SCGB1A1

Summary

SCGB1A1 (secretoglobin family 1A member 1, HGNC:12523) is a protein-coding gene on chromosome 11q12.3, encoding Uteroglobin (P11684). Binds phosphatidylcholine, phosphatidylinositol, polychlorinated biphenyls (PCB) and weakly progesterone, potent inhibitor of phospholipase A2.

This gene encodes a member of the secretoglobin family of small secreted proteins. The encoded protein has been implicated in numerous functions including anti-inflammation, inhibition of phospholipase A2 and the sequestering of hydrophobic ligands. Defects in this gene are associated with a susceptibility to asthma.

Source: NCBI Gene 7356 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_003357

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12523
Approved symbol	SCGB1A1
Name	secretoglobin family 1A member 1
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	CC10, CCSP, CC16
Ensembl gene	ENSG00000149021
Ensembl biotype	protein_coding
OMIM	192020
Entrez	7356

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000278282, ENST00000534397, ENST00000875107

RefSeq mRNA: 1 — MANE Select: NM_003357 NM_003357

CCDS: CCDS8020

Canonical transcript exons

ENST00000278282 — 3 exons

Exon	Start	End
ENSE00001143425	62419033	62419150
ENSE00001312155	62423059	62423195
ENSE00003630769	62422221	62422408

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 99.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 21.7248 / max 10507.2717, expressed in 102 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114688	21.7248	102

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.99	gold quality
epithelium of bronchus	UBERON:0002031	99.99	gold quality
right lung	UBERON:0002167	99.93	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.82	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.78	gold quality
bronchus	UBERON:0002185	99.57	gold quality
urethra	UBERON:0000057	99.23	gold quality
adult organism	UBERON:0007023	99.13	gold quality
nasal cavity epithelium	UBERON:0005384	99.08	gold quality
nasal cavity mucosa	UBERON:0001826	98.19	gold quality
lower lobe of lung	UBERON:0008949	97.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.24	gold quality
trachea	UBERON:0003126	95.94	gold quality
upper lobe of lung	UBERON:0008948	93.91	gold quality
upper lobe of left lung	UBERON:0008952	93.56	gold quality
lung	UBERON:0002048	93.41	gold quality
epithelium of nasopharynx	UBERON:0001951	92.12	gold quality
nasopharynx	UBERON:0001728	92.10	gold quality
lower esophagus mucosa	UBERON:0035834	87.62	gold quality
prostate gland	UBERON:0002367	80.03	gold quality
oral cavity	UBERON:0000167	72.56	gold quality
esophagus mucosa	UBERON:0002469	71.94	gold quality
islet of Langerhans	UBERON:0000006	65.92	gold quality
adenohypophysis	UBERON:0002196	60.66	gold quality
apex of heart	UBERON:0002098	60.56	gold quality
esophagus	UBERON:0001043	59.86	gold quality
pancreatic ductal cell	CL:0002079	58.48	silver quality
oocyte	CL:0000023	58.07	gold quality
cerebellar hemisphere	UBERON:0002245	58.06	gold quality
cerebellar cortex	UBERON:0002129	57.89	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	243259.46
E-HCAD-15	yes	162614.84
E-MTAB-6653	yes	132706.57
E-GEOD-86618	yes	11668.84
E-HCAD-1	yes	20.24
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPD, CEBPG, FOXA1, FOXA2, FOXF1, FOXJ1, FOXM1, FOXP1, FOXP2, JUN, NKX2-1, NKX2-5, PAX3, SOX17, SOX2, SP1, SPI1, TBP, TTF1, YY1

miRNA regulators (miRDB)

8 targeting SCGB1A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-299-5P	98.56	71.14	1140
HSA-MIR-4708-5P	97.77	67.82	831
HSA-MIR-203A-5P	96.33	65.03	714
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-885-3P	95.14	63.08	448

Literature-anchored findings (GeneRIF, showing 40)

• The effect of G38A may be apparent under stimulation as sex steroids or infections, and homozygotes of the G38A mutation cannot produce sufficient UG in response to stimulation and may be predisposed to IgA nephropathy, especially in childhood. (PMID:11774099)
• Role of uteroglobin G38A polymorphism in the progression of IgA nephropathy in Japanese patients. (PMID:11967037)
• is a regulator of the inflammatory process in respiratory diseases (PMID:12014016)
• Lys 43 and Asp 46 in rhUG are critical residues for the sPLA2-inhibitory activity of UG (PMID:12127976)
• In IgA nephropathy, circulating UGB is not reduced and is even increased in IgA-Fn complexes, suggesting a feedback mechanism to downregulate the formation and circulation of IgA1-Fn complexes. (PMID:12200800)
• COUP-transcription factors may play a pivotal role in cell specificity of the human CC10 gene by inhibiting its expression in nonpermissive cells (PMID:12204889)
• CC16*A38G single-nucleotide polymorphism influences bronchial hyperreactivity and might be a genetic determinant of asthma severity in German children. (PMID:12642831)
• results suggest that rP1 inhibits platelet aggregation by participation in the actin polymerization through which store mediated calcium entry is mediated (PMID:12927696)
• G38A polymorphism in the CC10 gene may influence protein expression and be associated with the development of progressive sarcoidosis (PMID:14551164)
• The presence of UG significantly correlated with the expression of estrogen receptor alpha and Progesterone rseceptor in endometrial cancer. (PMID:14719079)
• uteroglobin expression is regulated by progesterone in the normal endometrium but regulation by progesterone receptor is lost in endometrial hyperplasia and carcinoma according to acquirement of tumorigenesis (PMID:14735466)
• Uteroglobin G38A polymorphism had no association with the development of IgA nephropathy. (PMID:14990020)
• Uteroglobin is an essential component of a novel innate homeostatic mechanism in the mammalian airways to repress allergen-induced inflammatory responses. (PMID:15148333)
• Combination of CC16, GSTM1, and GSTT1 genetic polymorphisms is associated with asthma. (PMID:15148962)
• These data provide new insights into the role of CC-10 in lung diseases and the possibility that the CC-10 concentration in serum could be a new marker indicating the severity of bronchial asthma. (PMID:15467329)
• CC10 was the most down-regulated gene in human nasal polyp tissues studied by means of DNA microarray (PMID:15480316)
• Uteroglobin suppresses SCCA gene expression associated with airway inflammation in asthma (PMID:15677460)
• Polymorphism A38G and its role in asthma is studied. (PMID:15744536)
• Reduction in anti-inflammatory activity by CC16 may contribute to the pathogenesis of allergic rhinitis. (PMID:15813809)
• induction of uteroglobin expression has inhibitory effect on COX-2 expression in lung cancer cells via suppression of nuclear factor kappa-B activity (PMID:15829319)
• uteroglobin plays important roles in maintaining homeostasis in organs that are vulnerable to inadvertent stimulation of FP-mediated inflammatory response by inhibiting the prostaglandin F2alpha receptor (PMID:16061484)
• Given that inflammation may lead to functional compromise, these data suggest that early intervention with rhCC10 may enhance SF therapy. (PMID:16081627)
• Subjects with CC16 38AA were more likely to have moderate or severe acute asthma. (PMID:16387800)
• CC10 is detectable in the blood of newborn infants, and a production surge occurs at birth; surge is more pronounced in term infants and may confer them with superior extrauterine pulmonary protection compared with preterm infants (PMID:16690962)
• These results do not support a role for UG in susceptibility to childhood Henoch-Schonlein purpura. (PMID:16703373)
• Uteroglobin induces the development and cellular proliferation of the mouse early embryo. (PMID:17094107)
• The genetic polymorphism in CC16 38 A/G is not associated with susceptibility to COPD in a southern Chinese population of Han nationality. (PMID:17207022)
• The metabolic pathway of CC10 was studied. (PMID:17507989)
• Uteroglobin is present in the human fallopian tube as a secretory protein and appears to be involved in immunosuppressive responses in the fallopian tube. (PMID:17531233)
• Serum Clara cell protein 16(CC16) concentrations decreased in silica-exposed miners and may be a useful biomarker for early diagnosis of silicosis. (PMID:17693780)
• study found that infant frequent wheezing is associated with the CC10 G+38A polymorphism and lower CC10 levels but not infant atopy (PMID:17716718)
• Study provides evidence for the first time for AF-1 binding with uteroglobin(UG)-binding protein, and preliminarily characterized UG-binding protein as a point downstream of AF-1 in mediating ERK phosphorylation. (PMID:17928103)
• Newborn piglets with meconium aspiration syndrome have physiologic dysfunction, inflammatory changes and histologic abnormalities, partially counteracted by a single dose of exogenous surfactant and CC10. (PMID:17957145)
• Uteroglobin interacts with the heparin-binding site of fibronecti(Fn) and propose that small molecules competing for interaction with this site may reduce the level of circulating Fn-IgA complexes in immunoglobulin A (IgA)-nephropathy. (PMID:18243143)
• Higher levels of the anti-inflammatory protein CC10 are associated with improvement in bronchial dysplasia (PMID:18316584)
• CC16 protein is a peripheral blood biomarker of lung injury in ventilated preterm neonates. (PMID:18521628)
• The CC10 A + 38G SNP may not exert a substantial influence on the development of CRS in the Chinese Han population. (PMID:18702901)
• serum CC16 levels elevated in children with respiratory syncytial virus infection (PMID:18976364)
• CC10 may take part in the pathogenesis of CRS and correlates with disease severity. Different cytokines can regulate CC10 expression in nasal mucosa differentially through modulating mRNA stability and certain transcriptional factors expression. (PMID:19076932)
• SCGB1A1 A38G may play a role in the development and persistence of the asthma phenotype in childhood. (PMID:19128353)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Scgb1a1	ENSMUSG00000024653
rattus_norvegicus	Scgb1a1	ENSRNOG00000020196

Paralogs (2): SCGB1C1 (ENSG00000188076), SCGB1C2 (ENSG00000268320)

Protein

Protein identifiers

Uteroglobin — P11684 (reviewed: P11684)

Alternative names: Club cell phospholipid-binding protein, Club cells 10 kDa secretory protein, Secretoglobin family 1A member 1, Urinary protein 1

All UniProt accessions (3): P11684, A0A0S2Z4R6, E9PN95

UniProt curated annotations — full annotation on UniProt →

Function. Binds phosphatidylcholine, phosphatidylinositol, polychlorinated biphenyls (PCB) and weakly progesterone, potent inhibitor of phospholipase A2.

Subunit / interactions. Antiparallel homodimer; disulfide-linked. Interaction with LMBR1L has been observed in PubMed:16423471, but not in PubMed:23964685.

Subcellular location. Secreted.

Tissue specificity. Club cells (nonciliated cells of the surface epithelium of the pulmonary airways).

Similarity. Belongs to the secretoglobin family.

RefSeq proteins (1): NP_003348* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000329	Uteroglobin	Family
IPR016126	Secretoglobin	Family
IPR035960	Secretoglobin_sf	Homologous_superfamily
IPR043215	Secretoglobin_1C-like	Family

Pfam: PF01099

UniProt features (14 total): helix 6, disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, strand 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7VF3	X-RAY DIFFRACTION	2.29
7VG7	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11684-F1	89.32	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 24, 90

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 182 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_RESPONSE_TO_CORTICOSTEROID, MODULE_64, MODULE_418, GOZGIT_ESR1_TARGETS_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, MODULE_404

GO Biological Process (19): negative regulation of transcription by RNA polymerase II (GO:0000122), signal transduction (GO:0007165), female pregnancy (GO:0007565), embryo implantation (GO:0007566), response to xenobiotic stimulus (GO:0009410), response to ozone (GO:0010193), response to lipopolysaccharide (GO:0032496), negative regulation of type II interferon production (GO:0032689), negative regulation of interleukin-13 production (GO:0032696), negative regulation of interleukin-4 production (GO:0032713), negative regulation of interleukin-5 production (GO:0032714), response to silicon dioxide (GO:0034021), response to cytokine (GO:0034097), T cell proliferation (GO:0042098), negative regulation of T cell proliferation (GO:0042130), regulation of mRNA stability (GO:0043488), regulation of inflammatory response (GO:0050727), response to glucocorticoid (GO:0051384), response to fibroblast growth factor (GO:0071774)

GO Molecular Function (3): phospholipase A2 inhibitor activity (GO:0019834), polychlorinated biphenyl binding (GO:0097160), protein binding (GO:0005515)

GO Cellular Component (6): obsolete extracellular space (GO:0005615), nuclear envelope (GO:0005635), cytoplasm (GO:0005737), secretory granule (GO:0030141), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of cytokine production	4
response to oxygen-containing compound	2
binding	2
endomembrane system	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
multi-organism reproductive process	1
multi-multicellular organism process	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
response to chemical	1
response to reactive oxygen species	1
response to molecule of bacterial origin	1
response to lipid	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-13 production	1
regulation of interleukin-13 production	1
interleukin-4 production	1
regulation of interleukin-4 production	1
interleukin-5 production	1
regulation of interleukin-5 production	1
response to peptide	1
T cell activation	1
lymphocyte proliferation	1
T cell proliferation	1
regulation of T cell proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of T cell activation	1
regulation of RNA stability	1
regulation of mRNA catabolic process	1
inflammatory response	1

Protein interactions and networks

STRING

1150 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCGB1A1	SCGB3A2	Q96PL1	860
SCGB1A1	SFTPC	P11686	856
SCGB1A1	SFTPB	P07988	800
SCGB1A1	FOXJ1	Q92949	791
SCGB1A1	AQP5	P55064	781
SCGB1A1	SCGB3A1	Q96QR1	778
SCGB1A1	ROM1	Q03395	773
SCGB1A1	AHNAK	Q09666	770
SCGB1A1	COX8A	P10176	765
SCGB1A1	PLCB3	Q01970	765
SCGB1A1	SF1	Q15637	765
SCGB1A1	PYGM	P11217	764
SCGB1A1	FTH1	P02794	764
SCGB1A1	FKBP2	P26885	764
SCGB1A1	FOSL1	P15407	763
SCGB1A1	MAP3K11	Q16584	763

IntAct

30 interactions, top by confidence:

A	B	Type	Score
TRIM32	SCGB1A1	psi-mi:“MI:0915”(physical association)	0.830
SCGB1A1	TRIM32	psi-mi:“MI:0915”(physical association)	0.830
SCGB1A1	FN1	psi-mi:“MI:0407”(direct interaction)	0.620
SCGB1A1	TMEM43	psi-mi:“MI:0915”(physical association)	0.560
SCGB1A1	AQP6	psi-mi:“MI:0915”(physical association)	0.560
FOS	SCGB1A1	psi-mi:“MI:0915”(physical association)	0.560
SCGB1A1	GATM	psi-mi:“MI:0915”(physical association)	0.560
SCGB1A1	HSF1	psi-mi:“MI:0915”(physical association)	0.560
SCGB1A1	ACTA2	psi-mi:“MI:0915”(physical association)	0.560
SCGB1A1	E6	psi-mi:“MI:0915”(physical association)	0.370
SCGB1A1	BLK	psi-mi:“MI:0914”(association)	0.350
SCGB1A1	TRIM32	psi-mi:“MI:0915”(physical association)	0.000
SCGB1A1	TMEM43	psi-mi:“MI:0915”(physical association)	0.000
SCGB1A1	AQP6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): TRIM32 (Two-hybrid), SCGB1A1 (Two-hybrid), ACTB (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), BLK (Affinity Capture-MS), SCGB1A1 (Affinity Capture-MS), SCGB1A1 (Two-hybrid), SCGB1A1 (Two-hybrid), TMEM43 (Two-hybrid), LRP2 (Reconstituted Complex), CUBN (Reconstituted Complex), ACTA2 (Affinity Capture-MS), SCGB1A1 (Two-hybrid), SCGB1A1 (Co-fractionation), SCGB1A1 (Co-fractionation)

ESM2 similar proteins: A0A8M9PDM1, A0JNP2, O09051, O75556, O95968, O95969, P02779, P02780, P02781, P02782, P04769, P06913, P09320, P0DMR2, P11684, P17559, P28902, P30438, P30440, P33578, P33579, P33580, P33680, P70664, P70668, P79897, Q02747, Q05702, Q06318, Q0PGP2, Q13296, Q16661, Q28358, Q2VPS3, Q4G0G5, Q6UGQ3, Q6XE38, Q7M742, Q7M747, Q8CGZ9

Diamond homologs: A0JNP2, O95968, O95969, P02781, P02782, P06913, P11684, Q6XE38, P02779, P17559, Q06318, Q2VPS3, Q65C83, Q8MKG2, Q8VD96, Q9TS45, P0DMR2, Q8TD33

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

12 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

486 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62422219:A:AG	acceptor_gain	1.0000
11:62422220:G:GG	acceptor_gain	1.0000
11:62422216:TGCA:T	acceptor_loss	0.9900
11:62422218:CA:C	acceptor_loss	0.9900
11:62422220:G:A	acceptor_loss	0.9900
11:62422220:GC:G	acceptor_gain	0.9800
11:62422220:GCTT:G	acceptor_gain	0.9800
11:62419148:CCGGT:C	donor_loss	0.9700
11:62419149:CGGTG:C	donor_loss	0.9700
11:62419150:GGTG:G	donor_loss	0.9700
11:62419151:G:GC	donor_loss	0.9700
11:62419151:G:GG	donor_gain	0.9700
11:62419152:TGAG:T	donor_loss	0.9700
11:62419153:GA:G	donor_loss	0.9700
11:62422213:T:TA	acceptor_gain	0.9700
11:62422220:GCT:G	acceptor_gain	0.9700
11:62422220:GCTTC:G	acceptor_gain	0.9700
11:62422216:TGCAG:T	acceptor_gain	0.9600
11:62422217:GCAGC:G	acceptor_gain	0.9600
11:62422389:A:T	donor_gain	0.9600
11:62422437:TTAG:T	donor_gain	0.9600
11:62419154:AG:A	donor_loss	0.9500
11:62422106:GCTGC:G	donor_gain	0.9500
11:62422218:CAGC:C	acceptor_gain	0.9500
11:62422219:AGCT:A	acceptor_gain	0.9400
11:62419155:G:C	donor_loss	0.9300
11:62419347:G:GT	donor_gain	0.9300
11:62422211:T:A	acceptor_loss	0.9300
11:62422220:G:T	acceptor_gain	0.9300
11:62422334:G:T	donor_gain	0.9300

AlphaMissense

599 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62422354:G:C	K63N	0.962
11:62422354:G:T	K63N	0.962
11:62422310:T:C	F49L	0.910
11:62422312:C:A	F49L	0.910
11:62422312:C:G	F49L	0.910
11:62422353:A:C	K63T	0.878
11:62422350:T:C	L62P	0.875
11:62422311:T:G	F49C	0.841
11:62422266:T:C	L34P	0.823
11:62419124:T:A	V10D	0.791
11:62422404:T:C	L80P	0.778
11:62422337:G:C	A58P	0.776
11:62422311:T:C	F49S	0.775
11:62422352:A:G	K63E	0.771
11:62422235:T:C	C24R	0.769
11:62422237:C:G	C24W	0.765
11:62422266:T:G	L34R	0.762
11:62422266:T:A	L34H	0.756
11:62423085:T:G	C90W	0.749
11:62422289:T:G	Y42D	0.748
11:62422353:A:T	K63M	0.747
11:62422235:T:A	C24S	0.746
11:62422236:G:C	C24S	0.746
11:62422350:T:G	L62R	0.733
11:62423083:T:A	C90S	0.727
11:62423084:G:C	C90S	0.727
11:62422245:T:G	F27C	0.725
11:62422298:G:C	A45P	0.711
11:62422236:G:A	C24Y	0.709
11:62419133:C:A	A13D	0.708

dbSNP variants (sampled 300 via entrez): RS1000177743 (11:62423154 G>A,T), RS1000862508 (11:62422917 C>A,T), RS1000947752 (11:62418708 C>T), RS1001496405 (11:62417600 T>A), RS1001679917 (11:62423508 C>T), RS1002823628 (11:62418803 C>T), RS1003507778 (11:62420400 G>A,C,T), RS1003976478 (11:62422795 A>G), RS1004238249 (11:62420146 C>G), RS1004282325 (11:62417752 G>A), RS1005583965 (11:62417987 A>C,G), RS1006434125 (11:62420738 C>T), RS1007722590 (11:62420676 T>C), RS1008313105 (11:62421413 A>C), RS1008636578 (11:62420999 A>G)

Disease associations

OMIM: gene MIM:192020 | disease phenotypes: MIM:606963, MIM:600807

GenCC curated gene-disease

Mondo (2): chronic obstructive pulmonary disease (MONDO:0005002), inherited susceptibility to asthma (MONDO:0010940)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001737_21	Chronic obstructive pulmonary disease-related biomarkers	1.000000e-26
GCST005956_12	Waist-to-hip ratio adjusted for BMI	2.000000e-06
GCST005956_2	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_37	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-07
GCST005962_51	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-07
GCST006019_36	Gamma glutamyl transferase levels	3.000000e-17
GCST010989_100	Body size at age 10	2.000000e-08
GCST011456_5	Serum CC16 levels	2.000000e-59
GCST90011898_2	Alanine aminotransferase levels	8.000000e-12
GCST90020025_937	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020025_938	Waist-to-hip ratio adjusted for BMI	9.000000e-10
GCST90020027_1473	Waist-hip index	2.000000e-08
GCST90020027_1474	Waist-hip index	4.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005080	CC16 measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0009819	comparative body size at age 10, self-reported

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D029424	Pulmonary Disease, Chronic Obstructive	C08.381.495.389; C23.550.291.500.875

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression, decreases secretion	3
sodium arsenite	increases expression	2
Vehicle Emissions	decreases expression	2
Silicon Dioxide	increases expression, decreases expression, decreases reaction	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
2,3-pentanedione	increases expression	1
naphthalene	decreases expression, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Aluminum	decreases expression	1
Arsenic	decreases expression	1
Arsenicals	decreases expression	1
Atrazine	increases expression	1
Calcium	increases expression	1
Heterocyclic Compounds, 3-Ring	decreases expression	1
Nitric Oxide	decreases expression	1
Paraquat	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Aflatoxin B1	increases methylation	1
Trihalomethanes	affects expression	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
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.
NCT00335621	PHASE4	WITHDRAWN	Replacement of Nebulised Ipratropium With Inhaled Tiotropium in Stable Chronic Obstructive Pulmonary Disease (COPD)
NCT00354354	PHASE4	COMPLETED	Bronchodilators and Oxygen Kinetics With Exercise in Chronic Obstructive Pulmonary Disease (COPD) Patients
NCT00379028	PHASE4	COMPLETED	Airway Clearance Study
NCT00405236	PHASE4	COMPLETED	Effect of Tiotropium on Inflammation and Exacerbations in COPD
NCT00412204	PHASE4	COMPLETED	Study to Evaluate the Effects of Tiotropium Bromide on Chronic Obstructive Pulmonary Disease (COPD) During Exercise
NCT00424528	PHASE4	COMPLETED	Efficacy Safety Study of Arformoterol/Tiotropium Combination Versus Either Therapy Alone in Chronic Obstructive Pulmonary Disease (COPD)
NCT00440245	PHASE4	COMPLETED	Bronchoprotection of Salbutamol in Asthma and Chronic Obstructive Pulmonary Disease
NCT00440687	PHASE4	COMPLETED	Withdrawal of Inhaled Corticosteroids in Patients With COPD in Primary Care
NCT00489853	PHASE4	COMPLETED	Evaluation of Efficacy on Exercise Tolerance of Symbicort (Budesonide/Formoterol) Compared to Placebo and Oxis in Patients With Severe COPD
NCT00491803	PHASE4	COMPLETED	Sildenafil Effects on Pulmonary Haemodynamics and Gas Exchange in Chronic Obstructive Pulmonary Disease (COPD)
NCT00495586	PHASE4	COMPLETED	Effectiveness of Antibiotic Therapy for Exacerbations of Chronic Obstructive Pulmonary Disease
NCT00525564	PHASE4	COMPLETED	Effects of Salmeterol on Walking Capacity in Patients With COPD
NCT00532584	PHASE4	WITHDRAWN	Effect of Steroids on Gene Expression in the Healthy Smokers Lungs
NCT00542880	PHASE4	COMPLETED	Evaluation of Onset of Effect in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD) Treated With Symbicort® Compared to Seretide®
NCT00561886	PHASE4	COMPLETED	Change of Inspiratory Peak Flow in COPD
NCT00569270	PHASE4	COMPLETED	Dynamic Hyperinflation and Tiotropium
NCT00571428	PHASE4	COMPLETED	Efficacy Safety Study of Arformoterol QD Dosing Versus BID Dosing in COPD
NCT00578968	PHASE4	COMPLETED	Cardiac Limitations in Chronic Obstructive Pulmonary Disease: Benefits of Bronchodilation
NCT00592033	PHASE4	COMPLETED	Effect of Oxygen in Normoxaemic COPD Patients Who Desaturate During Exercise
NCT00628225	PHASE4	COMPLETED	Smoking Cessation in Patients With COPD (SMOCC) in General Practice
NCT00633776	PHASE4	WITHDRAWN	Perforomist Versus Foradil Evaluated by Inspiratory Capacity and High Resolution Computed Tomography (HRCT)
NCT00639236	PHASE4	COMPLETED	Effectiveness and Safety of Inhaling Hypertonic Saline in Patients With Chronic Obstructive Pulmonary Disease