188266	A2RU49	Hydroxylysine kinase	gwas,clinvar
HMOX1	HGNC:5013	ENSG00000100292	P09601	Heme oxygenase 1	gencc,clinvar
RPL17	HGNC:10307	ENSG00000265681	P18621	Large ribosomal subunit protein uL22	gwas
RREB1	HGNC:10449	ENSG00000124782	Q92766	Ras-responsive element-binding protein 1	gwas
RUVBL1	HGNC:10474	ENSG00000175792	Q9Y265	RuvB-like 1	gwas
SEC24C	HGNC:10705	ENSG00000176986	P53992	Protein transport protein Sec24C	gwas
BMP6	HGNC:1073	ENSG00000153162	P22004	Bone morphogenetic protein 6	gwas
SFN	HGNC:10773	ENSG00000175793	P31947	14-3-3 protein sigma	gwas
SFTPD	HGNC:10803	ENSG00000133661	P35247	Pulmonary surfactant-associated protein D	gwas
SIX5	HGNC:10891	ENSG00000177045	Q8N196	Homeobox protein SIX5	gwas
ARID1A	HGNC:11110	ENSG00000117713	O14497	AT-rich interactive domain-containing protein 1A	gwas
SNRPD2	HGNC:11159	ENSG00000125743	P62316	Small nuclear ribonucleoprotein Sm D2	gwas
SNRPF	HGNC:11162	ENSG00000139343	P62306	Small nuclear ribonucleoprotein F	gwas
BTBD1	HGNC:1120	ENSG00000064726	Q9H0C5	BTB/POZ domain-containing protein 1	gwas
SOX9	HGNC:11204	ENSG00000125398	P48436	Transcription factor SOX-9	gwas
BTC	HGNC:1121	ENSG00000174808	P35070	Probetacellulin	gwas
BTN2A1	HGNC:1136	ENSG00000112763	Q7KYR7	Butyrophilin subfamily 2 member A1	gwas
SYN2	HGNC:11495	ENSG00000157152	Q92777	Synapsin-2	gwas
SYN3	HGNC:11496	ENSG00000185666	O14994	Synapsin-3	gwas
SYNGAP1	HGNC:11497	ENSG00000197283	Q96PV0	Ras/Rap GTPase-activating protein SynGAP	gwas
HNF1A	HGNC:11621	ENSG00000135100	P20823	Hepatocyte nuclear factor 1-alpha	gwas
TCF19	HGNC:11629	ENSG00000137310	Q9Y242	Transcription factor 19	gwas
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	clinvar
TESK2	HGNC:11732	ENSG00000070759	Q96S53	Dual specificity testis-specific protein kinase 2	gwas
TFAP2C	HGNC:11744	ENSG00000087510	Q92754	Transcription factor AP-2 gamma	gwas
TGFB2	HGNC:11768	ENSG00000092969	P61812	Transforming growth factor beta-2 proprotein	gwas
THRA	HGNC:11796	ENSG00000126351	P10827	Thyroid hormone receptor alpha	gwas
TNFSF15	HGNC:11931	ENSG00000181634	O95150	Tumor necrosis factor ligand superfamily member 15	gwas
TNRC6A	HGNC:11969	ENSG00000090905	Q8NDV7	Trinucleotide repeat-containing gene 6A protein	gwas
TNS1	HGNC:11973	ENSG00000079308	Q9HBL0	Tensin-1	gwas
TOP2B	HGNC:11990	ENSG00000077097	Q02880	DNA topoisomerase 2-beta	gwas
LINC00470	HGNC:1225	ENSG00000132204	Q9BZP3	Putative uncharacterized protein encoded by LINC00470	gwas
USP3	HGNC:12626	ENSG00000140455	Q9Y6I4	Ubiquitin carboxyl-terminal hydrolase 3	gwas
VARS1	HGNC:12651	ENSG00000204394	P26640	Valine–tRNA ligase	gwas
VDR	HGNC:12679	ENSG00000111424	P11473	Vitamin D3 receptor	clinvar
MIR99AHG	HGNC:1274	ENSG00000215386		mir-99a-let-7c cluster host gene	gwas
WNT7A	HGNC:12786	ENSG00000154764	O00755	Protein Wnt-7a	gwas
ZKSCAN1	HGNC:13101	ENSG00000106261	P17029	Zinc finger protein with KRAB and SCAN domains 1	gwas
EML4	HGNC:1316	ENSG00000143924	Q9HC35	Echinoderm microtubule-associated protein-like 4	gwas
ZSCAN12	HGNC:13172	ENSG00000158691	O43309	Zinc finger and SCAN domain-containing protein 12	gwas
LXN	HGNC:13347	ENSG00000079257	Q9BS40	Latexin	gwas
RBMS3	HGNC:13427	ENSG00000144642	Q6XE24	RNA-binding motif, single-stranded-interacting protein 3	gwas
MACF1	HGNC:13664	ENSG00000127603	O94854	Microtubule-actin cross-linking factor 1, isoforms 6/7	gwas
GFM1	HGNC:13780	ENSG00000168827	Q96RP9	Elongation factor G, mitochondrial	gwas
ADGRG6	HGNC:13841	ENSG00000112414	Q86SQ4	Adhesion G-protein coupled receptor G6	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCGB1A1	Uteroglobin	Binds phosphatidylcholine, phosphatidylinositol, polychlorinated biphenyls (PCB) and weakly progesterone, potent inhibitor of phospholipase A2.
HHIP	Hedgehog-interacting protein	Modulates hedgehog signaling in several cell types including brain and lung through direct interaction with members of the hedgehog family.
CHRNB4	Neuronal acetylcholine receptor subunit beta-4	Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection…
DSP	Desmoplakin	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
HYKK	Hydroxylysine kinase	Catalyzes the GTP-dependent phosphorylation of 5-hydroxy-L-lysine.
HMOX1	Heme oxygenase 1	Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron.
RPL17	Large ribosomal subunit protein uL22	Component of the large ribosomal subunit.
RREB1	Ras-responsive element-binding protein 1	Transcription factor that binds specifically to the RAS-responsive elements (RRE) of gene promoters.
RUVBL1	RuvB-like 1	Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3’ to 5’) activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activ…
SEC24C	Protein transport protein Sec24C	Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER).
BMP6	Bone morphogenetic protein 6	Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes including cartilage and bone formation.
SFN	14-3-3 protein sigma	Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways.
SFTPD	Pulmonary surfactant-associated protein D	Contributes to the lung’s defense against inhaled microorganisms, organic antigens and toxins.
SIX5	Homeobox protein SIX5	Transcription factor that is thought to be involved in regulation of organogenesis.
ARID1A	AT-rich interactive domain-containing protein 1A	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
SNRPD2	Small nuclear ribonucleoprotein Sm D2	Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome.
SNRPF	Small nuclear ribonucleoprotein F	Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome.
BTBD1	BTB/POZ domain-containing protein 1	Probable substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
SOX9	Transcription factor SOX-9	Transcription factor that plays a key role in chondrocytes differentiation and skeletal development.
BTC	Probetacellulin	Growth factor that binds to EGFR, ERBB4 and other EGF receptor family members.
SYN2	Synapsin-2	Neuronal phosphoprotein that coats synaptic vesicles, binds to the cytoskeleton, and is believed to function in the regulation of neurotransmitter release.
SYN3	Synapsin-3	May be involved in the regulation of neurotransmitter release and synaptogenesis.
SYNGAP1	Ras/Rap GTPase-activating protein SynGAP	Major constituent of the PSD essential for postsynaptic signaling.
HNF1A	Hepatocyte nuclear factor 1-alpha	Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver.
TCF19	Transcription factor 19	Potential transcription factor that may play a role in the regulation of genes involved in cell cycle G1/S transition.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TESK2	Dual specificity testis-specific protein kinase 2	Dual specificity protein kinase activity catalyzing autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues.
TFAP2C	Transcription factor AP-2 gamma	Sequence-specific DNA-binding transcription factor that interacts with cellular enhancer elements to regulate transcription of selected genes, and which plays a key role in early embryonic development.
TGFB2	Transforming growth factor beta-2 proprotein	Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively.
THRA	Thyroid hormone receptor alpha	Nuclear hormone receptor that can act as a repressor or activator of transcription.
TNFSF15	Tumor necrosis factor ligand superfamily member 15	Receptor for TNFRSF25 and TNFRSF6B.
TNRC6A	Trinucleotide repeat-containing gene 6A protein	Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs).
TNS1	Tensin-1	May act as a protein phosphatase and/or a lipid phosphatase.
TOP2B	DNA topoisomerase 2-beta	Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken stra…
USP3	Ubiquitin carboxyl-terminal hydrolase 3	Deubiquitinase that plays a role in several cellular processes including transcriptional regulation, cell cycle progression or innate immunity.
VARS1	Valine–tRNA ligase	Catalyzes the attachment of valine to tRNA(Val).
VDR	Vitamin D3 receptor	Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells.
WNT7A	Protein Wnt-7a	Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway.
ZKSCAN1	Zinc finger protein with KRAB and SCAN domains 1	May be involved in transcriptional regulation.
EML4	Echinoderm microtubule-associated protein-like 4	Essential for the formation and stability of microtubules (MTs).
ZSCAN12	Zinc finger and SCAN domain-containing protein 12	May be involved in transcriptional regulation.
LXN	Latexin	Hardly reversible, non-competitive, and potent inhibitor of CPA1, CPA2 and CPA4.
RBMS3	RNA-binding motif, single-stranded-interacting protein 3	Binds poly(A) and poly(U) oligoribonucleotides.
GFM1	Elongation factor G, mitochondrial	Mitochondrial GTPase that catalyzes the GTP-dependent ribosomal translocation step during translation elongation.
ADGRG6	Adhesion G-protein coupled receptor G6	Adhesion G-protein coupled receptor (aGPCR) for steroid hormones, such as progesterone and 17alpha-hydroxyprogesterone (17OHP).
CCHCR1	Coiled-coil alpha-helical rod protein 1	May be a regulator of keratinocyte proliferation or differentiation.
OR12D3	Olfactory receptor 12D3	Odorant receptor.
OR2B2	Olfactory receptor 2B2	Odorant receptor.
PRDM15	PR domain zinc finger protein 15	Sequence-specific DNA-binding transcriptional regulator.
CSMD1	CUB and sushi domain-containing protein 1	Potential suppressor of squamous cell carcinomas.

Protein-family classification

Druggable: 21 · Difficult: 16 · Unknown: 38 · Druggable fraction: 0.28

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
Nuclear receptor	2	10.3×	0.178
Complement	1	3.6×	0.732
Phosphatase	2	2.2×	0.732
Scaffold/PPI	6	1.4×	0.732
Kinase	3	1.1×	0.747
Transcription factor	10	1.1×	0.747
Protease	2	1.0×	0.747
Enzyme (other)	6	1.0×	0.747
GPCR	3	1.0×	0.747
Antibody/Immunoglobulin	2	0.8×	0.806
Other/Unknown	38	0.9×	0.845

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCGB1A1	Other/Unknown	no		Uteroglobin, Secretoglobin, Secretoglobin_sf
HHIP	Other/Unknown	no		EGF, Quinoprot_gluc/sorb_DH_b-prop, 6-blade_b-propeller_TolB-like
FAM13A	Other/Unknown	no		RhoGAP_dom, Rho_GTPase_activation_prot, FAM13
CHRNB4	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
DSP	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Spectrin/alpha-actinin
HYKK	Kinase	yes	2.7.1.81	Aminoglycoside_PTrfase, Kinase-like_dom_sf, Pseudomonas-type_ThrB
HMOX1	Enzyme (other)	yes	1.14.14.18	Haem_Oase, Haem_Oase-like, Haem_Oase-like_multi-hlx
RPL17	Other/Unknown	no		Ribosomal_uL22, Ribosomal_uL22_euk_arc, Ribosomal_uL22_CS
RREB1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, RREB1
RUVBL1	Other/Unknown	no		AAA+_ATPase, TIP49_P-loop, RuvB-like
SEC24C	Transcription factor	no		Znf_Sec23_Sec24, Sec23/24_trunk_dom, Sec23/24_helical_dom
BMP6	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
SFN	Other/Unknown	no		14-3-3, 14-3-3_CS, 14-3-3_domain
SFTPD	Other/Unknown	no		C-type_lectin-like, Collagen, Surfac_D-trimer
SIX5	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
ARID1A	Other/Unknown	no		ARID_dom, ARM-like, ARM-type_fold
SNRPD2	Other/Unknown	no		Sm_dom_euk/arc, LSM_dom_sf, Sm_D2
SNRPF	Other/Unknown	no		Sm_dom_euk/arc, LSM_dom_sf, Lsm6/sSmF
BTBD1	Other/Unknown	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, BACK
SOX9	Transcription factor	no		HMG_box_dom, Sox_N, HMG_box_dom_sf
BTC	Other/Unknown	no		EGF
BTN2A1	Antibody/Immunoglobulin	yes		B30.2/SPRY, Ig_sub, SPRY_dom
SYN2	Other/Unknown	no		Synapsin, ATP_grasp_subdomain_1, PreATP-grasp_dom_sf
SYN3	Other/Unknown	no		Synapsin, ATP_grasp_subdomain_1, PreATP-grasp_dom_sf
SYNGAP1	Scaffold/PPI	no		C2_dom, PH_domain, RasGAP_dom
HNF1A	Transcription factor	no		HD, HNF1b_C, HNF1a_C
TCF19	Transcription factor	no		FHA_dom, Znf_PHD, SMAD_FHA_dom_sf
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TESK2	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS
TFAP2C	Transcription factor	no		TF_AP2, TF_AP2_gamma, TF_AP2_C
TGFB2	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGFb2
THRA	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
TNFSF15	Other/Unknown	no		TNF_dom, TNF, Tumour_necrosis_fac-like_dom
TNRC6A	Other/Unknown	no		Nucleotide-bd_a/b_plait_sf, Argonaute_hook_dom, TNRC6_PABC-bd
TNS1	Phosphatase	yes		SH2, PKC_DAG/PE, Tyr_Pase_cat
TOP2B	Enzyme (other)	yes	5.6.2.2	TopoII_euk, Topo_IIA, Topo_IIA_dom_A
LINC00470	Other/Unknown	no
USP3	Protease	yes		Peptidase_C19_UCH, Znf_UBP, Znf_RING/FYVE/PHD
VARS1	Enzyme (other)	yes	6.1.1.9	aa-tRNA-synth_I_CS, aa-tRNA-synth_Ia, Valyl-tRNA_ligase
VDR	Nuclear receptor	yes		VitD_rcpt, Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt
MIR99AHG	Other/Unknown	no
WNT7A	Other/Unknown	no		Wnt, Wnt7, Wnt_CS
ZKSCAN1	Transcription factor	no		KRAB, SCAN_dom, Znf_C2H2_type
EML4	Scaffold/PPI	no		WD40_rpt, HELP, Quinoprotein_ADH-like_sf
ZSCAN12	Transcription factor	no		SCAN_dom, Znf_C2H2_type, Znf_C2H2_sf
LXN	Other/Unknown	no		Latexin, Cystatin_sf, CYSTATIN_LXN
RBMS3	Other/Unknown	no		RRM_dom, Hud_Sxl_RNA, Nucleotide-bd_a/b_plait_sf
MACF1	Scaffold/PPI	no		Spectrin_repeat, EF_hand_dom, GAR_dom
GFM1	Other/Unknown	no		EFG_V-like, T_Tr_GTP-bd_dom, EFTu-like_2
ADGRG6	GPCR	yes		GPS, GPCR_2_secretin-like, CUB_dom

Expression context

Cohort genes with no expression data: 0.

63 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	1
broad (>20)	73
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	11
primordial germ cell in gonad	7
calcaneal tendon	7
right testis	6
cartilage tissue	5
cortical plate	5
left testis	5
endothelial cell	4
jejunal mucosa	4
oocyte	4
upper leg skin	4
ileal mucosa	4
right uterine tube	4
embryo	4
endometrium epithelium	4
testis	4
bronchial epithelial cell	3
secondary oocyte	3
male germ line stem cell (sensu Vertebrata) in testis	3
hair follicle	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCGB1A1	170	tissue_specific	marker	bronchial epithelial cell, epithelium of bronchus, right lung
HHIP	206	ubiquitous	marker	corpus callosum, endothelial cell, globus pallidus
FAM13A	293	ubiquitous	marker	secondary oocyte, oocyte, jejunal mucosa
CHRNB4	125	broad	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, right testis
DSP	253	ubiquitous	marker	skin of hip, upper leg skin, hair follicle
HYKK	170	ubiquitous	marker	olfactory segment of nasal mucosa, calcaneal tendon, ileal mucosa
HMOX1	230	ubiquitous	marker	cartilage tissue, spleen, monocyte
RPL17	134	ubiquitous	marker	left ovary, ovary, right ovary
RREB1	278	ubiquitous	marker	buccal mucosa cell, epithelium of nasopharynx, oral cavity
RUVBL1	134	ubiquitous	marker	right uterine tube, ventricular zone, primordial germ cell in gonad
SEC24C	290	ubiquitous	marker	lower esophagus mucosa, esophagus squamous epithelium, epithelium of esophagus
BMP6	197	ubiquitous	marker	secondary oocyte, cartilage tissue, oocyte
SFN	278	broad	marker	cervix squamous epithelium, gingival epithelium, squamous epithelium
SFTPD	180	tissue_specific	marker	lower lobe of lung, visceral pleura, upper lobe of lung
SIX5	205	ubiquitous	yes	cardiac muscle of right atrium, right uterine tube, right ovary
ARID1A	286	ubiquitous	marker	bone marrow cell, ventricular zone, embryo
SNRPD2	295	ubiquitous	marker	adult organism, type B pancreatic cell, embryo
SNRPF	283	ubiquitous	marker	endometrium epithelium, oocyte, embryo
BTBD1	290	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, vastus lateralis, quadriceps femoris
SOX9	274	ubiquitous	marker	ventricular zone, cranial nerve II, hair follicle
BTC	201	broad	marker	muscle layer of sigmoid colon, upper leg skin, lower esophagus muscularis layer
BTN2A1	286	ubiquitous	marker	granulocyte, spleen, cerebellar hemisphere
SYN2	217	broad	marker	middle temporal gyrus, endothelial cell, Brodmann (1909) area 23
SYN3	176	broad	marker	primordial germ cell in gonad, cortical plate, primary visual cortex
SYNGAP1	137	ubiquitous	marker	pituitary gland, right uterine tube, adenohypophysis
HNF1A	81	tissue_specific	yes	right lobe of liver, mucosa of transverse colon, liver
TCF19	133	ubiquitous	yes	primordial germ cell in gonad, ventricular zone, lymph node
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
TESK2	218	ubiquitous	yes	cartilage tissue, ileal mucosa, C1 segment of cervical spinal cord
TFAP2C	198	broad	marker	endometrium epithelium, ventricular zone, epithelium of mammary gland

Protein interactions among cohort

Intra-cohort edges: 22.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VARS1	5,848
GFM1	5,789
TERT	5,717
SFN	5,552
RPL17	5,372
TOP2B	5,298
SOX9	4,935
SNRPF	4,334
HMOX1	4,054
ARID1A	3,476

Intra-cohort edges

A	B	Sources
CAMK2G	SYN2	string_interaction
CAMK2G	SYN3	string_interaction
CCHCR1	OR12D3	string_interaction
CCHCR1	TCF19	string_interaction
CHRNB4	HYKK	string_interaction
ELOVL4	HMOX1	intact
FAM13A	HHIP	string_interaction
FAM13A	HYKK	string_interaction
FAM13A	SFN	intact
GAB2	TESK2	biogrid_interaction
HDAC7	SFN	intact
OR12D3	TCF19	string_interaction
RUVBL1	TERT	intact
SCGB1A1	SFTPD	string_interaction
SEC24C	SYNGAP1	intact
SFN	TESK2	intact
SNRPD2	SNRPF	intact
SYN2	SYN3	biogrid_interaction, intact
SYN2	SYNGAP1	intact
SYN3	SYNGAP1	intact
SYNGAP1	TOP2B	intact
VARS1	VWA7	string_interaction

Structural data

PDB: 43 · AlphaFold-only: 31 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SFN	P31947	524
RPL17	P18621	195
SNRPF	P62306	84
SNRPD2	P62316	81
VDR	P11473	52
RUVBL1	Q9Y265	36
BTN2A1	Q7KYR7	33
SFTPD	P35247	31
HMOX1	P09601	26
TERT	O14746	23
TOP2B	Q02880	20
HHIP	Q96QV1	11
TGFB2	P61812	11
THRA	P10827	10
GAB2	Q9UQC2	10
ARID1A	O14497	7
TNFSF15	O95150	7
HNF1A	P20823	6
HDAC7	Q8WUI4	6
BMP6	P22004	5
GFM1	Q96RP9	5
CHRNB4	P30926	4
DSP	P15924	4
BTC	P35070	4
NUF2	Q9BZD4	4
SEC24C	P53992	3
WNT7A	O00755	3
MACF1	O94854	3
SCGB1A1	P11684	2
TNRC6A	Q8NDV7	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HYKK	A2RU49	93.89
VARS1	P26640	88.12
BTBD1	Q9H0C5	87.99
ELOVL4	Q9GZR5	84.53
VWA7	Q9Y334	84.03
CACNA2D3	Q8IZS8	83.30
PRSS23	O95084	82.18
OR12D3	Q9UGF7	81.77
ASB1	Q9Y576	80.61
OR2B2	Q9GZK3	79.53
CCHCR1	Q8TD31	79.52
USP3	Q9Y6I4	79.40
SYN2	Q92777	75.24
ZSCAN12	O43309	70.20
RSPH6A	Q9H0K4	68.76
PICALM	Q13492	67.38
TESK2	Q96S53	66.52
TFAP2C	Q92754	66.37
ADAMTSL3	P82987	65.99
RBMS3	Q6XE24	63.30
TCF19	Q9Y242	63.17
RGS20	O76081	62.78
FAM13A	O94988	61.00
LINC00470	Q9BZP3	60.83
SYNGAP1	Q96PV0	60.43
ZKSCAN1	P17029	59.61
PRDM15	P57071	56.66
TNS1	Q9HBL0	53.42
SIX5	Q8N196	53.21
RREB1	Q92766	48.28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 644. Enrichment computed across 250 evidence-associated genes (136 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 136 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Highly calcium permeable nicotinic acetylcholine receptors	4	37.3×	0.001	CHRNB4, CHRNA3, CHRNA4, CHRNA5
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	4	30.5×	0.002	CHRNB4, CHRNA3, CHRNA4, CHRNA5
Presynaptic nicotinic acetylcholine receptors	4	28.0×	0.002	CHRNB4, CHRNA3, CHRNA4, CHRNA5
Acetylcholine binding and downstream events	4	24.0×	0.002	CHRNB4, CHRNA3, CHRNA4, CHRNA5
Postsynaptic nicotinic acetylcholine receptors	4	24.0×	0.002	CHRNB4, CHRNA3, CHRNA4, CHRNA5
Highly sodium permeable postsynaptic acetylcholine nicotinic receptors	3	36.0×	0.006	CHRNB4, CHRNA3, CHRNA4
Transmission across Chemical Synapses	9	5.0×	0.007	CHRNB4, SYN2, SYN3, CAMK2G, CACNA2D3, CHRNA3, CHRNA4, CHRNA5 (+1 more)
TFAP2 (AP-2) family regulates transcription of other transcription factors	2	42.0×	0.060	TFAP2C, CITED2
Invadopodia formation	2	42.0×	0.060	ADAM19, SH3PXD2A
Extension of Telomeres	3	13.3×	0.090	RUVBL1, TERT, STN1
Neurotransmitter receptors and postsynaptic signal transmission	6	4.4×	0.139	CHRNB4, CAMK2G, CHRNA3, CHRNA4, CHRNA5, ADCY5
Neuronal System	9	2.9×	0.198	CHRNB4, SYN2, SYN3, CAMK2G, CACNA2D3, CHRNA3, CHRNA4, CHRNA5 (+1 more)
Regulation of CDH11 mRNA translation by microRNAs	2	18.7×	0.225	TNRC6A, CDH11
Uptake of dietary cobalamins into enterocytes	2	16.8×	0.225	CTRB1, CTRB2
Telomere Maintenance	3	8.1×	0.225	RUVBL1, TERT, STN1
Regulation of MECP2 expression and activity	3	8.1×	0.225	TNRC6A, CAMK2G, TBL1XR1
SARS-CoV-2-host interactions	5	4.4×	0.225	SEC24C, SFN, SFTPD, SNRPD2, SNRPF
Processing of Capped Intronless Pre-mRNA	2	15.3×	0.232	SNRPF, SYMPK
Regulation of CDH11 function	2	15.3×	0.232	CDH11, ADAM19
SARS-CoV-2 Infection	6	3.5×	0.232	SEC24C, SFN, SFTPD, SNRPD2, SNRPF, CSNK1A1
Activation of the TFAP2 (AP-2) family of transcription factors	2	14.0×	0.259	TFAP2C, CITED2
Transcriptional Regulation by MECP2	3	7.0×	0.259	TNRC6A, CAMK2G, TBL1XR1
Specification of primordial germ cells	2	12.9×	0.282	TFAP2C, TET2
Regulation of CDH11 Expression and Function	2	12.0×	0.313	CDH11, ADAM19
Class I MHC mediated antigen processing & presentation	6	3.1×	0.341	SEC24C, BTBD1, ASB1, SEC61A1, ANAPC10, RNF220
O-linked glycosylation	4	4.2×	0.360	ADAMTSL3, POFUT4, C1GALT1, THSD4
Transcriptional regulation of testis differentiation	2	10.5×	0.361	SOX9, ZFPM2
Regulation of Homotypic Cell-Cell Adhesion	2	9.9×	0.378	CDH11, ADAM19
Regulation of Expression and Function of Type II Classical Cadherins	2	9.9×	0.378	CDH11, ADAM19
Serotonin Neurotransmitter Release Cycle	2	9.3×	0.395	SYN2, SYN3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 215 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
behavioral response to nicotine	4	34.8×	0.004	CHRNB4, CHRNA3, CHRNA4, CHRNA5
acetylcholine receptor signaling pathway	5	14.5×	0.013	CHRNB4, CHRM3, CHRNA3, CHRNA4, CHRNA5
synaptic transmission, cholinergic	4	14.9×	0.050	CHRNB4, CHRNA3, CHRNA4, CHRNA5
cartilage condensation	4	14.2×	0.050	SOX9, TGFB2, THRA, WNT7A
positive regulation of male gonad development	3	23.5×	0.059	SOX9, ZFPM2, CITED2
keratinocyte development	3	21.4×	0.067	SFN, TFAP2C, KDF1
regulation of epidermal cell division	2	52.2×	0.088	SFN, KDF1
regulation of smooth muscle contraction	3	16.8×	0.107	CHRNB4, CHRM3, CHRNA3
synaptic transmission involved in micturition	2	39.2×	0.111	CHRNB4, CHRNA3
mammary gland branching involved in pregnancy	2	39.2×	0.111	VDR, CSMD1
membrane depolarization	4	9.5×	0.111	CHRNB4, CHRNA3, CHRNA4, CHRNA5
nuclear envelope organization	3	13.8×	0.125	LEMD2, DMPK, TMEM170A
positive regulation of transcription by RNA polymerase II	27	1.9×	0.125	RREB1, BMP6, SOX9, HNF1A, TFAP2C, THRA, VDR, WNT7A (+19 more)
intermediate filament cytoskeleton organization	3	13.1×	0.133	DSP, MACF1, CSNK1A1
response to nicotine	4	7.8×	0.140	HMOX1, CHRNA3, CHRNA4, CHRNA5
positive regulation of bone mineralization	4	7.3×	0.172	BMP6, VDR, ADGRV1, ADRB2
smooth muscle contraction	3	11.2×	0.173	CHRNB4, CHRM3, ADRB2
RNA-templated transcription	1	78.4×	0.194	TERT
deoxyribonucleoside triphosphate metabolic process	1	78.4×	0.194	RRM2B
regulation of acetylcholine secretion, neurotransmission	1	78.4×	0.194	CHRNA3
regulation of excitatory postsynaptic membrane potential involved in skeletal muscle contraction	1	78.4×	0.194	DMPK
polysaccharide transport	1	78.4×	0.194	SMPD3
cranial nerve morphogenesis	1	78.4×	0.194	CITED2
DNA strand elongation	1	78.4×	0.194	TERT
regulation of myeloid cell apoptotic process	1	78.4×	0.194	THRA
obsolete L-asparagine catabolic process via L-aspartate	1	78.4×	0.194	ASRGL1
negative regulation of syncytium formation by plasma membrane fusion	1	78.4×	0.194	RAPGEF3
pronephric nephron development	1	78.4×	0.194	SEC61A1
asymmetric protein localization involved in cell fate determination	1	78.4×	0.194	WNT7A
regulation of timing of catagen	1	78.4×	0.194	TGFB2

Therapeutics

Drugs indicated for this disease

8 approved, 52 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Albuterol	Approved (phase 4)
Azithromycin	Approved (phase 4)
Budesonide	Approved (phase 4)
Ensifentrine	Approved (phase 4)
Fluticasone Furoate	Approved (phase 4)
Fluticasone Propionate	Approved (phase 4)
Revefenacin	Approved (phase 4)
Roflumilast	Approved (phase 4)
.ALPHA.1-PROTEINASE INHIBITOR HUMAN	Phase 3 (in late-stage trials)
Acetylcysteine	Phase 3 (in late-stage trials)
Albumin Human	Phase 3 (in late-stage trials)
Arformoterol	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Astegolimab	Phase 3 (in late-stage trials)
Beclomethasone Dipropionate	Phase 3 (in late-stage trials)
Benralizumab	Phase 3 (in late-stage trials)
Cilomilast	Phase 3 (in late-stage trials)
Ciprofloxacin	Phase 3 (in late-stage trials)
Clopidogrel	Phase 3 (in late-stage trials)
Dupilumab	Phase 3 (in late-stage trials)
Erdosteine	Phase 3 (in late-stage trials)
Fenoterol	Phase 3 (in late-stage trials)
Fluticasone	Phase 3 (in late-stage trials)
Formoterol	Phase 3 (in late-stage trials)
Furosemide	Phase 3 (in late-stage trials)
Glycopyrronium	Phase 3 (in late-stage trials)
Helium	Phase 3 (in late-stage trials)
Indacaterol	Phase 3 (in late-stage trials)
Infliximab	Phase 3 (in late-stage trials)
Ipratropium	Phase 3 (in late-stage trials)
Itepekimab	Phase 3 (in late-stage trials)
Ivospemin	Phase 3 (in late-stage trials)
Levosalbutamol	Phase 3 (in late-stage trials)
Magnesium Sulfate Anhydrous	Phase 3 (in late-stage trials)
Mepolizumab	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Mometasone Furoate	Phase 3 (in late-stage trials)
Morphine	Phase 3 (in late-stage trials)
Moxifloxacin	Phase 3 (in late-stage trials)
Nicotine	Phase 3 (in late-stage trials)
Olodaterol	Phase 3 (in late-stage trials)
Oxitropium	Phase 3 (in late-stage trials)
Oxygen	Phase 3 (in late-stage trials)
Prednisolone	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Procalcitonin	Phase 3 (in late-stage trials)
Resveratrol	Phase 3 (in late-stage trials)
Salmeterol	Phase 3 (in late-stage trials)
Simvastatin	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Temazepam	Phase 3 (in late-stage trials)
Terbutaline	Phase 3 (in late-stage trials)
Tiotropium	Phase 3 (in late-stage trials)
Tozorakimab	Phase 3 (in late-stage trials)
Triamcinolone	Phase 3 (in late-stage trials)
Umeclidinium	Phase 3 (in late-stage trials)
Vilanterol	Phase 3 (in late-stage trials)
Vitamin E	Phase 3 (in late-stage trials)
Zabofloxacin	Phase 3 (in late-stage trials)
Zileuton	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aclidinium, Bimagrumab, Bosentan, Carbon Monoxide, Chlorhexidine, Cholecalciferol, Ciclesonide, Erythromycin, Etanercept, Ferric Carboxymaltose, Fevipiprant, Human Immunoglobulin G, INTERFERON BETA-1A, Iloprost, Ivacaftor, Lactose, Anhydrous, Lebrikizumab, Levomenthol, Losmapimod, Lovastatin, Megestrol Acetate, Metformin, Nitrogen, Omalizumab, Onabotulinumtoxina, Ramelteon, Reldesemtiv, Rosiptor, Rosuvastatin, Sapropterin, Solithromycin, Tesamorelin, Testosterone Enanthate, Tetomilast, Tezepelumab, Ticagrelor, Treprostinil, Valacyclovir.

Drug target analysis

Approved (phase 4): 11 · Phase ≥3: 11 · Phased (≥1): 16 · Undrugged: 59

Druggability breadth: 74 of 250 evidence-associated genes (30%) 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
CHRNB4	VARENICLINE
RPL17	GENTAMICIN SULFATE
TERT	BERBERINE
THRA	LIOTHYRONINE
TOP2B	AMSACRINE
VDR	CHOLECALCIFEROL
EML4	ALECTINIB
HDAC7	CELECOXIB
SMPD3	LAROTRECTINIB
CAMK2G	MOMELOTINIB
CACNA2D3	NIMODIPINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CAMK2G	39	4
HDAC7	28	4
CHRNB4	20	4
THRA	12	4
TOP2B	11	4
TERT	10	4
VDR	10	4
EML4	10	4
EGLN2	2	2
CACNA2D3	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VARENICLINE	4	CHRNB4
NICOTINE	4	CHRNB4
BUPROPION	4	CHRNB4
MECAMYLAMINE	4	CHRNB4
ONDANSETRON	4	CHRNB4
TROPISETRON	4	CHRNB4
ACETYLCHOLINE	4	CHRNB4
GENTAMICIN SULFATE	4	RPL17
BERBERINE	4	TERT
DOXORUBICIN	4	TERT, TOP2B
LIOTHYRONINE	4	THRA
LEVOTHYROXINE	4	THRA
ROXADUSTAT	4	THRA
RESMETIROM	4	THRA
AMIODARONE	4	THRA
AMSACRINE	4	TOP2B
ETOPOSIDE	4	TOP2B
TENIPOSIDE	4	TOP2B
CIPROFLOXACIN	4	TOP2B
TOPOTECAN	4	TOP2B
DEXRAZOXANE	4	TOP2B
CHOLECALCIFEROL	4	VDR
CALCIPOTRIENE	4	VDR
DOXERCALCIFEROL	4	VDR
TACALCITOL	4	VDR
CALCITRIOL	4	VDR
ALECTINIB	4	EML4
ENTRECTINIB	4	EML4
CERITINIB	4	EML4
LORLATINIB	4	EML4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 10.

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

Symbol	Assays	Type breakdown
HDAC7	1,710	Binding:1695, ADMET:10, Functional:4, Toxicity:1
VDR	561	Binding:459, Functional:99, ADMET:3
CHRNB4	407	Binding:309, Functional:96, ADMET:2
TERT	391	Binding:389, Functional:2
EML4	304	Binding:304
CAMK2G	291	Binding:290, Functional:1
TOP2B	284	Binding:247, Functional:36, ADMET:1
THRA	140	Binding:115, Functional:23, ADMET:2
RPL17	90	Binding:90
EGLN2	31	Binding:31
HMOX1	23	Binding:22, ADMET:1
SFN	21	Binding:21
RUVBL1	15	Binding:15
TESK2	13	Binding:13
CACNA2D3	13	Binding:13
SNRPD2	8	Binding:8
SMPD3	8	Binding:8
VARS1	7	Binding:7
ARID1A	6	Binding:6
SOX9	3	Binding:3
TGFB2	3	Binding:3
USP3	3	Binding:3
DSP	2	Binding:2
SFTPD	2	Binding:2
ADGRG6	2	Binding:2
SEC24C	1	Binding:1
BMP6	1	Binding:1
SNRPF	1	Binding:1
BTN2A1	1	Binding:1
HNF1A	1	Binding:1
GFM1	1	Binding:1
ELOVL4	1	Binding:1
PICALM	1	Binding:1
KLHL7	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HYKK	2.7.1.81	hydroxylysine kinase
HMOX1	1.14.14.18	heme oxygenase (biliverdin-producing)
TESK2	2.7.10.2	non-specific protein-tyrosine kinase
TOP2B	5.6.2.2, 5.99.1.3	DNA topoisomerase (ATP-hydrolysing), DNA topoisomerase (ATP-hydrolysing)
VARS1	6.1.1.9	valine-tRNA ligase
HDAC7	3.5.1.98	histone deacetylase
SMPD3	3.1.4.12	sphingomyelin phosphodiesterase
CAMK2G	2.7.11.17	Ca2+/calmodulin-dependent protein kinase
EGLN2	1.14.11.2, 1.14.11.29	procollagen-proline 4-dioxygenase, hypoxia-inducible factor-proline dioxygenase
POFUT1	2.4.1.221	peptide-O-fucosyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CHRNB4	407
TERT	391
THRA	140
TOP2B	284
VDR	561
EML4	304
HDAC7	1,710
CAMK2G	291

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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	CHRNB4
NICOTINE	4	CHRNB4
BUPROPION	4	CHRNB4
MECAMYLAMINE	4	CHRNB4
ONDANSETRON	4	CHRNB4
TROPISETRON	4	CHRNB4
ACETYLCHOLINE	4	CHRNB4
GENTAMICIN SULFATE	4	RPL17
BERBERINE	4	TERT
DOXORUBICIN	4	TERT, TOP2B
LIOTHYRONINE	4	THRA
LEVOTHYROXINE	4	THRA
ROXADUSTAT	4	THRA
RESMETIROM	4	THRA
AMIODARONE	4	THRA
AMSACRINE	4	TOP2B
ETOPOSIDE	4	TOP2B
TENIPOSIDE	4	TOP2B
CIPROFLOXACIN	4	TOP2B
TOPOTECAN	4	TOP2B
DEXRAZOXANE	4	TOP2B
CHOLECALCIFEROL	4	VDR
CALCIPOTRIENE	4	VDR
DOXERCALCIFEROL	4	VDR
TACALCITOL	4	VDR
CALCITRIOL	4	VDR
ALECTINIB	4	EML4
ENTRECTINIB	4	EML4
CERITINIB	4	EML4
LORLATINIB	4	EML4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	11	CHRNB4, RPL17, TERT, THRA, TOP2B, VDR, EML4, HDAC7, SMPD3, CAMK2G (+1 more)
B	Phased (≥1) drug, not yet approved	5	RUVBL1, SNRPD2, TESK2, TGFB2, EGLN2
C	Druggable family + PDB, no drug	5	HMOX1, BTN2A1, ADGRG6, CSMD1, POFUT1
D	Druggable family + AlphaFold only, no drug	8	HYKK, TNS1, USP3, VARS1, OR12D3, OR2B2, PRSS23, ADAMTSL3
E	Difficult family or no structure, no drug	46	SCGB1A1, HHIP, FAM13A, DSP, RREB1, SEC24C, BMP6, SFN, SFTPD, SIX5 (+36 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
HYKK	0	CHRNB4
SCGB1A1	0	—
HHIP	0	—
FAM13A	0	—
DSP	2	—
HMOX1	23	—
RREB1	0	—
SEC24C	1	—
BMP6	1	—
SFN	21	—
SFTPD	2	—
SIX5	0	—
ARID1A	6	—
SNRPF	1	—
BTBD1	0	—
SOX9	3	—
BTC	0	—
BTN2A1	1	—
SYN2	0	—
SYN3	0	—
SYNGAP1	0	—
HNF1A	1	—
TCF19	0	—
TFAP2C	0	—
TNFSF15	0	—
TNRC6A	0	—
TNS1	0	—
LINC00470	0	—
USP3	3	—
VARS1	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3,782.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	306
PHASE4	287
PHASE2	283
PHASE1	126
PHASE1/PHASE2	47
PHASE2/PHASE3	30
EARLY_PHASE1	21

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02989935	PHASE4	ACTIVE_NOT_RECRUITING	RELVAR Effects on Parasternal Muscle Activity, Diaphragm, and Ventilation in Severe COPD
NCT03566667	PHASE4	ACTIVE_NOT_RECRUITING	Beta-blockers to Patients With Chronic Obstructive Pulmonary Disease
NCT04238221	PHASE4	NOT_YET_RECRUITING	Effect of add-on Doxofylline on Lung Function in Stable COPD
NCT04339270	PHASE4	RECRUITING	Chronic Airway Disease, Mucus Rheology and Exacerbations
NCT04789057	PHASE4	ACTIVE_NOT_RECRUITING	Atorvastatin Effect on Reduction of COPD Exacerbations
NCT05772013	PHASE4	RECRUITING	Optimising Azithromycin Prevention Treatment in COPD to Reduce Exacerbations
NCT06152653	PHASE4	RECRUITING	The Effects of Positive Airway Pressure on the Mucolytic Effects of NAC (TEAM)
NCT06334575	PHASE4	RECRUITING	Molecular Signatures Associated With Response to ICS Treatment in Patients With COPD Stratified by Eosinophil Levels
NCT06552364	PHASE4	NOT_YET_RECRUITING	Air Pollution and Inhaled Corticosteroids in COPD
NCT06825013	PHASE4	RECRUITING	Bronchodilators and Lung Mechanics During Exercise in COPD
NCT06825728	PHASE4	NOT_YET_RECRUITING	Metoprolol in Patients With HFrEF and COPD
NCT06892210	PHASE4	RECRUITING	Comparing Hydrocortisone and Prednisolone for Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)
NCT06929767	PHASE4	NOT_YET_RECRUITING	Do Blood Tests Help to Decide Which Patients With Flares of Chronic Obstructive Pulmonary Disease (COPD) Need Antibiotics and Steroids?
NCT06991426	PHASE4	NOT_YET_RECRUITING	Effects of CreaSafe® on Kidney, Muscle, and Cardiopulmonary Function in Athletes and COPD Patients
NCT07053423	PHASE4	RECRUITING	A Study to Investigate Airway Inflammation With Dupilumab Subcutaneously in Participants Aged ≥40 to ≤85 Years With Chronic Obstructive Pulmonary Disease.
NCT07073950	PHASE4	RECRUITING	A Study to Investigate the Effect of Budesonide/Glycopyrronium/Formoterol Fumarate Metered Dose Inhaler (BGF MDI) Compared With Placebo MDI on Heart and Lung Function in Participants With Chronic Obstructive Pulmonary Disease (COPD) and Hyperinflation
NCT07114120	PHASE4	RECRUITING	Clinical Study on the Treatment of Stable Bronchiectasis With Bailing Capsules Combined With Guben Kechuan Granules
NCT07133880	PHASE4	RECRUITING	Compare the Effects of Nebulizer Versus Inhaler Based Therapy for COPD Using Long-acting Bronchodilators
NCT07135427	PHASE4	RECRUITING	Genetic Variation in IgG in Alpha 1 Antitrypsin Deficiency
NCT07192016	PHASE4	NOT_YET_RECRUITING	129-Xe MRI Study of Single Triple Therapy Inhaler Effects in COPD Patients With Moderate-severe Dyspnea and/or Poor Health Status With High or Low Risk of Exacerbation
NCT07508644	PHASE4	NOT_YET_RECRUITING	RSV Vaccination to Reduce Recurrent AECOPD
NCT07587658	PHASE4	NOT_YET_RECRUITING	This After Market Study is Seeing if Dupilumab Plus Usual Standard of Care (SOC) is Better Than Usual Care Alone for Adult Participants After a Severe Chronic Obstructive Pulmonary Disease (COPD) Flare-Up Requiring Hospitalization
NCT00120978	PHASE4	UNKNOWN	Can Advair and Flovent Reduce Systemic Inflammation Related to Chronic Obstructive Pulmonary Disease (COPD)? A Multi-Center Randomized Controlled Trial
NCT00134979	PHASE4	COMPLETED	Formoterol Certihaler, Tiotropium HandiHaler and Tiotropium HandiHaler in Combination With Formoterol Certihaler in Patients With Stable Chronic Obstructive Pulmonary Disease
NCT00158847	PHASE4	TERMINATED	Modification Of Disease Outcome In COPD
NCT00170222	PHASE4	COMPLETED	Placebo Versus Antibiotics in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
NCT00175565	PHASE4	COMPLETED	Inhaled Steroid Reduces Systemic Inflammation in COPD
NCT00181207	PHASE4	COMPLETED	Airway Clearance for Prevention of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
NCT00186706	PHASE4	COMPLETED	Selenium Supplementation in Chronic Obstructive Pulmonary Disease (COPD) Patients
NCT00190437	PHASE4	COMPLETED	ANTEAB: a Study of Early Antibiotherapy in the ICU Management of Acute Exacerbations of COPD
NCT00202176	PHASE4	COMPLETED	Effects of Bronchodilators in Mild Chronic Obstructive Pulmonary Disease (COPD)
NCT00202189	PHASE4	COMPLETED	Effects of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease (COPD)
NCT00232674	PHASE4	COMPLETED	Efficacy Study of the Effect of Budesonide on Emphysema
NCT00288548	PHASE4	UNKNOWN	Metoprolol and Formoterol in Chronic Obstructive Pulmonary Disease (COPD)
NCT00291408	PHASE4	WITHDRAWN	Effect of Symbicort on HAT and HDAC in Sputum Macrophages of COPD
NCT00291460	PHASE4	UNKNOWN	Inspiratory Muscle Training in Hypercapnic COPD
NCT00292838	PHASE4	COMPLETED	Relative Potency of Inhaled Corticosteroids
NCT00311961	PHASE4	COMPLETED	Intravenous Versus Oral Administration of Prednisolone in Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
NCT00316992	PHASE4	COMPLETED	Safety of Ramelteon in Subjects With Chronic Obstructive Pulmonary Disease
NCT00331656	PHASE4	UNKNOWN	Comparative Study of Non-Invasive Mask Ventilation vs Cuirass Ventilation in Patients With Acute Respiratory Failure.

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FORMOTEROL	4	133
GLYCOPYRRONIUM	4	119
TIOTROPIUM	4	90
INDACATEROL	4	76
ARFORMOTEROL	4	71
ACLIDINIUM	4	57
DARIFENACIN	4	57
ROFLUMILAST	4	28
SALMETEROL	4	28
ALBUTEROL	4	23
BUDESONIDE	4	23
IPRATROPIUM	4	21
VILANTEROL	4	20
THEOPHYLLINE ANHYDROUS	4	18
BECLOMETHASONE DIPROPIONATE	4	14
BISOPROLOL	4	12
FLUTICASONE PROPIONATE	4	12
SILDENAFIL	4	12
REVEFENACIN	4	11
ACETAZOLAMIDE	4	10
UMECLIDINIUM	4	10
DOXYCYCLINE ANHYDROUS	4	9
ENSIFENTRINE	4	9
FLUTICASONE FUROATE	4	8
MOXIFLOXACIN	4	5
OXYGEN	4	5
BENRALIZUMAB	4	4
DUPILUMAB	4	4
MEPOLIZUMAB	4	4
TEZEPELUMAB	4	4